%0 Journal Article %J J Alzheimers Dis %D 2016 %T Efficacy and Safety of ABT-126 in Subjects with Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Study. %A Florian, Hana %A Meier, Andreas %A Gauthier, Serge %A Lipschitz, Stanley %A Lin, Yunzhi %A Tang, Qi %A Othman, Ahmed A %A Robieson, Weining Z %A Gault, Laura M %K Activities of Daily Living %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Cholinesterase Inhibitors %K Disease Progression %K Dose-Response Relationship, Drug %K Double-Blind Method %K Female %K Humans %K Indans %K International Cooperation %K Male %K Medication Adherence %K Middle Aged %K Piperidines %K Psychiatric Status Rating Scales %K Treatment Outcome %X

BACKGROUND: ABT-126 is a potent, selective α7 nicotinic acetylcholine receptor agonist with putative procognitive effects as a monotherapy in treating Alzheimer's disease (AD).

OBJECTIVE: This randomized, double-blind, placebo-controlled multicenter study (NCT01549834) investigated the efficacy and safety of ABT-126 in subjects with mild-to-moderate AD who were taking stable doses of acetylcholinesterase inhibitors (AChEIs).

METHODS: Subjects received 25 mg ABT-126 (n = 143), 75 mg ABT-126 (n = 145), or placebo (n = 146) once daily for 24 weeks. Subjects who completed the 24-week double-blind study were eligible to enroll in a 28-week open-label extension study (NCT01690195) and received 75 mg ABT-126 daily. The primary efficacy endpoint was the change from baseline to week 24 in the 11-item total score of the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog).

RESULTS: Neither dose of ABT-126 demonstrated significant improvement compared with placebo in the primary efficacy endpoint. However, 25 mg ABT-126 demonstrated significant improvement compared with placebo in ADAS-Cog scores at week 4 (least squares mean difference, -1.21; standard error, 0.51; p <  0.010, one-sided); 75 mg ABT-126 did not demonstrate significant improvements in ADAS-Cog scores compared with placebo at any time point. A treatment effect was not observed for any secondary efficacy measures of cognition, function, or global improvement. ABT-126 was generally well tolerated; the most common adverse events were agitation, constipation, diarrhea, fall, and headache.

CONCLUSIONS: Overall, the efficacy profile of ABT-126 did not warrant further development as add-on therapy to AChEIs to treat mild-to-moderate AD.

%B J Alzheimers Dis %V 51 %P 1237-47 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26967214?dopt=Abstract %R 10.3233/JAD-150978