title: AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials.
abstract: 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.
authors.affiliation: University of Tübingen, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Jana
authors.initials: J
authors.lastname: Godau
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Karla
authors.initials: K
authors.lastname: Eggert
authors.forename: Iiona
authors.initials: I
authors.lastname: Csoti
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Heiko
authors.initials: H
authors.lastname: Huber
authors.forename: Monica
authors.initials: M
authors.lastname: Morelli-Canelo
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.forename: Vincent
authors.initials: V
authors.lastname: Ries
authors.forename: Martin
authors.initials: M
authors.lastname: Wolz
authors.forename: Christine
authors.initials: C
authors.lastname: Schneider
authors.forename: Thérèse
authors.initials: T
authors.lastname: Di Paolo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: Sam
authors.initials: S
authors.lastname: Hariry
authors.forename: Marc
authors.initials: M
authors.lastname: Vandemeulebroecke
authors.forename: Walid
authors.initials: W
authors.lastname: Abi-Saab
authors.forename: Katy
authors.initials: K
authors.lastname: Cooke
authors.forename: Donald
authors.initials: D
authors.lastname: Johns
authors.forename: Baltazar
authors.initials: B
authors.lastname: Gomez-Mancilla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D007980:Levodopa