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.

Abstract

OBJECTIVE
To assess the anti-choreatic efficacy, safety and tolerability of AFQ056 in Huntington’s disease (HD).
BACKGROUND
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.
DESIGN/METHODS
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.
RESULTS
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.
CONCLUSIONS
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
URI:	https://oak.novartis.com/id/eprint/9409