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

Reilmann, Ralf, Rouzade-Dominguez, Marie-Laure, Saft, Carsten, Süssmuth, Sigurd D., Priller, Josef, Rosser, Anne Elizabeth, Rickards, Hugh, Schöls, Ludger, Pezous, Nicole, Gasparini, Fabrizio, Johns, Donald, Landwehrmeyer, Georg Bernhard and Gomez-Mancilla, Baltazar 2015. A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease. Movement Disorders 30 (3) , pp. 427-431. 10.1002/mds.26174

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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. © 2015 International Parkinson and Movement Disorder Society

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Huntington's disease; chorea; mGluR5 antagonist; AFQ056
Publisher: John Wiley & Sons
ISSN: 0885-3185
Date of Acceptance: 16 January 2015
Last Modified: 11 Mar 2019 13:35
URI: http://orca.cf.ac.uk/id/eprint/72142

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