Safety and Efficacy of Perampanel in Advanced Parkinson's Disease: A Randomized, Placebo-Controlled Study
Identifieur interne : 002205 ( PascalFrancis/Curation ); précédent : 002204; suivant : 002206Safety and Efficacy of Perampanel in Advanced Parkinson's Disease: A Randomized, Placebo-Controlled Study
Auteurs : Karla Eggert [Allemagne] ; David Squillacote [États-Unis] ; Paolo Barone [Italie] ; Richard Dodel [Allemagne] ; Regina Katzenschlager [Autriche] ; Murat Emre [Turquie] ; Andrew J. Lees [Royaume-Uni] ; Olivier Rascol [France] ; Werner Poewe [Autriche] ; Eduardo Tolosa [Espagne] ; Claudia Trenkwalder [Allemagne] ; Marco Onofrj [Italie] ; Fabrizio Stocchi [Italie] ; Giuseppe Nappi [Italie] ; Vladimir Kostic [Serbie] ; Jagoda Potic [Serbie] ; Evzen Ruzicka [République tchèque] ; Wolfgang Oertel [Allemagne]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Perampanel, a novel, noncompetitive, selective AMPA-receptor antagonist demonstrated evidence of efficacy in reducing motor symptoms in animal models of Parkinson's disease (PD). We assessed the safety and efficacy of perampanel for treatment of "wearing off" motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once-daily add-on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose-response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least-squares (LS) mean change from baseline to week 12 in percent "off' time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1-sided Williams test for dose-response trend at the 0.025 level of significance. At week 12, dose-response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent "off" time during the waking day (P = 0.061, with significance defined as P ≤ 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced non-significant reductions from baseline to week 12 in percent "off" time during the waking day versus placebo (7.59%, P = 0.421 [1 mg], 8.60%, P = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as P ≤ 0.05). There were no significant changes in dyskinesia or cognitive function in any perampanel group versus placebo. Adverse events were similar across treatment groups. Perampanel treatment was well tolerated and safe, but failed to achieve statistical significance in primary and secondary endpoints.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Safety and Efficacy of Perampanel in Advanced Parkinson's Disease: A Randomized, Placebo-Controlled Study</title>
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<author><name sortKey="Dodel, Richard" sort="Dodel, Richard" uniqKey="Dodel R" first="Richard" last="Dodel">Richard Dodel</name>
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<author><name sortKey="Katzenschlager, Regina" sort="Katzenschlager, Regina" uniqKey="Katzenschlager R" first="Regina" last="Katzenschlager">Regina Katzenschlager</name>
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<author><name sortKey="Lees, Andrew J" sort="Lees, Andrew J" uniqKey="Lees A" first="Andrew J." last="Lees">Andrew J. Lees</name>
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<author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name>
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<author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name>
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<author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name>
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<author><name sortKey="Stocchi, Fabrizio" sort="Stocchi, Fabrizio" uniqKey="Stocchi F" first="Fabrizio" last="Stocchi">Fabrizio Stocchi</name>
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<s2>Prague</s2>
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<author><name sortKey="Oertel, Wolfgang" sort="Oertel, Wolfgang" uniqKey="Oertel W" first="Wolfgang" last="Oertel">Wolfgang Oertel</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>German Competence Network on Parkinson's Disease, Department of Neurology, Philipps-University Marburg</s1>
<s2>Marburg</s2>
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<sZ>18 aut.</sZ>
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<series><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMPA receptor</term>
<term>Advanced stage</term>
<term>Dyskinesia</term>
<term>Fluctuations</term>
<term>Nervous system diseases</term>
<term>Parkinson disease</term>
<term>Perampanel</term>
<term>Placebo</term>
<term>Safety</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Dyskinésie</term>
<term>Pathologie du système nerveux</term>
<term>Sécurité</term>
<term>Pérampanel</term>
<term>Stade avancé</term>
<term>Placebo</term>
<term>Fluctuation</term>
<term>Récepteur AMPA</term>
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<front><div type="abstract" xml:lang="en">Perampanel, a novel, noncompetitive, selective AMPA-receptor antagonist demonstrated evidence of efficacy in reducing motor symptoms in animal models of Parkinson's disease (PD). We assessed the safety and efficacy of perampanel for treatment of "wearing off" motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once-daily add-on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose-response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least-squares (LS) mean change from baseline to week 12 in percent "off' time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1-sided Williams test for dose-response trend at the 0.025 level of significance. At week 12, dose-response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent "off" time during the waking day (P = 0.061, with significance defined as P ≤ 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced non-significant reductions from baseline to week 12 in percent "off" time during the waking day versus placebo (7.59%, P = 0.421 [1 mg], 8.60%, P = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as P ≤ 0.05). There were no significant changes in dyskinesia or cognitive function in any perampanel group versus placebo. Adverse events were similar across treatment groups. Perampanel treatment was well tolerated and safe, but failed to achieve statistical significance in primary and secondary endpoints.</div>
</front>
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<fA06><s2>7</s2>
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<fA08 i1="01" i2="1" l="ENG"><s1>Safety and Efficacy of Perampanel in Advanced Parkinson's Disease: A Randomized, Placebo-Controlled Study</s1>
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<fA11 i1="01" i2="1"><s1>EGGERT (Karla)</s1>
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<fA11 i1="02" i2="1"><s1>SQUILLACOTE (David)</s1>
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<fA11 i1="03" i2="1"><s1>BARONE (Paolo)</s1>
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<fA14 i1="07"><s1>Reta Lila Weston Institute of Neurological Studies, University College London</s1>
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<fA14 i1="08"><s1>Clinical Investigation Center, INSERM CIC9302, University Hospital Toulouse</s1>
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<s3>FRA</s3>
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<sZ>9 aut.</sZ>
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<fA14 i1="13"><s1>Clinica Neurologica, Università Chieti-Pescara</s1>
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<sZ>12 aut.</sZ>
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<fA14 i1="14"><s1>Department of Neurology, IRCCS San Raffaele</s1>
<s2>Rome</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
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<fA14 i1="15"><s1>Chair of Neurology, University "La Sapienza</s1>
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<sZ>14 aut.</sZ>
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<fA14 i1="16"><s1>IRCCS "C. Mondino Institute of Neurology" Foundation</s1>
<s2>Pavia</s2>
<s3>ITA</s3>
<sZ>14 aut.</sZ>
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<sZ>15 aut.</sZ>
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<sZ>16 aut.</sZ>
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<fA14 i1="19"><s1>Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General Teaching Hospital</s1>
<s2>Prague</s2>
<s3>CZE</s3>
<sZ>17 aut.</sZ>
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<fA17 i1="01" i2="1"><s1>Cooperation with the German Competence Network on Parkinson's Disease</s1>
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<fC01 i1="01" l="ENG"><s0>Perampanel, a novel, noncompetitive, selective AMPA-receptor antagonist demonstrated evidence of efficacy in reducing motor symptoms in animal models of Parkinson's disease (PD). We assessed the safety and efficacy of perampanel for treatment of "wearing off" motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once-daily add-on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose-response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least-squares (LS) mean change from baseline to week 12 in percent "off' time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1-sided Williams test for dose-response trend at the 0.025 level of significance. At week 12, dose-response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent "off" time during the waking day (P = 0.061, with significance defined as P ≤ 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced non-significant reductions from baseline to week 12 in percent "off" time during the waking day versus placebo (7.59%, P = 0.421 [1 mg], 8.60%, P = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as P ≤ 0.05). There were no significant changes in dyskinesia or cognitive function in any perampanel group versus placebo. Adverse events were similar across treatment groups. Perampanel treatment was well tolerated and safe, but failed to achieve statistical significance in primary and secondary endpoints.</s0>
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