AFQ056 Treatment of Levodopa-Induced Dyskinesias: Results of 2 Randomized Controlled Trials
AFQ056 Treatment of Levodopa-Induced Dyskinesias: Results of 2 Randomized Controlled Trials
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DOI：
10.1002/mds.23616
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发表时间：
2011-06-01
影响因子：
8.6
通讯作者：
Gomez-Mancilla, Baltazar
中科院分区：
文献类型：
--
作者：
Berg, Daniela;Godau, Jana;Gomez-Mancilla, Baltazar
研究目的是评估AFQ 056在左旋多巴诱导的运动障碍的帕金森病患者中的疗效、安全性和耐受性。对接受稳定多巴胺能治疗的中度至重度左旋多巴诱导的运动障碍（研究1）和重度左旋多巴诱导的运动障碍（研究2）的帕金森病患者进行了两项随机、双盲、安慰剂对照、平行组、住院患者研究。患者接受25-150 mg AFQ 056或安慰剂，每日两次，持续16天（两项研究）。研究2包括4天剂量下调。主要结果是Lang-Fahn日常生活活动运动障碍量表（研究1），改良的异常不自主运动量表（研究2）和统一帕金森病评定量表-第三部分（两项研究）。次要结果包括统一帕金森病评定量表第四部分第32-33项。主要分析是所有结局从基线至第16天的变化。评估治疗差异。在研究1中，15例患者随机分配至AFQ 056组，16例患者随机分配至安慰剂组;在研究2中，14例患者随机分配至每组。AFQ 056治疗组患者在第16天的运动障碍较安慰剂组显著改善（例如，Lang-Fahn日常生活活动运动障碍量表，P = .021 [研究1];改良异常不自主运动量表，P = .032 [研究2]）。在两项研究中，第16天统一帕金森病评定量表第三部分与基线相比均未观察到显着变化。两项研究均报告了不良事件，包括头晕。研究1中4名AFQ 056治疗患者和研究2中3名患者（2名AFQ 056治疗患者和1名安慰剂组患者）报告了严重不良事件（最常见的是运动障碍恶化，显然与停止治疗相关）。AFQ 056显示出临床相关和显著的抗运动障碍作用，而不改变多巴胺能治疗的抗帕金森病作用。(C)2010年运动障碍协会
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. (C) 2010 Movement Disorder Society