title: SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study.
abstract: 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.
authors.affiliation: GlaxoSmithKline, Uxbridge, Middlesex, UK. Gareth.C.Maher-Edwards@gsk.com
authors.forename: Gareth
authors.initials: G
authors.lastname: Maher-Edwards
authors.forename: Ruth
authors.initials: R
authors.lastname: Dixon
authors.forename: Jackie
authors.initials: J
authors.lastname: Hunter
authors.forename: Michael
authors.initials: M
authors.lastname: Gold
authors.forename: Gillian
authors.initials: G
authors.lastname: Hopton
authors.forename: Gemma
authors.initials: G
authors.lastname: Jacobs
authors.forename: Jo
authors.initials: J
authors.lastname: Hunter
authors.forename: Pauline
authors.initials: P
authors.lastname: Williams
mesh_terms: 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*
chemical_list: C548140:3-benzenesulfonyl-8-piperazin-1-ylquinoline; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011804:Quinolines; D012702:Serotonin Antagonists; D013450:Sulfones; D000077265:Donepezil