Toxicology a. The ingredients in the formulated product do not pose a significant risk to human or animal health.
Toxicology. 1. Collect required toxicological samples
Toxicology. An inventory of archived tissues and samples for each of the completed toxicology studies is included in the final study report for each study. Transfer of the storage of these samples to Bukwang needs to be discussed. • Additional samples located at Triangle include: • Thirty-two wet tissues to Trump’s fixative for electron microscopy from study TOX045 from Week 119 (one female sacrificed moribund) and from Week 148 (3 females and 4 males, control and high dose). There are 4 tissues from each animal - heart, kidney, liver, and skeletal muscle. • Photomicrographs of liver, heart, and skeletal muscle and negatives of same; lepon blocks; glass slides; and 44 vials of heart, muscle, kidney, and liver (in formalin) from the woodchuck study 98-11-A conducted by Cornell. The 44 vials contain huge chunks of issue that would not have fixed well and were removed from dead animals, and therefore may have been subject to significant autolysis. • Another set of positives (slides) and photographs taken during examination by light microscopy of skeletal muscle (myopathy) from selected monkeys from study TOX045.
Toxicology. The draft report for TOX142 “A Study of the Effects of Orally Administered TP-0239 on Pre- and Postnatal Development, Including Maternal Function, in the Rat” is due Sept. 23, 2003. The date for delivery of the final report is targeted for November 1, 2003.
Toxicology. In preparation for the initial IND filing, Scopus Biopharma will contract with qualified CRO(s) to perform sc rat and dog rising single dose + 7-day repeated-dose range-finding toxicity studies with toxicokinetics and sc rat and dog 28-day repeated-dose toxicity studies with toxicokinetics. Scopus Biopharma will contract out the performance of an in vitro hemolysis assay and an IV two species, single dose local tolerance study. Clinical Development Scopus Biopharma will contract out clinical trial related tasks to qualified CRO(s). The initial trial (i.e., the protocol to be included in the original IND filing) is anticipated to be a Phase 1 open label dose escalation study of safety tolerance PK including bioavailability in healthy volunteers, (non-visceral injection SB-001FCDP vs comparator) to be followed by an IV version of the same study. Following the completion of two Phase 1 safety, tolerability, and PK studies in healthy volunteers, Scopus Biopharma plans to move to a Phase 2 randomized double-blind study of tolerance including dose response, safety and PK in patients (non-visceral injection SB-001FCDP vs comparator). Following the successful completion of the Phase 2 study, Scopus Biopharma intends to enter into two pivotal Phase 3 trials randomized double-blind study of efficacy, safety and population PK in patients (non-visceral injection SB-001FCDP vs comparator). PORTIONS OF THIS EXHIBIT HAVE BEEN REDACTED AND ARE SUBJECT TO A CONFIDENTIAL INFORMATION REQUEST FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.
Toxicology. In preparation for the initial IND filing, Scopus Biopharma will contract with qualified CRO(s) to perform sc rat and dog rising single dose +7-day repeated-dose rangefinding toxicity studies with toxicokinetics and sc rat and dog 28-day repeated-dose toxicity studies with toxicokinetics. Scopus Biopharma will contract out the performance of an in vitro hemolysis assay and an IV two species single dose local tolerance study. Clinical Development Scopus Biopharma will contract out clinical trial related tasks to qualified CRO(s). The initial trial (i.e., the protocol to be included in the original IND filing) is anticipated to be a Phase 1 open label does escalation study of safety tolerance PK including bioavailability in healthy volunteers. Following the completion of two Phase 1 safety, tolerability, and PK study in healthy volunteers, Scopus Biopharma plans to move to a Phase 2 randomized double blind study of tolerance including dose response, safety and PK in patients. Following the successful completion of the preliminary Phase 2 study, Scopus Biopharma will enter into a Phase 2b dose response study. Following the successful completion of the Phase 2b study, 2 pivotal Phase 3 trials randomized double blind study of efficacy, safety and population PK in patients. tolerance including dose response, safety and PK in patients. Regulatory Submission At the appropriate time, Scopus Biopharma plans to file a pre-IND meeting request with FDA to confirm that the planned CMC and nonclinical tasks will support the initiation of the proposed Phase 1 clinical trial. In this way, course corrections in the development plan can be made early on, expediting development and avoiding waste of resources. Following the completion of the Phase 1 clinical studies Scopus Biopharma will for and end of phase 1 (EOP) meeting. At the completion of the Phase 2 study we will file for an EOP2 meeting. Following the completion of the Phase 3 pivotal trials a pre-NDA meeting will be requested and an NDA will be filed. Development Stage Anticipated Timeline Lead and indication selection In vivo efficacy and preliminary toxicity Complete IND enabling Pre-clinical studies Phase 1 clinical studies start Clinical studies may take between years depending on indication Phase 2 start Phase 3 start NDA NB: This development plan is subject to change based on circumstance and regulatory requirements. DEVELOPMENT PLAN (For Commercial Products) (Cannabinoid Synthetic Pathway) Following the filin...
Toxicology. In preparation for the initial IND filing, Licensee will contract with qualified CRO(s) to perform oral rat and dog rising single dose + 7-day repeated-dose range-finding toxicity studies with toxicokinetics and oral rat and dog 28-day repeated-dose toxicity studies with toxicokinetics. Additionally, Licensee will contract out the performance of a standard battery of GLP genotoxicity studies, including in vitro bacterial reverse mutation test, in vitro mouse lymphoma thymidine kinase assay, and in vivo rat micronucleus test. Also, to support the single IV dose of MRI-1867 in the initial Phase I trial to determine absolute bioavailability, Licensee will contract out the performance of an in vitro hemolysis assay and an IV single species single dose local tolerance study. To support subsequent clinical trials and eventual marketing, Licensee will contract out the performance of oral rat 3-month and 6-month repeated-dose toxicity studies, oral dog 3-month and 9-month repeated-dose toxicity studies, carcinogenicity studies, and reproductive and developmental toxicity studies. Overall, the timeline and cost to complete the IND-enabling nonclinical studies is estimated at approximately[ ] and [ ]. Clinical Development Licensee will contract out clinical trial related tasks to qualified CRO(s). The initial trial (i.e., the protocol to be included in the original IND filing) is anticipated to be a Phase 1 safety, tolerability, and PK study in healthy volunteers. The study will include a single IV and oral dose to determine absolute bioavailability, followed by 28-days of oral dosing. During the latter part of the conduct of this trial, Licensee plans to contract out a Phase 1 clinical mass balance study (single oral dose of radiolabeled drug). This will allow for an early determination of relevant PK metabolites and parameters to follow in subsequent trials. Additionally, Licensee plans to collaborate with NIH to perform a Phase 1 study of MRI-1867 binding to CB1R in the brain (via positron emission tomography scanning). A-034-2016 NIH Patent License Agreement—Exclusive PORTIONS OF THIS EXHIBIT HAVE BEEN REDACTED AND ARE SUBJECT TO A CONFIDENTIAL INFORMATION REQUEST FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. Following the completion of the Phase 1 safety, tolerability, and PK study in healthy volunteers, Licenseeplans to move to a Phase 1 safety, tolerance, PK, and PD study in patients with systemic sclerosis. This trial will include [ ] of oral...
Toxicology. 4.4.1 Brief summary • Maximum tolerated, single IV dose escalation studies of ETX2514 performed in rats and dogs did not result in serious test article–related events. Exposure across the dose ranges evaluated were generally dose proportional, and there were no significant differences between males and females. • 7-day IV repeat-dose range-finding studies in rats and dogs at doses up to the limit dose of 2000 mg/kg/day did not identify serious test article–related findings. • In pivotal 14-day IV repeat-dose toxicity studies conducted in rats and dogs, ETX2514 administered up to the limit dose of 2000 mg/kg/day was not associated with mortality or significant changes in clinical signs, ophthalmology, urinalysis or hematology parameters, organ weight changes, or changes in gross pathology or histopathology, and there were no toxicologically significant changes in clinical chemistry parameters. Based on these findings, the NOAEL was 2000 mg/kg/day in both species. The associated combined-sex mean steady state Cmax and AUC0-24 values on Day 14 in the most sensitive species, rat, at the NOAEL were 1340 µg/mL and 3140 µg⋅h/mL, respectively. The exposure margin based on AUC0-24 relative to human exposures was 6.3-fold. • In a 7-day IV repeat-dose study of ETX2514 in combination with sulbactam, minimal decreases in body weight gain were noted, and there were no adverse effects on clinical pathology parameters, organ weights, or macroscopic tissue findings. Based on the mild severity of the findings, the NOAEL was the highest combination dose tested, 400 mg/kg/day of each compound. • The toxicity of ETX2514 alone or in combination with sulbactam was evaluated in a pivotal (GLP) study in rats administered the treatments IV daily for 28 days. ETX2514 administered alone (600 mg/kg/day) was devoid of toxicity. Notable effects in rats treated with the combination of sulbactam/ETX2514 (300 or 600 mg/kg/day of each compound) were consistent with known, monitorable effects of sulbactam. Dose-related inflammatory changes noted microscopically at the infusion site and in liver and lung with both combination doses were considered adverse effects of treatment; however, inflammatory changes in liver and lung were not associated with necrosis and were not present at the end of the recovery period. Thus, while there was no NOAEL identified in the study due to inflammatory changes noted with both combination doses, the adverse changes were monitorable and reversible and occurred ...
Toxicology. In conjunction with FDA requirements, standard toxicology studies were performed with the aim of inducing and identifying drug-related toxicities. The clinically relevant toxicities observed in these studies were mechanistically based; that is, attributed to activation of the innate immune system via TLR8. The most frequent of these included transient constitutional symptoms consistent with the influenza-like response frequently seen with immunomodulatory agents. As noted in §2.3, these flu-like symptoms identified in preclinical toxicology studies have subsequently been observed in clinical trials of VTX-2337, and include pyrexia, chills, myalgia, and fatigue. As detailed in the VTX-2337 IB, organ-based toxicity was also observed in preclinical toxicology studies. Organ-based toxicities have not been observed in any clinical trial of VTX-2337 to date, and are not described herein.
Toxicology. LDH, Grant Homogenous-Phase assays – CELL Assays Commercial Kits Reduce cost/test by 2-5 fold "home made" Assays Reduce by 3-20 the cost of reagents ..ccoomm 74 votre source d’innovations ■ Antifade Kit for Microplate When exposed to excitation light, fluorescence intensity of dyes decreases due to their photooxidation or other photoreactions. There are very few fluorescent dyes that completely resist photobleaching. Frequently, when a section has been scanned repeatedly under strong excitation light, dyes could lose significant fluorescence signal before visual evaluation or photography can be accomplished. For examples, the photobleaching of fluoresceins (such as FITC-labeled antibodies) has become a major problem in fluorescence microscopy. In severe cases (such as phycoprotein-labeled bioconjugates), a fluorescence image of high resolution can not even be taken due to the extremely high photobleaching rate. The Antifade Kit is to reduce the dye photobleaching rate, giving researchers longer observation time. The kit contains all the essential components that can be readily applied to imaging experiments. They are all premixed and ready- to-use solutions. This kit is designed for microplate format. Description P/N : Qty Antifade Kit for Microplate FP-CL0530 1 plate Accessory tools ■ Legals - Trademarks Acella from CellTechnologies Cytonin, PeroxyGlow, and TACS from Trevigen CyToxiLux and GranToxiLux from OncoImmun DeepBlue C from BioSignal Packard FluoProbes, PrimAb and UptiBlue from Interchim MUP plus, Phospholite, and Rhod-4 from ABD PMA from Biotium Twister from Caliper 75
