The epsilon (early Parkinson with L-dopa/DDCi and opicapone) study in early Parkinson's disease: Design and rationale of a phase III, double-blind, randomized, placebo-controlled study

Background and aims: Opicapone (OPC) proved to be effective in the treatment of end-of-dose motor fluctuations in Parkinson's disease (PD) patients. When OPC is co-administered with levodopa (L-dopa) and dopa decarboxylase inhibitor (DDCis), peripheral catechol-O-methyltransferase (COMT) is inhibited which increases L-dopa bioavailability. This study aims to explore the potential of OPC to enhance the clinical benefit of L-dopa/DDCi in patients with early-stage PD on stable treatment. Methods: Patients (aged 30–80 years) with idiopathic PD, treated with 3–4 daily oral doses of up to 500 mg L-dopa, with signs of treatable motor disability but no motor complications will be randomized (1:1) to receive OPC 50 mg once-daily or placebo during a 6-month double-blind evaluation period. The L-dopa/DDCi regimen should remain stable throughout the double-blind period. At the end of this period, patients may enter a 1-year, open-label period of OPC 50 mg treatment (Fig. 1);162 patients in each group are necessary to detect a minimum clinically-relevant magnitude of effect between arms. [Formula presented] Results: Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III is the primary endpoint. Secondary endpoints include tolerability, functional motor and non-motor assessments (MDS-UPDRS, Non-Motor Symptoms Scale, Parkinson's Disease Questionnaire-39, Parkinson's Disease Sleep Scale-2), and global impression of change scales (Clinical-Global-Impression-of-Change, Patient-Global-Impression-of-Change). First-patient-in is expected for early 2021 and last-patient-out from double-blind period in late 2022. Timelines might be impacted by the COVID-19 pandemic situation. Conclusions: This study will evaluate the effect of OPC on motor symptoms when given as add-on to stable L-dopa/DDCi therapy in patients with early-stage PD.