Study Rationale Sample Clauses

Study Rationale. This study is designed as a randomized, double-blind, placebo-controlled, comparative Phase 3 study of BA058 in the treatment of postmenopausal women with severe osteoporosis and at risk of fracture. The purpose of the study is to evaluate the efficacy and safety of BA058 80 µg in the prevention of fracture in otherwise healthy ambulatory postmenopausal women with severe osteoporosis. The dose chosen for this study is based on the safety and pharmacodynamic information derived in study BA058-05-002 according to predetermined criteria provided in the protocol. The population to be studied is the recommended and intended population for treatment, postmenopausal women with severe osteoporosis (17-19). Daily SC doses of BA058 80 µg, Placebo or teriparatide 20 µg will be self-administered for 18 months (78 weeks) to patients randomized [equally] to one of 3 treatment groups.

Study Rationale. COPD is a disease with rising morbidity and mortality. The recent Global Burden of Disease Study [▇▇▇▇▇▇, 1997] ranks COPD as the 6th leading cause of mortality and the 12th leading cause of morbidity (defined as disability-adjusted life years [DALYs]) world-wide. These figures are expected to rise, with COPD becoming the 3rd leading cause of mortality and the 5th leading cause of morbidity by the year 2020. Furthermore, trends in the use of medical care resources indicate that the economic cost of COPD continues to rise in direct relation to the ageing population, the increase in prevalence of disease, and the cost of new and existing medical and public health interventions (▇▇▇▇▇ S; ERS 1999). The largest share of medical care costs for COPD is a consequence of an acute exacerbation resulting in hospitalisation. COPD exacerbations have also been associated with decrements in pulmonary function, and contribute substantially to the reduced quality of life in patients with the disease. In much of the world, the full effect of existing smoking patterns has not been seen so that COPD mortality is rising. Post-hoc analysis of data from ISOLDE [▇▇▇▇▇, 2000] suggests a reduced mortality rate in COPD subjects randomised to FP compared with placebo, during the 3 years post-randomisation. Although ▇▇▇▇▇▇ was not designed to investigate mortality, and therefore the study should be regarded as a pilot, the data provide a rationale on which to base a definitive mortality study. No prospective mortality data are available for subjects treated with salmeterol. However, it can be hypothesised that the properties of salmeterol, particularly its cytoprotective effects and hence its potential to reduce infective exacerbations, could have a significant impact on subject survival. If this is the case, there could be, at least, an additive effect of salmeterol and FP in reducing mortality in subjects with COPD. The purpose of the present study is to determine the effects on mortality and morbidity of the salmeterol/FP combination product (SERETIDE) at a dose of 50/500µg bd compared with each component alone and with placebo, when added to usual COPD therapy (defined as any treatment but excluding inhaled corticosteroids, inhaled long-acting † SERETIDE, ▇▇▇▇▇, ADVAIR, DISKUS and ACCUHALER are Trade Marks of GlaxoSmithKline group of companies. Registered in US Patent and Trademark Office. bronchodilators, and long term oral corticosteroids), in moderate to severe COPD subjects w...

Study Rationale. KPL-716 is a first-in-class, fully-human monoclonal antibody against Oncostatin M Receptor beta (OSMRβ). OSMRβ is a cell surface receptor that heterodimerizes with IL-31 receptor alpha (IL-31Rα) to mediate signaling of IL-31. It also heterodimerizes with gp130 to mediate signaling of oncostatin (OSM). By targeting a single epitope , KPL-716 simultaneously inhibits signaling of IL-31 and OSM, two (2) cytokine pathways important in pruritus, inflammation, hyperkeratosis and fibrosis. KPL-716 does not inhibit signaling of OSM down the Leukemia Inhibitory Factor Receptor (LIFR) pathway, a pathway implicated in hematopoiesis and platelet synthesis.21 KPL-716 via its dual pathway mechanism is predicted to reduce pruritus in chronic pruritic diseases and potentially modulate many aspects of disease pathology related to inflammation, hyperkeratosis and fibrosis. A clinical effect on pruritus intensity is anticipated at therapeutic doses based on the Phase 1b study results (Protocol KPL-716-C001). The targeted nature of the KPL-716 mechanism of action is expected to offer safety advantages compared to immunosuppressive therapies as well as systemic and topical corticosteroids. The role of IL-31 in pruritus is well established, as IL-31 receptor inhibition has been shown to decrease pruritus in subjects with atopic dermatitis.22, 23 The published literature suggests that IL-31 plays a role in many chronic pruritic diseases. Serum IL-31 levels are elevated in CIU patients compared to healthy controls and IL-31 levels decrease upon successful treatment of CIU.24 Similarly, serum IL-31 levels are increased in patients with psoriasis and levels decrease after UVB irradiation with treatment response.25 IL-31 levels are also elevated in patients with LP although pruritus intensity does not appear to correlate with IL- 31 levels in this disease.15 Despite absence of a primary dermatologic process in CIP, histologic analysis of CIP skin demonstrates lymphocytic and, in many cases, eosinophilic infiltration, accompanied by increased IgE and peripheral blood eosinophilia pointing to TH2 polarization as a potential source of IL-31.3 Chronic scratching, disruption of epidermal barrier function, staphylococcal colonization and subsequent staphylococcal enterotoxin B production promote IL-31 production26 and may ultimately contribute to the itch-scratch cycle that underlies many chronic pruritic diseases such as atopic dermatitis and LSC. OSM, the other cytokine pathway inhibited...

Study Rationale. Nitrogen Dioxide: simply a marker of traffic and air pollution or a significant respiratory health threat on its own right?

Study Rationale. Severe hypotension is associated with significant mortality, and the use of high doses of catecholamines in patients with severe hypotension is associated with poor outcomes. Given that LJPC-501 has recently been demonstrated to be efficacious and well-tolerated in adults with hypotension who do not respond to fluids and vasopressor therapy (Section 4.5), it is reasonable to hypothesize that LJPC-501 may also be efficacious and well-tolerated in pediatric patients with the same diagnosis. This is an open-label, multi-center study. Pediatric patients, age 2 to 17 years, who remain hypotensive despite receiving fluid therapy and vasopressor therapy and are hospitalized in an ICU setting may be eligible to participate. Because severe hypotension is life threatening, and because the treatment options are limited for pediatric patients who remain hypotensive despite fluids and vasopressors, this study will examine a single LJPC-501 treatment arm, without a placebo-controlled arm. Efficacy of LJPC-501 will be measured by each patient’s response over time. To assess multiple possible improved outcomes, the primary endpoint is a composite of the proportion of patients with an increase of 25% over Baseline MAP at Hour 2 after the initiation of LJPC-501, or with a 25% reduction in sum ▇▇▇ at Hour 2 after the initiation of LJPC-501. Secondary endpoints will include the change in MAP at Hour 24, and the change in serum lactate concentrations. The risk of mortality will be assessed using the PELOD score at Hour 24. Safety and tolerability will be assessed throughout the study. Exploratory endpoints will include tissue oxygen levels, HR, reduction in sum ▇▇▇ at Hour 24, all-cause mortality at 28 days, the number of days that patients spend on mechanical ventilation, and the number of days on vasopressors. Exploratory measures of the risk of mortality will include PRISM and PIM2 scores at Hour 24.

Study Rationale. This study is designed to specifically target subjects with PED secondary to neovascular macular degeneration. This study will aim to describe the effects of brolucizumab on baseline PED status and height as well as visual and anatomic outcomes in patients with neovascular AMD treated with brolucizumab on a fixed dosing regimen according to the product label. Brolucizumab is an inhibitor of VEGF with a mechanism of action similar to ranibizumab but with a smaller molecular size (26 kDa and 48 kDa respectively). Nonclinical studies have demonstrated that RTH258 is at least as potent as ranibizumab, with a similar vitreal half-life and a significantly lower systemic exposure. The low systemic exposure should confer a good safety profile even at a high dose. The higher dose, similar half-life, and potency of RTH258 may confer a longer treatment duration compared to currently available treatments. Two clinical studies, C-10-083 and C-12-006, have demonstrated that RTH258 is as effective as ranibizumab and aflibercept in improving BCVA outcomes whilst having a reduced treatment frequency, thus providing a potential benefit to patients and their caregivers/physicians. The ocular and systemic safety profile of single or repeated doses of RTH258 were also evaluated in the C-10-083 and C-12-006 studies, respectively, and demonstrated similar safety profiles to ranibizumab and aflibercept. Further details of the known and potential risks and benefits associated with RTH258 are presented in the Investigator’s Brochure. Summarized, the results from the Phase 2 studies demonstrate that brolucizumab has similar efficacy to currently available treatment options with potentially greater duration. These data support the further development of RTH258 with a treatment regimen including q12 maintenance dosing.

Study Rationale. Trichomoniasis is the most prevalent nonviral sexually transmitted infection in the United States, affecting an estimated 3.7 million persons (▇▇▇▇▇▇▇▇▇▇▇ 2013); Lupin is developing Solosec as an available treatment option to provide an alternative, effective, single dose therapy for women diagnosed with trichomoniasis that, in turn, should decrease the known serious sequelae that occur when this infection is left untreated or ineffectively treated. Drugs of the 5-nitroimidazole family are the only known medications to be effective against trichomoniasis (CDC 2015). Metronidazole, tinidazole, and secnidazole are reported to have about approximately 90-95% success rate in curing T. vaginalis (▇▇▇▇▇▇▇ 2004, Forna 2003, ▇▇▇▇▇ 1980, Manorama 1978, ▇▇▇▇▇ 2015) depending on study design. Members of the 5-nitroimidazole family vary in half-life, Cmax, and side effects. Secnidazole has been widely used outside the U.S. for many years. CDC currently recommends metronidazole 2 g orally in a single dose or tinidazole 2 g orally in a single dose (CDC 2015); metronidazole 500 mg BID for 7 days is recommended as the alternative treatment regimen. Since cure rates with Solosec are anticipated to be high, this trial was designed to avoid the possibility of unprotected sex resulting in reinfection which becomes more likely the longer the interval between treatment and TOC. Peterman et. al. found a reinfection rate of 16.5% among women initially diagnosed and treated for T. vaginalis at baseline (▇▇▇▇▇▇▇▇ 2006). In light of these data on clearance and chance for re-infection, a window for the TOC visit to be 6-12 days was selected. Since it is possible that this timing will create false positive NAAT (TMA) results and since reinfection in this group of women at high risk for STD is of greater importance to assess the efficacy of Solosec, trichomonas culture was selected as the criterion for cure.

Study Rationale. KPT-9274 is a first-in-class orally bioavailable, non-competitive, small molecule, dual modulator of PAK4 and NAMPT. PAK4 is a key downstream effector for RAS and forms a critical link between RAS-driven oncogenic transformation and activation of the WNT/β-catenin signaling pathway. NAMPT is the rate-limiting enzyme in the metabolic scavenging pathway that utilizes nicotinamide to replenish nicotinamide adenine dinucleotide (NAD), an essential metabolic cofactor and second messenger. Hematologic and solid tumor cells are susceptible to single-agent cytotoxicity by KPT-9274 as they become dependent on both the PAK4 and NAMPT pathways. KPT-9274 demonstrated potent anti-proliferative activity against cancer cell lines with minimal toxicity to normal cells. In mouse xenograft studies, KPT-9274 was well tolerated and resulted in a marked reduction/elimination of tumors, tumor growth inhibition or disease control across a variety of tumors, including colon, pancreatic, lung, sarcoma, multiple myeloma, leukemia, and lymphoma. In approximately half of the tumor types studied, complete elimination of tumors in as short as 3 weeks was observed with no regrowth after cessation of treatment (for up to 3 additional weeks). Moreover, KPT-9274 has shown preliminary efficacy in companion dogs with spontaneous advanced lymphomas and multiple myeloma.

Study Rationale. There is no shortage of studies linking academic outcomes with health-related behaviors. A 2013 systematic review of the literature from 1985 to 2010 identified 122 original research papers that addressed academic outcomes such as grade point average (GPA), letter grades in specific subjects, standardized test scores, grade level retention, years of schooling completed, and high school graduation and their relationships with health-related behaviors. While many of the associations identified in these studies did not indicate causation in either direction, a reciprocal pattern was established that can greatly alter the life trajectory of adolescents [74]. In 2017, an MMWR paper was published by the CDC that examined 30 health- related behaviors and their associations with academic achievement using 2015 Youth Risk Behavior Survey (YRBS) data. The study reported significantly higher prevalence estimates for protective health behaviors (like eating breakfast everyday), and significantly lower prevalence estimates for health related risk behaviors (such as drinking alcohol) among students with higher academic achievement (mostly As, Bs, and Cs) when compared with students with lower academic achievement (mostly Ds and Fs) in 29 of the 30 behaviors. Tobacco use in any form, however, was not assessed in the analysis [81]. While previous studies have established a strong association between cigarette use and low academic achievement as measured through GPA, standardized test scores, grade level retention, and education level attainment, very little has been published on electronic nicotine delivery systems (ENDS) use and academic achievement suggesting a gap in the literature [74] [50]. The merit in addressing this gap lies not only in the significance of low academic achievement on adolescents’ future life trajectory, but also in the profound effect of ENDS use on adolescents’ current and future health. As the vast majority of tobacco usage is initiated in adolescents, the time an adolescent spends in high school is a crucial time for tobacco prevention [7]. While two studies have been conducted looking at the association between ENDS use and academic achievement using MTF and PATH study data, none to date have stratified by gender, been published using YRBS data, or data that was collected after 2014 [47, 51]. Due to the change in adolescent ENDS use prevalence every year, there is a need to understand whether ENDS use, like many other health-related behaviors,...