Long-term safety profile of opicapone in patients with Parkinson’s disease and early fluctuations
18 affiliations
- 1Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade Lisboa
- 2CNS – Campus Neurológico
- 3Institute for Research and Medical Care IRCCS San Raffaele
- 4Department of Neurology, San Raffaele University
- 5Neurodegenerative Disease Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova
- 6IRCCS San Camillo Venice
- 7Department of Clinical Pharmacology and Neurosciences, Parkinson Expert Centre, Clinical Investigation Centre CIC1436, University Hospital of Toulouse, INSERM, University of Toulouse 3
- 8French Clinical Research Network for Parkinson's Disease and Movement Disorders (NS-PARK)
- 9Clinical Ageing Research Unit, Newcastle University
- 10Movement Disorders Hospital
- 11Movement Disorders Unit, Neurology Department, Sant Pau Hospital
- 12Biomedical Research Institute (IIB-Sant Pau)
- 13Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED)
- 14Department of Neurology, Ludwig-Maximilians-Universität Hospital, Ludwig-Maximilians-Universität
- 15German Center for Neurodegenerative Diseases
- 16Munich Cluster for Systems Neurology (SyNergy)
- 17BIAL – Portela & Ca S.A.
- 18Department of Neurology, Medical University of Innsbruck
Abstract
Background: Motor fluctuations frequently emerge within the first few years of levodopa treatment in Parkinson’s disease (PD), increasing symptom burden and treatment complexity. While opicapone is an established adjunct therapy for motor fluctuations, its safety profile when initiated early in the course of fluctuating disease remains incompletely characterized.
Methods: This pooled post-hoc analysis integrated individual patient-level data from two randomized, double-blind, placebo-controlled trials of opicapone 50 mg and their open-label extensions. Analyses focused on patients with recent onset of motor fluctuations (≤2 years). Safety outcomes included the incidence, severity, timing, and evolution of treatment-emergent adverse events (TEAEs) during double-blind and up to 1 year of open-label exposure, with comparisons between earlier (OPC–OPC) and delayed (PLC–OPC) initiation.
Results: A total of 269 patients with recent motor fluctuations were included, of whom 228 entered open-label treatment. During the double-blind phase, TEAEs were reported in 55.9% of patients receiving opicapone and 50.9% receiving placebo, with no statistically significant difference between groups. Adverse events were mainly mild to moderate and occurred predominantly within the first 2–3 weeks declining thereafter. Dyskinesia was the most frequent TEAE (10.2% vs. 3.6%, p = 0.09), occurring early and resolving in most patients, either spontaneously or following modest levodopa dose adjustment. Across the combined study period, overall TEAE incidence and cumulative dyskinesia rates were comparable between early and delayed initiation groups (15.3% vs. 15.5%, p = 1.0), with no increase over time.
Conclusion: Opicapone demonstrated a favorable and consistent safety profile in patients with recent onset of motor fluctuations, with adverse events predominantly transient and manageable. Earlier initiation was not associated with an increased safety burden and showed numerically lower rates of overall TEAEs and dyskinesia compared with broader trial populations. These findings support the hypothesis that early optimization of levodopa therapy with opicapone does not accelerate the development of motor complications, supporting early COMT-inhibition in fluctuating PD.
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BibTeX
@article{ferreira2026longterm,
title = {{Long-term safety profile of opicapone in patients with Parkinson’s disease and early fluctuations}},
author = {Joaquim J. Ferreira and Fabrizio Stocchi and Angelo Antonini and Olivier Rascol and Nicola Pavese and Georg Ebersbach and Jaime Kulisevsky and Günter Höglinger and Daniel Ramos and José Francisco Rocha and Helena C. Brigas and Joerg Holenz and Werner Poewe},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1920359},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1920359/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-term safety profile of opicapone in patients with Parkinson’s disease and early fluctuations
AU - Joaquim J. Ferreira
AU - Fabrizio Stocchi
AU - Angelo Antonini
AU - Olivier Rascol
AU - Nicola Pavese
AU - Georg Ebersbach
AU - Jaime Kulisevsky
AU - Günter Höglinger
AU - Daniel Ramos
AU - José Francisco Rocha
AU - Helena C. Brigas
AU - Joerg Holenz
AU - Werner Poewe
PY - 2026
DA - 2026/10/13
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1920359
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1920359/full
AB - Background: Motor fluctuations frequently emerge within the first few years of levodopa treatment in Parkinson’s disease (PD), increasing symptom burden and treatment complexity. While opicapone is an established adjunct therapy for motor fluctuations, its safety profile when initiated early in the course of fluctuating disease remains incompletely characterized. Methods: This pooled post-hoc analysis integrated individual patient-level data from two randomized, double-blind, placebo-controlled trials of opicapone 50 mg and their open-label extensions. Analyses focused on patients with recent onset of motor fluctuations (≤2 years). Safety outcomes included the incidence, severity, timing, and evolution of treatment-emergent adverse events (TEAEs) during double-blind and up to 1 year of open-label exposure, with comparisons between earlier (OPC–OPC) and delayed (PLC–OPC) initiation. Results: A total of 269 patients with recent motor fluctuations were included, of whom 228 entered open-label treatment. During the double-blind phase, TEAEs were reported in 55.9% of patients receiving opicapone and 50.9% receiving placebo, with no statistically significant difference between groups. Adverse events were mainly mild to moderate and occurred predominantly within the first 2–3 weeks declining thereafter. Dyskinesia was the most frequent TEAE (10.2% vs. 3.6%, p = 0.09), occurring early and resolving in most patients, either spontaneously or following modest levodopa dose adjustment. Across the combined study period, overall TEAE incidence and cumulative dyskinesia rates were comparable between early and delayed initiation groups (15.3% vs. 15.5%, p = 1.0), with no increase over time. Conclusion: Opicapone demonstrated a favorable and consistent safety profile in patients with recent onset of motor fluctuations, with adverse events predominantly transient and manageable. Earlier initiation was not associated with an increased safety burden and showed numerically lower rates of overall TEAEs and dyskinesia compared with broader trial populations. These findings support the hypothesis that early optimization of levodopa therapy with opicapone does not accelerate the development of motor complications, supporting early COMT-inhibition in fluctuating PD.
SN - 1664-2295
ER -