The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II

José-Francisco Rocha; Georg Ebersbach; Andrew Lees; Eduardo Tolosa; Joaquim J Ferreira; Werner Poewe; Olivier Rascol; Fabrizio Stocchi; Angelo Antonini; Diogo Magalhães; Helena Gama; Patrício Soares-da-Silva

doi:10.3389/fneur.2021.754016

The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II

Front Neurol. 2021 Nov 5:12:754016. doi: 10.3389/fneur.2021.754016. eCollection 2021.

Affiliations

¹ BIAL - Portela & Ca, S.A., Coronado, Portugal.
² Movement Disorders Clinic, Beelitz-Heilstätten, Germany.
³ National Hospital for Neurology and Neurosurgery, London, United Kingdom.
⁴ Parkinson Disease and Movement Disorder Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
⁵ Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
⁶ Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁷ Toulouse Parkinson's Expert Center, Departments of Neurosciences and Clinical Pharmacology, Centre d'Investigation Clinique de Toulouse CIC 1436, NS-Park/FCRIN Network, and NeuroToul COEN Center, University Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France.
⁸ Department of Neurology, IRCCS San Raffaele Pisana, Rome, Italy.
⁹ Parkinson and Movement Disorders Unit, Center for Neurodegenerative Disease (CESNE), Department of Neurosciences, University of Padova, Padova, Italy.

Abstract

Introduction: Opicapone (OPC) was efficacious in reducing OFF-time in two pivotal trials in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (BIPARK-I and -II). Post-hoc analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD. Methods: Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory post-hoc analyses were performed to investigate the efficacy of OPC 50 mg vs. PLC in subgroups of patients who were in "earlier" vs. "later" stages of both their disease course (e.g., duration of PD <6 years vs. ≥6 years) and levodopa treatment pathway (e.g., number of daily levodopa intakes <4 vs. ≥4). Efficacy variables included changes from baseline in absolute OFF-time and total ON-time. Results: The Full Analysis Set included 517 patients (PLC, n = 255; OPC 50 mg, n = 262). OPC 50 mg was significantly more effective than PLC in reducing OFF-time and increasing ON-time in the majority of subgroup analyses (p < 0.05). Moreover, patients in "earlier" stages of both their disease course and levodopa treatment pathway experienced numerically greater efficacy when using OPC 50 mg, in comparison with those in "later" stages. Conclusion: OPC 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in PD patients. There was also a signal for enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway.

Keywords: Parkinson's disease; catechol-O-methyltransferase inhibitor; levodopa; motor fluctuations; opicapone; wearing-off.