Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease

Tiffini Voss, Jerry Li, Jeffrey Cummings, Martin Farlow, Christopher Assaid, Samar Froman, Heather Leibensperger, Linda Snow-Adami, Kerry Budd McMahon, Michael Egan, David Michelson

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Introduction: We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease. Methods: A randomized, double-blind, proof-of-concept trial was performed. Participants with mild-to-moderate Alzheimer's disease, being treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of MK-7622 or placebo for 24 weeks. Endpoints included the mean change from baseline in Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) at 12 weeks and Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory at 24 weeks. Results: Two hundred forty participants were randomized. The trial was stopped for futility after meeting prospectively defined stopping criteria. MK-7622 did not improve cognition at 12 weeks (group difference in ADAS-Cog11: 0.18 [95% confidence interval: −1.0 to 1.3]) or function at 24 weeks (group difference in Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory: 0.06 [95% confidence interval: −2.4 to 2.5]). More participants taking MK-7622 discontinued study medication because of adverse events than those taking placebo (16% vs 6%) and who experienced cholinergically related adverse events (21% vs 8%). Discussion: MK-7622 (45 mg) does not improve cognition or function when used as adjunctive therapy in mild-to-moderate Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume4
DOIs
StatePublished - Jan 1 2018

Keywords

  • Allosteric modulator
  • Alzheimer's disease
  • Cholinergic
  • Clinical trial
  • MK-7622
  • Muscarinic

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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    Voss, T., Li, J., Cummings, J., Farlow, M., Assaid, C., Froman, S., Leibensperger, H., Snow-Adami, L., McMahon, K. B., Egan, M., & Michelson, D. (2018). Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 4, 173-181. https://doi.org/10.1016/j.trci.2018.03.004