Pharmacokinetics and Safety of Single and Multiple Daily Dosing of 75-mg Rimegepant Orally Disintegrating Tablets in Healthy Chinese Adults: A Randomized Placebo-Controlled Trial

Abstract

Rimegepant is an oral small-molecule calcitonin gene-related peptide antagonist for acute migraine treatment with or without aura and prevention of episodic migraine in adults. This was a rimegepant single- and multiple-dose phase 1, randomized, placebo-controlled, double-blind study to evaluate the pharmacokinetics and confirm safety in healthy Chinese participants. Participants received a 75-mg rimegepant orally disintegrating tablet (ODT) (N = 12) or matching placebo (N = 4) ODT on days 1 and 3–7 after fasting for pharmacokinetic assessments. Safety assessments included 12-lead electrocardiograms, vital signs, clinical laboratory data, and adverse events (AEs). After a single dose (9 females, 7 males) median time to maximum plasma concentration was 1.5 hours; mean values were 937 ng/mL (maximum concentration), 4582 h*ng/mL (area under the concentration–time curve, 0 to infinity), 7.7 hours (terminal elimination half-life), and 19.9 L/h (apparent clearance). Similar results were seen after 5 daily doses, with minimal accumulation. Six (37.5%) participants experienced ≥1 treatment-emergent AE: 4 (33.3%) had received rimegepant and 2 (50.0%) had received placebo. All AEs were grade 1 and resolved by the end of the study with no deaths, serious/significant AEs, or AEs leading to discontinuation. Overall, single- and multiple-dose rimegepant ODT 75 mg was safe and well-tolerated in healthy Chinese adults with similar pharmacokinetics to non-Asian healthy participants. Trial registration: This trial is registered with the China Center for Drug Evaluation (CDE): CTR20210569.