O3-04-01: Safety and efficacy of tarenflurbil in subjects with mild Alzheimer's disease: Results from an 18-month multi-center phase 3 trial

Background: Tarenflurbil is a selective Aβ42-lowering agent that modulates γ-secretase activity to preferentially reduce production of Aβ42 in vivo and in vitro. Preliminary evidence for potential benefit of tarenflurbil 800 mg bid in subjects with mild AD was recently observed in a randomized, double-blind Phase 2 trial. This multi-center Phase 3 study assessed the safety and efficacy of tarenflurbil in subjects with mild Alzheimer's disease (AD). Methods: In this randomized, double-blind, placebo-controlled trial, individuals with mild AD (MMSE score 20-26, inclusive) were randomized (1:1) to receive tarenflurbil 800 mg bid or placebo for 18 months. Randomization was stratified according to use/non-use of acetylcholinesterase inhibitors and/or memantine. The co-primary outcome measures of efficacy were the ADAS-cog and the ADCS-ADL, with assessments conducted every 3 months. The secondary outcome was the CDR-sb, and exploratory outcomes included the NPI, Quality of Life-AD, and Caregiver Burden Inventory. Analysis was conducted by comparing the rate of change (slope) in the outcome measures between treatment and placebo arms. Adverse events were monitored throughout the study. Results: The study was originally powered for 1600 participants, and 1684 participants were randomized at 133 sites throughout the US between Feb 21, 2005 and Sep 1, 2006, of which 1653 had mild AD and are included in the primary analysis. At baseline, participants were 51.1% female, had a mean age (± standard deviation, range) of 74.6 (± 8.3, 53-94) and mean MMSE score of 23.3 (± 2.0, 20-26). Conclusions: This Phase 3 protocol was powered to evaluate the efficacy of tarenflurbil with respect to the primary outcomes using an analytic strategy comparing rate of change. Results for primary and secondary efficacy outcomes will be presented, along with safety results including adverse events and lab parameters.