You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

A Randomized Study of H3 Antagonist ABT-288 in Mild-To-Moderate Alzheimer's Dementia1

Article type: Research Article

Authors: Haig, George M.a; * | Pritchett, Yilia; 2 | Meier, Andreasa | Othman, Ahmed A.a; b | Hall, Coleena | Gault, Laura M.a | Lenz, Robert A.a; 3

Affiliations: [a] AbbVie, North Chicago, IL, USA | [b] Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt

Correspondence: [*] Correspondence to: George M. Haig, PharmD, MBA, AbbVie, Neuroscience Development, Global Pharmaceutical Research and Development, One Waukegan Road, North Chicago, IL 60064, USA. Tel.: +1 847 938 1900; Fax: +1 847 937 0745; E-mail: george.haig@abbvie.com.

Note: [1] Data previously presented at the Alzheimer’s Association International Conference, July 14–19, 2012, Vancouver, British Columbia, Canada.

Note: [2] Present address: Astellas Pharma Global Development Inc., Northbrook, IL, USA.

Note: [3] Present address: Amgen, Thousand Oaks, CA, USA.

Keywords: ABT-288, Alzheimer's dementia, cognition, drug therapy, H3 antagonists, humans

DOI: 10.3233/JAD-140291

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 959-971, 2014

Accepted 29 April 2014
|
Published: 16 September 2014
Get PDF open access

Abstract

Background:

ABT-288, a highly selective histamine-3 receptor antagonist, demonstrated efficacy across several preclinical cognitive domains, and safety in healthy subjects and elderly volunteers.

Objective:

Evaluate the efficacy and safety of ABT-288 in subjects with mild-to-moderate Alzheimer’s dementia.

Methods:

The study used a randomized, double-blind, placebo- and active-controlled, parallel group design with pre-defined futility criteria to permit early study termination. A total of 242 subjects were randomized in an equal ratio to ABT-288 1 mg or 3 mg, donepezil 10 mg, or placebo once daily for 12 weeks. The primary efficacy endpoint was the change from baseline to final evaluation on the 13-item Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score.

Results:

The study was prematurely terminated because futility criteria were met. Point estimates on the ADAS-Cog scores for both ABT-288 dose groups were numerically inferior to placebo but no statistical differences were detected. Donepezil demonstrated statistically significant improvement. Adverse events were generally mild and self-limiting.

Conclusion:

ABT-288 did not demonstrate efficacy in the symptomatic treatment of Alzheimer’s dementia.

Show more