title: Effects of the Acetylcholine Release Agent ST101 with Donepezil in Alzheimer's Disease: A Randomized Phase 2 Study.
abstract: OBJECTIVE
  ST101, an acetylcholine release agent with efficacy in rodent memory and cognition models, was assessed for clinical safety and efficacy.
  
  
  METHODS
  A phase 2 double blind, placebo-controlled study enrolled 210 AD patients (MMSE 10-20) on 10 mg donepezil QD. Patients received ST101 (10, 60, or 120 mg QD) or placebo for 12 weeks. The primary endpoint was change in cognitive function measured by ADAS-cog in the modified Intent To Treat (MITT) population and the Per Protocol (PP) population.
  
  
  RESULTS
  Mean ADAS-cog change favored ST101 over placebo in the MITT population (p = 0.0957, one-sided) and in the PP population (p = 0.0434, one-sided, ∼1.5 point drug-placebo difference) comparing all ST101 dose groups combined to placebo. Among secondary and exploratory outcome measures the ADCS-CGIC also showed a beneficial trend (p = 0.0294, one-sided). In a post-hoc analysis, the subgroup with more severe disease (MMSE 10-17) showed a dose response in the ADAS-cog with the greatest efficacy at 120 mg (p = 0.0067, one sided). No significant ST101-related safety concerns were identified.
  
  
  CONCLUSIONS
  The study supports the possibility that ST101, in patients receiving a stable dose of donepezil, may provide additional symptomatic benefit in moderate AD.
authors.affiliation: McGill Centre for Studies in Aging (MCSA), McGill University, Montreal, QC, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Rountree
authors.affiliation: Sonexa Therapeutics Inc., San Diego, CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Finn
authors.affiliation: Sonexa Therapeutics Inc., San Diego, CA, USA.
authors.forename: Barbra
authors.initials: B
authors.lastname: LaPlante
authors.affiliation: Sonexa Therapeutics Inc., San Diego, CA, USA.
authors.forename: Eckard
authors.initials: E
authors.lastname: Weber
authors.affiliation: Sonexa Therapeutics Inc., San Diego, CA, USA.
authors.forename: Tilman
authors.initials: T
authors.lastname: Oltersdorf
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D018678:Cholinergic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D000077265:Donepezil; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018678:Cholinergic Agents; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D013141:Spiro Compounds; C511224:spiro(imidazo-(1,2-a)pyridine-3,2-indan)-2(3H)-one; D000077265:Donepezil
keywords: Alzheimer’s disease; Phase II; cholinergic agents; clinical trial; donepezil