AFQ056 Treatment of Levodopa-Induced Dyskinesias: Results of 2 Randomized Controlled Trials

被引：150

作者：

Berg, Daniela ^{[2
,3
]}

Godau, Jana ^{[2
,3
]}

Trenkwalder, Claudia ^{[4
,5
]}

Eggert, Karla ^{[6
]}

Csoti, Iiona ^{[7
]}

Storch, Alexander ^{[8
]}

Huber, Heiko ^{[2
,3
]}

Morelli-Canelo, Monica ^{[4
,5
]}

Stamelou, Maria ^{[6
]}

Ries, Vincent ^{[6
]}

Wolz, Martin ^{[8
]}

Schneider, Christine ^{[8
]}

Di Paolo, Therese ^{[9
,10
]}

Gasparini, Fabrizio ^{[1
]}

Hariry, Sam ^{[1
]}

Vandemeulebroecke, Marc ^{[11
]}

Abi-Saab, Walid ^{[1
]}

Cooke, Katy ^{[12
]}

Johns, Donald ^{[1
]}

Gomez-Mancilla, Baltazar ^{[1
]}

机构：

[1] Novartis Pharma AG, Neurosci Discovery, CH-4002 Basel, Switzerland

[2] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[3] German Ctr Neurodegenerat Dis, Tubingen, Germany

[4] Univ Gottingen, D-3400 Gottingen, Germany

[5] Paracelsus Elena Klin, Kassel, Germany

[6] Univ Marburg, Marburg, Germany

[7] Gertrudis Klin, Biskirchen, Germany

[8] Tech Univ Dresden, Dept Neurol, D-8027 Dresden, Germany

[9] Univ Laval, Med Ctr, Mol Endocrinol & Genom Res Ctr, Quebec City, PQ, Canada

[10] Univ Laval, Fac Pharm, Quebec City, PQ, Canada

[11] Novartis Pharma AG, Translat Sci Biostat, CH-4002 Basel, Switzerland

[12] Alpha Plus Med Commun Ltd, High Wycombe, Bucks, England

来源：

MOVEMENT DISORDERS | 2011年 / 26卷 / 07期

关键词：

parkinsonism; levodopa; glutamate antagonists; dyskinesias; METABOTROPIC GLUTAMATE RECEPTORS; DOPA-INDUCED DYSKINESIAS; PARKINSONS-DISEASE; MONKEYS; ANTAGONIST; MODEL; AMANTADINE; BLOCKADE;

D O I：

10.1002/mds.23616

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：1243 / 1250

页数：8

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