Adoption (early levodopa with opicapone in Parkinson's patients with motor fluctuations) study in Parkinson's disease: Design and rationale of a randomized prospective, open-label exploratory trial

ABSTRACT

Background and aims: Opicapone (OPC) proved to be effective in the treatment of end-of-dose motor fluctuations in Parkinson's disease (PD) patients. About 80–100% of PD patients show some degree of wearing-off within 10 years of levodopa (L-dopa) therapy. Approaches to optimize the L-dopa regimen include increasing the dose or ‘fractionating’ the total daily dose. This study aims to explore the potential of adjunctive OPC versus an additional dose of L-dopa/dopa decarboxylase inhibitor (DDCi) to optimize the L-dopa/DDCi regimen as first-line approach to treat wearing-off. Methods: Approximately 100 patients (aged ≥30 years) with idiopathic PD, treated with 3–4 daily oral L-dopa doses up to 600 mg, and signs of wearing-off (<2 years) will be equally randomized to receive OPC 50 mg once daily or an additional dose of 100 mg/25 mg L-dopa/DDCI during a 4-week open-label evaluation period (Fig. 1). [Formula presented] Results: Primary endpoint is the change from baseline in OFF-time. Secondary endpoints include tolerability, functional motor and non-motor assessments (Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale, MDS-Non-Motor Symptoms, Parkinson's Disease Questionnaire-8), and global impression of change scales (Clinical Global Impression of Change, Patient Global Impression of Change). As this is a descriptive/exploratory study, no formal sample size calculation was performed. Study sites are in Germany, Italy, Portugal, Spain, and the UK. First-patient-in is expected for 2021 and last-patient-out for late 2022. Timelines might be impacted by the COVID-19 situation. Conclusions: This study will evaluate the potential of adjunctive OPC versus an additional dose of L-dopa/DDCi as first-line approach to treat wearing-off in PD patients.