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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: [email protected].

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
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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.

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