Lang Frederick M, Mo Yi, Sabbagh Marwan, Solomon Paul, Boada Merce, Jones Roy W, Frisoni Giovanni B, Grimmer Timo, Dubois Bruno, Harnett Mark, Friedhoff Sarah R, Coslett Shari, Cummings Jeffrey L
Axovant Sciences New York New York USA.
Roivant Sciences New York New York USA.
Alzheimers Dement (N Y). 2021 May 31;7(1):e12136. doi: 10.1002/trc2.12136. eCollection 2021.
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.
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).
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], = 0.2249) and ADCS-ADL (-0.09 [-0.90, 0.72], = 0.8260). Intepirdine demonstrated a favorable safety profile similar to placebo.
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.
先前的一项2b期研究支持将5-HT6受体拮抗剂因他卡林用作多奈哌齐治疗阿尔茨海默病（AD）痴呆的辅助疗法。为此开展了一项3期研究MINDSET来验证这一假设。
MINDSET是一项全球性、双盲、随机、安慰剂对照试验，纳入1315例正在接受稳定剂量多奈哌齐治疗的轻至中度AD痴呆患者。患者接受35毫克/天的因他卡林或安慰剂治疗，为期24周。共同主要终点为从基线至第24周时阿尔茨海默病评估量表认知分量表（ADAS-Cog）和阿尔茨海默病协作研究日常生活活动量表（ADCS-ADL）的变化。
在共同主要终点ADAS-Cog（-0.36 [-0.95, 0.22]，P = 0.2249）和ADCS-ADL（-0.09 [-0.90, 0.72]，P = 0.8260）方面，因他卡林组与安慰剂组之间无统计学显著差异。因他卡林显示出与安慰剂相似的良好安全性。
在轻至中度AD痴呆患者中，因他卡林作为多奈哌齐的辅助疗法，在认知或日常生活活动方面未比安慰剂产生统计学上的改善。
