Safety and efficacy of perampanel in advanced Parkinson's disease: A randomized,placebo‐controlled study |
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| Authors: | Karla Eggert MD David Squillacote MD Paolo Barone MD Richard Dodel MD Regina Katzenschlager MD Murat Emre MD Andrew J Lees MD Olivier Rascol MD PhD Werner Poewe MD Eduardo Tolosa MD Claudia Trenkwalder MD Marco Onofrj MD Fabrizio Stocchi MD PhD Giuseppe Nappi MD Vladimir Kostic MD Jagoda Potic MD Evzen Ruzicka MD DSc Wolfgang Oertel MD and in cooperation with the German Competence Network on Parkinson's Disease |
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| Institution: | 1. German Competence Network on Parkinson's Disease, Department of Neurology, Philipps‐University Marburg, Marburg, Germany;2. Eisai Global Clinical Development, Eisai Medical Research Inc., Woodcliff Lake, New Jersey, USA;3. Department of Neurological Sciences, University of Naples Federico II‐IDC Hermitage‐Capodimonte, Naples, Italy;4. Department of Neurology, Rheinische Friedrich‐Wilhelms‐University, Bonn, Germany;5. Department of Neurology, Donauspital, Vienna, Austria;6. Department of Neurology, Istanbul Medical School, Istanbul, Turkey;7. Reta Lila Weston Institute of Neurological Studies, University College London, London, United Kingdom;8. Clinical Investigation Center, INSERM CIC9302, University Hospital Toulouse, Toulouse, France;9. Departments of Clinical Pharmacology and Neurosciences, INSERM UMR825, University Hospital Toulouse, Toulouse, France;10. Department of Neurology, Medical University Innsbruck, Innsbruck, Austria;11. Neurology Service, Hospital Clinic, Universitat de Barcelona, CIBERNED, Barcelona, Spain;12. Paracelsus‐Elena Klinik, Kassel, Germany;13. Clinica Neurologica, Università Chieti‐Pescara, Italy;14. Department of Neurology, IRCCS San Raffaele, Rome, Italy;15. Chair of Neurology, University “La Sapienza,” Rome, Italy;16. IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy;17. Institute of Neurology, Clinical Centre of Serbia, Belgrade, Serbia;18. Clinic for Neurology and Psychiatry, Clinical Hospital Centre “Zvezdara,” Belgrade, Serbia;19. Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic |
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| 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 nonsignificant 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. © 2010 Movement Disorder Society |
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| Keywords: | Parkinson's disease motor fluctuations dyskinesia perampanel AMPA receptor antagonist |
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