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

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 4 - Trang 173-181 - 2018
Tiffini Voss1, Jerry Li1, Jeffrey Cummings2, Martin Farlow3, Christopher Assaid1, Samar Froman1, Heather Leibensperger1, Linda Snow-Adami1, Kerry Budd McMahon4, Michael Egan1, David Michelson1
1Merck & Co. Inc., Kenilworth, NJ, USA
2Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
3Indiana University School of Medicine, Indianapolis, IN, USA
4Merck & Co., Inc., Kenilworth, NJ, USA

Tóm tắt

AbstractIntroductionWe evaluated the selective M1 muscarinic positive allosteric modulator, MK‐7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease.MethodsA 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.ResultsTwo 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%).DiscussionMK‐7622 (45 mg) does not improve cognition or function when used as adjunctive therapy in mild‐to‐moderate Alzheimer's disease.

Tài liệu tham khảo

10.1007/978-3-642-23274-9_7 10.1016/j.neuropharm.2014.11.018 10.2174/156720507783018163 10.1001/archneur.1997.00550160091022 10.1385/JMN:20:3:349 McArthur R.A., 2010, Cognitive effects of muscarinic M1 functional agonists in non‐human primates and clinical trials, Curr Opin Investig Drugs, 11, 740 10.1073/pnas.0900903106 10.1016/j.nbd.2013.09.013 10.1124/jpet.117.245894 10.1212/WNL.34.7.939 2000, Diagnostic and Statistical Manual of Mental Disorders 10.1016/0022-3956(75)90026-6 10.1001/archneur.1975.00490510088009 10.1176/ajp.141.11.1356 Mohs R., 1997, Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's disease Assessment Scale that broadens its scope, Alzheimer Dis Assoc Disord, 11, 10.1097/00002093-199700112-00003 Galasko D., 1997, An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study, Alzheimer Dis Assoc Disord, 11, S33, 10.1097/00002093-199700112-00005 10.1097/00002093-199700112-00004 10.1212/WNL.44.12.2308 Liang K., 2000, Longitudinal data analysis of continuous and discrete responses for pre‐post designs, Sankhyā: Indian J Stat, 62, 134 10.1002/sim.4780040211 10.3233/JAD-130575 10.1093/jnen/59.9.751 10.1056/NEJMoa1312889 10.1124/jpet.115.226910 10.1212/WNL.0000000000000364 10.3233/JAD-140291
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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 4

173-181

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