Adjunctive opicapone helps prolong plasma levodopa levels in patients with Parkinson’s
Key takeaways:
- Once-daily opicapone 50 mg with carbidopa/levodopa helped achieve and maintain plasma concentrations of levodopa in patients with PD.
- Maximum COMT inhibition was nearly 85% at day 14.
Adding once-daily opicapone 50 mg to carbidopa/levodopa therapy helped achieve and maintain plasma concentrations of levodopa in patients with Parkinson’s disease, according to research in Clinical Neuropharmacology.
“The findings presented in this study address a major unmet need in the treatment of PD and more consistent delivery of [levodopa] to the brain, which continues to be a challenge for optimizing treatment of PD,” Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences, told Healio in an email.
Researchers from Neurocrine Biosciences and other academic and research institutions sought to evaluate the pharmacokinetics and pharmacodynamics of once-daily opicapone 50 mg — a catechol-O-methyltransferase (COMT) inhibitor — as adjunctive therapy to carbidopa/levodopa (CD/LD) in patients with stable Parkinson’s disease.
They conducted an open-label, phase 1 study at three U.S. sites and included 16 adults aged 18 to 85 years (mean age, 64.3 years; 62.5% men) with PD and improvement of PD motor symptoms from LD treatment. Participants were randomly assigned to receive CD/LD (25/100 mg) every 3 hours or 4 hours on days 1, 2 and 15; they continued their usual CD/LD regimen from days 3 to 14. Participants also started 50 mg opicapone in the evenings of days 1 to 14.
Researchers collected serial blood samples to determine plasma opicapone, LD and 3-O-methyldopa (3-OMD) concentrations and erythrocyte soluble COMT activity.
At day 14, peak plasma concentration for opicapone and area under the curve (AUC)-time curve were 459 ng/mL and 2,022 ng/mL per hour, respectively. Researchers also reported maximum COMT inhibition was 83.4% of baseline on day 14.
Further, total AUC increased from day 1 to day 15 with every 3-hour dosing (from 7,339 to 11,714 ng/mL per hour) and every 4-hour dosing (from 7,570 to 13,159 ng/mL per hour) after 14 days of opicapone. Opicapone also decreased 3-OMD peak and trough concentrations as well as overall 3-OMD exposure, researchers wrote.
“Enhanced COMT inhibition has been shown to be a promising approach to improve symptomatic control of motor fluctuations in patients with PD,” Roberts told Healio. “This pharmacokinetics data show that COMT inhibition with once-daily opicapone 50 mg plus LD resulted in a greater increase of trough LD concentrations than peak LD concentrations, which resulted in a decreased peak-to-trough fluctuation index for LD.”
Roberts continued: “With these results, patients may achieve and maintain enhanced plasma concentrations of LD for a longer duration than patients receiving immediate-release CD/LD alone.”