Objective: To assess the effects of opicapone 50 mg on the pharmacokinetics (PK) of levodopa (LD) and its metabolite, 3-O-methyldopa (3-OMD), when administered with oral carbidopa/levodopa (CD/LD) extended-release (ER) capsules in healthy individuals.
Background: Opicapone, an oral long-acting catechol-O-methyltransferase inhibitor, is approved as a once-daily adjunctive treatment to CD/LD in patients with Parkinson’s disease (PD) experiencing OFF-episodes. It has been previously demonstrated that the addition of opicapone to immediate-release CD/LD decreases plasma peak-to-trough fluctuation index, thus providing more consistent exposure to LD in patients with PD. There has been no prior evaluation of opicapone with the CD/LD-ER formulation, a common treatment used in the United States.
Method: 18 healthy subjects (9 male, 9 female) were included in this Phase 1 open-label study. CD/LD-ER 23.75/95 mg was administered as follows: 1 capsule three times a day (TID) on Days 1 and 16; 2 capsules TID on Days 2-3 and Days 17-18 every 7 hours at 07:00, 14:00, and 21:00. Opicapone 50 mg once-daily was administered at 22:00 on Days 4-18. Blood samples for the assessment of LD and 3-OMD plasma concentrations were collected on Days 3-4 (CD/LD-ER without opicapone) and Days 18-19 (CD/LD-ER with opicapone) every 30 minutes from 07:00 to 21:00, and every 2 hours from 23:00 until 09:00 the next morning. Samples for soluble COMT (S-COMT) activity were collected on Day 1 and Day 19.
Results: Administration of once-daily opicapone with CD/LD-ER resulted in increased trough, peak, and overall LD exposure; decreased peak and overall exposure to 3-OMD; and markedly decreased S-COMT activity.
Conclusion: Providing more consistent LD levels through the day is a central treatment strategy for the management of motor fluctuations in PD. Administering once-daily opicapone with CD/LD-ER resulted in increased overall LD exposure, decreased 3-OMD exposure, and reduced S-COMT activity. The effects of OPC on this extended-release formulation of CD/LD may contribute to more consistent LD exposure throughout the day, which continues to be a challenge and goal in treating PD.
To cite this abstract in AMA style:
G. Loewen, A. Vijan, K. Olson, T. O’Reilly, G. Liang, O. Klepitskaya. Effects of Once-Daily Opicapone 50 mg on the Pharmacokinetics of Levodopa Administered as Carbidopa/Levodopa Extended-Release Capsules: An Open-Label Phase 1 Study [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/effects-of-once-daily-opicapone-50-mg-on-the-pharmacokinetics-of-levodopa-administered-as-carbidopa-levodopa-extended-release-capsules-an-open-label-phase-1-study/. Accessed June 16, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-once-daily-opicapone-50-mg-on-the-pharmacokinetics-of-levodopa-administered-as-carbidopa-levodopa-extended-release-capsules-an-open-label-phase-1-study/