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

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.

SUBMITTER: Voss T

PROVIDER: S-EPMC6021552 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Voss Tiffini T Li Jerry J Cummings Jeffrey J Farlow Martin M Assaid Christopher C Froman Samar S Leibensperger Heather H Snow-Adami Linda L McMahon Kerry Budd KB Egan Michael M Michelson David D

Alzheimer's & dementia (New York, N. Y.) 20180426

<h4>Introduction</h4>We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease.<h4>Methods</h4>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 Alzheim ...[more]

PMID: 29955661

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

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

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