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

doi:10.1002/mds.26174

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 journal › Article › peer-review

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 language	English
Pages (from-to)	427-31
Number of pages	5
Journal	Movement Disorders
Volume	30
Issue number	3
Early online date	17 Feb 2015
DOIs	https://doi.org/10.1002/mds.26174
Publication status	E-pub ahead of print - 17 Feb 2015

Keywords / Materials (for Non-textual outputs)

Adult
Aged
Aged, 80 and over
Analysis of Variance
Chorea
Disability Evaluation
Double-Blind Method
Excitatory Amino Acid Antagonists
Female
Humans
Huntington Disease
Indoles
Male
Middle Aged
Severity of Illness Index
Time Factors
Treatment Outcome
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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10.1002/mds.26174

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Reilmann, R., Rouzade-Dominguez, M.-L., Saft, C., Süssmuth, S. D., Priller, J., Rosser, A., Rickards, H., Schöls, L., Pezous, N., Gasparini, F., Johns, D., Landwehrmeyer, G. B., & Gomez-Mancilla, B. (2015). A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease. Movement Disorders, 30(3), 427-31. Advance online publication. https://doi.org/10.1002/mds.26174

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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.",

keywords = "Adult, Aged, Aged, 80 and over, Analysis of Variance, Chorea, Disability Evaluation, Double-Blind Method, Excitatory Amino Acid Antagonists, Female, Humans, Huntington Disease, Indoles, Male, Middle Aged, Severity of Illness Index, Time Factors, Treatment Outcome, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",

author = "Ralf Reilmann and Marie-Laure Rouzade-Dominguez and Carsten Saft and S{\"u}ssmuth, {Sigurd D} and Josef Priller and Anne Rosser and Hugh Rickards and Ludger Sch{\"o}ls and Nicole Pezous and Fabrizio Gasparini and Donald Johns and Landwehrmeyer, {Georg Bernhard} and Baltazar Gomez-Mancilla",

note = "{\textcopyright} 2015 International Parkinson and Movement Disorder Society.",

year = "2015",

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doi = "10.1002/mds.26174",

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journal = "Movement Disorders",

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Reilmann, R, Rouzade-Dominguez, M-L, Saft, C, Süssmuth, SD, Priller, J, Rosser, A, Rickards, H, Schöls, L, Pezous, N, Gasparini, F, Johns, D, Landwehrmeyer, GB & Gomez-Mancilla, B 2015, 'A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease', Movement Disorders, vol. 30, no. 3, pp. 427-31. https://doi.org/10.1002/mds.26174

TY - JOUR

T1 - A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease

AU - Reilmann, Ralf

AU - Rouzade-Dominguez, Marie-Laure

AU - Saft, Carsten

AU - Süssmuth, Sigurd D

AU - Priller, Josef

AU - Rosser, Anne

AU - Rickards, Hugh

AU - Schöls, Ludger

AU - Pezous, Nicole

AU - Gasparini, Fabrizio

AU - Johns, Donald

AU - Landwehrmeyer, Georg Bernhard

AU - Gomez-Mancilla, Baltazar

PY - 2015/2/17

Y1 - 2015/2/17

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Analysis of Variance

KW - Chorea

KW - Disability Evaluation

KW - Double-Blind Method

KW - Excitatory Amino Acid Antagonists

KW - Female

KW - Humans

KW - Huntington Disease

KW - Indoles

KW - Male

KW - Middle Aged

KW - Severity of Illness Index

KW - Time Factors

KW - Treatment Outcome

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/mds.26174

DO - 10.1002/mds.26174

M3 - Article

C2 - 25689146

SN - 1531-8257

VL - 30

SP - 427

EP - 431

JO - Movement Disorders

JF - Movement Disorders

IS - 3

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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