Department of Neurology, Boston University School of Medicine, 72 E Concord St, L-320, Boston, MA 02118, USA.
JAMA. 2009 Dec 16;302(23):2557-64. doi: 10.1001/jama.2009.1866.
Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial.
To determine the efficacy, safety, and tolerability of tarenflurbil.
DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted.
Tarenflurbil, 800 mg, or placebo, administered twice a day.
Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification.
Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections.
Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD.
clinicaltrials.gov Identifier: NCT00105547.
淀粉样β肽（Abeta（42））与阿尔茨海默病（AD）的发病机制有关。在早期的 2 期临床试验中，一种选择性的 Abeta（42）降低药物他仑氟贝，在轻度受影响的患者的认知和功能结果方面显示出可喜的结果。
确定他仑氟贝的疗效、安全性和耐受性。
设计、地点和患者：这项多中心、随机、双盲、安慰剂对照试验在美国 133 个试验点进行，招募了 2005 年 2 月 21 日至 2008 年 4 月 30 日期间患有轻度 AD 的患者。允许同时使用胆碱酯酶抑制剂或美金刚。
他仑氟贝，800mg，或安慰剂，每天两次给药。
从基线到第 18 个月时，根据阿尔茨海默病评估量表认知子量表（ADAS-Cog，80 分版本）和阿尔茨海默病合作研究日常生活活动量表（ADCS-ADL）子量表的总分变化。额外的预设斜率分析探索了疾病修饰的可能性。
在 1684 名随机患者中，有 1649 名患者纳入分析，有 1046 名患者完成了试验。他仑氟贝对主要结局无有益影响（基于最小二乘均值的组间差异，与安慰剂相比，从基线到第 18 个月的变化：ADAS-Cog 为 0.1；95%CI，-0.9 至 1.1；P=.86 和 ADCS-ADL 为-0.5；95%CI，-1.9 至 0.9；P=.48），采用意向治疗分析。次要结局无显著差异。ADAS-Cog 评分在 18 个月内下降了 7.1 分。他仑氟贝组头晕、贫血和感染的频率略有增加。
他仑氟贝不能减缓轻度 AD 患者的认知能力下降或日常生活活动丧失。
clinicaltrials.gov 标识符：NCT00105547。
