title: A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease.
abstract: BACKGROUND
  This study investigated the hypothesis that AFQ056 (mavoglurant), a selective metabotropic glutamate receptor 5 antagonist, reduces chorea in Huntington's disease (HD).
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Overall, 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.
  
  
  CONCLUSIONS
  AFQ056 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.
authors.affiliation: George-Huntington-Institute, Münster, Germany; Institute for Clinical Radiology, University of Münster, Münster, Germany; Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Rouzade-Dominguez
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
authors.forename: Sigurd D
authors.initials: SD
authors.lastname: Süssmuth
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Anne
authors.initials: A
authors.lastname: Rosser
authors.forename: Hugh
authors.initials: H
authors.lastname: Rickards
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Nicole
authors.initials: N
authors.lastname: Pezous
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: Donald
authors.initials: D
authors.lastname: Johns
authors.forename: Georg Bernhard
authors.initials: GB
authors.lastname: Landwehrmeyer
authors.forename: Baltazar
authors.initials: B
authors.lastname: Gomez-Mancilla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002819:Chorea / Q000188:drug therapy* / Q000209:etiology*; D004185:Disability Evaluation; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; C581397:mavoglurant
keywords: AFQ056; Huntington's disease; chorea; mGluR5 antagonist