An Assessment of Dependence in Dementia Using A Conversion Algorithm of ADCS-ADL to Dependence Scale From a Double Blind Placebo Controlled Trial of Intepirdine (RVT-101) (P3.088)

Objective: To estimate impact of intepirdine on dependence in Alzheimer’s disease. Background: Alzheimer’s disease (AD) trials typically focus on cognitive and functional outcomes to assess drug efficacy. However, there has been increased interest in using the Dependence Scale, a 13-item scale that assesses the degree of assistance a patient needs. The Dependence Scale captures a combination of cognitive, functional, and behavioral changes that occur in AD and can be correlated to cost. We examined dependence as a potential outcome in a study of intepirdine (RVT-101), an orally administered, 5-HT6 receptor antagonist being investigated for the treatment of mild-to-moderate Alzheimer’s disease (AD) and dementia with Lewy bodies. Design/Methods: Data are taken from a double-blind, placebo controlled trial of intepirdine in subjects with mild to moderate AD receiving stable donepezil treatment and randomized to receive 35 mg intepirdine, 15 mg intepirdine, or placebo. The placebo and 35 mg data are included in this analysis. ADCS-ADL was converted to Dependence Level (DL) using a published algorithm which assigns DL based on patterns of IADL/BADL impairment to compare DL progression in active vs placebo treated arms. Results: Baseline DL was similar across treatment groups. Correlation between DL and ADCS-ADL was 0.448 at baseline (0.360 for all visits, both p The proportion of DL progressors (increase in DL by one or more levels representing worsening ADL/greater care needs) was higher in the placebo group at all follow-up assessments and the treatment difference grew over time reaching statistical significance at Weeks 36 and 48. Conclusions: Add-on therapy of intepirdine was estimated to have reduced progression in DL over 48 weeks, indicating patients spent more time in less dependent stages of AD. Because the scale is readily translated into cost and the need for full-time care, it is a potentially powerful approach for quantifying the impact and value of a therapeutic effect. Study Supported by: Axovant Sciences Disclosure: Dr. Asare has received personal compensation for activities with Axovant Sciences as an employee. Dr. Lombardo has received personal compensation for activities with Axovant Sciences Inc. as an employee. Dr. Zhu has received personal compensation for activities with Axovant and Xcenda as a consultant. Dr. Stern has received personal compensation for activities with Takeda, Axovant, and Eli Lilly and Company as an advisor and/or consultant. Dr. Stern has received license fees from Columbia. Dr. Stern has received research support from Axovant, Piramal and the California Walnut Commission. Dr. Friedhoff has received personal compensation for activities with Axovant Sciences Inc and Roivant Sciences Inc. as an employee.