A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia
George M Haig1, Yili Pritchett1, Andreas Meier1
1AbbVie, North Chicago, IL, USA.
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.
Insights
ABT-288, a histamine-3 receptor antagonist, failed to show efficacy for Alzheimer's dementia symptoms in a clinical trial. The study was stopped early due to futility, with ABT-288 performing worse than placebo on cognitive measures.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- ABT-288 is a selective histamine-3 receptor antagonist with preclinical cognitive benefits.
- Previous studies indicated safety in healthy and elderly populations.
Purpose of the Study:
- To assess the efficacy and safety of ABT-288 in mild-to-moderate Alzheimer's dementia.
- Investigate ABT-288's potential as a symptomatic treatment for Alzheimer's disease.
Main Methods:
- A 12-week, randomized, double-blind, placebo- and active-controlled trial involving 242 subjects.
- Participants received ABT-288 (1 mg or 3 mg), donepezil (10 mg), or placebo daily.
- Primary endpoint: change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score.
Main Results:
- The study was terminated early due to futility criteria being met.
- ABT-288 groups showed numerically lower ADAS-Cog scores than placebo, without statistical significance.
- Donepezil demonstrated a statistically significant cognitive improvement.
Conclusions:
- ABT-288 did not prove effective for the symptomatic treatment of Alzheimer's dementia.
- The drug's development for this indication was halted based on study findings.
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