A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease

Ralf Reilmann, Marie Laure Rouzade-Dominguez, Carsten Saft, Sigurd D. Süssmuth, Josef Priller, Anne Rosser, Hugh Rickards, Ludger Schöls, Nicole Pezous, Fabrizio Gasparini, Donald Johns, Georg Bernhard Landwehrmeyer, Baltazar Gomez-Mancilla

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish
Pages (from-to)427-431
Number of pages5
JournalMovement Disorders
Volume30
Issue number3
DOIs
StatePublished - 1 Mar 2015
Externally publishedYes

Keywords

  • AFQ056
  • Chorea
  • Huntington's disease
  • MGluR5 antagonist

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