2026 American Academy of Neurology Abstract Website

Joaquim Ferreira¹, Olivier Rascol², Fabrizio Stocchi³, Angelo Antonini⁴, Bruno Dias⁵, Francisco Rocha⁵, Daniel Ramos⁵, Ghazal Banisadr⁶, Helena Brigas⁵, Joerg Holenz⁵, Werner Poewe⁷
¹Faculdade de Medicina, Universidade Lisboa, ²Departments of Neurosciences and Clinical Pharmacology, University of Toulouse, University Hospital of Toulouse, INSERM, Clinical Investigation Center CIC1436, ³Department of Neurology, IRCCS San Raffaele Pisana, ⁴Department of Neurosciences, University of Padova, ⁵BIAL – Portela & Ca S.A., ⁶Amneal Pharmaceuticals, ⁷Department of Neurology, Medical University of Innsbruck

Objective:

This post-hoc analysis of EPSILON study evaluated whether levodopa dose and timing of Opicapone initiation (double-blind [DB] vs open-label extension [OLE] baseline) influenced the risk of motor complications (MCs) over 1.5 years.

Background:

Levodopa is the most effective Parkinson’s disease (PD) treatment, yet higher doses increase the risk of MCs, namely wearing-off and dyskinesia. In the 24-week DB EPSILON study, adjunctive OPC improved motor impairment in early PD without increasing MCs. After the 1-year OLE, sustained efficacy was observed without increased MC risk.

Design/Methods:

EPSILON was a randomised, DB, placebo-controlled study, followed by a 1-year OLE. Levodopa-treated PD patients without MCs received OPC 50 mg or placebo (DB phase). In the OLE phase, all received OPC 50 mg; key endpoint was change in MDS-UPDRS IV (motor complications). This exploratory analysis compared time to MCs onset, and subitems for dyskinesia (item 4.1) and OFFs (item 4.3) over 1.5 years in early OPC users (OPC-OPC) and those switching from placebo (PLC-OPC), stratified by Levodopa dose (<400mg/day vs. ≥400mg/day) at event onset. Kaplan–Meier curves with log-rank tests were used.

Results:

Higher levodopa dose (≥400mg/day) showed a trend for increased MCs risk, particularly in patients who started OPC later. The proportion without MCs was 81.9% (<400mg/day) and 79.0% (≥400mg/day) in the OPC-OPC group, versus 73.3% (<400mg/day) and 66.7% (≥400mg/day) in the PLC-OPC group (p=0.04). The proportion of patients free of dyskinesia followed a similar trend (p=0.06). The proportion without OFFs was slightly higher in the OPC-OPC group regardless of baseline levodopa dose (p=0.7).

Conclusions:

Although most patients remain MC-free with early OPC initiation, this exploratory analysis reports a trend towards higher risk of MC in those with higher levodopa doses (≥400mg/day) who started OPC later. Early OPC introduction may promote motor stability even in patients on higher levodopa doses.