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.


METHODS
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.
Maher-Edwards
Gareth
G
GlaxoSmithKline, Uxbridge, Middlesex, UK. Gareth.C.Maher-Edwards@gsk.com
Dixon
Ruth
R
Hunter
Jackie
J
Gold
Michael
M
Hopton
Gillian
G
Jacobs
Gemma
G
Hunter
Jo
J
Williams
Pauline
P
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*
C548140:3-benzenesulfonyl-8-piperazin-1-ylquinoline; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011804:Quinolines; D012702:Serotonin Antagonists; D013450:Sulfones; D000077265:Donepezil