Objective: This study aims to evaluate the effect of once-daily opicapone (OPC) 50 mg on the pharmacokinetics (PK) of levodopa (LD) in different LD/carbidopa (LD/CD) dosage regimens in patients with Parkinson’s disease (PD) and motor fluctuations (MF).

Background: LD therapy remains the most effective symptomatic treatment for PD, but its long-term use is associated with the development of MF. Strategies to optimise LD regimen include increasing the total daily dose and/or increasing the number of intakes. The catechol-O-methyltransferase inhibitor OPC proved efficacious for treating end-of-dose MF in two large multinational Phase 3 trials (BIPARK-I and II).

Method: This Phase 2 study enrolled 24 patients with PD receiving baseline total daily LD/CD dose of 500/125 mg [figure1]. During 14±2 days, patients received an LD/CD reference treatment of 100/25 mg five times a day. At baseline, patients were equally randomised to:
– Total daily LD/CD dose of 400/100 mg 4 intakes a day every 4 hours (Q4H) plus OPC 50 mg
– Total daily LD/CD dose of 400/100 mg 5 intakes a day every 3 hours (Q3H) plus OPC 50 mg
Patients maintained their regimens for up to 14±2 days. PK were assessed at Visits 3 (baseline) and 4 (day 14±2).

Results: Compared with the LD/CD 500/125 mg regimen, both OPC-containing regimens showed a ~30% increase in LD exposure. The Q3H plus OPC regimen was also associated with an increase in LD C_min with no significant impact on LD C_max, leading to a ~60–90% decrease in the LD fluctuation (variation between C_max and C_min) [figure2].

Conclusion: These preliminary data show that OPC 50 mg surpasses at least 100 mg LD in terms of LD exposure.

Supported by Bial

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-pharmacokinetics-in-different-levodopa-treatment-regimens-plus-opicapone-in-parkinsons-disease-patients-with-motor-fluctuations/