SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study

OBJECTIVE: To estimate the treatment effects of SB-742457 and donepezil in Alzheimer disease (AD) in a contemporary clinical trial. METHOD: Randomized, controlled, parallel-group, exploratory study with a 4-week, single-blind, placebo run-in phase and 24-week, double-blind treatment phase. Primary endpoints were Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). RESULTS: One hundred ninety eight subjects with mild-to-moderate probable AD (MMSE scores 12-26) were randomized; 196 were included in the intent-to-treat population (placebo, n = 61; SB-742457 35 mg/day, n = 68; donepezil 10 mg/day, n = 67), and 161 completed. Drug-placebo treatment differences in CIBIC+ score at week 24 were -0.17 (90% confidence interval [CI]: -0.50, 0.16) for SB-742457 and -0.28 (90% CI: -0.61, 0.05) for donepezil. Drug-placebo treatment differences (90% CI) in change from baseline ADAS-Cog score at Week 24 were -0.4 (-2.2, 1.4) for SB-742457 and -1.2 (-3.0, 0.6) for donepezil. All treatments were generally safe and well tolerated. CONCLUSIONS: In this exploratory study, SB-742457 and donepezil were associated with improvements in global function. Treatment effect on cognition for both SB-742457 and donepezil was smaller than those previously observed in previous clinical studies with donepezil.