DT‐01‐04: The efficacy of RVT‐101, a 5‐ht6 receptor antagonist, as an adjunct to donepezil in adults with mild‐to‐moderate Alzheimer's disease: Completer analysis of a phase 2b study

RVT-101 is a 5-hydroxytryptamine 6 (5-HT6) receptor antagonist for the treatment of dementia with a number of favorable properties including once daily dosing, lack of food effect, and low potential for drug interactions. We present the results of an analysis of observed data from a randomized, double-blind, placebo-controlled Phase 2b study. In this study, 684 subjects with mild to moderate Alzheimer's disease were randomized to receive 35 mg RVT-101, 15 mg RVT-101, or placebo as an adjunct to stable donepezil treatment. The study included a 24-week double-blind randomized phase and an optional, additional 24-week blinded extension. An analysis of covariance (ANCOVA) method was used to evaluate multiple endpoints on cognition and function based on observed data, including the ADAS-cog, CDR-SB, and ADCS-ADL at weeks 12, 24, 36, and 48. The proportion of subjects completing the study ranged from 86-89% from week 0 to week 24 and from 87-89% from week 24 to week 48. On ADAS-cog and ADCS-ADL respectively, subjects who received 35 mg RVT-101 achieved a 1.29 (p = 0.008) and 1.72 (p = 0.016) point benefit at week 12; a 1.63 (p = 0.007) and 2.11 (p = 0.016) point benefit at week 24; and a 1.82 (p = 0.018) and 2.34 (p = 0.048) point benefit at week 48, all compared to donepezil alone. Subjects who received 35 mg RVT-101 achieved a statistically significant benefit on CDR-SB compared to subjects who received donepezil alone only at 12 weeks after initiation of treatment. Mean ADAS-cog, ADCS-ADL and CDR-SB values for the 15-mg group were generally numerically superior to placebo but the differences were not statistically significant. In this analysis of subjects completing a Phase 2b study in subjects with mild-to-moderate Alzheimer's disease, the 35 mg dose of RVT-101 was shown to be effective in improving cognition and function as an adjunct to stable donepezil at multiple time points. Given the low drop-out rate, this analysis provides an accurate representation of the study. The 35 mg dose of RVT-101 will be advanced into a Phase 3 study in the second half of 2015.