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Efficacy, Safety and Tolerability of AFQ056 for the treatment of chorea in patients with Huntington’s disease

Reilmann, Ralf, Saft, Carsten, Süssmuth, Sigurd, Priller, Joseph, Rosser, Anne, Rickards, Hugh, Schöls, Ludger, Pezous, Nicole, Landwehrmeyer,, Bernhard, Gomez-Mancilla, Baltazar, Rouzade-Dominguez, Marie-Laure, Gasparini, Fabrizio and Johns, Donald (2013) Efficacy, Safety and Tolerability of AFQ056 for the treatment of chorea in patients with Huntington’s disease. Movement DIsorders.


To assess the anti-choreatic efficacy, safety and tolerability of AFQ056 in Huntington’s disease (HD).
HD is characterised by involuntary choreatic movements. Treatments of chorea have limited efficacy and side effects. AFQ056, a selective metabotropic glutamate-receptor-5 antagonist shown to reduce levodopa-induced dyskinesia in Parkinson’s disease, was hypothesized to reduce chorea in HD.
32-day, randomized, double-blind, parallel-group, placebo-controlled, proof-of-concept study. Patients were 30–85 years, with HD (CAG≥36) in clinical stage I–III, and a Unified HD Rating Scale-Total Motor Score (UHDRS-TMS) maximal chorea sum score >10. Patients were randomized (1:1) to AFQ056 (Days 1–12, titration from 25mg to 150mg twice-daily [bid]; Days 13–28, maintenance [150mg bid]; Days 29–32, down-titration [50 mg bid]) or placebo. Primary objectives were to assess the efficacy of AFQ056 versus placebo at Day 28 on the UHDRS-TMS maximal chorea sum score and the orientation index (non-dominant hand) from the quantitative-motor (Q-Motor) grasping task; and to evaluate safety and tolerability of AFQ056. Key secondary efficacy assessments included total UHDRS-TMS, UHDRS-TMS luria score, UHDRS-TMS finger taps, and additional Q-Motor measures.
42 patients (mean age 55.2 years, HD duration 6.6 years) were randomized. At Day 28, there were no significant improvements on the UHDRS-TMS maximal chorea sum score (p=0.155) or orientation index (non-dominant hand, p=0.626) in AFQ056-treated patients versus placebo. A significant reduction in Q-Motor speeded-tapping variability was observed favouring AFQ056 versus placebo and reverting at study end ; this was accompanied by UHDRS-TMS finger-tapping scores exhibiting a trend towards improvement. No significant treatment effects were observed at Day 28 on other key secondary assessments.
AFQ056 did not reduce involuntary choreatic movements in HD. The Q-Motor finding in speeded-tapping may reflect an improvement in fine motor coordination, but the clinical relevance of this observation is unknown. Overall, AFQ056 was well-tolerated in HD.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13