A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.

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.

• Authors: George M Haig, Yili Pritchett, Andreas Meier, Ahmed A Othman, Coleen Hall, Laura M Gault, Robert A Lenz
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 42 Issue 3 Pg. 959-71 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 25024314 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-(5-methylhexahydropyrrolo(3,4-b)pyrrol-1-yl)biphenyl-4-yl)-2H-pyridazin-3-one
• Histamine H3 Antagonists
• Indans
• Nootropic Agents
• Piperidines
• Pyridazines
• Pyrroles
• Donepezil

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (drug therapy)
• Analysis of Variance
• Donepezil
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Histamine H3 Antagonists (pharmacokinetics, therapeutic use)
• Humans
• Indans (therapeutic use)
• Male
• Middle Aged
• Nootropic Agents (therapeutic use)
• Piperidines (therapeutic use)
• Psychiatric Status Rating Scales
• Pyridazines (pharmacokinetics, therapeutic use)
• Pyrroles (pharmacokinetics, therapeutic use)
• Treatment Outcome