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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 1 2 3, Yi Mo 1, Marwan Sabbagh 4, Paul Solomon 5, Merce Boada 6 7, Roy W Jones 8, Giovanni B Frisoni 9, Timo Grimmer 10, Bruno Dubois 11, Mark Harnett 1, Sarah R Friedhoff 1 2, Shari Coslett 1, Jeffrey L Cummings 12
Abstract:
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 and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (-0.36 [-0.95, 0.22], P = 0.2249) and ADCS-ADL (-0.09 [-0.90, 0.72], P = 0.8260). Intepirdine demonstrated a favorable safety profile similar to placebo.
Discussion: Intepirdine as adjunctive therapy to donepezil did not produce statistical improvement over placebo on cognition or activities of daily living in mild-to-moderate AD dementia patients.
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 and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (-0.36 [-0.95, 0.22], P = 0.2249) and ADCS-ADL (-0.09 [-0.90, 0.72], P = 0.8260). Intepirdine demonstrated a favorable safety profile similar to placebo.
Discussion: Intepirdine as adjunctive therapy to donepezil did not produce statistical improvement over placebo on cognition or activities of daily living in mild-to-moderate AD dementia patients.
PMID: 34095437
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165732/
