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

• Published in: Journal of Alzheimer's disease Vol. 51; no. 4; p. 1237
• Main Authors: Florian, Hana, Meier, Andreas, Gauthier, Serge, Lipschitz, Stanley, Lin, Yunzhi, Tang, Qi, Othman, Ahmed A, Robieson, Weining Z, Gault, Laura M
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2016
• Subjects: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Cholinesterase Inhibitors - therapeutic use; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Indans - therapeutic use; International Cooperation; Male; Medication Adherence; Middle Aged; Piperidines - therapeutic use; Psychiatric Status Rating Scales; Treatment Outcome; alzheimer’s disease; Acetylcholinesterase inhibitors; dementia; ABT-126; nicotinic acetylcholine receptors
• ISSN: 1875-8908
• DOI: 10.3233/JAD-150978

ABT-126 is a potent, selective α7 nicotinic acetylcholine receptor agonist with putative procognitive effects as a monotherapy in treating Alzheimer's disease (AD). 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). 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). 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. Overall, the efficacy profile of ABT-126 did not warrant further development as add-on therapy to AChEIs to treat mild-to-moderate AD.