Study-design to assess the effect of opicapone on Levodopa PK at different levodopa-optimized treatment regimens

ABSTRACT

Background and aims: Opicapone (OPC), a once-daily (QD) catechol-O-methyltransferase inhibitor, proved effective in the treatment of end-of-dose motor fluctuations in Parkinson's Disease (PD) patients [1,2]. Levodopa (L-DOPA) is considered the gold standard treatment of PD, yet comes with side effects including motor fluctuations and dyskinesia. Therefore, many physicians follow a dopaoptimization strategy. This study was designed to assess the effect of OPC 50mg QD on L-DOPA pharmacokinetics (PK) in different L-DOPA/Carbidopa (LD/CD) treatmentoptimized regimens in patients with end-of-dose motor fluctuations. Methods: 24 medically stable PD patients with a total daily LD/CD dose of 500/125mg [preferred on five administrations per day (Q5)]. From enrolment (V2) up to 14±2 days, a LD/CD-reference treatment of 100/25mg LD/ CD Q5 (500/125mg total daily dose) will be applied. At baseline (V3), patients will be equally randomized to • Q4 LD/CD-regimen of 400/100mg total daily dose plus OPC 50mg • Q5 LD/CD-regimen of 400/100mg total daily dose plus OPC 50mg Patients will maintain the LD/CD regimen for up to 14±2 days (V4). PK assessments for LD/ CD-reference will be performed at V3 and for both LD/ CD+OPC regimens at V4 (Figure 1). Results: Primary endpoint will be PK based. Secondary endpoints include tolerability, functional motor assessments (subject diary charts for ON/OFF periods) and patient Global-Impression-of-Change scale (PGI-C). First-patientin and last-patient-out are expected to 2021. Timelines might be impacted by COVID-19 pandemic situation. Conclusion: This study will evaluate OPC effect on L-DOPA PK in different LD/CD treatment-optimized regimens in patients with end-of-dose motor fluctuations. (Figure Presented).