Open AccessRandomized, controlled, proof‐of‐concept trial of MK‐7622 in Alzheimer's disease
Author(s) -
Voss Tiffini,
Li Jerry,
Cummings Jeffrey,
Farlow Martin,
Assaid Christopher,
Froman Samar,
Leibensperger Heather,
SnowAdami Linda,
McMahon Kerry Budd,
Egan Michael,
Michelson David
Publication year - 2018
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1016/j.trci.2018.03.004
Subject(s) - randomized controlled trial , placebo , confidence interval , adverse effect , alzheimer's disease , medicine , clinical endpoint , psychology , cognition , disease , physical therapy , psychiatry , pathology , alternative medicine
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‐Cog 11 ) 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‐Cog 11 : 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.