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首页> 外文期刊>Lancet Neurology >TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.
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TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.

机译:TCH346作为帕金森氏病的神经保护药:一项双盲,随机,对照试验。

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摘要

BACKGROUND: There is an important unmet medical need in Parkinson's disease for a neuroprotective treatment that slows or stops disease progression. TCH346 is a potent anti-apoptotic drug that protects against loss of dopaminergic neurons in laboratory models. Our aim was to assess TCH346 as a neuroprotective drug in patients with Parkinson's disease. METHODS: Patients presenting at 45 international movement disorder clinics with early untreated Parkinson's disease were assessed as part of this parallel-group, double-blind, randomised controlled trial. 301 eligible patients were randomly assigned 12-18 months' treatment with TCH346 at a daily dose of 0.5 mg (n=78), 2.5 mg (n=79), or 10 mg (n=73), or placebo (n=71), followed by a 4 week washout period. The primary outcome measure was time to development of a disability requiring dopaminergic treatment. Secondary outcome measures were the annual rate of change in the unified Parkinson's disease rating scale (UPDRS) and the PDQ-39, a measure of quality oflife. Analyses were by intention-to-treat. This study is pending registration with . FINDINGS: 255 patients completed the study. TCH346 did not differ from placebo for any of the study outcomes. Treatment was needed in 26 (34%) patients in the TCH346 0.5 mg group, 30 (38%) in the TCH346 2.5 mg group, 24 (33%) in the TCH346 10 mg group, and 23 (32%) in the placebo group. There were no significant differences between groups. There were no differences between groups in the annual change in the UPDRS or PDQ-39 either. Few patients withdrew because of adverse events and none was judged to be related to the study intervention. INTERPRETATION: TCH346 did not show evidence of a neuroprotective effect. The discrepancy between the preclinical promise of TCH346 and the clinical outcome could have arisen because of the use of laboratory models that do not accurately reflect the pathogenesis of Parkinson's disease, the doses of study drug used, insensitive clinical endpoints, and the patient population selected for study.
机译:背景:帕金森氏病对延缓或阻止疾病进展的神经保护性治疗存在重要的未满足医疗需求。 TCH346是一种有效的抗凋亡药物,可防止实验室模型中多巴胺能神经元的丢失。我们的目的是评估TCH346作为帕金森氏病患者的神经保护药物。方法:在这45个国际性运动障碍诊所就诊的早期帕金森氏病未得到治疗的患者被评估为该平行组,双盲,随机对照试验的一部分。 301名合格患者被随机分配为TCH346的12-18个月治疗,每日剂量为0.5 mg(n = 78),2.5 mg(n = 79)或10 mg(n = 73)或安慰剂(n = 71 ),然后进行4周的清除期。主要结果指标是需要多巴胺能治疗的残疾发生时间。次要结果指标是统一的帕金森氏病评分量表(UPDRS)和PDQ-39(生活质量量度)的年度变化率。按意向进行分析。这项研究正在向申请注册。结果:255名患者完成了研究。对于任何研究结果,TCH346与安慰剂均无差异。 TCH346 0.5 mg组中的26(34%)名患者需要治疗,TCH346 2.5 mg组中的30(38%)名患者,TCH346 10 mg组中的24(33%)名患者,安慰剂组23名(32%)患者需要治疗组。两组之间无显着差异。 UPDRS或PDQ-39的年度变化在两组之间也没有差异。很少有患者因不良事件而退出,并且没有患者被判定与研究干预措施有关。解释:TCH346没有显示出神经保护作用的证据。由于使用的实验室模型不能准确反映帕金森氏病的发病机理,所用研究药物的剂量,不敏感的临床终点以及所选择的患者人群,因此可能会出现TCH346的临床前期预期与临床结果之间的差异。研究。

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