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Abstract Details

Effect of Once-Daily Opicapone on the Pharmacokinetics of Repaglinide
Movement Disorders
P9 - Poster Session 9 (12:00 PM-1:00 PM)
3-004
To evaluate the effect of once-daily opicapone 50 mg on the pharmacokinetics (PK) of repaglinide.

Opicapone is a catechol-O-methyltransferase (COMT) inhibitor approved in Europe and under US FDA review as an adjunct to carbidopa/levodopa for Parkinson’s disease patients experiencing OFF episodes. In vitro studies suggested a potential for opicapone and its primary circulating inactive metabolite, BIA 9-1103, to inhibit cytochrome P450 (CYP) 2C8 metabolism and organic anion transporting polypeptide (OATP) 1B1 transport. Repaglinide is a substrate of both CYP2C8 and OATP1B1.
Healthy men and women were enrolled in an open-label, single-sequence crossover study. Subjects received a single dose of 0.5 mg repaglinide on Days 1 and 15 and once-daily opicapone 50 mg on Days 2 through 15. Doses were administered following an overnight fast for at least 8 hours. Blood samples for determination of repaglinide plasma PK were collected at intervals up to 24 hours post-dose on Days 1 and 15. Plasma repaglinide concentrations were determined using a validated bioanalytical method. PK parameters were determined using noncompartmental methods. The 90% confidence intervals (CIs) about the geometric mean ratios (GMRs) of Cmax, AUC0-tlast, and AUC0-inf for repaglinide administered with opicapone versus repaglinide administered alone were determined. Safety was analyzed descriptively for subjects who received ≥1 dose of study drug.
All 18 enrolled subjects were included in the safety analysis and 17 were included in the PK analysis. Mean plasma repaglinide concentration-time profiles were similar when administered alone or during a once-daily opicapone regimen. GMRs (CI) of repaglinide Cmax, AUC0-tlast, and AUC0-inf were 0.93 (0.82-1.05), 0.97 (0.90-1.05), and 1.00 (0.93-1.08), respectively. Opicapone and repaglinide were generally well tolerated.
Once-daily administration with opicapone 50 mg did not affect the PK of repaglinide, a CYP2C8 and OATP1B1 substrate. Opicapone would not be expected to affect the PK of other CYP2C8 or OATP1B1 substrates.
Authors/Disclosures

PRESENTER 		No disclosure on file
Grace L. Liang, MD Dr. Liang has received personal compensation for serving as an employee of Neurocrine Biosciences. Dr. Liang has stock in Neurocrine Biosciences.
No disclosure on file
Kurt Olson Kurt Olson has received personal compensation for serving as an employee of Neurocrine Biosciences Inc. Kurt Olson has stock in Neurocrine Biosciences Inc.
No disclosure on file
No disclosure on file