Long-term safety profile of opicapone in patients with Parkinson's disease and early fluctuations.

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.