Affiliations: [a] McGill Centre for Studies in Aging (MCSA), McGill University, Montreal, QC, Canada | [b] Department of Neurology, Baylor College of Medicine, Houston, TX, USA | [c] Sonexa Therapeutics Inc., San Diego, CA, USA
Correspondence:
[*]
Correspondence to: Tilman Oltersdorf, MD, 427 Bristol Rd., Cardiff, CA 92007, USA. Tel.: +1 760 274 5789; [email protected]
Abstract:
Background and 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.
Conclusion: The study supports the possibility that ST101, in patients receiving a stable dose of donepezil, may provide additional symptomatic benefit in moderate AD.
Keywords: Alzheimer’s disease, cholinergic agents, clinical trial, Phase II, donepezil
