Lenz_2015_Alzheimer.Dis.Assoc.Disord_29_192

Reference

Title : Adaptive, Dose-finding Phase 2 Trial Evaluating the Safety and Efficacy of ABT-089 in Mild to Moderate Alzheimer Disease - Lenz_2015_Alzheimer.Dis.Assoc.Disord_29_192
Author(s) : Lenz RA , Pritchett YL , Berry SM , Llano DA , Han S , Berry DA , Sadowsky CH , Abi-Saab WM , Saltarelli MD
Ref : Alzheimer Disease & Associated Disorders , 29 :192 , 2015
Abstract :

ABT-089, an alpha4beta2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

PubMedSearch : Lenz_2015_Alzheimer.Dis.Assoc.Disord_29_192
PubMedID: 25973909

Related information

Citations formats

Lenz RA, Pritchett YL, Berry SM, Llano DA, Han S, Berry DA, Sadowsky CH, Abi-Saab WM, Saltarelli MD (2015)
Adaptive, Dose-finding Phase 2 Trial Evaluating the Safety and Efficacy of ABT-089 in Mild to Moderate Alzheimer Disease
Alzheimer Disease & Associated Disorders 29 :192

Lenz RA, Pritchett YL, Berry SM, Llano DA, Han S, Berry DA, Sadowsky CH, Abi-Saab WM, Saltarelli MD (2015)
Alzheimer Disease & Associated Disorders 29 :192