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AFQ056 treatment of levodopa-induced dyskinesias: Results of 2 randomized controlled trials

Authors

  • Daniela Berg MD,

    1. University of Tübingen, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Jana Godau MD,

    1. University of Tübingen, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Claudia Trenkwalder MD,

    1. Paracelsus-Elena-Klinik, Kassel, University of Goettingen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Karla Eggert MD,

    1. Phillipps-University of Marburg, Marburg, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • IIona Csoti MD,

    1. Gertrudis Klinik, Biskirchen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Alexander Storch MD,

    1. Department of Neurology, Dresden University of Technology, Dresden, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Heiko Huber MD,

    1. University of Tübingen, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Monica Morelli-Canelo MD,

    1. Paracelsus-Elena-Klinik, Kassel, University of Goettingen, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Maria Stamelou MD,

    1. Phillipps-University of Marburg, Marburg, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Vincent Ries MD,

    1. Phillipps-University of Marburg, Marburg, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Martin Wolz MD,

    1. Department of Neurology, Dresden University of Technology, Dresden, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Christine Schneider MD,

    1. Department of Neurology, Dresden University of Technology, Dresden, Germany
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    • Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group.

  • Thérèse Di Paolo PhD,

    1. Molecular Endocrinology and Genomic Research Center, Laval University Medical Center, Québec, Canada and Faculty of Pharmacy, Laval University, Québec, Canada
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  • Fabrizio Gasparini PhD,

    1. Neuroscience Discovery, Novartis Pharma AG, Basel, Switzerland
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  • Sam Hariry BSc,

    1. Neuroscience Discovery, Novartis Pharma AG, Basel, Switzerland
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  • Marc Vandemeulebroecke PhD,

    1. Translational Science Biostatistics, Novartis Pharma AG, Basel, Switzerland
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  • Walid Abi-Saab MD,

    1. Neuroscience Discovery, Novartis Pharma AG, Basel, Switzerland
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  • Katy Cooke PhD,

    1. Alpha-Plus Medical Communications Ltd., High Wycombe, United Kingdom
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  • Donald Johns MD,

    1. Neuroscience Discovery, Novartis Pharma AG, Basel, Switzerland
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  • Baltazar Gomez-Mancilla MD

    Corresponding author
    1. Neuroscience Discovery, Novartis Pharma AG, Basel, Switzerland
    • Neuroscience Discovery, Novartis Pharma AG, CH-4002 Basel, Switzerland

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  • Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Funding agencies: This study was funded by Novartis Pharma AG, Basel, Switzerland, which provided the study drugs. These studies are registered: NCT00582673 and NCT00888004. Daniela Berg has received financial contributions from Novartis Pharma AG for taking part in an expert meeting, for giving a talk at its Community Health Day, and for being on an advisory board. Jana Godau received honoraria for lectures from Novartis Pharma AG. Ilona Csoti has received financial contributions from Novartis Pharma AG for being on an advisory board. Alexander Storch has received honoraria for presentations and advisory board meetings from Novartis Pharma AG. Theéreése Di Paolo has received honoraria for presentations and contracts from Novartis Pharma AG. Heiko Huber has received travel grants from Novartis Pharma AG. Fabrizio Gasparini, Sam Hariry, Marc Vandemeulebroecke, Walid Abi-Saab, Donald Johns, and Baltazar Gomez-Mancilla are employees of Novartis Pharma AG. Katy Cooke is a full-time employee of Alpha-Plus Medical Communications Ltd. (UK), which received support from Novartis Pharma AG for the time spent on the production of this manuscript.

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25–150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale–part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale–part IV items 32–33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society

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