Joaquim J Ferreira1, Andrew J Lees1, Werner Poewe1, Olivier Rascol1, José-Francisco Rocha1, Birgit Keller1, Patricio Soares-da-Silva2. 1. From the Instituto de Medicina Molecular (J.J.F.), Faculty of Medicine, University of Lisbon; CNS-Campus Neurológico Sénior (J.J.F.), Torres Vedras, Portugal; University College London (A.J.L.), Reta Lila Weston Institute, UK; Department of Neurology (W.P.), Medical University Innsbruck, Austria; Université de Toulouse (O.R.), CHU de Toulouse, Institut National de la Santé et de la Recherche Médicale, Department of Neurosciences and Clinical Pharmacology, Clinical Investigation Center 1436, and NeuroToul Center of Excellence in Neurodegeneration France; Department of Research and Development (J.-F.R., P.S.-d.-S.), BIAL-Portela & Ca SA, S. Mamede do Coronado, Portugal; Department of Biostatistics (B.K.), Clinipace Worldwide, Eschborn, Germany; and Department of Pharmacology and Therapeutics (P.S.-d.-S.), Faculty of Medicine, University Porto, Portugal. 2. From the Instituto de Medicina Molecular (J.J.F.), Faculty of Medicine, University of Lisbon; CNS-Campus Neurológico Sénior (J.J.F.), Torres Vedras, Portugal; University College London (A.J.L.), Reta Lila Weston Institute, UK; Department of Neurology (W.P.), Medical University Innsbruck, Austria; Université de Toulouse (O.R.), CHU de Toulouse, Institut National de la Santé et de la Recherche Médicale, Department of Neurosciences and Clinical Pharmacology, Clinical Investigation Center 1436, and NeuroToul Center of Excellence in Neurodegeneration France; Department of Research and Development (J.-F.R., P.S.-d.-S.), BIAL-Portela & Ca SA, S. Mamede do Coronado, Portugal; Department of Biostatistics (B.K.), Clinipace Worldwide, Eschborn, Germany; and Department of Pharmacology and Therapeutics (P.S.-d.-S.), Faculty of Medicine, University Porto, Portugal. psoares.silva@bial.com.
Abstract
OBJECTIVE: To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease. METHODS: After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated withopicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute "off" time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments. RESULTS: One year of treatment with opicapone reduced "off" time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in "off" time (-64.9, -39.3, -27.5, and -23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration. CONCLUSION: Long-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) ofopicapone is well tolerated and reduces "off" time.
RCT Entities:
OBJECTIVE: To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease. METHODS: After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute "off" time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments. RESULTS: One year of treatment with opicapone reduced "off" time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in "off" time (-64.9, -39.3, -27.5, and -23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration. CONCLUSION: Long-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) of opicapone is well tolerated and reduces "off" time.