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

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.