2025 American Academy of Neurology Abstract Website

Joaquim Ferreira¹, Jee-Young Lee², Hyeo-il Ma³, Beomseok Jeon⁴, Werner Poewe⁵, Angelo Antonini⁶, Fabrizio Stocchi⁷, Daniela Rodrigues⁸, Stanley Fisher⁹, Miguel Fonseca⁸, José-Francisco Rocha⁸, Guillermo Castilla-Fernández⁸, Joerg Holenz⁸, Olivier Rascol¹⁰
¹IMM Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa; CNS-Campus Neurológico, ²Department of Neurology, SMG-SNU Boramae Medical Center, ³Department of Neurology, Hallym University Sacred Heart Hospital, ⁴Department of Neurology, Seoul National University Hospital, ⁵Department of Neurology, Medical University of Innsbruck, ⁶Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, ⁷University San Raffaele Roma and Institute for Research and Medical Care IRCCS San Raffaele, ⁸BIAL – Portela & Ca S.A., ⁹Amneal Pharmaceuticals, ¹⁰Clinical Investigation Centre CIC1436 Departments of Neurosciences and Clinical Pharmacology, Centre of Excellence for Neurodegeneration COEN NeuroToul, and NS-Park/FCRIN network; University of Toulouse 3, University Hospital of Toulouse, INSERM

Objective:

The Korean and European ADOPTION studies aimed to explore the efficacy of opicapone (OPC) 50 mg versus an additional 100 mg levodopa dose to treat early wearing-off in patients with Parkinson’s disease (PD).

Background:

OPC 50 mg was efficacious in treating end-of-dose motor fluctuations in levodopa/dopa decarboxylase inhibitor (DDCi)-treated patients with PD and motor fluctuations in two large pivotal clinical trials.

Design/Methods:

Patient-level data from matching treatment arms in the two ADOPTION studies were combined. Trials had similar designs, eligibility criteria and methods. Both were prospective, multicentre, randomised, active-controlled, 4-week studies that recruited patients on stable regimen of immediate-release levodopa/DDCi (3–4 daily intakes, maximum 600 mg of levodopa, for ≥4 weeks pre-screening). Patients with an average daily OFF-time >5 hours while awake were excluded. Primary endpoint was change from baseline in absolute OFF-time. Secondary endpoints included tolerability, Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS), 8-item PD Questionnaire (PDQ-8), Clinical Global Impression of Improvement (CGI-I) and Patient Global Impression of Change (PGI-C).

Results:

At week 4, mean (standard error [SE]) change from baseline in absolute OFF-time was -68.1 min (7.8) for OPC 50 mg and -33.6 min (9.7) for levodopa 100 mg, resulting in a significant difference of -34.6 min (p=0.0056). The Korean study showed that a daytime reduction in OFF-time was consistently observed at all hours in the OPC 50 mg group but was less consistent with the addition of L-dopa 100 mg. Numerically greater differences in favour of OPC were observed for MDS-UPDRS-III and IV, and PDQ-8. OPC-treated patients tended to show greater improvements on CGI-I and PGI-C. OPC was generally well-tolerated.

Conclusions:

OPC 50 mg was superior to an increased daily levodopa dose in reducing wearing-off, suggesting that adding OPC may also be considered as first-line therapeutic option in PD patients with early/less severe motor fluctuations.