SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study
SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study
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DOI：
10.1002/gps.2562
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发表时间：
2011-05-01
影响因子：
4
通讯作者：
Williams, Pauline
中科院分区：
文献类型：
--
作者：
Maher-Edwards, Gareth;Dixon, Ruth;Williams, Pauline
目的：方法：采用随机、对照、平行分组、探索性研究，包括4周单盲安慰剂导入期和24周双盲治疗期，评价SB-742457和多奈哌齐对阿尔茨海默病（AD）的治疗效果。主要终点是临床医生访谈的变化印象与护理人员输入（CIBIC+）和阿尔茨海默病评估量表-认知子量表结果：198例轻中度疑似AD患者，（MMSE评分12-26）进行随机化; 196例纳入意向治疗人群（安慰剂，n = 61; SB-742457 35 mg/天，n = 68;多奈哌齐10 mg/天，n = 67），161例完成。SB-742457和多奈哌齐第24周CIBIC+评分的药物-安慰剂治疗差异分别为-0.17（90%置信区间[CI]：-0.50，0.16）和-0.28（90% CI：-0.61，0.05）。SB-742457组第24周ADAS-Cog评分较基线变化的药物-安慰剂治疗差异（90% CI）为-0.4（-2.2，1.4），多奈哌齐组为-1.2（-3.0，0.6）。所有的治疗一般都是安全的，耐受性良好。结论：在这项探索性研究中，SB-742457和多奈哌齐与全球功能的改善。SB-742457和多奈哌齐对认知的治疗效果小于先前在多奈哌齐的临床研究中观察到的效果。版权所有（c）2010约翰威利父子有限公司。
Objective: To estimate the treatment effects of SB-742457 and donepezil in Alzheimer disease (AD) in a contemporary clinical trial.Method: Randomized, controlled, parallel-group, exploratory study with a 4-week, single-blind, placebo run-in phase and 24-week, double-blind treatment phase. Primary endpoints were Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog).Results: One hundred ninety eight subjects with mild-to-moderate probable AD (MMSE scores 12-26) were randomized; 196 were included in the intent-to-treat population (placebo, n = 61; SB-742457 35 mg/day, n = 68; donepezil 10 mg/day, n = 67), and 161 completed. Drug-placebo treatment differences in CIBIC+ score at week 24 were -0.17 (90% confidence interval [CI]: -0.50, 0.16) for SB-742457 and -0.28 (90% CI: -0.61, 0.05) for donepezil. Drug-placebo treatment differences (90% CI) in change from baseline ADAS-Cog score at week 24 were -0.4 (-2.2, 1.4) for SB-742457 and -1.2 (-3.0, 0.6) for donepezil. All treatments were generally safe and well tolerated.Conclusions: In this exploratory study, SB-742457 and donepezil were associated with improvements in global function. Treatment effect on cognition for both SB-742457 and donepezil was smaller than those previously observed in previous clinical studies with donepezil. Copyright (c) 2010 John Wiley & Sons, Ltd.