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

Article type: Research Article

Authors: Florian, Hana^{a; *} | Meier, Andreas^{a; 1} | Gauthier, Serge^b | Lipschitz, Stanley^c | Lin, Yunzhi^{a; 2} | Tang, Qi^a | Othman, Ahmed A.^{a; d} | Robieson, Weining Z.^a | Gault, Laura M.^a

Affiliations: [a] AbbVie Inc., North Chicago, IL, USA | [b] McGill University Research Center for Studies in Aging, McGill University, Montreal, Quebec, Canada | [c] The Dr. Stanley Lipschitz Clinic, Rosebank, Johannesburg, South Africa | [d] Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt

Correspondence: [*] Correspondence to: Hana Florian, AbbVie, Inc., 1 North Waukegan Rd, Bldg AP31-1, North Chicago, IL 60064, USA. Tel.: +1 847 937 9260; Fax: +1 847 937 0745; E-mail: hana.florian@abbvie.com.

Note: [1] Current address: Pfizer Inc., Cambridge, Massachusetts, USA.

Note: [2] Current address: Takeda Pharmaceuticals U.S.A., Inc., Deerfield, Illinois, USA.

Abstract: 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.

Keywords: ABT-126, Acetylcholinesterase inhibitors, alzheimer’s disease, dementia, nicotinic acetylcholine receptors

DOI: 10.3233/JAD-150978

Journal: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1237-1247, 2016