Targacept Inc., Winston Salem, NC, USA.
J Psychopharmacol. 2011 Aug;25(8):1020-9. doi: 10.1177/0269881110367727. Epub 2010 Jun 11.
Cognitive decline is a feature of ageing and can be defined as normal (age-associated memory impairment) or pathological (mild cognitive impairment/Alzheimer's disease). Stimulation of selective brain-specific neuronal nicotinic acetylcholine receptors might offer symptomatic treatment for normal ageing. The objective of this study was to assess the safety, tolerability and efficacy of TC-1734 (AZD3480), a selective α4β2 nicotinic agonist, in the treatment of age-associated memory impairment. A randomized placebo-controlled trial was conducted in 16 community-based centers within the USA. Subjects who met objective criteria for age-associated memory impairment were recruited between November 2004 and December 2005. Subjects were randomly assigned to receive orally 25 mg (n = 59), 50 mg (n = 68) TC-1734 (AZD3480) or placebo (n = 66) in a double-blind fashion for 16 weeks. Main outcome measures included routine clinical safety measures, tolerability, cognitive assessment via the Cognitive Drug Research computerized test battery and a Subject Global Impression Scale of Cognition (SCI-Cog). Two outcomes from the computerized test battery - a factor assessing attention and one assessing episodic memory, along with the SGI-Cog were defined as co-primary outcome variables. Baseline to Week 16 differences from placebo for 50 mg TC-1734 (AZD3480) were considered of primary importance. For 50 mg TC-1734 (AZD3480) attention factor the mean drug-placebo difference was 22.9 (95% confidence interval 4.8 to 41.4) p = 0.01 for episodic memory factor the difference was -7.6 (95% confidence interval -14.4 to -0.8), p = 0.029, and for the SGI-Cog the difference was 0.99 (95% confidence interval 0.2 to 1.8), p = 0.015. As all three co-primary outcomes were positive it can be concluded the compound likely had a beneficial effect on cognition. TC-1734 (AZD3480) appeared safe and well tolerated in this study.
认知能力下降是衰老的一个特征，可以定义为正常（与年龄相关的记忆障碍）或病理性（轻度认知障碍/阿尔茨海默病）。刺激选择性脑特异性烟碱型乙酰胆碱受体可能为正常衰老提供对症治疗。本研究的目的是评估 TC-1734（AZD3480），一种选择性α4β2 烟碱激动剂，治疗与年龄相关的记忆障碍的安全性、耐受性和疗效。在美国的 16 个社区中心进行了一项随机、安慰剂对照试验。符合与年龄相关的记忆障碍客观标准的受试者于 2004 年 11 月至 2005 年 12 月期间招募。受试者以双盲方式随机接受口服 25 mg（n = 59）、50 mg（n = 68）TC-1734（AZD3480）或安慰剂（n = 66），疗程为 16 周。主要观察指标包括常规临床安全性指标、耐受性、通过认知药物研究计算机测试电池和受试者全球印象认知量表（SCI-Cog）进行的认知评估。计算机测试电池中的两个结果 - 一个评估注意力的因子和一个评估情景记忆的因子，以及 SCI-Cog 被定义为共同主要结果变量。从基线到第 16 周，与安慰剂相比，50 mg TC-1734（AZD3480）的差异被认为是主要重要的。对于 50 mg TC-1734（AZD3480）注意力因子，药物与安慰剂的平均差值为 22.9（95%置信区间 4.8 至 41.4），p = 0.01；对于情景记忆因子，差值为-7.6（95%置信区间-14.4 至-0.8），p = 0.029；对于 SCI-Cog，差值为 0.99（95%置信区间 0.2 至 1.8），p = 0.015。由于所有三个共同主要结果均为阳性，可以得出结论，该化合物可能对认知功能有有益影响。在这项研究中，TC-1734（AZD3480）似乎安全且耐受良好。
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