University of Tübingen, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany.
Mov Disord. 2011 Jun;26(7):1243-50. doi: 10.1002/mds.23616. Epub 2011 Apr 11.
Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society.
研究目的在于评估 AFQ056 在伴有左旋多巴诱导运动障碍的帕金森病患者中的疗效、安全性和耐受性。进行了两项随机、双盲、安慰剂对照、平行分组、住院患者研究，研究对象为伴有中重度左旋多巴诱导运动障碍的帕金森病患者（研究 1）和伴有重度左旋多巴诱导运动障碍的帕金森病患者（研究 2），这些患者正在接受稳定的多巴胺能治疗。患者每日两次接受 25-150mg 的 AFQ056 或安慰剂治疗 16 天（两项研究均如此）。研究 2 还包括为期 4 天的滴定过程。主要结局指标为 Lang-Fahn 日常生活活动运动障碍量表（研究 1）、改良不自主运动量表（研究 2）和统一帕金森病评定量表第三部分（两项研究均如此）。次要结局指标包括统一帕金森病评定量表第四部分项目 32-33。主要分析为所有结局指标从基线到第 16 天的变化。评估了治疗差异。在研究 1 中，15 名患者被随机分配至 AFQ056 组，16 名患者被随机分配至安慰剂组；在研究 2 中，14 名患者被随机分配至每组。与安慰剂相比，AFQ056 治疗患者在第 16 天的运动障碍明显改善（例如，Lang-Fahn 日常生活活动运动障碍量表，P=0.021[研究 1]；改良不自主运动量表，P=0.032[研究 2]）。在两项研究中，从基线到第 16 天，统一帕金森病评定量表第三部分均未见显著变化。两项研究均报告了不良事件，包括头晕。在研究 1 中，4 名 AFQ056 治疗患者报告了严重不良事件（最常见的是运动障碍恶化，显然与停药有关），而在研究 2 中，3 名患者（2 名 AFQ056 治疗患者和 1 名安慰剂组患者）报告了严重不良事件。AFQ056 表现出了具有临床意义的、显著的抗运动障碍作用，而没有改变多巴胺能治疗的抗帕金森病作用。©2011 运动障碍学会。
