Examining recruitment in a phase 2 multisite industry sponsored interventional trial in mild to moderate Alzheimer's disease (CTAD 2011) - Dec 3, 2011 - P2, N=338; CN156-013; The primary study objective was to assess the safety and tolerability of BMS-708163 in patients with mild-to-moderate AD four doses of BMS-708163 were tested against placebo; Results of latest analysis presented at conference
P2 data • Alzheimer's Disease
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Introduction: Clinical trials in Alzheimer’s disease (AD) struggle to enroll, with most failing to meet their recruitment timelines. Research is needed to understand factors that impact site enrollment and retention. Identification of modifiable factors that impact enrollment may enhance AD trial recruitment through alternate study designs or improved trial conduct. Objectives: To examine the impact of site-related factors on clinical trial recruitment, retention, and other study outcomes from one multisite Phase II AD trial. Materail and methods: BMS-013 was a phase II, multicenter, double-blind, 5-arm placebocontrolled study of a gamma secretase inhibitor, BMS-708163, in patients with mild-tomoderate AD (ClinicalTrials.gov id#NCT00810147). The primary study objective was to assess the safety and tolerability of BMS-708163 in patients with mild-to-moderate AD Four doses of BMS-708163 were tested against placebo. Among 41 study sites, 35 were in the US and 6 were international (Sweden, Finland, Denmark). Patients age 50-90 who met NINCDS-ADRDA criteria for AD and scored within the range 16-26 on the MMSE at screen were eligible. Patients were excluded for cognitive impairment due to some other cause, a history of stroke (MRI required within 12 months or one was performed in the screen window), or concomitant medications that might interact with BMS-708163. The risks discussed in the informed consent document included possible gastrointestinal complications associated with the therapy under study. At study initiation, the treatment period was 12 weeks, followed by a 12-week washout. In-study protocol amendments subsequently extended the treatment period to 24 weeks and discontinued the washout period. Study visits were conducted every-other week. Standard laboratory, clinical, and cognitive outcome measures (e.g. ADAS-cog, MMSE, CDR, Trails, Category and Letter Fluency tests, Digit Span Forward and Backward, ADCS-ADL) were performed. Optional substudies utilizing MRI and CSF biomarker outcomes were conducted. Quantitative analyses of trial enrollment data are ongoing. The total enrollment (number baselined) and enrollment rate (number baselined per month of open enrollment) of each site will be considered. Specific factors such as the type of site (academic vs commercial) and the type of IRB utilized (local vs. central) will be examined for effects on total enrollment and enrollment rate. The demographic characterization of enrolled subjects will be analyzed. Longitudinal analyses will assess study completion and placebo decline. Results: BMS-013 was conducted from February 2009 through June 2010. 338 mild-to-moderate AD subjects signed informed consent (or had consent provided by a legally acceptable representative) and 209 were successfully randomized. Enrollment was completed about 1 month ahead of an anticipated 8 month recruitment time line. Among those enrolled 141 subjects completed the trial. Further analysis are on going and results are pending and will be be presented. Discussion: Late phase multicenter trials in AD enroll large patient populations, necessitating many sites to complete recruitment. Larger trials bring greater challenges, such as increased regulatory burden and potential for site variance in study conduct and results. This analysis is intended to guide the development of future AD clinical trials. Conclusion: BMS-013 is a unique AD clinical trial in that it completed enrollment ahead of schedule.
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