Gault Laura M, Ritchie Craig W, Robieson Weining Z, Pritchett Yili, Othman Ahmed A, Lenz Robert A
AbbVie Inc., North Chicago, IL, USA.
Division of Brain Sciences, Imperial College London, London, UK.
Alzheimers Dement (N Y). 2015 Jun 23;1(1):81-90. doi: 10.1016/j.trci.2015.06.001. eCollection 2015 Jun.
The safety and efficacy of the novel α7 nicotinic acetylcholine receptor agonist ABT-126 were investigated in subjects with mild-to-moderate Alzheimer's dementia (AD).
Subjects not currently receiving acetylcholinesterase inhibitors were randomized to ABT-126 (5 or 25 mg once daily), donepezil 10 mg once daily, or placebo for 12 weeks. The primary efficacy end point was the change from baseline to final evaluation in the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score.
A total of 274 subjects were randomized. Although the study did not meet its primary end point, trends toward improvement were seen with ABT-126 25 mg (least squares mean [standard error] difference from placebo -1.19 [0.90]; one-sided = .095) and donepezil (-1.43 [0.90]; one-sided = .057) on the 11-item ADAS-Cog total score change from baseline to the final evaluation. ABT-126 5 mg was numerically similar to placebo. An exposure-response analysis indicated a statistically significant relationship between ABT-126 exposure and the change from baseline in ADAS-Cog, with no evidence of a plateau. No clinically meaningful differences in safety were observed among treatment groups.
Although the ABT-126 25 mg dose did not demonstrate statistically significant improvement, results of the exposure-response analysis suggest that higher doses may produce better efficacy, and the safety profile of ABT-126 in this study supports additional studies with higher doses in subjects with mild-to-moderate AD.
NCT00948909.
在轻度至中度阿尔茨海默病（AD）患者中研究了新型α7烟碱型乙酰胆碱受体激动剂ABT-126的安全性和有效性。
未接受过乙酰胆碱酯酶抑制剂治疗的受试者被随机分为ABT-126组（5或25mg，每日一次）、多奈哌齐10mg每日一次组或安慰剂组，治疗12周。主要疗效终点是11项阿尔茨海默病评定量表认知分量表（ADAS-Cog）总分从基线到最终评估的变化。
共有274名受试者被随机分组。尽管该研究未达到其主要终点，但在11项ADAS-Cog总分从基线到最终评估的变化方面，ABT-126 25mg组（与安慰剂相比的最小二乘均值[标准误]差异为-1.19[0.90]；单侧P=0.095）和多奈哌齐组（-1.43[0.90]；单侧P=0.057）呈现出改善趋势。ABT-126 5mg组在数值上与安慰剂相似。暴露-反应分析表明，ABT-126暴露与ADAS-Cog从基线的变化之间存在统计学显著关系，且无平台期迹象。各治疗组在安全性方面未观察到具有临床意义的差异。
尽管ABT-126 25mg剂量未显示出统计学显著改善，但暴露-反应分析结果表明，更高剂量可能产生更好的疗效，且本研究中ABT-126的安全性特征支持在轻度至中度AD患者中进行更高剂量的进一步研究。
NCT00948909。
