A Randomized, Placebo-Controlled Trial of AFQ056 for the Treatment of Chorea in Huntington's Disease
A Randomized, Placebo-Controlled Trial of AFQ056 for the Treatment of Chorea in Huntington's Disease
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DOI：
10.1002/mds.26174
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发表时间：
2015-03-01
影响因子：
8.6
通讯作者：
Gomez-Mancilla, Baltazar
中科院分区：
文献类型：
--
作者：
Reilmann, Ralf;Rouzade-Dominguez, Marie-Laure;Gomez-Mancilla, Baltazar
BackgroundThis study investigated the hypothesis that AFQ056（mavoglurant），a selective metabotropic glutamate receptor 5 antagonist，reduces chorea in亨廷顿's disease（HD）.MethodsThis 32-day randomized，double-blind，parallel-group，proof-of-concept study investigated AFQ056（25-150 mg [incremental doses]，twice of day）versus placebo in patients with HD.主要疗效评估为第28天定量运动（Q-Motor）抓握任务的舞蹈综合评分和定向指数（非优势手）。关键的次要疗效评估包括统一亨廷顿氏病评定量表-总运动评分和Q-运动测量中的手指敲击。安全性和耐受性进行了assessed.ResultsOverall，42例患者进行了随机分组。在第28天，与安慰剂相比，AFQ 056在主要功效评估上没有观察到改善（P>0.10）。对于非优势手，AFQ 056组与安慰剂组相比，Q-Motor快速敲击发作间期变异性降低（P=0.01）。不良反应发生率AFQ 056组为66.7%，安慰剂组为57.1%。结论AFQ 056不能减少HD患者的舞蹈病运动，但耐受性良好。Q-Motor结果（快速叩击）的临床相关性未知，可能需要进一步研究。(c)2015年国际帕金森和运动障碍协会
BackgroundThis study investigated the hypothesis that AFQ056 (mavoglurant), a selective metabotropic glutamate receptor 5 antagonist, reduces chorea in Huntington's disease (HD).MethodsThis 32-day randomized, double-blind, parallel-group, proof-of-concept study investigated AFQ056 (25-150 mg [incremental doses], twice-daily) versus placebo in patients with HD. Primary efficacy assessments were the chorea-sum score and orientation index (nondominant hand) from the quantitative motor (Q-Motor) grasping task at day 28. Key secondary efficacy assessments included finger-tapping in the Unified Huntington's Disease Rating Scale-Total Motor Score and Q-Motor measures. Safety and tolerability were assessed.ResultsOverall, 42 patients were randomized. At day 28, no improvement was observed on the primary efficacy assessments (P>0.10) with AFQ056 versus placebo. The Q-Motor speeded-tapping interonset interval variability was reduced with AFQ056 versus placebo for the nondominant hand (P=0.01). The incidence of adverse events was 66.7% with AFQ056 and 57.1% with placebo.ConclusionsAFQ056 did not reduce choreatic movements in HD, but was well tolerated. The clinical relevance of the Q-Motor findings (speeded-tapping) are unknown and may warrant further investigation. (c) 2015 International Parkinson and Movement Disorder Society