Clinical Services Master Agreement

Clinical Services Master Agreement

Exhibit 10.26

CLINICAL SERVICES MASTER AGREEMENT

THIS CLINICAL SERVICES MASTER AGREEMENT (this “Master Agreement”) is entered into as of this 1st day of June, 2005, by and between Peplin Operations Pty Ltd ACN 093 317 367 (“Sponsor”) of Level 2, 1 Breakfast Creek Road, Newstead in the state of Queensland, Australia and Omnicare CR, Inc., (“Omnicare CR”) a Delaware corporation.

WHEREAS, Sponsor requires various clinical research services from time to time in support of various projects (individually, a “Project,” and collectively, the “Projects”), which shall be set forth in Exhibits to this Master Agreement; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR hereby agree as follows:

 

1. Scope of Master Agreement; Obligations

 

  1.1. The specific responsibilities and obligations to be performed by Omnicare CR with respect to a Project (the “Services”), as set forth in the applicable Protocol(s), are expressly set forth in Exhibit(s) attached to this Master Agreement, which, together with the Exhibit(s) attached hereto, are incorporated by reference herein. No Exhibit will be attached to this Master Agreement or become effective without first being executed by duly authorized representatives of the parties hereto. To the extent any terms set forth in an Exhibit shall conflict with the terms set forth in this Master Agreement, the terms of this Master Agreement will take precedence unless the Exhibit expressly states that a conflicting term is intended to modify a specific term in this Master Agreement. The responsibility for the Services is being transferred to Omnicare CR in accordance with 21 C.F.R. §312.52. Those responsibilities and obligations not specifically transferred to and assumed by Omnicare CR in this Master Agreement or the Exhibit(s) as constituting part of the Services shall be and remain the sole responsibility of Sponsor.

 

  1.2. Omnicare CR agrees that Omnicare CR will provide the Services in accordance with (a) all applicable federal laws and regulations, including standards of Good Clinical Practices; and (b) the standards and practices that are generally accepted in the industry and exercised by other persons engaged in performing similar services.

 

  1.3. In the discharge of its duties, Omnicare CR shall comply with all reasonable directions of Sponsor as may be given in writing from time to time in respect of the Services.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.


  1.4. Omnicare CR shall at all times provide sufficient appropriately-trained and qualified clinical research personnel on a given Project to meet the demands of said Project.

 

  1.5. In the event that Sponsor or a third-party engaged by Sponsor performs an audit of the Project, Omnicare CR will respond in writing to the audit findings within thirty (30) days of receipt of same.

 

  1.6. Omnicare CR shall use its commercially reasonable efforts, skills and abilities to promote the interests of Sponsor and to diligently and competently perform its duties under this Master Agreement.

 

2. Payment

 

  2.1. In consideration of the Services, Sponsor shall pay to Omnicare CR: (a) the Service Fees (as defined in Section 2.2); and (b) the Pass-Through Costs (as defined in Section 2.3).

 

  2.2. As used in this Master Agreement, the term “Service Fees” means all amounts due for the Services, exclusive of the Pass-Through Costs. The estimated Service Fees and the payment schedule therefor are set forth in the Exhibit(s), and shall be increased to include: (a) the costs of any additional Services required as a result of Project changes by Sponsor; (b) any costs that arise out of or relate to a Force Majeure as outlined in Section 10 below, and (c) where a Project requires more time than allotted in the Exhibit(s), and the parties agree to continue such Project beyond the expected conclusion date, any additional costs that may be incurred in order to complete such Project, at the contractual rates set forth in the applicable Exhibit(s). All payments of Service Fees shall be made within thirty (30) days of receipt of invoice. If any payment of Service Fees is late by more than thirty (30) days, such payment shall be subject to a liquidated damages fee of 1.5% per month of the outstanding balance.

 

  2.3. As used in this Agreement, the term “Pass-Through Costs” means all investigator, Institutional Review Board or other applicable pass-through costs actually and reasonably incurred by Omnicare CR under this Agreement or the Exhibit(s) in order to expedite successful completion of a Project, which costs are normal and routine to studies similar to such Project (e.g., advancing an investigator’s Institutional Review Board fee and investigator grant payments or reimbursing reasonable additional, unbudgeted patient expenses). In order to enable Omnicare CR to maintain a balance to be applied towards investigator-related Pass-Through Costs, Omnicare CR shall invoice Sponsor for all reasonably anticipated Pass-Through Costs (the “Estimated Pass-Through Costs”) in advance of the expected payment date therefor. Except with respect to investigator-related payments, which are payable upon receipt, all Pass-Through Costs shall be paid within thirty (30) days of receipt of invoice. If any payment Pass-Through Costs is late by more than thirty (30) days, such payment shall be subject to liquidated damages of 1.5% per month of the outstanding balance. The anticipated Pass-Through Costs and Estimated Pass-Through Costs and the payment schedule therefor are set forth in the Exhibit(s).

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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  2.4. Where applicable, language pertaining to annual price increases will be included in each Exhibit.

 

  2.5. Taxes (and any penalties thereon) imposed on any payment made by Sponsor to Omnicare CR will be the responsibility of Omnicare CR. Any sales tax, usage tax, Value Added Tax (VAT), or other similar taxes shall be the responsibility of the Sponsor.

 

  2.6. Sponsor shall make payment direct to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

First Union National Bank

Philadelphia, PA

ABA # ****

Acct # ****

 

3. Confidentiality

 

 

3.1.

That certain Confidentiality Agreement by and between Omnicare CR and Sponsor dated as of 25th November 2004 (the “Confidentiality Agreement”) is hereby terminated and of no further force or effect.

 

  3.2. In connection with the performance of the Services, Sponsor shall provide to Omnicare CR, and Omnicare CR shall have access to, Sponsor’s Confidential Information. As used in this Master Agreement, “Sponsor’s Confidential Information” means any (a) information provided by, or developed for, Sponsor within the framework of or in undertaking activity pursuant to this Master Agreement, the Exhibit(s) or the Confidentiality Agreement; or (b) data collected during a Project.

 

  3.3. In connection with this Master Agreement, Sponsor will have access to, or become acquainted with, Omnicare CR’s Confidential Information. As used in this Master Agreement, “Omnicare CR’s Confidential Information” means any (a) information generated or obtained in connection with Omnicare CR’s pricing, proposals or contracts (including the provisions of this Master Agreement and the Exhibit(s)); (b) of Omnicare CR’s procedures, programs, guidelines or policies (including, without limitation, its Standard Operating Procedures); or (c) information designated in writing as “confidential.”

 

  3.4. Neither Sponsor’s Confidential Information nor Omnicare CR’s Confidential Information (collectively, “Confidential Information”) shall include any information that:

 

  (a)

was known by the receiving party at the time of disclosure to it by the disclosing party, or that is independently developed or discovered by the receiving party, after disclosure by the disclosing party, without the aid, application or use of any

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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item of the disclosing party’s Confidential Information, as evidenced by written records;

 

  (b) is now or subsequently becomes, through no act or failure to act on the part of the receiving party, generally known or available;

 

  (c) is disclosed to the receiving party by a third party authorized to disclose it; or

 

  (d) is required by law or by court or administrative order to be disclosed; provided, that the receiving party shall have first given prompt notice to the other party of such required disclosure.

 

  3.5. Each party shall exercise due care to prevent the unauthorized use or disclosure of the other party’s Confidential Information, and shall not, without the other party’s prior written consent, (a) use the other party’s Confidential Information for any purpose other than performing its obligations under this Master Agreement and the Exhibit(s); or (b) disclose or otherwise make available, directly or indirectly, any item of the other party’s Confidential Information to any person or entity other than those employees, independent contractors, agents or investigators of such party and/or its affiliate entities (collectively, “Representatives”) who reasonably need to know the same in the performance of such party’s obligations under this Master Agreement (including the Exhibit(s)), or in order to make decisions or render advice in connection therewith. For the convenience of the parties, each party acknowledges that unless precluded in writing by the other party, Confidential Information may be transmitted to a party and/or its Representatives via the Internet. Each party shall advise its Representatives who have access to the other party’s Confidential Information of the confidential nature thereof, and agrees that such Representatives will be bound by terms of confidentiality and restrictions on use with respect thereto that are at least as restrictive as the terms of this Section 3.

 

  3.6. The provisions of this Section 3 shall survive for a period of five (5) years from the date of any expiration or termination of this Master Agreement, however caused.

 

  3.7 Omnicare CR acknowledges that in accordance with Section 1043A of the Corporations Act of the Commonwealth of Australia:

 

  (a) Omnicare CR may from time to time as a consequence of the services provided hereunder possess confidential information which may have a material effect on the price or value of the securities of Sponsor and may therefore constitute “inside information” for the purposes of the Corporations Act; and

 

  (b) as an insider one must not (whether as principal or agent in possession of such inside information):

 

   

apply for, acquire or dispose of such securities, or enter into an agreement to apply for, acquire or dispose of any such securities; or

 

   

procure another person to apply for, acquire or dispose of, or to enter into an agreement to apply for acquire or dispose of, any such securities.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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and acknowledges further that:

 

  (c) once in possession of confidential information, a party may be subject to the insider trading restrictions imposed by the Corporations Act and may be prohibited from trading in the securities (as noted above) and/or communicating the confidential information to any other person who would be likely to subscribe for, purchase or sell securities, or procure a third person to do the same until such date when this confidential information has been made “public” in terms of the requirements of the Corporations Act; and

 

  (d) it must seek its own legal advice on its responsibilities under the Corporations Act and that neither party purports that the comments in this clause are either advice or a comprehensive description of the provisions of the Corporations Act.

 

4. Property of Sponsor

 

  4.1. All (a) of Sponsor’s Confidential Information (including, without limitation, all original Project records and reports), (b) unused clinical supplies provided by Sponsor, and (c) complete and incomplete Case Report Forms, which in any case are in Omnicare CR’s possession, shall be and remain Sponsor’s property; provided, however, that Omnicare CR may retain one copy of Sponsor’s Confidential Information in its files for archival purposes, as a means of determining any continuing obligations under this Master Agreement (including the Exhibit(s)).

 

  4.2. All inventions, improvements in know-how, new uses, processes and compounds involving the study drug(s) and/or product(s) covered by this Master Agreement and/or the Exhibit(s) that are conceived or reduced to practice as a direct result of the Project(s) (“Inventions”) shall be and remain the sole property of Sponsor. Omnicare CR shall cooperate with Sponsor in obtaining, at Sponsor’s sole cost and expense, any patent protection as may be available for the Inventions, and shall execute all documents reasonably deemed necessary by Sponsor for purposes of procuring such patent protection. Omnicare CR agrees that Omnicare CR shall endeavor to ensure contractually the prompt disclosure to Sponsor by any investigator, employee or other individual retained by Omnicare CR for a Project of any Inventions, as well as the cooperation of such persons in securing patent protection as set forth herein.

 

  4.3.

Notwithstanding the foregoing, Sponsor acknowledges that Omnicare CR and their respective professional staff currently possess certain inventions, processes, know-how, trade secrets, methods, approaches, analyses, improvements, other intellectual properties and other assets including, but not limited to, clinical trial management analyses, analytical methods, procedures and techniques, computer technical expertise and proprietary software, and technical and conceptual expertise in the area of conducting clinical trials, all of which have been developed independently by Omnicare CR without the benefit of any information provided by Sponsor (collectively, “Omnicare CR Property”). Sponsor agrees that any Omnicare CR Property which is used, improved, modified or developed by Omnicare CR under or

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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during the term of this Master Agreement shall be and remain the sole and exclusive property of Omnicare CR.

5. Restrictions on Announcements

Omnicare CR shall not make any announcement, oral presentation or publication relating to any Project without Sponsor’s prior written consent (which consent shall not be unreasonably withheld), except as required by law or by court or administrative order. Neither Omnicare CR nor Sponsor shall employ or use the name of the other party in any publication or promotional material or in any form for public distribution, without the prior written consent of the other party, except as required by law or by court or administrative order.

6. FDA Inspection

In the event that Omnicare CR receives a Notice of Inspection (a “Notice”) from the Food and Drug Administration (“FDA”) which relates to any Project Omnicare CR shall: (a) notify Sponsor promptly of such Notice; (b) keep Sponsor informed of the progress of the inspection; and (c) provide to Sponsor a copy of any documents produced to the FDA pursuant to such Notice. Sponsor acknowledges that it is Omnicare CR’s obligation to respond to a Notice directed to Omnicare CR and that Omnicare CR must respond to the Notice without advice from, or consultation with, Sponsor concerning the contents thereof.

7. Access to Facilities and Records

 

  7.1. Sponsor’s authorized representatives may visit Omnicare CR’s site and facilities at reasonable times and with reasonable frequency during normal business hours and upon reasonable advance written notice, to observe the progress of any Services. All such visits shall be subject to Omnicare CR’s restrictions and procedures relating to safety, security and protection of Confidential Information, and in connection therewith, Sponsor’s authorized representatives may be required to sign a confidentiality agreement, or an access agreement for special access-controlled areas.

 

  7.2. During the term of this Master Agreement, Omnicare CR shall maintain all materials and all other data obtained or generated by Omnicare CR in the course of providing the Services hereunder, including all computerized records and files. Omnicare CR shall cooperate with any reasonable internal review or audit by Sponsor and make available to Sponsor for examination and duplication, during normal working hours and at mutually agreeable times, all documentation, data and information relating to a Project.

 

  7.3.

Upon the expiration or termination of this Master Agreement, all materials and all other data and information obtained or generated by Omnicare CR as a direct result of providing the Services hereunder will, at Sponsor’s option and cost and expense, be (i) delivered to Sponsor’s offices at the address provided herein in such form as is then currently in the possession of Omnicare CR, (ii) retained by Omnicare CR for Sponsor for a period of two years, or (iii) disposed of as directed in writing by Sponsor, unless such materials are otherwise required to be stored or maintained by

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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Omnicare CR under applicable law. In no event shall Omnicare CR dispose of any materials or data or other information obtained or generated by Omnicare CR as a direct result of providing the Services without first giving Sponsor sixty (60) days prior written notice of its intent to dispose same. Notwithstanding the foregoing, Omnicare CR may retain copies of any such materials, data and information as is reasonably necessary for regulatory purposes or to demonstrate the satisfaction of its obligations hereunder, all subject to the confidentiality obligations set forth herein.

8. Indemnification

 

  8.1. Sponsor agrees to indemnify, defend and hold harmless Omnicare CR and its Affiliate Entities, and their respective officers, directors and employees from and against any and all claims, demands, investigations, suits or actions (each a “Claim”) for any and all liabilities, losses, damages, penalties, costs or expenses of every kind whatsoever (including but not limited to court costs, legal fees, awards of settlements) arising out of, in connection with or related to this Master Agreement and/or the Exhibit(s); provided, however, that Sponsor’s indemnity obligations under this Section 8 shall not apply to any Claim to the extent arising directly from Omnicare CR’s negligence or willful malfeasance.

 

  8.2. Omnicare CR agrees to indemnify, defend and hold harmless Sponsor and its respective officers, directors and employees from and against any and all Claims for any and all liabilities, losses, damages, penalties, costs or expenses of every kind whatsoever (including but not limited to court costs, legal fees, awards or settlements) arising out of, in connection with or related to any breach of this Master Agreement and/or the Exhibit(s) by Omnicare CR, including any breach of warranties, or any willful, unlawful or negligent act or omission of Omnicare CR.

 

  8.3. Each person or entity seeking indemnification under this Section 8 (the “Indemnified Party”) shall, as a condition thereto, notify the other party within twenty (20) days after the receipt of notice of the Claim; provided, however, that the other party shall not be released from its obligations under this Section 8 if the failure to notify that other party within twenty (20) days does not materially prejudice the defense of such Claim. That other party shall have the right to select defense counsel and to direct the defense or, with the consent of the indemnified party (which consent shall not be unreasonably withheld) settlement of, any Claim. In the event that representation of an Indemnified Party and the other party by the same counsel would be a conflict of interest for such counsel, the Indemnified Party may select its own independent counsel without relieving the other party of its obligations under this Section 8. Under no circumstances shall an Indemnified Party settle or otherwise compromise any Claim without the other party’s prior written consent.

 

  8.4. This clause shall survive the expiration or termination of the Master Agreement and/or the Exhibit(s).

9. Termination

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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  9.1. Either party may terminate this Master Agreement and/or any Exhibit at any time and for any reason upon a minimum of thirty (30) days’ prior notice, provided that Omnicare CR may only terminate under this sub-clause in the event that there are no active Exhibits, ie, all tasks under all Exhibits have been completed.

 

  9.2. Without limiting the generality of any other clause in this Master Agreement or the remedies available to either party, either party may terminate this Master Agreement immediately by notice in writing if:

 

  (a) the other party is in material breach of any terms of this Master Agreement or any Exhibit and, where such breach is remediable, such party fails to remedy such material breach or establish a corrective action plan to cure such material breach (which plan shall outline actions to be taken and relevant dates) acceptable to the non-breaching party within fifteen (15) days of receiving notice to do so from the non-breaching party;

 

  (b) the other party is in serious and/or presistent breach of any terms of this Master Agreement or any Exhibit. Failure to perform in accordance with the corrective action plan outlined above shall be deemed a serious breach; or

 

  (c) the other party becomes, threatens to become or is in jeopardy of becoming insolvent.

 

  9.3. Upon receipt of any notice of termination, a party shall avoid or limit, to the extent practicable, incurring any futher commitments, obligations or costs which would otherwise result in Service Fees and Pass-Through Costs.

 

  9.4. Upon any early termination, Sponsor shall pay to Omnicare CR all Service Fees and Pass-Through Costs due and owing based upon Services completed and costs incurred through the effective date of termination, including costs for materials and/or services previously acquired or contracted for which will not be used for the Services as a result of such termination.

 

  9.5. Any funds held by Omnicare CR which by contract definition or amendment are deemed unearned (including, without limitation, any Estimated Pass-Through Costs not used to satisfy Pass-Through Costs) shall be returned to Sponsor within sixty (60) days after conclusion or termination of the Project(s) set forth in the applicable Exhibit(s).

 

  9.6. Following completion or termination of any Project, Omnicare CR shall forward all original Project records and reports to Sponsor (or to a repository designated by Sponsor in writing) at Sponsor’s sole cost and expense. Thereafter, Omnicare CR shall retain any documentation related to such Project in compliance with Omnicare CR’s corporate policy on retention and destruction of records.

10. Force Majeure

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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If either party’s performance of this Master Agreement or any Exhibit is prevented, restricted or delayed (either totally or in part) by reason of any cause beyond the reasonable control of the parties, such as acts of God, explosion, disease, weather, war, insurrection, civil strike, riot or power failure, the party so affected shall, upon giving notice thereof to the other party, be free and be excused from such performance to the extent of such prevention, restriction or delay; provided, that the affected party shall use its commercially reasonable efforts to avoid or remove such causes of non-performance and shall continue performance with the utmost dispatch whenever such causes are removed; and provided further, that nothing herein shall relieve either party from the obligation to pay promptly in full all payments that may be due to the other party under this Master Agreement or the Exhibit(s). In addition to the above, the affected party shall be free from any liabilities, losses, damages, penalties, costs or expenses arising out of or related to such cause beyond the reasonable control of such affected party. If such cause for non-performance exceeds or is likely to exceed thirty (30) days, a party other than the affected party may immediately terminate the Master Agreement and/or the Exhibit(s).

11. No Conflict

Each party represents and warrants that it is authorized to enter into this Master Agreement, that it is not prevented from or impeded in carrying out its obligations under the Master Agreement and/or the Exhibit(s) by way of any agreement, arrangement or understanding that it may have with any other person and that the terms hereof are not inconsistent with or a violation of any other legal obligation to which it is subject.

12. Limitations

 

  12.1. Sponsor acknowledges that the results of the Project(s) are inherently uncertain and that, accordingly, there can be no assurance, representation or warranty by Omnicare CR that the study drug(s) and/or product(s) covered by this Master Agreement and/or the Exhibit(s) can, either during the term of this Master Agreement or thereafter, be developed successfully or, if so developed, will receive the required approval(s) from the FDA other regulatory agency or authority.

 

  12.2 Both parties acknowledge that the Services constitute research and development. Accordingly, Sponsor’s sole remedy for any breach or default hereof by Omnicare CR shall be termination of this Master Agreement or the applicable Exhibit as herein provided or a return of any Service Fees paid to Omnicare CR for Services improperly performed or not performed. In no event shall Omnicare CR be liable for any special, indirect, incidental or consequential damages (whether in contract or tort).

13. Non-Debarment

 

  13.1. Omnicare CR represents and warrants that Omnicare CR has not been nor is currently:

 

  (a)

an individual who has been debarred by the FDA pursuant to 21 U.S.C. §335a (a) or (b) (a “Debarred Individual”) from providing services in any capacity to a

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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person that has an approved or pending drug product application, or an employer, employee or partner of a Debarred Individual; or

 

  (b) a corporation, partnership, or association that has been debarred by the FDA pursuant to 21 U.S.C. §335a (a) or (b) (a “Debarred Entity”) from submitting or assisting in the submission of an abbreviated new drug application, or an employee, partner, shareholder, member, subsidiary or affiliate entity of a Debarred Entity.

 

  13.2. Omnicare CR further represents and warrants that Omnicare CR has no knowledge of any circumstances which may affect the accuracy of the representations and warranties set forth in Section 13.1 including, but not limited to, FDA investigations of, or debarment proceedings against, Omnicare CR or any person or entity performing, or rendering assistance related to, the Services. Omnicare CR will notify Sponsor promptly upon becoming aware of any such circumstances during the term of this Master Agreement.

14. Independent Contractor

The status of the parties under this Master Agreement is that of independent contractors, and, except as specifically set forth herein, or in the Exhibit(s), neither party has any authority to bind or act on behalf of the other party without its express written consent.

15. Notices

Any notices, requests or other communications given under this Master Agreement shall be in writing and shall be given by, personal delivery, or sent by (a) facsimile transmission (with message confirmed during normal business hours); (b) first class mail, postage prepaid; or (c) Federal Express (or equivalent nationally recognized overnight delivery service), delivery charges prepaid. All notices shall be given to a party at its respective address set forth below, or at such other address as such party from time to time may specify by notice in accordance with this Section 15. A notice shall be deemed given when actually received; provided, that if any facsimile notice is received after 5:00 P.M. local time at the place of receipt, it shall be deemed to have been given as of the next following business day.

 

   If to Omnicare CR:    Omnicare CR, Inc.
      630 Allendale Road
      King of Prussia, PA 19406
      Attention: Global Client Contracts
   If to Sponsor:    Peplin Operations Pty Ltd
      Level 2, 1 Breakfast Creek Road
      Newstead
      QLD 4006
      Australia

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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Attention: Dr Peter Welbum

16. Entire Agreement

This Master Agreement, together with all corresponding Exhibits, Amendments or Change Orders, constitutes the entire agreement between Sponsor and Omnicare CR with respect to the subject matter hereof, and replaces and supersedes any and all prior and contemporaneous agreements and/or understandings, whether oral or written, between Sponsor and Omnicare CR with respect to the subject matter hereof. This Master Agreement (including the Exhibit(s)) may be amended or modified only by a written instrument executed by a duly authorized officer of each party.

17. Construction of Agreement

The descriptive headings of the Sections of this Master Agreement are for convenience only and shall not affect the meaning or construction of any of the provisions of this Master Agreement. The failure of either party to enforce any provision of this Master Agreement (including the Exhibit(s)) shall not be construed as a waiver or limitation of that party’s subsequent rights to enforce and compel strict compliance with every provision of this Master Agreement. To the extent any provision of this Master Agreement or the application thereof is found by a proper authority to be invalid or unenforceable, it shall be considered deleted herefrom, and the remainder of this Master Agreement shall continue in full force and effect.

18. Assignment and Sub-contracting

Neither Sponsor nor Omnicare CR may assign this Master Agreement or any rights hereunder or delegate the performance of any duties hereunder without the prior written approval of the other party, which approval shall not be unreasonably delayed or withheld; provided, however, that without such consent, either party may assign this Master Agreement in connection with the transfer or sale of all or substantially all of its assets, stock or business, or its merger, reorganization, consolidation or combination with or into another entity; provided, further, however, without such consent, Omnicare CR may assign any rights hereunder to an Affiliate Entity and Sponsor may assign any rights hereunder to its parent company or a subsidiary of said parent company without the consent of Omnicare CR. Omnicare CR shall not sub-contract any Services under an Exhibit to any legal entity other than an Affiliate Entity without the prior written consent of Sponsor, such consent not to be unreasonably withheld. Subject to the foregoing, this Master Agreement shall be binding upon, inure to the benefit of and be enforceable by the parties and their respective successors and permitted assigns.

19. Timely Review

Sponsor acknowledges that Omnicare CR will require, among other things: (a) timely review of Omnicare CR’s work product; and (b) timely supplies of documents, data, records, and investigational drug product(s) from Sponsor in order to properly perform the Services hereunder and that Omnicare CR are not responsible for errors, delays or other consequences arising from the failure of Sponsor to provide such review and/or materials. Sponsor therefore agrees that it will: (a) promptly review Omnicare CR’s work product where such review is required and/or

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

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necessary; and (b) provide all documents, data, records, investigational drug product(s) and other materials necessary for completion of Omnicare CR’s tasks and Services in a timely manner and in accordance with the schedule or timeline for the applicable Project.

Sponsor agrees to reasonably extend all deadlines hereunder due to delays (by Sponsor or contractors under its control) in (a) reviewing Omnicare CR’s work product; and (b) providing documents, data, records and investigational drug product(s) and other materials needed for the completion of Omnicare CR’s tasks and Services.

20. Restriction

For the period commencing on the date of execution of the last party to sign this Master Agreement and continuing for a period of one (1) year after the termination or expiration of this Master Agreement, each party agrees that it shall not knowingly solicit (as defined below) any of the other party’s or any of the other party’s affiliates’ then current personnel, whether employees or independent contractors under agreement with that other party. As used in this Section 20, “solicit” means the initiation of a contact with any of the other party’s or any of the other party’s affiliates’ then current personnel for the purpose of offering employment to such personnel, but shall not include the circumstance where any such personnel initiate a contact with the party for the purpose of obtaining employment with that party, whether in response to a general advertisement of employment placed by that party or otherwise, or where such contact is initiated by a third party who was not instructed to contact such personnel by that party. In the event a party breaches the terms of this Section, that party agrees to pay the other party as liquidated damages and not as a penalty a sum equal to twenty-five percent (25%) of the starting salary of such employee.

21. Survival

Any terms of this Master Agreement which by their nature extend beyond its performance, expiration or termination (including, without limitation, Sections 2 through 5, 8 through 10, 12, 20 and this Section 21) shall remain in effect indefinitely until fulfilled in accordance with their terms.

22. Governing Law

This Agreement will be governed by and construed in accordance with the laws of the State of Queensland in Australia without giving effect to any choice of law principles that would require the application of the laws of a different jurisdiction.

23. Signatories

This Master Agreement may be executed in counterparts, each of which, when executed and delivered, shall be deemed to be an original, and all of which, when joined, shall together constitute one and the same agreement. Any photocopy or facsimile of this Master Agreement, or of any counterpart, shall be deemed the equivalent of an original.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

12


IN WITNESS WHEREOF, the parties have executed this Master Agreement by their duly authorized officers as of the date first above written.

 

Peplin Operations Pty Ltd     Omnicare CR, Inc.  
By:  

/s/ Michael Aldridge

    By:  

/s/ Kevin D. Duffy

 
Name:   Michael Aldridge     Name:   Kevin D. Duffy  
Title:   Director     Title:   Senior Vice President  
        Global Marketing & Business Development  
        APPROVED  
        LEGAL DEPT.  
  29-July-05       28-July-05  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.


Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc., dated 24-8-05

THIS EXHIBIT A is entered into this 24th day of August, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a Clinical Services, Master Agreement, dated 1 st Jun 05 (hereinafter the “Master Agreement”), wherein Omnicare CR agreed to provide clinical services; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR shall provide the services set forth in this Exhibit A, subject to the terms and conditions set forth in the Master Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

I. Project Plan

Based on the Project Specifications, Omnicare CR has provided a description of services to be performed for Sponsor’s “An Open, Dose-escalation, Cohort study to determine the Safety of PEP005 Topical Gel when applied on Day 1 and Day 2 to Actinic Keratoses on the Shoulders, Chest, Back, and/or Arms followed by Post-Treatment Follow-Up Period Lasting at Least 4 weeks.” Protocol # PEP005-004, Version 3 (hereinafter “the Project”) and associated costs. Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs.

II. Project Roles and Responsibilities

 

Task

   Peplin    Omnicare    Joint

CT Approvals

        

1.      Submit regulatory documents to authorities /US

   X      

2.      IEC Applications

      X   

Investigator’s Brochure Preparation

        

1.      Protocol development (literature review, background research)

   X      

2.      Design and write protocol

   X      

3.      Approve protocol

   X      

4.      Print and bind protocol

   X      

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Task

   Peplin    Omnicare    Joint

5.      Distribute protocol to sites

   X    X   

6.      Investigator Drug Brochure Preparation

   X      

7.      Write Prototype informed consent (Template)

   X      

CRF Preparation

        

1.      Design and draft CRFs

      X   

2.      Approve CRFs

   X    X   

3.      Print and assemble CRFs

      X   

4.      Distribute CRFs to sites

      X   

5.      Write CRF conventions guide

      X   

Qualification visits

        

1.      Develop list of potential investigators

   X      

2.      Screen Investigators via surveys/telephone interviews

   X      

3.      Conduct site qualification visit

      X   

4.      Provide written site evaluation report

      X   

5.      Prepare Investigator contract

   X      

6.      Negotiate Investigator grants

   X      

Pre-Study Activities

        

1.      Collect all regulatory documents from each site (1572 IRB approval/informed consent, CVs etc)

      X   

2.      Select central laboratory

   X      

3.      Select drug packaging facility

   X      

4.      Select central ethics committee (if applicable)

      X   

5.      Prepare study file notebooks for sites

      X   

6.      Generate monitoring plan

      X   

7.      Generate data entry/management plan

      X   

8.      Set up project master files

      X   

Investigator’s Meeting

   NA      

1.      Plan Investigator’s Meeting-include vendors, agenda, logistics

   NA      

2.      Prepare binders for the meeting

   NA      

3.      Present Investigator’s meeting

   NA      

4.      Attendance at meeting

   NA      

Initiation Visits

        

1.      Conduct site initiation Visits

         X

2.      Provide site initiation report in Omnicare compatible format

         X
On-Site Monitoring         

1.      Conduct monitoring visits

      X   

2.      Provide site monitoring reports (due 10 days from visit)

      X   

3.      Verify 100% of source documentation

      X   

4.      Review drug records

      X   

5.      Review lab storage

      X   

6.      Review monitoring and data retrieval plan

      X   

Close-out visits

        

1.      Conduct site close-out visit

      X   

2.      Provide close-out trip report

      X   

Site Management

        

1.      Manage all sites questions and prepare a Q&A document

      X   

2.      Pay investigators

   X      

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Task

   Peplin    Omnicare    Joint

3.      Pay drug packaging facility

   X      

4.      Pay central laboratory

   X      

5.      Maintain weekly telephone contact log with site

      X   

Project Management

        

1.      Regular enrollment updates (patients screened, entered, discontinued, completed)

      X   

2.      Regular update of cumulative monitoring visit schedule

      X   

3.      Regular updates of CRFs status ( received, data entered, cleaned and number of queries outstanding)

      X   

4.      Team meetings with minutes

      X   

5.      Provision of status reports to Sponsors of performance against deliverables

      X   

Medical Management

        

1.      Document and manage all SAEs

      X   

2.      Cover medical emergencies after hours (pager)

      X   

3.      Develop and maintain safety database

      X   

4.      Submit SAE reports to regulatory authorities

   X      

5.      Prepare safety updates

   NA      

Study Drug Management

        

1.      Supply Study Drug

   X      

2.      Package Study Drug

   X      

3.      Produce Randomization Code

   NA      

4.      Label study drug

   X      

5.      Ship study drug to site

   X      

6.      Store study drug

   X      

7.      Perform post-study drug accountability

      X   

8.      Study drug disposition

      X   

9.      Update Master Drug File

   NA      

Data Entry

        

1.      Design/develop data collection system

      X   

2.      Validate data collection system

      X   

3.      Document control of CRFs

      X   

4.      Enter and verify data

      X   

Data Management

        

1.      Design/develop data cleaning system

      X   

2.      Validate cleaning system

      X   

3.      Write data management guidelines and edit specifications

      X   

4.      Review CRF and edit system

      X   

5.      Resolve edit queries

      X   

6.      Incorporate laboratory data into database

      X   

7.      Document corrections to CRFs

      X   

8.      Provide weekly patient listing of AEs

      X   

9.      Perform QC audits-electronic data compared to paper CRFs

      X   

10.    Code drug dictionary

      X   

11.    Code adverse events

      X   

12.    Code medications

      X   

13.    Test data transfer 1 standard and 1 subsequent transfer.

      X   

Statistical Analysis Plan

        

1.      Prepare an abbreviated analysis plan prior to CRF finalization

      X   

2.      Define efficacy tables and listings

      X   

3.      Define safety tables and listings

      X   

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


Task

   Peplin    Omnicare    Joint

4.      Produce efficacy tables and listings

      X   

5.      Produce safety tables and listings

      X   

6.      Provide draft report template and analysis plan

      X   

7.      Approve report template

      X   

8.      Validate efficacy tables and listings

      X   

9.      Validate safety tables and listings

      X   

10.    Perform quality assurance audit of the tables and listings

      X   

11.    Provide final tables and listings

      X   

12.    Provide statistical study report

      X   

Report Preparation

        

1.      Prepare draft report template

      X   

2.      Approve final report templates

   X      

3.      Draft study reports

      X   

4.      Final study reports

      X   

5.      Perform quality control verification of study reports

      X   

6.      Approval of final study reports

   X      

7.      Database transfer to Sponsor

      X   

Regulatory Site Audits

        

1.      Audit study sites for regulatory compliance

      X   

2.      Provide audit report

      X   

3.      Prepare annual safety report

   NA      

III. Project Timeline

The parties acknowledge that Omnicare CR will commence performance of the Service on or about June 20, 2005. The projected timeline for this Project is as follows:

The following timeline is meant as a guide only.

 

Task

      

Anticipated Timeline

Omnicare CR Activities to Commence

     June 2005

Drug Shipment to Site

     ****

First Patient In

     ****
Maximum Tolerable Dose — Data Available for Sponsor to discuss with the FDA      ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


A detailed timeline and milestone will be developed based on the different assumptions of how the study is conducted.

To achieve the above milestones, Omnicare Clinical Research requires the final protocol to be available no later than 20 June 2005 for Ethics Submission. Please note Omnicare are dependent upon Sponsor providing all necessary documents in order for them to meet the above timeline.

IV. Omnicare CR Services

A. Study Management

Project Leader

The Project Leader will act as a single point of contact for Sponsor during the course of the Project. The Project Leader is responsible for the generation of detailed Project timelines and ensures that these milestones are met. The Project, Leader will provide on-going Project status reports as agreed with Sponsor and will proactively identify and resolve critical Project issues. The Project Leader is also responsible fox managing the study budget and addressing all out-of-scope items with Sponsor.

In addition, the Project Leader is acting in a dual role this person will also be responsible for usual Clinical Trial Manager (CTM) activities including overseeing all site and clinical research associate (CRA) activity for the project in the US. The CTM is also responsible for developing case report forms (CRF’s) and monitoring guidelines; overseeing regulatory document management for the investigational site and for reviewing and tracking the Project CRA activities which include the scheduling of site visits, site visit reports, monitoring logs and follow-up correspondence.

Project Administrative Support/Coordination

The Project Coordinator provides the necessary administrative support for all functional areas with administrative related tasks.

B. Clinical Trial Initiation

Setup & Maintenance of Study Master File

Omnicare CR will establish and maintain the Study Master file in accordance with Omnicare CR’s Standard Operating Procedure (SOP). The individual investigator file, and patient CRFs will be maintained in a locked, limited access, area. In addition, it is the responsibility of all Omnicare CR Project team members to ensure that the documents related to the study are forwarded on a regular and frequent basis to the Study Master File. A transmittal sheet accompanies all documents forwarded to the Study Master File. The transmittal sheet clearly identifies the documents being submitted to the Study Master File. Upon receipt, the file room verifies that the documents noted on the transmittal sheet have been received, signs and dates the

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 5


transmittal sheet, and forwards a copy of the transmittal sheet back to the sender to confirm receipt.

Regulatory Document Collection

Document collection will cover all criteria required under the principles of Good Clinical Practices (GCP) and International Committee for Harmonization (ICH) guidelines, as well as Omnicare CR Standard Operating Procedures (SOPs).

Omnicare CR will track the retrieval of documents on an ongoing basis and provide updates to Sponsor as requested. The fee for document collection, processing, and tracking is based upon the number of sites required for the Project.

Protocol Amendments and IND Safety Reports and Investigator Brochure Updates

Protocol amendments will be billed at an additional processing fee (see budget). IND safety reports and revised Investigator Brochures will be sent to sites at an additional fee (see budget).

Site Qualification

Omnicare CR’s site management and monitoring procedure will be performed in accordance with ICH-GCP to ensure each investigative site’s compliance with regulations and protocol requirements, and to enhance expeditious enrollment of appropriate patients into the clinical study. Regulatory documents will be reviewed by the CRA on an ongoing basis during the study conduct phase, including verification of signed informed consent forms and investigator IRB notifications.

The Ominicare CR CRA will review the following information at the pre-study site visit:

 

   

Latest version of the Protocol for this study

 

   

Consent form process

 

   

AE and SAE reporting procedures and contact information

 

   

Case report form completion and maintenance

 

   

Source documentation requirements

 

   

Drug accountability requirements

Sites that have recently had a pre-study site visit performed by Sponsor or have worked with Omnicare CR in the preceding six months may be exempt from a pre-study site visit. Sponsor will provide Omnicare CR with a list of any exempt investigators for this study.

Site Initiation

Once all regulatory documents and approvals are received, a site initiation visit will be scheduled. During this visit, the CRA will review the following with the principal investigator and his/her staff as appropriate and the CTM will provide training:

 

   

Study goals and obligations

 

   

Investigator brochure

 

   

Protocol procedures (with particular attention to inclusion/exclusion criteria, enrollment goals, adverse events, primary efficacy variables and GCP compliance)

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 6


   

Informed consent procedure

 

   

dose escalation request procedure

 

   

AE/SAE reporting

 

   

CRF completion and error correction/need for adequate source documentation

 

   

Maintenance of the investigator binder and site visit log

 

   

Laboratory sample handling procedures and results reporting procedures

 

   

Clinical supply dispensation, accountability and storage procedures

Site Interim Visits

Omnicare CR CRAs will perform ****% source document verification of CRF data for accuracy and completeness. They will also review source data for appropriate identification, documentation, and reporting of both serious and non-serious adverse event for the first **** patients enrolled at the investigational site and source documentation for ****% of all subjects enrolled at the investigational site after the first **** patients Omnicare CR will supply to Sponsor weekly the monitoring schedule with at least **** weeks notice of anticipated visits. CRFs will be retrieved during each monitoring visit, as well as pages for completed subject courses, running log pages and one-year follow-up pages. Pages and information for patients who fail screening will be reviewed and monitored.

The following issues are addressed at each interim visit as appropriate:

 

   

Source document verification

 

   

CRF completion

 

   

Expedient data retrieval and query resolution

 

   

Drug accountability

 

   

Check and review of the regulatory binder and its contents

 

   

Clinical supply inventory

 

   

SAE reporting

 

   

Enrollment issues and targets

 

   

Protocol amendments

 

   

Significant protocol deviations

 

   

Acceptability of facilities

 

   

Personnel changes

 

   

Updated regulatory documentation

 

   

Laboratory sample handling

Following each monitoring visit, Omnicare CR will complete follow-up letters and site visit reports within two weeks of each visit. These follow-up letters and monitoring reports will be forwarded to Sponsor on a monthly basis.

Site Closeouts

At the conclusion of the study, after all completed CRFs have been returned to Omnicare CR for logging and tracking, and after all unused CRF binders have been returned to Omnicare CR for destruction, the Omnicare CR CRA will perform a close-out visit.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 7


The following issues are evaluated and/or reviewed with the investigator and his/her staff at the close-out visit:

 

   

Reason for termination (if study is not complete)

 

   

Reconciliation and removal of clinical supplies per Sponsor’s requirements (including hazardous materials)

 

   

All original CRFs retrieved from the site at the previous visit

 

   

Signed informed consents retained by investigator

 

   

Record retention requirements

 

   

Notification to IRB or ethics committee of study termination

 

   

Collection of randomization codes for return to Sponsor

 

   

Resolution of all data queries

 

   

Investigator binder contents (complete and updated)

 

   

Informed consent log

 

   

Financial agreements and disclosure (filed separately)

 

   

Signature log and screening log

 

   

Site visit and subject enrollment log

 

   

Laboratory certification and renewals

 

   

Summary/discussion of study from investigator and/or staff

Site Maintenance

Omnicare CR maintains a minimum of bi-weekly contact with investigational sites via telephone, facsimile, e-mail and/or mail correspondence, based on the requirements of each investigational site.

Activities that are performed in-house between monitoring visits include, but are not limited to:

 

   

Discussion of study protocol and any amendments to the protocol

 

   

Inclusion/exclusion questions or issues

 

   

Review of clinical laboratory results

 

   

New staff or team member orientation

 

   

Additional site training

 

   

Clinical supply activities or issues

 

   

Enrollment updates (via weekly fax updates)

 

   

AE and SAE updates

 

   

Data query resolution

 

   

Scheduling activities

Included in Site Maintenance activities, Omnicare CR CRAs will assist Sponsor in resolving data queries for data from the investigational site, which are unclear, conflicting or incomplete. The status of all queries resolved by Omnicare CR will be communicated to Sponsor. The CTM will provide Sponsor with an up-to-date report on the status of queries on an as-needed basis. The fee for resolution of data queries is included in the CRA site maintenance estimate.

Project Team Training

Omnicare CR will rely on Sponsor and internal experts to provide specific therapeutic area training and orientation to the protocol and the CRF prior to study initiation and on an ongoing

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 8


basis. This training will be designed to ensure that various team members are familiar with the Project requirements and their role within the team. Items discussed at these meetings will include, but will not be limited to:

 

   

Therapeutic area and clinical development background

 

   

Protocol and CRF

 

   

Discussion of therapeutic implications for this study

 

   

Monitoring guidelines

Sponsor Meeting Attendance

Omnicare CR assigned Project team will attend face-to-face meetings with Sponsor’s clinical team at assigned times throughout the Project.

C. Medical and Safety

Medical Monitoring (during business hours)

The Medical Advisor will be responsible for the following:

 

   

Participation in team training and/or team meetings if required

 

   

Monitoring of dose limiting toxicity for each cohort and making decision in relation to dose escalation, cohort expansion or maximum tolerated dose (MTD)

 

   

Availability for receipt of calls mainly during business hours

 

   

Answering protocol specific questions from investigators, Clinical Research Associates (CRAs) or other members of the project team

 

   

Answering patient specific questions (e.g. patient eligibility, evaluability etc.) from investigators, CRAs, or other members of the project team

 

   

Serious Adverse Event (SAE) medical review

 

   

The maintenance of the full records of all communications regarding medical monitoring of the study

 

   

Communication of medical monitoring matters to the client as appropriate

Any out of hours requests, will be billed at the out of hours rate, presented in the budget.

Global Safety Coordinator

The Global Safety Coordinator is responsible for the coordination of all activities relating to safety. They will also be responsible for the generation of, and any required revisions to, the Study Safety Plan, a comprehensive document, which defines the process and flow for contracted safety services. Safety coordination also includes assistance with the SAE reconciliation process, and completion of sponsor derived queries of the sites.

The Global Safety Coordinator will be based in the US and will be responsible for receiving SAE reports, preparing narratives, arranging medical review and reviewing reportability.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 9


SAE Reporting — Initial Descriptive Narratives

Omnicare CR assumes that the descriptive summaries will be written from information provided by the investigator on the SAE report forwarded to Omnicare CR at the time of the event. If significant follow-up information becomes available, the narrative will be updated accordingly. Omnicare CR will be responsible for notifying Sponsor and relevant regulatory agencies (FDA) of expedited events. Omnicare CR will fax to Sponsor all initial and follow-up SAE reports received from site personnel or Omnicare CR’s CRAs within one business day.

The Safety Coordinator assigned to the project will coordinate all activities relating to safety. These activities include attendance of internal and external team meetings, safety training of project staff or sites, communication of safety information to Omnicare CR project management and data management departments as well as to Sponsor, and tracking the flow of safety information for the life of the project. The Safety Coordinator will also generate and update, the Study Safety Plan, which defines the process and flow for contracted safety services. Safety coordination also includes assistance with the SAE reconciliation process and completion of sponsor derived queries of the sites.

D. Clinical Data Management

Data Management Project Team

Due to the nature of the deliverables for this study, Omnicare CR has assumed a Clinical Data Leader (CDL) will be assigned to the Project for almost **** days per month for just over **** months. The LCDM will provide oversight of the management team as well as ensure that all deliverables are achieved.

On a continual basis, the Omnicare CR team, CRAs, Project Leader/CTM and the CDL will work in concert, will evaluate number and type of queries being generated by Clinical Data Management, in order to proactively manage the retrieval of quality data for both the studies and site release status. Plans will be implemented to inspect the data for trends and issues in order to provide focused training at both the project team and the site levels. This will commence as soon as the first CRF pages are submitted in order to proactively resolve data issues.

It is Omnicare CR’s policy to perform a quality control (QC) of the final database to ensure the error rate is within an acceptable range. Each CRF will be printed as a data listing with 100% QC of pre-defined critical data fields against the hard-copy CRF. In addition, a sampling of the patient data will undergo quality control for 100% of the data fields, prior to declaration of a clean database. The processes and outcomes of these QC audits will be documented, with audit findings corrected within the timeframe identified with the Data Management Plan. Omnicare CR supports the plan for transfer of clean data to give both Sponsor and the Omnicare CR Biometrics Group an opportunity to review clean data periodically, ensuring that guidelines are complete and accurate, and that the data is represented correctly in preparation for the analysis.

Omnicare CR believes that these strategies will ensure:

 

   

Cleaner cases and data.

 

   

Minimises queries — assumption of one query every **** CRF pages.

 

   

Timely resolution of study and site issues.

 

   

Cohesiveness between Sponsor, Omnicare CR and the study site.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 10


   

On-time delivery of final clean clinical study database.

 

   

No surprises when preparing for data analysis.

Data Management Plan (DMP)

The DMP will include descriptions to the following Data Management activities:

 

   

Project data flow

 

   

Database development overview

 

   

Edit specifications

 

   

Data entry guidelines

 

   

Data handling guidelines

 

   

Study assumptions (Level 1)

 

   

SAE reconciliation process

 

   

External data load procedures / External Data Cleaning parameters / Discrepancy identification flow

 

   

Dictionary coding guidelines and processes

 

   

Database closure procedures

Prior to the start of Data Management activities, the DMP and edit specifications must be agreed to and signed by the Omnicare CR designee and Sponsor representative. The agreement to all data handling rules will ensure an accurate and timely final database lock leading to a successful data analysis. It is assumed that all portions of the DMP related to any specific task will be agreed upon prior to the start of those activities.

Review of Data Management Plan

Omnicare CR assumes **** Sponsor review cycles including up to **** major and **** minor revision in order to finalize the DMP.

CRF Design and CRF Completion Guidelines

Omnicare CR assumes work on the CRF design will commence once the protocol is finalized. Upon receipt of the final draft comments, the final printable version of the CRF is prepared and provided to Sponsor for approval signature. The cost associated with this task will comprise of **** Sponsor review cycles with **** major and **** minor revision. The CRF completion guidelines will follow the same process as the CRF and will need to be finalized prior to commencement of study monitoring.

Database Development

Omnicare CR’s Data Management Department uses Oracle Clinical for a standardized, validated approach to database design, edit development, data collection and storage.

Edit Checks

The edit specifications identified in the DMP require Sponsor approval prior to the initiation of the programming of the edit checks (budget includes **** edits). It is Omnicare CR’s goal and in the project’s best interest to have all edits programmed and tested prior to any CRF data being

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 11


submitted to Data Management. This will ensure there are no delays in reviewing and querying the data. Omnicare CR suggests a periodic review of the edit specifications and data review guidelines to ensure that the rules and edit checks meet the project needs.

Data Entry

Omnicare CR assumes the CRFs for screen failure patients will not be received in-house, unless otherwise specified. All CRF and ancillary data received from the investigative Site are logged into a tracking database on a page-by-page basis. Each page is identified by type of page and date received. Working copies will be maintained in CDM and used for any annotations during processing and cleaning. All original (white) CRF and query pages will be immediately sent for filing in the Project Master File.

Data Review and Query Processing

Omnicare CR assumes that the study data will be received in TBD retrieval / retrievals per subject. Data review includes **** (****) manual review data checks and the application of **** (****) study assumptions for every **** (****) pages of the CRF per subject. Omnicare CR assumes that the manual review checks are not expected to exceed **** checks comparing **** datapoints.

Quality Control Check of the Database

It is Omnicare CR’s policy to perform a QC of the final database ensuring the error rate is within an acceptable range. Each CRF will be printed as a data listing with 100% QC of adverse events and the protocol identified primary efficacy parameters against the hard-copy CRF. Also, a random sample subset of the patients will under go a 100% QC of all data points vs. the CRFs, to ensure the estimate of the error rate for the database is within acceptable limits prior to declaration of clean database. The processes and outcomes of these QC procedures will be documented, with the findings, corrected within the timeframe identified within the DMP. Omnicare CR believes that these strategies will ensure the following results with respect to these studies:

 

   

Quality data

 

   

On-time delivery of Final Clean Clinical Study Databases

 

   

NO surprises when preparing for data analysis

Dictionary Coding

Omnicare CR is proficient in coding to both MedDRA and the WHO-Drug dictionaries. Additional dictionaries can also be accommodated.

Sponsor is required to have a current MedDRA license in good standing prior to receipt of any MedDRA coded terms. It is assumed under this Exhibit that Sponsor has a current MedDRA license in good standing and that such will be maintained throughout the course of the Project.

Reconciliation of the Safety and Clinical Database

Omnicare CR assumes a total of **** SAE for this project. A total of **** (****) Adverse Event (AE) qualifiers will be reconciled. Omnicare CR’s Clinical Data Leader will update Omnicare CR’s Safety group with the DCF responses and the Safety group will update Sponsor of the changes.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 12


E. Biometrics Analysis

Statistical Analysis Plan

Omnicare CR will develop a statistical analysis plan, including operational definition of endpoints to be analysed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling, and a detailed description of statistical methodology.

If Sponsor has a standard statistical analysis plan template then this can be used instead. Omnicare CR has budgeted for one Sponsor review and one revision.

Design of Table Shells (Mocks)

The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for each study. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included.

Tables, Listings and Graph Programming

Omnicare CR will perform the programming and will validate the following tables, listings and figures/graphs:

 

      Unique   Repeat   Total

Tables

   ****   ****   ****

Listings

   ****   ****   ****

Figures/Graphs

   ****   ****   ****

Database Transfer

Omnicare CR assumes **** standard and **** subsequent database transfers which will be submitted to Sponsor in the form of SAS datasets.

Statistical Report

A statistical report will be developed in accordance with Sponsor’s requirements and will summarise the results of the study, including findings that may not be appropriate for the body of the clinical report (tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses.

F. Clinical Writing

Clinical Study Report

Omnicare CR will draft the integrated clinical and statistical summary in accordance with ICH guidelines on the “Structure and Content of Clinical Study Reports”, appropriate agency regulations, and Omnicare CR SOPs and clinical study report format. A draft clinical report will

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 13


be generated within **** (****) weeks after receipt of source material and final summary tables and patient data listings.

Biometrics will produce up to **** tables and **** listings that will be summarised in the clinical study report. Sponsor will provide **** set of collated comments. Omnicare CR’s cost estimate includes **** major (up to **** days) and **** minor (up to **** day) revision. This fee does not include the compilation or collation of clinical study report appendices.

G. Regulatory

Filing and Reconciliation of CRFs in the Study Master File

CRFs tracked in clinical data management (CDM) are transferred to the Study Master File. CRFs and ancillary pages are verified against the CDM tracking log and then filed. Sponsor will be billed for the actual number of pages filed.

CRF Return

Omnicare CR will return the CRFs in accordance with Omnicare’s SOPs within **** (****) months of final study deliverable. The CRFs are reviewed and reconciled against the CRF tracker from Omnicare’s CDM department. Sponsor will be billed for the actual number of pages returned.

Return Study Master Files — Hard Copy

Omnicare will return the Study Master File in hard copy format in accordance with Omnicare’s SOPs within **** (****) months of final study deliverable. A final review of the study wide and individual investigator files is completed by Project Management for completeness and accuracy. Sponsor will be billed for the actual number of sites returned.

H. Clinical Quality Assurance and Validation

Quality Plan

Omnicare will develop a customised project-specific Quality Plan in partnership with Sponsor. The plan will include details such as the percentages of sites/patients/data to be audited, the timeline of audits, and the plan for generation of individual Audit Reports and Certificates. Sponsor will be requested to review and sign off on the plan and any necessary amendments to the original plan, prior to implementation.

CQA Site Audit

Omnicare will conduct **** site audit. The site audit will include ****% review of essential documents, including all informed consent documents and serious adverse event reporting compliance. In addition, for approximately ****% (with a minimum of ****) of subjects at the study site, CRF data will be audited against source documents with an emphasis on critical efficacy and safety data; drug accountability will also be verified for these subjects. The associated cost budgeted includes preparation and travel time, audit time, audit follow-up, and Audit Report and Audit Certificate generation.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 14


V. Budget

A. Estimated Project Budget

 

Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

STUDY MANAGEMENT

            

•    Project Leader / Clinical Trial Manager — Australia (assumes **** days per month for **** months)

   Days   ****   ****   ****   ****   ****

•    Project Administrative Support/Coordination —Australia (includes support for all functional areas)

   Days   ****   ****   ****   ****   ****

Subtotal — Study Management

         ****   ****   ****

CLINICAL TRIAL INITIATION

            

•    Study Master File (America; **** site for **** months)

   Site Months   ****   ****   ****   ****   ****

•    Regulatory Document Collection (US)

   Site   ****   ****   ****   ****   ****

Local IRB (pass-throughs are estimates only; actual fees will be billed based on specific IRB fees)

   Site   ****   ****   ****   ****   ****

•    Protocol Amendments excluding ICF change (US)

   Amendments/
site
  ****   ****   ****   ****   ****

•    Protocol Amendments including ICF change (US)

   Amendments/
site
  ****   ****   ****   ****   ****

•    IND Safety Report (US)

   Reports/Site   ****   ****   ****   ****   ****

•    Investigator Brochure Updates (US)

   IB Updates/
Site
  ****   ****   ****   ****   ****

•    CRA Training

   Hours   ****   ****   ****   ****   ****

Subtotal — Clinical Trial Initiation

         ****   ****   ****

CLINICAL TRIAL MANAGEMENT

            

•    Clinical Monitoring

            

>Site Qualification Visit (US): **** hrs on-site, **** hrs for prep, follow-up, and reports, and **** hrs for travel — IF REQUIRED (actual units provided will be billed)

   Visit   ****   ****   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 15


Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

>Site Initiation Visit (US): **** hrs on-site, **** hrs for prep follow-up, and reports, and **** hrs for travel

   Visit   ****   ****   ****   ****   ****

> Clinical Trial Manager Training at Site Initiation Visit

   Days   ****   ****   ****   ****   ****

>Site Interim Visits (US): assume **** visits/site, **** hrs on-site, **** hrs for prep, follow-up, and reports, and **** hrs for travel: ****-weekly visits

   Visits   ****   ****   ****   ****   ****

>Additional Day Interim Visits (IF REQUIRED; based on **** hours per day)

   Visit   ****   ****   ****   ****   ****

>Site Close-Out Visit (US): **** hrs on-site, **** hrs for prep, follow-up, and reports, and **** hrs for travel

   Visits   ****   ****   ****   ****   ****

•    Site Maintenance for **** hrs/month/site (**** site in the US x **** months)

   Site Months   ****   ****   ****   ****   ****

•    Project Team Training (to be held in Omnicare CR’s Sydney offices)

            

>CTM — Australia

   Days   ****   ****   ****   ****   ****

> Medical Monitor—Australia

   Days   ****   ****   ****   ****   ****

>Safety Officers — US (Via teleconference)

   Days   ****   ****   ****   ****   ****

Statistician: Australia

     ****   ****   ****   ****   ****

•    Sponsor Meeting Attendance (billed on actuals) by Project Leader/clinical Trial Manager (professional fees included in Study Management; pass-through expenses are included as it assumes some travel to Queensland for face-to-face meetings)

   Days   ****   ****   ****   ****   ****

Subtotal — Clinical Trial Management

         ****   ****   ****

MEDICAL AND SAFETY

            

•    Medical Monitoring, including does escalation, availability during business hours in Australia (actual hours expended will be billed)

   Hours   ****   ****   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 16


Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

•    Medical Monitoring availability out of business hours, between 6pm and 8am in Australia (actual hours expended will be billed)

   Hours   ****   ****   ****   ****   ****

•    Protocol Review by Medical Monitor plus project specific forms/ plan completed etc.(Australia)

   Project   ****   ****   ****   ****   ****

•    Medical Consulting requested in Australia

   Hours   ****   ****   ****   ****   ****

•    Safety Plan and Master File Set Up

   Site   ****   ****   ****   ****   ****

•    Safety Phone Cover (actuals months will be billed)

   Months   ****   ****   ****   ****   ****

•    Global Safety Coordinator in the US (assumes **** day per month for **** months)

   Days   ****   ****   ****   ****   ****

•    SAE Reporting (with narratives) Billed on actuals

   Reports   ****   ****   ****   ****   ****

•    Dear Dr Letters reporting Pls who report to IEC, tracking of IRB acknowledgement letter

   Letter   ****   ****   ****   ****   ****

•    SAE Reporting (Follow-up/Revision Reports >****) Billed on actuals

   Report   ****   ****   ****   ****   ****

Subtotal — Medical and Safety

         ****   ****   ****

CLINICAL DATA MANAGEMENT

            

•    Lead CDA — Americas (assumes ****% FTE x **** months Startup, ****% FTE x **** months, and ****% FTE x **** months Close-out)

   Days   ****   ****   ****   ****   ****

•    Development of Data Management Plan (includes **** major and **** minor revision; add **** revisions will be billed at per diem rates)

   Days   ****   ****   ****   ****   ****

•    CRF Design (assumes **** page CRF, **** unique CRF pages); includes **** major and **** minor revision

   Project   ****   ****   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 17


Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

•    Database Development, Testing and Maintenance (assumes **** page CRF, **** unique CRF pages)

   Project   ****   ****   ****   ****   ****

•    Estimated Data Entry (actuals will be billed) — Pages in US

   Pages   ****   ****   ****   ****   ****

•    Estimated Data Review and Query Resolution (assumes **** issue per **** CRF pages, **** manual checks and the application of **** study assumption for **** CRF pages); assumes **** CRF pages per enrolled patient. Queries will be billed on actuals (Based on issues)

   Issue   ****   ****   ****   ****   ****

•    Quality Control Check of Database versus CRF (assumes **** CRF pages per patient)

   Page   ****   ****   ****   ****   ****

•    Edit Development (actuals Will be billed)

   Edits   ****   ****   ****   ****   ****

•    Dictionary Coding of Adverse Event terms to MedDRA (estimated to be per patient; actuals will be billed)

   Term   ****   ****   ****   ****   ****

•    Dictionary Coding of Medication, Terms (estimated to be **** per patient; actuals will be billed)

   Term   ****   ****   ****   ****   ****

•    Dictionary Coding of Medical History (estimated to be **** per patient; actuals will be billed)

   Term   ****   ****   ****   ****   ****

•    PK Laboratory Data

            

>Initial Load

   Project   ****   ****   ****     ****

>Subsequent Loading (actuals will be billed)

   Load   ****   ****   ****     ****

>Lab Header Visit Verification (**** visits x **** patients; actuals will be billed)

   Visits   ****   ****   ****     ****

•    Reconciliation of the Safety and Clinical Database (actuals will be billed)

   SAE   ****   ****   ****     ****

Subtotal Clinical Data Management

         ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 18


Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

BIOMETRICS ANALYSIS

            

•    Biometrics Team Leader

   Days   ****   ****   ****   ****   ****

Statistical Consultation as requested

   Hours   ****   ****   ****   ****   ****

•    Statistical Plan + Mocks

   Project   ****   ****   ****   ****   ****

•    Programming/QC of Data Displays (actuals will be billed).

            

> Unique Tables

   Table   ****   ****   ****   ****   ****

>Repeat Tables

   Table   ****   ****   ****   ****   ****

> Unique Listings

   Listing   ****   ****   ****   ****   ****

>Repeat Listings

   Listing   ****   ****   ****   ****   ****

•    Statistical Analysis (Reg.)

   Project   ****   ****   ****   ****   ****

Statistical Report (Regular)

   Project   ****   ****   ****   ****   ****

Standard Data Transfer

            

>Initial

   Transfer   ****   ****   ****   ****   ****

>Subsequent (if required)

   Transfer   ****   ****   ****   ****   ****

Add’l Stats consulting, meeting attendance, etc. , will be charged at per diem rates as follows:

Team Leader

   Days     ****      

Statistician

   Days     ****      

Programmer

   Days     ****      

Subtotal — Biometrics Analysis

         ****   ****   ****

CLINICAL WRITING

            

•    Clinical Study Report
> includes **** major revision (up to **** days) and **** minor (up to **** day) revision >Per Omnicare CR’s SOPS
>Fee does not include CSR appendices

   Report   ****   ****   ****   ****   ****

•    Narrative (actuals will be billed)

   Narrative   ****   ****   ****   ****   ****

•    Clinical Writing Input to SAP

   Project   ****   ****   ****   ****   ****

•    Sponsor Meeting Attendance (Senior Writer; actuals will be billed)

   Days   ****   ****   ****   ****   ****

Attendance at Sponsor Requested Meetings:

Attendance at Sponsor requested meetings (teleconferences/video conferences or Sponsor review/planning meetings at Sponsor/Omnicare CR, Inc.) will be billed to Sponsor according to the following per diem rates:

Director:

   ****          

Senior Writer:

   ****          

Clinical Writer:

   ****          

Sponsor will be billed for actual time expended

Subtotal — Clinical Writing

         ****   ****   ****

REGULATORY SERVICES

            

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 19


Services

           Unit           #
        Units        
  Unit
        Cost        
AUD
  Service
      Fees      
AUD
  Estimated
    Pass-Thru    
AUD
  Estimated
    Total Cost    
AUD

•    CRF Filing and Reconciliation (bill on actuals)

   Pages   ****   ****   ****   ****   ****

•    Return of CRF (hard copy); bill on actuals

   Pages   ****   ****   ****   ****   ****

•    Return of Investigator and Study-Wide Documents (paper)

   Sites   ****   ****   ****   ****   ****

Subtotal — Regulatory Services

         ****   ****   ****

CLINICAL QUALITY ASSURANCE

            

•    Quality Plan

   Days   ****   ****   ****   ****   ****

•    CQA Site Audits — includes preparation and travel time, audit time, audit follow-up, and Audit Report and Audit Certificate generation at **** site in the US

   Sites   ****   ****   ****   ****   ****

Subtotal — Clinical Quality Assurance

         ****   ****   ****

MISCELLANEOUS PASS-THROUGH EXPENSES

            

•    CRF Printing (bill on actuals)

   Pages   ****       ****   ****

Subtotal — Miscellaneous PT Expenses

           ****   ****

Estimated Services Budget

         ****    

Estimated Pass Through

           ****  

Total Estimated Budget

             ****

B. Payment Schedules

1. Invoicing Process for Service Fees

Omnicare CR maintains a project accounting system, whereby all direct project costs (Service Fees or Pass-through Expenses) are coded by project.

An initial payment of AUD$****, representing approximately **** percent (****%) of the estimated Service Fees, is due and payable upon execution of this Exhibit A. Subsequent payments shall be made monthly, based on Project progress and upon submission of an invoice to Sponsor by Omnicare CR. The subsequent invoices shall be reduced by a prorated portion from the initial payment such that the initial payment is applied evenly over the term of the Project. All payments shall be processed within **** days. If any payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a liquidated damages fee of ****% per month of the outstanding balance.

2. Pass-Through Expense Invoicing

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 20


Omnicare CR’s project accounting system is able to capture and categorize in summary the following key Pass-Through Expenses related to a project:

 

 

Travel

 

 

Delivery costs

 

 

CRT and other printing or copying costs

 

 

Investigator Meeting costs

 

 

Telecommunication costs (which may include telephone, fax, pager, conference calls, or PC connectivity charges)

 

 

All other project related expenses that are not related to Service Fees and any additional detail to support Pass-Through Expenses will be provided on a fee basis.

3. Payments

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc. Westpac Banking Corporation, Maquarie Shopping Centre, North Ryde, NSW 2113 SWIFT ID: **** BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Exhibit A shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Exhibit A as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

ACCEPTANCE

The terms and conditions of the Master Agreement govern this Exhibit A and such document is incorporated herein by reference as if fully set forth herein.

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ Michael Aldridge

    By:  

/s/ Kevin D. Duffy

Name:   Michael Aldridge     Name:   Kevin D. Duffy
Title:   Director     Title:  

Senior Vice President

Global Marketing & Business Development

Dated:   24-Aug-05     Dated:   9/6/05

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 21


Change Order #01 to Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th August 2005.

THIS CHANGE ORDER is entered into this 24th day of October, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “ Sponsor “) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS , Sponsor and Omnicare CR entered into a certain Clinical Service Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as they same may have been amended or supplemented as of the date hereof, the “Agreement”) the terms of which are incorporated herein by reference; and

WHEREAS , Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS , Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit A to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE , for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND , Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

  

Changes and/or Additions

   Estimated Service
Fee (AUS$)
Pursuant to Exhibit A, Omnicare CR will provide additional clinical data management support for the Sponsor’s Cohort Study of PEP005 Topical Gel, Protocol # PEP005-004, Version 3    1.  CRF design (increase in CRF size):   
  

a.    Assumption used in the original contract was a ****-page CRF with **** unique pages. Actual CRF page was **** pages with **** unique and **** repeat pages per patient. Additional cost = AUS$****/ unique page (x **** pages) and AUS$****/ repeat page (x **** pages).

   $ ****
  

b.  Additional work associated with revisions requested by Sponsor on CRF design.

   $ ****
   2.  Database development (increase in CRF size):    $ ****
  

Assumption and actual as noted in (1a) above, Additional cost = AUS$****/ unique page (x **** pages) and AUS$****/ repeat page (x **** pages)

  
         
Total Estimated Service Fees    $ *****
         
Total Estimated Pass Through Expenses      ******
         
Total Estimated Budget    $ ****
         

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #01.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


3. Payment

The full payment of AUS$**** representing **** percent (****%) of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #01. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees, Set forth in this Change Order #01 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #01 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #01, all other terms and conditions of the Agreement shall continue in force and effect.

ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.      Omnicare CR, Inc.
By:  

/s/ Peter Welburn

     By:  

/s/ Kevin D. Duffy

Name:   Peter Welburn      Name:   Kevin D. Duffy
Title:   Director, Drug Development      Title:  

Senior Vice President

Marketing & Business Development

Dated:   October 3, 2005      Dated:   10/24/05

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


Change Order #02 to Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th August 2005.

THIS CHANGE ORDER is entered into this 24th day of October, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit thereto as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit A to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

 

Reference

  

Changes and/or Additions

  

Estimated Service

Fee (AUS$)

Pursuant to Exhibit A, Omnicare CR will provide additional clinical data management support for the Sponsor’s Cohort Study of PEP005 Topical Gel, Protocol # PEP005-004, Version 3     

Edit Development:

* Estimated number of edit checks in original budget = ****.

* Actual number of edit checks = ****.

* Variance = **** edit checks @ AUS$****

   ****
         

Total Estimated Service Fees

      ****
       

Total Estimated Pass-Through Expense

      ****
       

Total Estimated Budget

      ****
       

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project,

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #02.

3. Payment

The full payment of AUS$**** representing **** percent (****%) of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #01. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #02 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #02 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #02, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.   Omnicare CR, Inc.  
By:  

/s/ Peter Welburn

    By:  

/s/ Kevin D. Duffy

 
Name:   Peter Welburn     Name:   Kevin D. Duffy  
Title:   Director, Drug Development     Title:  

Senior Vice President

Global Marketing & Business Development

 
Dated:   October 3, 2005     Dated:   10/24/05  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


Change Order #03 to Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th Aug 2005.

THIS CHANGE ORDER is entered into this 23rd day of Dec, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit A to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

 

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following additional work and reduced services pursuant to the general terms and conditions set forth in the Agreement:

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

 

Services to be Billed

  Estimated Additional
Service Fee (AUS$)

Pursuant to Exhibit A, Omnicare CR will provide

additional biometrics support for the Sponsor’s Cohort

Study of PEP005 Topical Gel, Protocol # PEP005-004,

Version 3

 

Unique Tables:

 

*  Estimated number of unique tables in original budget = ****

    $  ****    
 

*  Actual number of unique tables = ****

     
 

*  Variance = **** unique tables @ AUS$****

     
  Unique Listings:     $  ****    
 

*  Estimated number of unique listings in original budget = ****

     
 

*  Actual number of unique listings = ****

     
 

*  Variance = **** unique listings @ AUS$****

     

Reference

 

Services to be Billed

  Estimated Reduced
Service Fee (AUS$)

Pursuant to Exhibit A, Omnicare CR will provide

additional biometrics support for the Sponsor’s Cohort

Study of PEP005 Topical Gel, Protocol # PEP005-004,

Version 3

 

Repeat Tables:

 

*  Estimated number of repeat tables in original budget = ****

    $  ****    
 

*  Actual number of repeat tables = ****

     
 

*  Variance = **** repeat tables @ AUS$****

     
  Repeat Listings:     $    ****    
 

*  Estimated number of repeat listings in original budget = ****

     
 

*  Actual number of repeat listings = ****

     
 

*  Variance = **** repeat listings @ AUS$****

     
           
Total Estimated Service Fees to be Billed     **** *  
           
Total Estimated Service Fees Not to be Billed     ****    
           
Total Estimated Pass Through Expenses     **** **  
           

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #03.

 

3. Payment

The full payment of AUS$**** of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #03. The payment of Service Fees and Pass-Through Expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

 

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #03 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #03 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

 

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #03, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.   Omnicare CR, Inc.  
By:  

/s/ Michael Aldridge

    By:  

/s/ Leonard Stigliano

 
Name:   Michael Aldridge     Name:   Leonard Stigliano  
Title:   Managing Director & CEO     Title:   Pres. & Global Chief Operating Officer  
Dated:   12-Dec-05     Dated:   12-23-05  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


Change Order #04 to Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th August 2005.

THIS CHANGE ORDER is entered into this 22nd day of September, 2006 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor” ) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any reference to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit A to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

 

Changes and/or Additions

  Estimated Service
Fee (AUS$)
 

 

Pursuant to Exhibit

A, Omnicare CR will

provide additional

Biometrics and

Clinical Data

Management support

for the Sponsor’s

Cohort Study of

PEP005

Topical Gel,

Protocol # PEP005-

004, Version 3

 

 

Additional Analysis:

 
   
  Tables produced for time to resolution and summary of mild and moderate local skin reactions:  
   
 

•    1 Unique Table @ $****

  $ ****  
   
 

•    2 Repeat Tables @ $****

  $ ****  
   
  Clinical Data Management Final Reconciliation:  
   
   
   
 

•    Data Entry — Contracted units ****, Actual

****, Variance = **** @ $****/unit

  $ ****  
 

•    QC Data Review — Contracted units ****,

Actual ****, Variance = **** @ $****/unit

  $ ****  
 

•    Query Resolution — Contracted units

****, Actual ****, Variance = **** @ $****/unit

  $ ****  
 

•    Dictionary Coding of AEs — Contracted units

****, Actual ****, Variance = **** @ $****/unit

  $ ****  
 

•    Dictionary Coding of Meds — Contracted units

****, Actual ****, Variance = **** @ $****/unit

  $ ****  
 

•    PK Lab Load (Subsequent) — Contracted units

****, Actual ****, Variance = **** @ $****/unit

    ****  
 

•    PK Lab Visit Verification — Contracted units

****, Actual ****, Variance = **** @ $****/unit

    ****  
 

•    Local Lab (Initial) — Contracted units ****,

Actual ****, Variance = **** @ $****/unit

  $ ****  
 

•    Local Lab (Subsequent) — Contracted units ****,

Actual ****, Variance = **** @ $****/unit

  $ ****  
Total Estimated Service Fees   $ **** *
         
Total Estimated Pass Through Expenses     **** **
         
Total Estimated Budget   $ ****  
         

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #04.

3. Payment

The full payment of AUS$**** representing **** percent (****%) of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #04. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the, estimated Service Fees set forth in this Change Order #04 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #04 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as Expressly provided to the contrary in this Change Order #04, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ Michael Aldridge

    By:  

/s/ Dale Evans

Name:   Michael Aldridge     Name:   Dale Evans
Title:   Director     Title:   CEO
Dated:   4-Oct-06     Dated:   10/10/06

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


Change Order #05 to Exhibit A to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th August 2005.

THIS CHANGE ORDER is entered into this 18th Day of January, 2007 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit A to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

  

Changes and/or Additions

   Estimated Service
Fee (AUS$)
 
Pursuant to Exhibit A, Omnicare CR will provide additional services to support the Sponsor’s Cohort Study of PEP005 Topical Gel. Protocol # PEP005-004. Version 3    Appendices to final Clinical Study report:   
  

 

•         Set-up and Management @ A$****/ project

   $ ****  
  

 

•         Estimated Hyperlinks = **** units @ A$**** unit

   $ ****  
  

•         Estimated Scanned and Cleaned Pages units = **** units @ A$****/ unit

   $ ****  
  

•         Estimated Volumes = **** units @ A$****/ unit

   $ ****  
  

•         Project Coordinator (Australia) = **** hours @ A$****/hour

   $ ****  
           

Total Estimated Service Fees

      $ **** *
           

Total Estimated Pass Through Expenses

      $ **** **
           

Total Estimated Budget

      $ ****  
           

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass Through Expenses incurred in support of the Project.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #05.

3. Payment

An initial payment of A$****, representing **** percent (****%) of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #05. The remaining balance of A$**** shall be due and payable upon completion of the above-mentioned activities. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #05 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #05 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #05, all other terms and conditions of the Agreement shall continue in force and effect.

ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ Peter Welburn

    By:  

/s/ Dale Evans

Name:   Peter Welburn     Name:   Dale Evans
Title:   General Manager, Aus     Title:   Chief Executive Officer
Dated:   24\1\07     Dated:   02\09\07

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


Initial Sponsor Notification Form    LOGO

Change in Project Scope

 

Protocol Number: PEP004        Date of Request:   

Omnicare PCN:

K01502

Omnicare Project Director:        ****     
Omnicare Account Director:        ****     
Sponsor Study Manager:        Janelle Katsamas     

Sponsor Outsourcing Manager:

 

             
Individual and Department making
request:
       ****, Project management     

 

Brief Description of Project Scope Change: Appendix to final CSR.

    

 

Setup and Management: US$ ****

    

 

Est. Hyper-links ($****/link): U$****

    

 

Est. Scanned and Cleaned Pages ($****/page): US$****

    

 

Est. Volumes ($****/Volume): US$****

    

 

Project coordinator (Australia): AUD****

    

 

Exchange rate: 1USD = 1.2683AUD

       Total: $****     

 

Implementation of this request will affect the budget as follows (provide

estimate of anticipated costs

associated with change, if available)

 

      

þ        Increase

 

¨        Decrease

 

¨        Other (Specify)

 

    

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates. OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgment received at OCR.

 

¨ OCR may proceed with the additional/changed services. It is understood that detail and full cost estimate will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

 

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via fax to                 , or 2) sending a confirming email to the Project Leader.

 

    Sponsor Acknowledgment          

/s/ Janelle Katsamas

    20/12/06  
Sponsor Signature     Date         

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

14 OCT 2005    Omnicare Clinical Research    Page 1 of 1
(Replaces version 01JUL2004)    CONFIDENTIAL   


Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc., dated 24-8-05.

THIS EXHIBIT B is entered into this 24th day of August, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a Clinical Services Master Agreement, dated 1st June 05 (hereinafter the “Master Agreement”), wherein Omnicare CR agreed to provide clinical services; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”, and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR shall provide the services set forth in this Exhibit B, subject to the terms and conditions set forth in the Master Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor CR agree as follows:

I. Project Plan

Based on the Project Specifications, Omnicare CR has provided a description of services to be performed for Sponsor’s “A multi-center, randomised, double-blind, parallel-group, vehicle-controlled study to determine the safety of PEP005 0.0025%, 0.01% and 0.05% gel with two treatment schedules, Day 1 and Day 2 or Day 1 and Day 8 applications to actinic keratoses”. Protocol #PEP005-001 dated 28 February 2005 Version 2 (hereinafter “the Project”) and associated costs, Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs.

II. Project Roles and Responsibilities

 

Task

  

    Peplin    

  

    Omnicare    

Project Management

     

1. Regular updates of CRFs status (received, data entered, cleaned and number of queries outstanding)

      X

2. Team meetings with minutes

      X

3. Provision of status reports to Sponsor of performance against deliverables

      X

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Task

       Peplin            Omnicare    

Data Entry

     

1. Design/develop data collection system

      X

2. Validate data collection system

      X

3. Document control of CRFs

      X

4. Enter and verify data

      X

Data Management

     

1. Design/develop data cleaning system

      X

2. Validate cleaning system

      X

3. Write data management guidelines and edit specifications

      X

4. Review CRF and edit system

      X

5. Resolve edit queries

      X

6. Incorporate laboratory data into database

      X

7. Document corrections to CRFs

      X

8. Provide weekly patient listing of AEs

      X

9. Perform QC audits-electronic data compared to paper CRFs

      X

10. Code drug dictionary

      X

11. Code adverse events

      X

12. Code medications

      X

13. Test data transfer after 25% amount of patients completed

      X

14. Test data transfer after 75% amount of patients completed

      X

Statistical Analysis Plan

     

1. Prepare an abbreviated analysis plan prior to CRF finalisation

      X

2. Define efficacy tables and listings

      X

3. Define safety tables and listings

      X

4. Produce efficacy tables and listings

      X

5. Produce safety tables and listings

      X

6. Provide draft report template and analysis plan

      X

7. Approve report template

   X   

8. Validate efficacy tables and listings

      X

9. Validate safety tables and listings

      X

10. Perform quality assurance audit of the tables and listings

      X

11. Provide final tables and listings

      X

12. Provide top line statistical summary report / statistical study report

      X

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Task

      

        Peplin        

  

        Omnicare        

Report Preparation

       

1. Prepare draft report template

        X

2. Approve final report template

     X   

3. Draft study report

        X

4. Final study report

        X

5. Perform quality assurance of study report

        X

6. Approval of final study report

     X   

7. Database transfer to Sponsor

        X

III. Project Timeline

The parties acknowledge that Omnicare CR will commence performance of the Service on or about 12 July 2005. The projected timeline for this Project is as follows:

The following timeline is meant as a guide only.

 

Activities

    

                    Anticipated Timeline                     

Start Database Set Up      w/c 11 July 2005
Complete Database Build      ****
Commence Data Entry      ****
Complete Validation      ****
First Batch of DCFs Issued      ****
Last Patient Out      ****
Last CRF to Omnicare CR      ****
Last DCF Issued      ****
Soft Lock      ****
Hard Lock      ****
Top Line Summary Statistical Results      ****
Final Statistical Analysis Complete      ****
Clinical Study Report Available (following 7 weeks)      ****

A detailed timeline and milestones will be developed based on the different assumptions of how the project is conducted.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


To achieve the above milestones, Omnicare CR requires the data specifications to be available no later than mid July 2005 for development of the database. In addition, collection of the last DCF is critical to achieving Top Line Summary Statistical Report. Please note Omnicare CR are dependent upon Sponsor providing all necessary documents in order for them to meet the above timeline.

IV. Omnicare CR Services

Services provided by Omnicare CR and the assumptions upon which associated costs were determined are based on the project specifications provided by Sponsor, and are outlined below. It should be noted, however, that the costs presented in this budget for these services are estimated pending review of the final specifications, protocol and CRF.

A. Project Specifications

Project Specifications

 

Total # of Sites

   11

Distribution of Sites

   Australia (1 x WA, 3 x VIC, 4 x NSW and 3 x QLD)

# of Screened / Randomised Patients

   60

# of CRF pages per patient (assumes **** unique pages)

   ****

# of Total CRF Pages processed

   ****

# of Serious Adverse Events

   ****; ****% of patients

Critical Milestone

   ****

Final Deliverable

   Clinical Study Report

B. Project Management

Project Management Team

 

Project Management Team

  

    Number of Days    
Allocated

  

    Number of    
Months

Project Leader (**** days per month between July-November; **** days per month December & January)

   ****    ****

Senior Clinical Data Manager — UK (****% FTE)

   ****    ****

Lead Clinical Data Analyst — UK (****% FTE at start up; ****% FTE for duration and ****% FTE at close out)

   ****    ****

Biometrics Team Leader

   ****    ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


The Project Leader will act as a single point of contact for Sponsor during the course of this study. The Project Leader is responsible for the generation of detailed project timelines and ensure that these milestones are met. The Project Leader will provide on-going project status reports as agreed with Sponsor and will proactively identify and resolve critical project issues. The Project Leader is also responsible for managing the project budget and addressing all out-of-scope items with Sponsor.

In addition, as the Project Leader is acting in a dual role, this person will also be responsible for usual Biometrics Team Leader activities that are discussed later in this section.

SOPs

All services outsources will be performed in accordance with Omnicare CR’s SOPs following review and approval by Sponsor, unless specified otherwise.

Study Documents and CRF Return

Omnicare CR will return all study documents in accordance with Omnicare CR’s SOP. This usually occurs within three months of study completion. The CRFs are reviewed and reconciled against the CRF tracker from Omnicare CR’s Clinical Data Management Department. Each CRF is reviewed for completeness and accuracy of filing. A CRF transfer form is completed listing the number of pages for each individual CRF returned.

C. Clinical Data Management

 

Activity

  

    Number    

# Unique CRF Pages

   ****

# Repeat CRF Pages

   ****

Total CRF Pages

   ****

# of Edit Checks

   ****

# of Adverse Events per Patient — MedDRA

   ****

# of Concomitant Medications per Patient — WHODrug

   ****

# of Transfers (including initial)

   ****

Data Management Project Team

A data management team will be assigned to this project to carry out all of the activities defined in the specifications. The team will consist of a Clinical Data Manager, Lead Clinical Data Analyst, Database Programming staff, Dictionary Manager, Data Technicians and Clinical Data Analysts. Team resources for the project will be developed by the Data Manager and will be based on the Case Report Form retrieval plan. Adjustments can be made as needed as the study progresses.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 5


Due to the nature of the deliverables for this Project, Omnicare CR has assumed a Clinical Data Manager (CDM) will be assigned to this project for almost **** days per month for just over **** months. The CDM will provide oversight of the data management team as well as ensure that all deliverables are achieved.

On a continual basis, the Omnicare CR team, Project Leader/Biostatistics Team Leader; the Clinical Data Manager and the Lead Clinical Data Analyst will work in concert, will evaluate the number and type of queries being generated by Clinical Data Management, in order to proactively manage the retrieval of quality data and site release status Plans will be implemented to inspect the data for trends and issues in order to suggest focused training at both the project team and the site levels. This will commence as soon as the first CRF pages are submitted in order to proactively resolve data issues.

It is Omnicare CR’s policy to perform a quality control (QC) of the final database to ensure the error rate is within an acceptable range. Each CRF will be printed as a data listing with 100% QC of pre-defined critical data fields against the hard-copy CRF. In addition, a ****% sampling of the patient data will undergo quality control for 100% of the data fields, prior to declaration of a clean database. The processes and outcomes of these QC audits will be documented, with audit findings corrected within the timeframe identified with Data Management Plan. Omnicare CR supports the plan for transfer of clean data to give both Sponsor and the Omnicare Biometrics Group an opportunity to review clean data periodically, ensuring that guidelines are complete and accurate, and that the data is represented Correctly in preparation for the analysis.

Omnicare CR believes that these strategies will ensure:

 

 

Cleaner cases and data.

 

 

Minimises queries.

 

 

Timely resolution of study and site issues.

 

 

Cohesiveness between Sponsor, Omnicare CR and the study site.

 

 

On-time delivery of final clean clinical study database.

 

 

No surprises when preparing for data analysis.

Clinical Data Manager

The Clinical Data Manager assigned to this project will oversee all Data Management activities throughout the life of the project. This dedicated Clinical Data Manager will act as the primary liaison for all Data Management activities. Many of the Clinical Data Manager’s activities are listed below:

 

 

Overseeing the completion of setup and maintenance of all data management activities

 

 

Creation and implementation of the Data Management Plans

 

 

Supporting the development of the CRF completion guidelines

 

 

Liaise with monitoring team to ensure expectations for recording data accurately are communicated to the project team and the study site

 

 

Managing the query generation

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 6


 

Proactively addressing data quality issues to reduce query generation

 

 

Ensuring high quality and timely data management deliverables

 

 

Maintain ongoing communication with Sponsor team members and Omnicare CR’s project team members

 

 

Oversee project training for Clinical Data Management team members

 

 

Provide status updates to both the Omnicare CR internal Project team and the Sponsor team members

 

 

Clinical Data Management Project resource plan to ensure proper staffing throughout the study

Lead Clinical Data Analyst (CDA)

Omnicare CR has assigning a lead CDA. The Lead CDA will provide additional team oversight for the project Data Technicians and CDAs. The Lead CDA will assist the Clinical Data Manager with the following activities in relation to the page-related staff:

 

 

Prioritisation of Clinical Data Management tasks

 

 

Directing the daily task Clinical Data Management team task assignments

 

 

Monitoring the status of task and work load

 

 

Ongoing project training within Data Management

 

 

Providing feedback to the Clinical Monitoring staff on query trends

 

 

Providing backup support to the Clinical Data Manager

 

 

Ensure a cohesive team that maintains high quality and data consistency

 

 

Generating metrics reports

Data Management Plan

Omnicare CR assumes **** (****) Sponsor review cycles including up to **** major and **** minor revision in order to finalise the data management plan.

Database Development

Omnicare CR will develop the study clinical database utilising Oracle Clinical with Omnicare CR standard specifications.

Edit Specifications

Edit programming will begin after receiving Sponsor’s signoff of the edit specifications. The budget includes **** edits.

MedDRA Dictionary

Sponsor is required to have a current MedDRA license in good standing prior to receipt of any MedDRA coded terms. It is assumed under this Exhibit that Sponsor has a current MedDRA license in good standing and that such will be maintained throughout the course of the Services.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 7


Data Management Plan

The Clinical Data Manager will develop the Data Management Plan. The Data Management Plan will include descriptions of the following Data Management activities:

 

 

Project data flow

 

 

Database development overview

 

 

Edit specifications

 

 

Data entry guidelines

 

 

Data handling guidelines

 

 

Study assumptions (Level 1)

 

 

SAE reconciliation process

 

 

External data load procedures / External Data Cleaning parameters / Discrepancy identification flow

 

 

Dictionary coding guidelines and processes

 

 

Database closure procedures

Prior to the start of Data Management activities, the Data Management Plan and edit specifications must be agreed to and signed by the Omnicare CR designee and Sponsor representative. The agreement to all data handling rules will ensure an accurate and timely final database lock leading to a successful data analysis. It is assumed that all portions of the Data Management Plan related to any specific task will be agreed upon prior to the start of those activities.

Data Tracking and Data Entry

The dual data entry strategy will be utilised for numeric and/or text fields. Data will be entered by one member of the data entry staff and re-entered on-line by a second member of the staff. CRF data for screen failure patients will be tracked and entered into the database but will not be cleaned.

All CRF and ancillary data received from the investigative sites are logged into a tracking database on a page-by-page basis. Each page is identified by type of page and date received. Working copies will be maintained in Clinical Data Management and used for any annotations during processing and cleaning. All original (white) CRF pages will be archived by the Sponsor prior to the working Copies being sent to Omnicare CR.

Data Review and Query Processing

Following the data handling rules and edits specifications listed in the Data Management Plan, the Lead CDA will be responsible for:

 

 

Reviewing the CRF data for obvious corrections and potential queries via the electronic Edit checks and the Manual review checks listed in the Data Management Plan

 

 

Applying any agreed upon self evident corrections or study assumptions

 

 

Transmitting queries to investigative sites via monitors

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 8


 

Tracking queries (issued and resolved) into Oracle Clinical Discrepancy Management System

 

 

Working with the Clinical Data Manager to ensure all Data Clarification Forms (DCFs) are signed by the investigator and received in house via fax or mail.

On a continual basis, the Clinical Data Manager will evaluate the number and type of queries being generated by Clinical Data Management, in order to proactively manage the retrieval of quality data on these studies. The team will frequently inspect the data for trends and identification of issues, providing feedback to both the project team and the site. This will begin as soon as sufficient CRF pages are received to identify the trends.

Reconciliation of Safety and Clinical Database

Omnicare CR assumes a total of **** SAEs for this project. A total of **** (****) Adverse Event (AE) qualifiers will be reconciled. Omnicare CR’s Clinical Data Manager will update with the DCF responses and inform Sponsor of the changes.

D. Biometrics

Statistical Analysis Plan

Omnicare CR will develop a statistical analysis plan, including operational definition of endpoints to be analysed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling, and a detailed description of statistical methodology.

If Sponsor has a standard statistical analysis plan template then this can be used instead. Omnicare CR has budgeted for one Sponsor review and one revision.

Design of Table Shells (Mocks)

The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for each study. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included.

Tables, Listings and Graph Programming

Omnicare CR will perform the programming and will validate the following tables, listings and figures/ graphs:

 

         Unique           Repeat           Total    

Tables

   ****   ****   ****

Listings

   ****   ****   ****

Figures/Graphs

   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 9


Database Transfer

Omnicare CR assumes **** standard database transfer that will be submitted to Sponsor in the form of SAS datasets.

Top Line Statistics Summary Report / Statistical Report

A report will be developed in accordance with Sponsor’s requirements and will summarise the results of the study, including findings that may not be appropriate for the body of the clinical report (tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses.

It has been assumed that the Top Line Statistics Summary Report will include a small number of safety and efficacy tables with a brief overview of the document that is sufficient for inclusion in a Press Release to be organised by Sponsor.

Lab Samples

Lab samples are being analysed centrally at QML in Australia.

E. Clinical Writing

Clinical Study Report

The integrated clinical and statistical summary will be prepared in accordance with ICH guidelines on the “Structure and Content of Clinical Study Reports”, appropriate agency regulations, and Omnicare CR’s SOI’s and clinical study report format. A draft clinical report will be generated within **** (****) weeks after receipt of source material and final summary tables and patient data listings.

The designated Omnicare CR clinical writers will liaise closely with the statistician and other team members. All clinical documents will receive two levels of quality control reviews before they are released. There will be a QC review by an independent clinical writer for accuracy and consistency, and a review by the writing manager for accuracy, client format consistency, and appropriate regulatory and clinical perspective. The first draft will then be provided to the Sponsor for review.

The second draft clinical study report will be produced after receipt of one set of collated comments from the Sponsor. It is our experience at Omnicare CR that this can be facilitated, more speedily, by ****. The second draft will be reviewed within the Clinical Writing Department at Omnicare CR to ensure that all Sponsor comments are addressed and that all changes are consistent with the supporting data. Following the Sponsor’s second review, minor revisions will be made and the report finalised.

Omnicare CR Biometrics will provide up to **** tables, **** listings and **** figures that will be summarised in the clinical study report.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 10


This fee includes **** major and **** minor revision. One major revision of the draft report is considered to be up to **** (****) days of requested changes and a minor revision is up to **** (****) day of requested changes. Patient narratives will be drafted from final patient data listings. Omnicare CR Clinical Writing will prepare patient narratives for SAEs and discontinuations due to adverse events based upon a $**** per narrative fee. This fee does not include the collation or compilation of clinical study report appendices.

Clinical Writing Input to SAP

Omnicare CR Clinical Writing will review the draft statistical analysis plan and mock summary tables and data listings for consistency with the protocol and ICH guidelines. Clinical Writing will provide feedback on the table design and format to facilitate the use of the data in the clinical study report.

V. Budget

A. Estimated Project Budget

 

Services

           Unit            #
        Units        
   Unit
        Cost        
(A$)
         Fees (A$)          Estimated
    Pass-Thru    
(A$)
   Estimated
    Total Cost    
(A$)

CLINICAL DATA MANAGEMENT

                 

  Clinical Data Management Oversight — Int’l (CDM Manager assumes ****% FTE x **** month for Start-up, ****% FTE for **** months for Duration, and ****% FTE for **** months for Close-out)    Days    ****    ****    ****    ****    ****

  Lead CDA Int’l (assumes ****% FTE x **** month for Start-up, ****% FTE for **** months for Duration and ****% FTE for **** months for Close-out) —Actual days will be billed    Days    ****    ****    ****    ****    ****

  Development of Data Management Plan (includes **** major and **** minor revision; add’l revisions will be billed at per diem rates)    Days    ****    ****    ****    ****    ****

  Database Development, Testing and Maintenance (assumes **** page CRF, **** unique CRF pages)    Project    ****    ****    ****    ****    ****

 

Estimated Data Entry

(actuals will be billed)

   Pages    ****    ****    ****    ****    ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 11


Services

           Unit            #
        Units        
   Unit
        Cost        
(A$)
         Fees (A$)          Estimated
    Pass-Thru    
(A$)
   Estimated
    Total Cost    
(A$)

CLINICAL DATA MANAGEMENT (continued)

           

  Estimated Data Review and Query Resolution (assumes **** issue per **** CRF pages, **** manual checks and the application of **** study assumption for **** CRF pages); assumes **** CRF pages per enrolled patient, **** pages per screen failure patient, and **** pages per drop out patient. Based on number of CRF Pages, actuals will be billed    Page    ****    ****    ****    ****    ****

  Quality Control Check of Database versus CRF (assumes **** CRF pages per patient)    Patient    ****    ****    ****    ****    ****

  Quality Control Check of Database versus CRF critical variables (**** minutes/patient)    Patient    ****    ****    ****    ****    ****

  Edit Development (actuals will be billed)    Edits    ****    ****    ****    ****    ****

  CRF and Query Tracking (includes all ancillary pages; actuals will be billed)    Page    ****    ****    ****    ****    ****

  Dictionary Coding of Adverse Event terms to MedDRA (estimated to be **** per patient; actuals will be billed)    Term    ****    ****    ****    ****    ****

  Dictionary Coding of Medication Terms (estimated to be **** per patient; actuals will be billed)    Term    ****    ****    ****    ****    ****

  External Vendor) — Initial Load (actuals will be billed)                   ****
  Initial Load    Load    ****    ****    ****    ****    ****
  > Subsequent Load (actuals will be billed)    Monthly    ****    ****    ****    ****    ****
  Lab Visit Verification (**** visits x 60 patient’s: actuals will be billed)    Visits    ****    ****    ****    ****    ****

  Reconciliation of the Safety and Clinical Database (actuals will be billed)    SAE    ****    ****    ****    ****    ****
 

Subtotal — Clinical Data Management

            ****    ****    ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 12


Services

           Unit            #
        Units        
   Unit
        Cost        
(A$)
         Fees (A$)          Estimated
    Pass-Thru    
(A$)
   Estimated
    Total Cost    
(A$)
BIOMETRICS                  

  Biometrics Team Manager (includes Project Management)    Days    ****    ****    ****    ****    ****

  Project Data Setup    Project    ****    ****    ****    ****    ****

  Statistical Plan    Project    ****    ****    ****    ****    ****

  Design of Table Shells (Mocks)    Project    ****    ****    ****    ****    ****

  Programming/QC of Data Displays (actuals will be billed).                  
  Unique Tables    Table    ****    ****    ****    ****    ****
  Repeat Tables    Table    ****    ****    ****    ****    ****
  Unique Listings    Listing    ****    ****    ****    ****    ****
  Repeat Listings    Listing    ****    ****    ****    ****    ****
  Unique Figures    Figure    ****    ****    ****    ****    ****
  Repeat Figures    Figure    ****    ****    ****    ****    ****

  Programmatic Evaluability/Outcome    Project    ****    ****    ****    ****    ****

  Statistical Analysis    Project    ****    ****    ****    ****    ****

  Statistical Report (Top Line Stats Summary Report)    Project    ****    ****    ****    ****    ****

  FDA Item 11 (if required)    Project    ****    ****    ****    ****    ****

  Standard Data Transfer                  
  > Initial    Transfer    ****    ****    ****    ****    ****
  > Subsequent    Transfer    ****    ****    ****    ****    ****

Add’l Stats consulting, meeting attendance, etc., will be charged at per diem rates as follows:

  Team Leader    Days       ****         
  Statistician    Days       ****         
  Programmer    Days       ****         
  Subtotal — Biometrics             ****    ****    ****

CLINICAL WRITING

                 

  Clinical Study Report - Phase II; includes **** major (up to **** days), and **** minor (up to **** day) revision: does not include compilation of Clinical Study Report Appendices; per Omnicare CR SOPs)    Report    ****    ****    ****    ****    ****

  Narratives (actuals will be billed)    Narrative    ****    ****    ****    ****    ****

  Clinical Writing Input to SAP    Project    ****    ****    ****    ****    ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 13


Services

           Unit            #
        Units        
   Unit
        Cost        
(A$)
     Fees (A$)      Estimated
Pass-Thru
(A$)
   Estimated
Total Cost
(A$)

CLINICAL WRITING (continued)

                 
  Attendance at Sponsor Requested Meetings:                  
  Sponsor will be billed for actual time expended. Attendance at Sponsor requested meetings (teleconferences/video conferences or client review/planning meetings at Sponsor/Omnicare CR) will be billed to Sponsor according to the following per diem rates:
  Director          ****         
  Senior Writer    Days       ****         
  Clinical Writer    Days       ****         
 

Subtotal — Clinical Writing

            ****    ****    ****

MISCELLANEOUS

                 

  Return of CRF (hard copy); bill on actuals    Pages    ****    ****    ****    ****    ****

Subtotal — Miscellaneous

            ****    ****    ****
                         

Estimated Services Budget

            ****      
                     

Estimated Pass Through

               ****   
                     

Total Estimated Budget

                  ****
                     

B. Payment Schedules

1. Invoicing Process for Service Fees

Omnicare CR maintains a project accounting system, whereby all direct project costs (Service Fees or Pass-Through Expenses) are coded by project.

An initial payment of AUD$****, representing approximately **** percent (****%) of the estimated Service Fees, is due and payable upon execution of this Exhibit B. Subsequent payments shall be made monthly, based on Project progress and upon submission of an invoice to Sponsor by Omnicare CR. The subsequent invoices shall be reduced by a prorated portion form the initial payment such that the initial payment is applied evenly over the term of the Project. All payments shall be processed within **** days. If any payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a liquidated damages fee of ****% per month of the outstanding balance.

2. Pass-Through Expense Invoicing

Omnicare CR’s project accounting system is able to capture and categorize in summary the following key Pass-Through Expenses related to a project:

 

 

Travel

 

 

Delivery costs

 

 

CRF and other printing or copying costs

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 14


 

Investigator Meeting costs

 

 

Telecommunication costs (which may include telephone, fax, pager, conference calls, or PC connectivity charges)

All other project related expenses that are not related to Service Fees and any additional detail to support Pass-Through Expenses will be provided on a fee basis.

3. Payments

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Maquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Exhibit B shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Exhibit B as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

ACCEPTANCE

The terms and conditions of the Master Agreement govern this Exhibit B and such document is incorporated herein by reference as if fully set forth herein.

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.     Omnicare CR, Inc.
BY:  

/s/ Michael Aldridge

    BY:  

/s/ Kevin D. Duffy

Name:   Michael Aldridge     Name:   Kevin D. Duffy
Title:   Director     Title:  

Senior Vice President

Global Marketing & Business Development

Date:   24-8-05     Date:   9-6-05

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 15


Change Order #01 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th Aug 2005.

THIS CHANGE ORDER is entered into this 23 rd day of Dec, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership, as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement.

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following additional work and reduced services pursuant to the general terms and conditions set forth in the Agreement:

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

 

Services to be Billed

  Estimated
Additional

Service Fee (AUS$)
 
Pursuant to Exhibit B, Omnicare CR will provide biometrics support for the Sponsor’s Cohort Study of PEP005 Topical Gel, Protocol #PEP0O5-001, Version 2  

Unique Tables:

 

*       Estimated number of unique tables in original budget = ****

 

*       Actual number of unique tables = ****

 

*       Variance = **** unique tables @ AUS$****

  ****  
  Repeat Tables:   ****  
 

*       Estimated number of repeat tables in original budget = ****

 
 

*       Actual number of repeat tables = ****

 
 

*       Variance = **** repeat table @ AUS$****

 
  Unique Listings:   ****  
 

*       Estimated number of unique listings in original budget = ****

 
 

*       Actual number of unique listings = ****

 
 

*       Variance = **** unique listings @ AUS$****

 
  Repeat Listings:   ****  
 

*       Estimated number of repeat listings in original budget = ****

 
 

*       Actual number of repeat listings = ****

 
 

*       Variance = **** repeat listings @ AUS$****

 

Reference

 

Services Not to be Billed

  Estimated
Reduced
Service Fee (AUS$)
 
Pursuant to Exhibit B, Omnicare CR will provide biometrics support for the Sponsor’s Cohort Study of PEP005 Topical Gel, Protocol # PEP005-001, Version 2  

Unique Figures:

 

*       Estimated number of unique figures in original budget = ****

 

*       Actual number of unique figures = ****

 

*       variance = **** unique figure @ AUS$****

  ****  
  Repeat Figures:   ****  
 

*       Estimated number of repeat figures in original budget = ****

 
 

*       Actual number of repeat figures = ****

 
 

*       Variance = **** repeat figure @ AUS$****

 
       
Total Estimated Service Fees to be Billed   **** *
       
Total Estimated Service Fees Not to be Billed   ****  
       
Total Estimated Pass Through Expenses   **** **
       

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #01.

3. Payment

The full payment of AUS$**** of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #01. The payment of Service Fees and Pass-Through Expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #01 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #01 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #01, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE

BY AND BETWEEN:

 

Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ Michael Aldridge

    By:  

/s/ Leonard Stigliano

Name:   Michael Aldridge     Name:   Leonard Stigliano
Title:   CEO & Managing Director     Title:   Pres. & Global Chief Operating Officer
Dated:   12-Dec-05     Dated:   12-23-05

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


 

Initial Sponsor Notification Form

 

   LOGO

Change in Project Scope

 

Protocol Number: PEP005-001

 

 

    Date of Request: 04OCT2005

 

 

    Omnicare PCN: KO1503

 

Omnicare Project Director:      

Omnicare Account Director:      

Sponsor Study Manager:      

Sponsor Outsourcing Manager:      

 

 

    ****

    ****

    Peter Welburn

Individual and Department making      

request:      

      ****, Biometrics

Brief Description of Project Scope Change:

 

Revised costing for tables and listings presented in Statistical Analysis Plan. The original proposal had an estimate of Tables (**** unique/**** repeat), Listings (**** unique/**** repeat) and Figures (**** unique/**** repeat). Due to reporting requirements and providing comprehensive efficacy analysis there has been an increase in the number of Tables and Listings designed and presented in the Statistical Analysis Plan (please see attached table of contents for flagging of Unique (P) and Repeat (S) displays.

 

The updated count of Tables is **** unique/**** repeat and Listings is **** unique/**** repeat.

 

The increase in cost to produce these data displays as set out in the Statistical Analysis Plan will be $****

 

   

Implementation of this request will      

affect the budget as follows (provide      

estimate of anticipated costs      

associated with change, if available):      

 

    þ    Increase

 

    ¨    Decrease

 

    ¨    Other (specify)

 

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgment received at OCR.

 

þ OCR may proceed with the additional/changed services It is understood that detail and full cost estimate will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 1 of 1


 

Initial Sponsor Notification Form

 

   LOGO

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via fax to                     , or 2) sending a confirming email to the Project Leader.

Sponsor Acknowledgment

 

/s/ Peter Welburn

      

7/10/05

Sponsor Signature        Date  

 

 

* Notification only — not legally binding

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 2 of 1


Change Order #02 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th Aug 2005.

THIS CHANGE ORDER is entered into this 18 th day of October, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


1. Schedule of Changes

Sponsor and Omnicare CR agree to the following additional work services pursuant to the general terms and conditions set forth in the Agreement:

 

Reference

  

Services to be Billed

   Estimated
        Additional Service        
Fee (AUS$)
Pursuant to Exhibit B, Omnicare CR will load Sponsor’s log of protocol deviations from monitoring of PEP005-001 into the clinical database    Development of an additional DCM/DCI module, loading the spreadsheet data and QC of received data.    $****

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #02.

3. Payment

The full payment of AUS$**** of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #02. The payment of Service Fees and Pass-Through Expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Change Order #02 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #02 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #01, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE        
BY AND BETWEEN:        
Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ JANELLE KATSAMAS

    By:  

/s/ KEVIN D. DUFFY

 
Name:   JANELLE KATSAMAS     Name:   KEVIN D. DUFFY  
Title:   CLINICAL RESEARCH MGR     Title:   EXECUTIVE VICE PRESIDENT  
        GLOBAL BUSINESS DEVELOPMENT  
        CHIEF RELATIONS OFFICER  
Dated:   21 February 2006     Dated:   3/7/06  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


 

Initial Sponsor Notification Form

 

  LOGO

Change in Project Scope

 

Protocol Number: PEP005-001

 

 

    Date of Request: 19OCT2005

 

 

    Omnicare PCN: KO1503

 

Omnicare Project Director:      

Omnicare Account Director:      

Sponsor Study Manager:      

Sponsor Outsourcing Manager:      

 

 

    ****

    ****

    Peter Welburn

Individual and Department making      

request:      

      ****, Clinical Data Management

Brief Description of Project Scope Change:

 

In order to load Peplin’s log of protocol deviations from monitoring of PEP005-001 into the clinical database an additional Oracle Clinical module is required to be built to receive this data. This will take as estimated **** hours to complete and would include building the DCM/DCL module, loading the spreadsheet data and QC of received data. The proposed cost is $****.

 

   

Implementation of this request will      

affect the budget as follows (provide      

estimate of anticipated costs      

associated with change, if available):      

 

    þ    Increase

 

    ¨    Decrease

 

    ¨    Other (specify)

 

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates. OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgement received at OCR.

 

þ OCR may proceed with the additional/changed services. It is understood that detail and full cost estimated will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via-fax to                     , or 2) sending a confirming email to the Project Leader.

Sponsor Acknowledgment

 

/s/ JANELLE KATSAMAS

     25 Oct 05  
Sponsor Signature      Date  

 

 

*

 

 

Notification only — not legally binding

 

****   Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 1 of 1


Change Order #03 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24th Aug 2005.

THIS CHANGE ORDER is entered into this 15th day of December, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Service Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity, (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

Following database close, data management reconciliation to CRF pages received, queries raised, QC performed SAE reconciliation has taken place.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes to the budget based on the final reconciliation pursuant to the general terms and conditions set forth in the Agreement:

 

Omnicare CR, Inc.

Clinical Budget for:

Sponsor:

PCN:

Services

 

Peplin

KO1503.03

Unit

  # Units       Unit Cost   Fees      

Estimated

Pass-Thru

 

Estimated

Total Cost

•    Estimated Data Entry (actuals will be billed)

           

>Pages in Int’l

  Pages   ****   ****   ****   ****   ****

•    Data Review and Query Resolution

           

> CRF Pages

  Page   ****   ****   ****   ****   ****

•    Quality Control Check of critical variables

  Patient   ****   ****   ****   ****   ****

•    Edit Development (actuals will be billed)

  Edits   ****   ****   ****   ****   ****

•    CRF and Query Tracking (includes all ancillary pages; actuals will be billed)

  Page   ****   ****   ****   ****   ****

•    Dictionary Coding of Adverse Event terms to MedDRA (estimated to be per patient; actuals will be billed)

  Term   ****   ****   ****   ****   ****

•    Dictionary Coding of Medication terms (estimated to be per patient; actuals will be billed)

  Term   ****   ****   ****   ****   ****

Lab Visit Verification

  Visits   ****   ****   ****   ****   ****

•    Reconciliation of the, Safety and Clinical Database (actuals will be billed)

  SAE   ****   ****   ****   ****   ****

Sub-Total Clinical Data Management

        ****   ****   ****
                 

Estimated Services Budget

        ****    
             

Estimated Pass Through

          ****  
             

Total Estimated Budget

            ****
             

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #03.

3. Payment

The full payment of AUS$**** of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #03. The payment of Service Fees and Pass-Through Expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Change Order #03 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #03 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #01, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE        
BY AND BETWEEN:        
Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ JANELLE KATSAMAS

    By:  

/s/ KEVIN D. DUFFY

 
Name:   JANELLE KATSAMAS     Name:   KEVIN D. DUFFY  
Title:   CLINICAL RESEARCH MGR     Title:   EXECUTIVE VICE PRESIDENT  
        GLOBAL BUSINESS DEVELOPMENT  
        CHIEF RELATIONS OFFICER  
Dated:   20 December 2005     Dated:   1-26-06  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


 

Initial Sponsor Notification Form

 

  LOGO

Change in Project Scope

 

Protocol Number: PEP005-001

 

 

    Date of Request: 21NOV2005

 

 

    Omnicare PCN: KO1503

 

Omnicare Project Director:      

Omnicare Account Director:      

Sponsor Study Manager:      

Sponsor Outsourcing Manager:      

 

 

    ****

    ****

    Peter Welburn

Individual and Department making      

request:      

      ****, Clinical Data Management

Brief Description of Project Scope Change:

 

Following database close, data management reconciliation of CRE pages received, queries raised, QC performed and SAE reconciliation has taken Place. These tasks are billed as actuals as per the contract and the final reconciliation of tasks is attached. This represents an overall increase of $**** in the clinical data management budget.

 

   

Implementation of this request will      

affect the budget as follows (provide      

estimate of anticipated costs      

associated with change, if available):      

 

    þ    Increase

 

    ¨    Decrease

 

    ¨    Other (specify)

 

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgement received at OCR.

 

þ OCR may proceed with the additional/changed services. It is understood that detail and full cost estimate will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via fax to                     , or 2) sending a confirming email to the Project Leader.

Sponsor Acknowledgment

 

/s/ Michael Aldridge

    

12-De-05                        

Sponsor Signature      Date

 

 

*

 

 

 

Notification only — not legally binding

****   Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 1 of 1


PEP005-001 (KO1503)

 

Contract item

  

unit

  

unit cost A$

  

# units per

contract

  

contract

cost

  

actual # units

  

actual cost

  

difference

Oversight—CDM manager

   days    ****    ****    ****    ****    ****    ****

Oversight — Lead CDA

   days    ****    ****    ****    ****    ****    ****

DMP

   days    ****    ****    ****    ****    ****    ****

database development

   project    ****    ****    ****    ****    ****    ****

data entry

   page    ****    ****    ****    ****    ****    ****

data review

   page    ****    ****    ****    ****    ****    ****

QC full

   patient    ****    ****    ****    ****    ****    ****

QC critical variables

   patient    ****    ****    ****    ****    ****    ****

Edit development

   edit    ****    ****    ****    ****    ****    ****

CRF tracking

   page    ****    ****    ****    ****    ****    ****

dictionary coding of AEs

   term    ****    ****    ****    ****    ****    ****

dictionary coding of meds

   term    ****    ****    ****    ****    ****    ****

lab load — initial

   load    ****    ****    ****    ****    ****    ****

lab visit verification

   visit    ****    ****    ****    ****    ****    ****

SAE reconciliation

   SAE    ****    ****    ****    ****    ****    ****
                          

Total

            ****       ****    ****
                          

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.


Change Order #03 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 18th October 2005.

THIS CHANGE ORDER is entered into this 15th day of December, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor” ) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

Following database close, data management reconciliation of CRF pages received, queries raised, QC performed and SAE reconciliation has taken place.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes to the budget based on the final reconciliation pursuant to the general terms and conditions set forth in the Agreement:

 

Omnicare CR, Inc.

   Peplin               

Clinical Budget for:

   KO1503.03               

Sponsor:

                 

PCN:

                 

Services

  

Unit

  

# Units

  

Unit Cost

  

Fees

  

Estimated

Pass-Thru

  

Estimated

Total Cost

Clinical Data Management

                 

•    Estimated Data Entry (actuals will be billed)

> Pages in Int’l

   Pages    ****    ****    ****    ****    ****

•    Data Review and Query Resolution

> CRF Pages

   Pages    ****    ****    ****    ****    ****

•    Quality Control Check of critical variables

   Patient    ****    ****    ****    ****    ****

•    Edit Development (actuals will be billed)

   Edits    ****    ****    ****    ****    ****

•    CRF and Query Tracking (includes all ancillary pages; actuals will be billed)

   Page    ****    ****    ****    ****    ****

•    Dictionary Coding of Adverse Event terms to MedDRA (estimated to be per patient; actuals will be billed)

   Term    ****    ****    ****    ****    ****

•    Dictionary Coding of Medication Terms (estimated to be per patient; actuals will be billed)

   Term    ****    ****    ****    ****    ****

Lab Visit Verification

   Visits    ****    ****    ****    ****    ****

•    Reconciliation of the Safety and Clinical Database (actuals will be billed)

   SAE    ****    ****    ****    ****    ****
                       

Sub-Total Clinical Data Management

            ****    ****    ****
                   

Estimated Services Budget

            ****      
                     

Estimated Pass Through

               ****   
                     

Total Estimated Budget

                  ****
                   

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.
** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.
**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended for a reasonable period of time to permit the completion of the additional work set forth in this Change Order #03.

3. Payment

The full payment of AUS $**** of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #03. The payment of Service Fees and Pass-Through Expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of Service Fees or Pass-Through Expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Change Order #03 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #03 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the Corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #01, all other terms and conditions of the Agreement shall continue in force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


ACCEPTANCE        
BY AND BETWEEN:        
Peplin Operations Pty Ltd.     Omnicare CR, Inc.
By:  

/s/ Peter Welburn

    By:  

/s/ Kevin Duffy

 
Name:   Peter Welburn     Name:  

Kevin Duffy

 
Title:   Director, Drug Development     Title:   Senior Vice President, Global Marketing  
       

& Business Development

 
Dated:   20/12/05     Dated:  

1/26/06

 

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


 

Initial Sponsor Notification Form

 

  LOGO

Change in Project Scope

 

Protocol Number: PEP005-001

 

 

    Date of Request: 21DEC2005

 

 

    Omnicare PCN: KO1503

 

Omnicare Project Director:      

Omnicare Account Director:      

Sponsor Study Manager:      

Sponsor Outsourcing Manager:       

 

 

    ****

    ****

    Peter Welburn

Individual and Department making      

request:      

      ****, Clinical Writing

Brief Description of Project Scope Change:

 

The final number of tables and listings represents a significant increase compared to the contracted number of TLs (**** tables and **** listings versus **** tables and **** listings). More time will be required to draft the Clinical Study Report based on the increased number of tables and listings. This additional work represents an additional $**** for production of the CSR.

 

   

Implementation of this request will      

affect the budget as follows (provide      

estimate of anticipated costs      

associated with change, if available)      

 

    þ    Increase

 

    ¨    Decrease

 

    ¨    Other (specify)

 

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates. OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgment received at OCR.

 

þ OCR may proceed with the additional/changed services. It is understood that detail and full cost estimate will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via fax to                     , or 2) sending a confirming email to the Project Leader.

Sponsor Acknowledgment

 

/s/ Peter Welburn

    30 December 2005
Sponsor Signature     Date

 

 

*

 

 

Notification only — not legally binding

 

****   Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 1 of 1


Change Order # 4 To Exhibit B To The Clinical Services Master Agreement

Between Peplin Operations Pty Ltd. And Omnicare CR, Inc.,

Dated 24th August 2005.

THIS CHANGE ORDER is entered into this 10 th day of January, 2006, by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor) and Omnicare CR, Inc. (hereinafter “Omnicare CR).

WHEREAS, Sponsor and Omnicare CR have entered into certain Clinical Services Master Agreement, dated 1st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare ,CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR hereby agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following additional work pursuant to the general terms and conditions set forth in the Agreement:

 

Reference

  

Services to be Billed

   Estimated
Additional Service
Fee (AUS$)

Pursuant to Exhibit B,

Omnicare CR will provide

Clinical Writing Services for the

Sponsor’s Cohort Study of

PEP005 Topical Gel, Protocol #PEP005-001, Version 2

  

More time will be required to draft the Clinical Study Report based on the increased number of tables and listings:

 

•        **** tables and **** listings were produced versus **** tables and **** listings originally contracted.

 

•        Estimated additional time:

**** days of a Senior Writer @ $****/day = $****

**** day of a Director CW @ $****/day = $****

     ****
     
         
Total Estimated Additional Service Fees    * ****
         
Total Estimated Pass Through Expenses      ******
         
Total Estimated Budget      ****
         

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

1


 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

In the event of any conflict between the provisions of this Change Order #4 and the Agreement, the terms of this Change Order #4 shall govern.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended as set forth above to permit completion of the additional work set forth in this Change Order #4.

3. Payment

The full payment of AUS$**** of the estimated additional Service Fees shall be due and payable to Omnicare CR upon execution of this Changes #4. The payment of Service Fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If any payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation

Macqarie Shopping Centre

North Ryde, NSW 2114

Swift ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary, the estimated service fees set forth in this Change Order #4 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining services under this Change Order #4 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #4, all other terms and conditions of the Agreement shall continue in full force and effect.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

2


ACCEPTED AND APPROVED BY AND BETWEEN:

 

Peplin Operations Pty Ltd.   Omnicare CR, Inc.  
22By:  

/s/ Peter Welburn

    By:   /s/ KEVIN D. DUFFY                                
Name:   Peter Welburn     Name:   KEVIN D. DUFFY  
Title:   Director, Drug Development     Title:  

EXECUTIVE VICE PRESIDENT

GLOBAL BUSINESS DEVELOPMENT

 

CHIEF RELATIONS OFFICER

 
Date: 30\1\06.   Date: 2-13-06  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

3


Change Order #05 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24 August 2005.

THIS CHANGE ORDER is entered into this 13th day of February, 2006 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

  

Changes and/or Additions

   Estimated Service
Fee (AUS$)
 
Pursuant lo Exhibit B, Omnicare CR will provide statistical support for the Sponsor’s Study of PEP005 Topical Gel, Protocol # PEP005-001    Sponsor has requested the production of **** (****) additional tables (**** unique and **** repeat tables) and the provision of a short flash report (up to **** (****) page) to accompany delivery of tables. These additional tables and flash report are to be delivered by 28 February 2006.   
   The estimated cost to produce the additional tables and flash report are:   
   * **** unique tables @ $****/table = $****    ****  
   * **** repeat table @ $****/table = $****    ****  
   * **** flash report (**** hours Biostatistician time @ $****/hour) = $****    ****  
   Actuals will be billed.   
         
Total Estimated Service Fees to be Invoiced    ****  
         
Total Estimated Pass Through Expenses    **** **
         

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended to 28 February 2006 to permit the completion of the additional work set forth in this Change Order #05.

3. Payment

The full payment of AUS$**** for Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #05. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If the payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a liquidated damages fee of ****% per month of the outstanding balance.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #05 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right to increase the price of the remaining Services under this Change Order #05 as of each ****; such increases shall not exceed the percentage change of the Medical Services Price Index for the corresponding period.

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #05, all other terms and conditions of the Agreement shall continue in force and effect.

 

ACCEPTANCE        
BY AN BETWEEN:        
Peplin Operations Pty Ltd.   Omnicare CR, Inc.  
By:  

/s/ Peter Welburn

    By:  

/s/ KEVIN D. DUFFY

 
Name:   Peter Welburn     Name:   KEVIN D. DUFFY  
Title:   Director, Drug Development     Title:  

EXECUTIVE VICE PRESIDENT

GLOBAL BUSINESS DEVELOPMENT

CHIEF RELATIONS OFFICER

 
Dated:   21 February 2006     Dated:   3/7/06  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


 

Initial Sponsor Notification Form

 

   LOGO

Change in Project Scope

 

Protocol Number: PEP005-001

 

 

    Date of Request: 10FEB2006

 

 

    Omnicare PCN: KO1503

 

Omnicare Project Director:      

Omnicare Account Director:      

Sponsor Study Manager:      

Sponsor Outsourcing Manager:      

 

 

    ****

    ****

    Peter Welburn

Individual and Department making      

request:      

      ****, Biometrics

Brief Description of Project Scope Change:

 

The sponsor has requested the production of **** additional tables (**** unique and **** repeat tables) and the provision of a short flash report (up to **** page) to accompany delivery of tables. These additional tables and flash report are to be delivered by 28FEB2006.

 

The estimate cost to produce **** unique tables (@ $**** each, is $****, **** repeat table (@ $**** each) is $**** and the flash report (**** hours @ $**** each) is $****. The Total estimated cost is $****.

 

Implementation of this request will      

affect the budget as follows (provide      

estimate of anticipated costs      

associated with change, if available):      

 

 

    þ    Increase

 

    ¨    Decrease

 

    ¨    Other (specify)

 

The above information briefly outlines a description of the additional/changed services, which relate to the referenced study/protocol. Costs above are estimates. OCR and Sponsor will discuss in detail the budgetary and/or timeline impact of the additional/changed services within five (5) business days of receipt of acknowledgment received at OCR.

 

þ OCR may proceed with the additional/changed services. It is understood that detail and full cost estimate will be provided by OCR.

 

¨ OCR may not proceed with additional/changed services.

 

 

Sponsor Comments:

 

Please acknowledge approval/refusal to proceed with the additional/changed services by sending written confirmation to the OCR Project Leader by one of the following methods: 1) signing and returning this document via fax to                     , or 2) sending a confirming email to the Project Leader.

Sponsor Acknowledgment

 

/s/ Peter Welburn

    16\2\06   
Sponsor Signature     Date   

 

 

*

 

 

Notification only — not legally binding

 

****   Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

 

01JUL2004 (Initial Version)  

Omnicare Clinical Research

CONFIDENTIAL

  Page 1 of 1


Change Order #06 to Exhibit B to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc.,

dated 24 August 2005.

THIS CHANGE ORDER is entered into this 22nd day of September, 2006 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a certain Clinical Services Master Agreement, dated 1 st June 2005 (collectively, with the Exhibit thereto, as the same may have been amended or supplemented as of the date hereof, the “Agreement”), the terms of which are incorporated herein by reference; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR desire to amend Exhibit B to the Agreement to provide for certain additional tasks or changes in the scope of the work provided under the Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

1. Schedule of Changes

Sponsor and Omnicare CR agree to the following changes and additional work pursuant to the general terms and conditions set forth in the Agreement:

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Reference

  

Changes and/or Additions

   Estimated Service
Fee (AUS$)
 
Pursuant to Exhibit B, Omnicare CR will provide Statistical and Clinical Writing support for the Sponsor’s Study of PEP005 Topical Gel, Protocol # PEP005-001    Sponsor has requested the additional production of tables and a graph as well as clinical writing additions.   
  

 

The cost to produce the additional tables and graph are:

  
  

 

*       **** unique tables @ $****/table

   ****  
  

 

*       **** repeat tables @ $****/table

   ****  
  

 

*       **** unique graph @ $****/graph

   ****  
  

 

The cost for the additional clinical writing are:

  
  

 

*       Senior Clinical Writer — ****[email protected] $****/day

   ****  
  

 

*       Clinical Writing Director — **** day @ $****/day

 

   ****

 

 

         
Total Estimated Service Fees    **** *
         
Total Estimated Pass Through Expenses    **** **
         
Total Estimated Budget    ****  
         

 

 

* The Estimated Service Fees set forth above represent the original unit costs set forth in the Agreement and are subject to any annual price increase(s) applied against the original unit costs.

 

** Sponsor will be billed for actual Pass-Through Expenses incurred in support of the Project.

 

2. Term

Notwithstanding any language to the contrary set forth in the Agreement, Sponsor and Omnicare CR agree that the term of the Agreement shall be extended to permit the completion of the additional work set forth in this Change Order #06.

 

3. Payment

The full payment of AUS$**** representing **** percent (****%) of the estimated Service Fees, shall be due and payable to Omnicare CR upon execution of this Change Order #06. The payment of service fees and pass through expenses shall be made by Sponsor within **** (****) days of receipt of invoice. If payment of service fees or pass through expenses is late by more than **** (****) days, such payment shall be subject to a penalty fee of ****% per month of the outstanding balance.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Sponsor shall make payment directly to the following bank account nominated by Omnicare CR:

Omnicare CR Inc.

Westpac Banking Corporation,

Macquarie Shopping Centre,

North Ryde, NSW 2113

SWIFT ID: ****

BSB/Account Number: ****

 

4. Annual Price Increase

Notwithstanding anything contained herein to the contrary and subject to any previous annual price increase(s), the estimated Service Fees set forth in this Change Order #06 shall remain in effect until ****. Thereafter, Omnicare CR reserves the right increase the price of the remaining Services under this Change Order #06 as of each ****; such increases shall not exceed the percentage change of the Medical Services Index for the corresponding period.

 

5. No Other Changes

Except as expressly provided to the contrary in this Change Order #06, all other terms and conditions of the Agreement shall continue in force and effect.

 

ACCEPTANCE      
BY AND BETWEEN:      
Peplin Operations Pty Ltd.     Omnicare CR, Inc.  
By:  

/s/ Michael Aldridge

    By:  

/s/ Dale Evans

 
Name:   Michael Aldridge     Name:   Dale Evans  
Title:   Managing Director & CEO     Title:   CEO  
Dated:   4-oct-06     Dated:   10/10/06  

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


Exhibit C to the Clinical Services Master Agreement

between Peplin Operations Pty Ltd. and Omnicare CR, Inc., dated 24-08-05.

THIS EXHIBIT C is entered into this 24th day of August, 2005 (“Effective Date”), by and between Peplin Operations Pty Ltd. (hereinafter “Sponsor”) and Omnicare CR, Inc. (hereinafter “Omnicare CR”).

WHEREAS, Sponsor and Omnicare CR entered into a Clinical Services Master Agreement, dated 1 st June 05 (hereinafter the “Master Agreement”), wherein Omnicare CR agreed to provide clinical services; and

WHEREAS, Omnicare CR and/or an affiliate entity (such entity being defined as an entity under direct or indirect beneficial common ownership as Omnicare CR’s; hereinafter referred to as “Affiliate Entity”) is willing and able to perform the services designated by Sponsor. Except for any references to invoicing or payment, any references to “Omnicare CR” shall be deemed to include “Omnicare CR and/or an Affiliate Entity”; and

WHEREAS, Sponsor and Omnicare CR agree that Omnicare CR shall provide the services set forth in this Exhibit C, subject to the terms and conditions set forth in the Master Agreement;

NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Sponsor and Omnicare CR agree as follows:

I. Project Plan

Based on the Project Specifications, Omnicare CR has provided a description of services to be performed for Sponsor’s “A multi-centre, randomised, double-blind, parallel-group, vehicle-controlled study to determine the safety of PEP005 0.0025%, 0.01% and 0.05% gel with two treatment schedules, Day 1 and Day 2 or Day 1 and Day 8 applications to nodular basal cell carcinoma”. Protocol #PEP005-002 dated 28 February 2005 Version 2 Amendment #1 dated 9 June 2005 (hereinafter “the Project”) and associated costs. Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs.

II. Project Roles and Responsibilities

 

Task

      

        Peplin        

      

      Omnicare      

Project Management

         

1. Regular updates of CRFs status (received, data entered, cleaned and number of queries outstanding)

          X

2. Team meetings with minutes

          X

3. Provision of status reports to Sponsor of performance against deliverables

          X

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 1


Task

      

        Peplin        

             Omnicare      

Data Entry

         

1. Design/develop data collection system

          X

2. Validate data collection system

          X

3. Document control of CRFs

          X

4. Enter and verify data

          X

Data Management

         

1. Design/develop data cleaning system

          X

2. Validate cleaning system

          X

3. Write data management guidelines and edit specifications

          X

4. Review CRF and edit system

          X

5. Resolve edit queries

          X

6. Incorporate laboratory data into database

          X

7. Document corrections to CRFs

          X

8. Provide weekly patient listing of AEs

          X

9. Perform QC audits-electronic data compared to paper CRFs

          X

10. Code drug dictionary

          X

11. Code adverse events

          X

12. Code medications

          X

13. Test data transfer after 25% amount of patients completed

          X

14. Test data transfer after 75% amount of patients completed

          X

Statistical Analysis Plan

         

1. Prepare an abbreviated analysis plan prior to CRF finalisation

          X

2. Define efficacy tables and listings

          X

3. Define safety tables and listings

          X

4. Produce efficacy tables and listings

          X

5. Produce safety tables and listings

          X

6. Provide draft report template and analysis plan

          X

7. Approve report template

     X     

8. Validate efficacy tables and listings

          X

9. Validate safety tables and listings

          X

10. Perform quality assurance audit of the tables and listings

          X

11. Provide final tables and listings

          X

12. Provide statistical analysis

          X

13. Database transfer to Sponsor

          X

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 2


Task

               Peplin                      Omnicare      

Report Preparation

         

1. Prepare draft report template

          X

2. Approve final report template

     X     

3. Draft study report

          X

4. Final study report

          X

5. Perform quality control of study report

          X

6. Approval of final study report

     X     

III. Project Timeline

The parties acknowledge that Omnicare CR will commence performance of the Service on or about 15 September 2005. The projected timeline for this Project is as follows:

The following timeline is meant as a guide only.

 

Activities

   Anticipated Timeline

Start Database Set Up

   Mid September

2005

Complete Database Build

   ****

Commence Data Entry

   ****

Complete Validation Programming

   ****

First Batch of DCFs Issued

   ****

Last Patient In

   ****

Treatment and Follow Up Period

   ****

Last Patient Out

   ****

Lasr CRF to Omnicare CR

   ****

Last DCF Issued

   ****

Soft Lock

   ****

Hard Lock

   ****

Final Statistical Analysis Complete

   ****

Clinical Study Report Available (following 7 weeks)

   ****

A detailed timeline and milestones will be developed based on the different assumptions of how the project is conducted.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 3


IV. Omnicare CR Services

Services provided by Omnicare CR and the assumptions upon which associated costs were determined are based on the project specifications provided by Sponsor, and are outlined below. It should be noted, however, that the costs presented in this budget for these services are estimated pending review of the final specifications, protocol and CRF.

A. Project Specifications

 

Project Specifications

Total # of Sites

   8

Distribution of Sites

   Australia (1 x WA, 3 x VIC, 2 x NSW and 2 x QLD)

# of Screened / Randomised Patients

  

Patients will be randomised into

one of **** PEP005 gel

concentrations or vehicle gel

  

**** treatment arms (****;

****)

   **** patients per arm
   Total of 60 to be enrolled

# of CRF pages per patient (assumes **** unique pages)

   ****

# of Total CRF Pages Processed

   ****

# of Serious Adverse Events

   ****; ****% of patients

Final Deliverable

   Clinical Study Report

B. Project Management

Project Management Team

 

Project Management Team

  

Number of Days

Allocated

  

Number of

Month

Project Leader (**** days per month for the first **** and last

**** months; plus **** day per month for **** months)

   ****    ****
Senior Clinical Data Manager — UK (****% FTE)    ****    ****
Lead Clinical Data Analyst — UK (****% FTE)    ****    ****
Biometrics Team Leader (**** day per month)    ****    ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 4


The Project Leader will act as a single point of contact for Sponsor during the course of this study. The Project Leader is responsible for the generation of detailed project timelines and ensure that that these milestones are met. The Project Leader will provide on-going project status reports as agreed with Sponsor and will proactively identify and resolve critical project issues. The Project Leader is also responsible for managing the project budget and addressing all out-of-scope items with Sponsor.

In addition, as the Project Leader is acting in a dual role, this person will also be responsible for usual Biometrics Team Leader activities that are discussed later in this section.

SOPs

All services outsources will be performed in accordance with Omnicare CR’s SOPs following review and approval by Sponsor, unless specified otherwise.

Study Documents and CRF Return

Omnicare CR will return all study documents in accordance with Omnicare CR’s SOP. This usually occurs within three months of study completion. The CRFs are reviewed and reconciled against the CRF tracker from Omnicare CR’s Clinical Data Management Department. Each CRF is reviewed for completeness and accuracy of filing. A CRF transfer form is completed listing the number of pages for each individual CRF returned.

C. Clinical Data Management

 

Activity

    

Number

# Unique CRF Pages      ****
# Repeat CRF Pages      ****
Total CRF Pages      ****
# of Edit Checks      ****
# of Adverse Events per Patient — MedDRA      ****
# of Concomitant Medications per Patient — WHODrug      ****
# of Transfers (including initial)      ****

Data Management Project Team

A data management team will be assigned to this project to carry out all of the activities defined in the specifications. The team will consist of a Clinical Data Manager, Lead Clinical Data Analyst, Database Programming staff, Dictionary Manager, Data Technicians and Clinical Data Analysts. Team resources for the project will be developed by the Data Manager and will be based on the Case Report Form retrieval plan. Adjustments can be made as needed as the study progresses.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 5


Due to the nature of the deliverables for this Project, Omnicare CR has assumed a Clinical Data Manager (CDM) will be assigned to this project for almost **** days per month for just over **** months. The CDM will provide oversight of the data management team as well as ensure that all deliverables are achieved.

On a continual basis, the Omnicare CR team, Project Leader/Biostatistics Team Leader, the Clinical Data Manager and the Lead Clinical Data Analyst will work in concert, will evaluate the number and type of queries being generated by Clinical Data Management, in order to proactively manage the retrieval of quality data and site release status. Plans Will be implemented to inspect the data for trends and issues in order to suggest focused training at both the project team and the site levels. This will commence as soon as the first CRF pages are submitted in order to proactively resolve data issues.

It is Omnicare CR’s policy to perform a quality control (QC) of the final database to ensure the error rate is within an acceptable range. Each CRF will be printed as a data listing with 100% QC of pre-defined critical data fields against the hard copy CRF in addition, a ****% sampling of the patient data will undergo quality control for l00% of the data fields, prior to declaration of a clean database. The processes and outcomes of these QC audits will be documented, with audit findings corrected within the timeframe identified with the Data Management Plan. Omnicare CR supports the plan for transfer of clean data to give both Sponsor and the Omnicare Biometrics Group an opportunity to review clean data periodically, ensuring that guidelines are complete and accurate, and that the data is represented correctly in preparation for the analysis.

Omnicare CR believes that these, strategies will ensure;

 

 

Cleaner cases and data.

 

 

Minimises queries.

 

 

Timely resolution of study and site issues.

 

 

Cohesiveness between Sponsor Omnicare CR and the study site.

 

 

On-time delivery of final clean clinical study database.

 

 

No surprises when preparing for data analysis.

Clinical Data Manager

The Clinical Data Manager assigned to this project will oversee all Data Management activities throughout the life of the project. This dedicated Clinical Data Manager will act as the primary liaison for all Data Management activities. Many of the Clinical Data Manager’s activities are listed below:

 

 

Overseeing the completion of setup and maintenance of all data management activities

 

 

Creation and implementation of the Data Management Plans

 

 

Supporting the development of the CRF completion guidelines

 

 

Liaise with monitoring team to ensure expectations for recording data accurately are communicated to the project team and the study site

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 6


 

Managing the query generation

 

 

Proactively addressing data quality issues to reduce query generation

 

 

Ensuring high quality and timely data management deliverables

 

 

Maintain ongoing communication with Sponsor team members and Omnicare CR’s project team members

 

 

Oversee project training for Clinical Data Management team members

 

 

Provide status updates to both the Omnicare CR internal Project team and the Sponsor team members

 

 

Clinical Data Management Project resource plan to ensure proper staffing throughout the study

Lead Clinical Data Analyst (CDA)

Omnicare CR has assigning a lead CDA. The Lead CDA will provide additional team oversight for the project Data Technicians and CDAs. The Lead CDA will assist the Clinical Data Manager with the following activities in relation to the page-related staff:

 

 

Prioritisation of Clinical Data Management tasks

 

 

Directing the daily task Clinical Data Management team task assignments

 

 

Monitoring the status of task and work load

 

 

Ongoing project training within Data Management

 

 

Providing feedback to the Clinical Monitoring staff on query trends

 

 

Providing backup support to the Clinical Data Manager

 

 

Ensure a cohesive team that maintains high quality and data consistency

 

 

Generating metrics reports

Data Management Plan

Omnicare CR assumes **** (****) Sponsor review cycles including up to **** major and **** minor revision in order to finalise the data management plan.

Database Development

Omnicare CR will develop the study clinical database utilising Oracle Clinical with Omnicare CR standard specifications.

Edit Specifications

Edit programming will begin after receiving Sponsor’s signoff of the edit specifications. The budget includes **** edits.

MedDRA Dictionary

Sponsor is required to have a current MedDRA license in good standing prior to receipt of any MedDRA coded terms. It is assumed under this Exhibit that Sponsor has a current MedDRA license in good standing and that such will be maintained throughout the course of the Services.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 7


Data Management Plan

The Clinical Data Manager will develop the Data Management Plan. The Data Management Plan will include descriptions of the following Data Management activities:

 

 

Project data flow

 

 

Database development overview

 

 

Edit specifications

 

 

Data entry guidelines

 

 

Data handling guidelines

 

 

Study assumptions (Level 1)

 

 

SAE reconciliation process

 

 

External data load procedures / External Data Cleaning parameters / Discrepancy identification flow

 

 

Dictionary coding guidelines and processes

 

 

Database closure procedures

Prior to the start of Data Management activities, the Data Management Plan and edit specifications must be agreed to and signed by the Omnicare CR designee and Sponsor representative. The agreement to all data handling rules will ensure an accurate and timely final database lock leading to a successful data analysis. It is assumed that all portions of the Data Management Plan related to any specific task will be agreed upon prior to the start of those activities.

Data Tracking and Data Entry

The dual data entry strategy will be utilised for numeric and/or text fields. Data will be entered by one member of the data entry staff and re-entered on-line by a second member of the staff CRF data for screen failure patients will be tracked and entered into the database but will not be cleaned.

All CRF and ancillary data received from the investigative sites are logged into a tracking database on a page-by-page basis. Each page is identified by type of page and date received. Working copies will be maintained in Clinical Data Management and used for any annotations during processing and cleaning. All original (white) CRF pages will be archived by the Sponsor prior to the working copies being sent to Omnicare CR.

Data review and Query Processing

Following the data handling rules and edits specifications listed in the Data Management Plan, the Lead CDA will be responsible for:

 

 

Reviewing the CRF data for obvious corrections and potential queries via the electronic Edit checks and the Manual review checks listed in the Data Management Plan

 

 

Applying any agreed upon self evident corrections or study assumptions

 

 

Transmitting queries to investigative sites via monitors

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 8


 

Tracking queries (issued and resolved) into Oracle Clinical Discrepancy Management System

 

 

Working with the Clinical Data Manager to ensure all Data Clarification Forms (DCFs) are signed by the investigator and received in house via fax or mail.

On a continual basis, the Clinical Data Manager will evaluate the number and type of queries being generated by Clinical Data Management, in order to proactively manage the retrieval of quality data on these studies. The team will frequently inspect the data for trends and identification of issues, providing feedback to both the project team and the site. This will begin as soon as sufficient CRF pages are received to identify the trends.

Reconciliation of Safety and Clinical Database

Omnicare CR assumes a total of **** SAEs for this project. A total of **** (****) Adverse Event (AE) qualifiers will be reconciled. Omnicare CR’s Clinical Data Manager will update with the DCF responses and inform Sponsor of the changes.

D. Biometrics

Statistical Analysis Plan

Omnicare CR will develop a statistical analysis plan, including operational definition of endpoints to be analysed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling and a detailed description of statistical methodology.

If Sponsor has a standard statistical analysis plan template then this can be used instead. Omnicare CR has budgeted for one Sponsor review and one revision.

Design of Table Shells (Mocks)

The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for each study. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included.

Tables, Listings and Graph Programming

Omnicare CR will perform the programming and will validate the following tables, listings and figures/ graphs:

 

         Unique           Repeat           Total    

Tables

   ****   ****   ****

Listings

   ****   ****   ****

Figures/Graphs

   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 9


Database Transfer

Omnicare CR assumes **** standard database transfer that will be submitted to Sponsor in the form of SAS datasets.

Lab Samples

Lab samples are being analysed centrally at QML in Australia.

E. Clinical Writing

Clinical Study Report

The integrated clinical and statistical summary will be prepared in accordance with ICH guidelines on the “Structure and Content of Clinical study Reports”, appropriate agency regulations, and Omnicare CR’s SOPs and clinical study report format. A draft clinical report will be generated within **** (****) weeks after receipt of source material and final summary tables and patient data listings.

The designated Omnicare CR clinical writers will liaise closely with the statistician and other team members. All clinical documents will receive two levels of quality control reviews before they are released. There will be an independent clinical writer for accuracy and consistency, and a review by the writing manager for accuracy, client format consistency, and appropriate regulatory and clinical perspective. The first draft will then be provided to the Sponsor for review.

The second draft clinical study report will be produced after receipt of one set of collated comments from the Sponsor. It is our experience at Omnicare CR that this can be facilitated, more speedily, by ****. The second draft will be reviewed within the Clinical Writing Department at Omnicare CR to ensure that all Sponsor comments are addressed and that all changes are consistent with the supporting data. Following the Sponsor’s second review, minor revisions will be made and the report finalised.

Omnicare CR Biometrics will provide up to **** tables, **** listings and **** figures that will be summarised in the clinical study report.

This fee includes **** major and **** minor revision. One major revision of the draft report is considered to be up to **** (****) days of requested changes and a minor revision is up to **** (****) day of requested changes. Patient narratives will be drafted from final patient data listings. Omnicare CR Clinical Writing will prepare patient narratives for SAEs and discontinuations due to adverse events based upon a $**** per narrative fee. This fee does not include the collation or compilation of clinical study report appendices.

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 10


Clinical Writing Input to SAP

Omnicare CR Clinical Writing will review the draft statistical analysis plan and mock summary tables and data listing for consistency with the protocol and ICH guidelines. Clinical Writing will provide feedback on the table design and format to facilitate the use of the data in the clinical study report.

V. Budget

A. Estimated Project Budget

 

Services

           Unit            #
    Units    
  Unit
Cost
    (A$)    
  Fees
    (A$)    
  Estimated
    Pass-Thru (A$)    
  Estimated
    Total Cost (A$)    

CLINICAL DATA MANAGEMENT

             

•   Clinical Data Management Oversight — Int’l
(CDM Manager assumes ****% FTE)

   Days    ****   ****   ****   ****   ****

•   Lead CDA — Int’l (assumes ****% FTE for **** months)

   Days    ****   ****   ****   ****   ****

•   Development of Data Management Plan
(includes **** major and **** minor revision; add’l revisions, will be billed at per diem rates)

   Days    ****   ****   ****   ****   ****

•   Database Development, Testing and Maintenance
(assumes **** page CRF, ****) unique CRF-pages

   Project    ****   ****   ****   ****   ****

•   Estimated Data Entry
(actual will be billed)

   Pages    ****   ****   ****   ****   ****

•   Estimated Data Review and Query Resolution
(assumes **** issue per **** CRF pages, **** manual checks and the application of **** study assumption for **** CRF pages); assumes **** CRF pages per enrolled patient, **** pages per screen failure patient, and **** pages per drop out patient. Queries will be billed on actuals.

   Page    ****   ****   ****   ****   ****

•   Quality Control Check of Database versus CRF
(assumes **** CRF pages per patient)

   Patient    ****   ****   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 11


Services

           Unit            #
    Units    
  Unit Cost
    (A$)    
  Fees
    (A$)    
  Estimated
    Pass-Thru (A$)    
  Estimated
    Total Cost (A$)    

CLINICAL DATA MANAGEMENT (continued)

             

•    Quality Control Check of Database versus CRF critical variables

   Patient    ****   ****   ****   ****   ****

•    Edit Development (actuals will be billed)

   Edits    ****   ****   ****   ****   ****

•    CRF and Query Tracking (includes all ancillary pages; actuals will be billed)

   Page    ****   ****   ****   ****   ****

•    Dictionary Coding of Adverse Event terms to MedDRA
(estimated to be **** per patient; actuals will be billed)

   Term    ****   ****   ****   ****   ****

•    Dictionary Coding of Medication Terms
(estimated to be **** per patient; actuals will be billed)

   Term    ****   ****   ****   ****   ****

•    External Vendor — Initial Load
(actuals will be billed)

              ****

>Initial Load

   Load    ****   ****   ****   ****   ****

>Subsequent Load
(actuals will be billed)

   Monthly    ****   ****   ****   ****   ****

>Lab Visit Verification
(**** visits x 60 patients; actuals will be billed)

   Visits    ****   ****   ****   ****   ****

•    Reconciliation of the safety and Clinical Database
(assumes ****% SAEs; actuals will be billed)

   SAE    ****   ****   ****     ****

Subtotal – Clinical Data Management

          ****   ****   ****

BIOMETRICS

             

•    Biometrics Team Manager

   Days    ****   ****   ****   ****   ****

•    Project Data Setup

   Project    ****   ****   ****   ****   ****

•    Statistical Plan

   Project    ****   ****   ****   ****   ****

•    Design of Table Shells
(Mocks)

   Project    ****   ****   ****   ****   ****

•    Programming/QC of Data Displays
(actuals will be billed)

             

Unique Tables

   Table    ****   ****   ****   ****   ****

Repeat Tables

   Table    ****   ****   ****   ****   ****

Unique Listings

   Listing    ****   ****   ****   ****   ****

Repeat Listings

   Listing    ****   ****   ****   ****   ****

Unique Figures

   Figure    ****   ****   ****   ****   ****

Repeat Figures

   Figure    ****   ****   ****   ****   ****

 

 

**** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.

Page 12


Services

           Unit            #
    Units    
  Unit Cost
    (A$)    
  Fees
    (A$)    
  Estimated
    Pass-Thru (A$)    
  Estimated
    Total Cost (A$)    

BIOMETRICS (continued)

             

•    Programmatic Evaluability/Outcome

   Project    ****   ****   ****   ****   ****

•    Statistical Analysis

   Project    ****   ****   *