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Full-Text Articles in Medicine and Health Sciences

The Alzheimer’S Disease Drug Development Landscape, Pieter Van Bokhoven, Arno De Wilde, Lisa Vermunt, Prisca S. Leferink, Sasja Heetveld, Jeffrey Cummings, Philip Scheltens, Everard G.B. Vijverberg Dec 2021

The Alzheimer’S Disease Drug Development Landscape, Pieter Van Bokhoven, Arno De Wilde, Lisa Vermunt, Prisca S. Leferink, Sasja Heetveld, Jeffrey Cummings, Philip Scheltens, Everard G.B. Vijverberg

Brain Health Faculty Publications

Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Numerous genetic risk factors for sporadic AD have been identified, providing further insight into the molecular underpinnings of the disease. For the last two decades, however, drug development for AD has been proven to be particularly challenging. Here, we provide a unique overview of the drug development …


Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings Mar 2021

Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings

Brain Health Faculty Publications

Introduction: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. Methods: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Results: There were no statistically significant differences between intepirdine …