Imbimbo B P, Lucca U, Lucchelli F, Alberoni M, Thal L J
Medical Department, Mediolanum Farmaceutici, Milan, Italy.
Alzheimer Dis Assoc Disord. 1998 Dec;12(4):313-22. doi: 10.1097/00002093-199812000-00011.
The efficacy and safety of eptastigmine in patients with probable Alzheimer disease was evaluated in a double-blind, placebo-controlled, parallel group study. Patients with mild to moderate dementia were randomly assigned to placebo, eptastigmine 10 mg three times a day (t.i.d.), or eptastigmine 15 mg t.i.d. over 25 weeks. The Alzheimer Disease Assessment Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus) were the primary outcome measures for efficacy. Twenty-six centers recruited 320 patients: 106 on placebo, 105 on eptastigmine 10 mg t.i.d., and 109 on eptastigmine 15 mg t.i.d. Six patients on placebo (6%), 18 patients on eptastigmine 10 mg t.i.d. (17%), and 10 patients on eptastigmine 15 mg t.i.d. (9%) discontinued study treatment. The intent-to-treat analysis on 315 patients showed a statistically significant (p=0.047) difference of 2.0 points on ADAS-Cog between the placebo and the eptastigmine 15 mg t.i.d. group at the end of treatment. Patients in the 10 mg t.i.d. group performed better than did placebo-treated patients on the Spontaneous Behavior Interview (SBI) total scores (p=0.015) and on the Activities of Daily Living (ADL, p=0.043) and Behavioral Problems (BP, p=0.028) subscales. The differences in favor of the eptastigmine groups on the CIBIC-Plus did not reach statistical significance. In a post hoc subgroup analysis by staging, the effect size of eptastigmine was found to be greater in the most severely impaired patients (Global Deterioration Scale rating of 4 and 5 at screening) reaching statistical significance in both ADAS-Cog (p=0.007) and CIBIC-Plus (p=0.038). In this patient subgroup (n=222), there was also a significant effect of eptastigmine on SBI (p=0.019). The drug was generally well tolerated, with 8% of patients withdrawing due to adverse events versus 5% on placebo. Adverse events were recorded in 35 patients (33%) on placebo compared with 41 (39%) on eptastigmine 10 mg t.i.d. and 38 (35%) on eptastigmine 15 mg t.i.d. This study shows that eptastigmine doses up to 15 mg t.i.d. for 25 weeks are well tolerated. The drug positively affects cognitive performance of Alzheimer patients. This effect appears greater in more severely impaired patients and also impacts on their behavioral performance.
在一项双盲、安慰剂对照、平行组研究中，评估了艾斯他明对可能患有阿尔茨海默病患者的疗效和安全性。轻度至中度痴呆患者被随机分配接受安慰剂、每日三次每次10毫克的艾斯他明或每日三次每次15毫克的艾斯他明治疗，为期25周。阿尔茨海默病评估认知分量表（ADAS - Cog）和基于临床医生访谈的变化印象加量表（CIBIC - Plus）是疗效的主要评估指标。26个中心招募了320名患者：106名接受安慰剂治疗，105名接受每日三次每次10毫克的艾斯他明治疗，109名接受每日三次每次15毫克的艾斯他明治疗。6名接受安慰剂治疗的患者（6%）、18名接受每日三次每次10毫克艾斯他明治疗的患者（17%）和10名接受每日三次每次15毫克艾斯他明治疗的患者（9%）停止了研究治疗。对315名患者的意向性分析显示，在治疗结束时，安慰剂组与每日三次每次15毫克艾斯他明组在ADAS - Cog上存在统计学显著差异（p = 0.047），差值为2.0分。每日三次每次10毫克组的患者在自发行为访谈（SBI）总分（p = 0.015）、日常生活活动（ADL，p = 0.043）和行为问题（BP，p = 0.028）分量表上的表现优于接受安慰剂治疗的患者。艾斯他明组在CIBIC - Plus上的优势差异未达到统计学显著水平。在一项按分期进行的事后亚组分析中，发现艾斯他明在受损最严重的患者（筛查时全球衰退量表评分为4和5）中的效应量更大，在ADAS - Cog（p = 0.007）和CIBIC - Plus（p = 0.038）中均达到统计学显著水平。在该患者亚组（n = 222）中，艾斯他明对SBI也有显著影响（p = 0.019）。该药物总体耐受性良好，8%的患者因不良事件退出，而安慰剂组为5%。安慰剂组有35名患者（33%）记录了不良事件，每日三次每次10毫克艾斯他明组有41名（39%），每日三次每次15毫克艾斯他明组有38名（35%）。这项研究表明，每日三次每次15毫克的艾斯他明剂量持续25周耐受性良好。该药物对阿尔茨海默病患者的认知表现有积极影响。这种影响在受损更严重的患者中似乎更大，并且也会影响他们的行为表现。
