Background: Rimegepant is an oral, small molecule calcitonin gene-related peptide receptor antagonist for acute treatment of migraine and migraine prevention.
Methods: This was a single-site, placebo-controlled, sequential, single and multiple ascending dose study in healthy males and females, aged 18-55 years, with no clinically significant medical history. The objectives were to assess the safety, tolerability, and pharmacokinetics of the oral capsule free-base formulation. Single oral doses of rimegepant from 25-1500 mg were evaluated in the single ascending dose phase, and 75-600 mg/day doses administered for 14 days were evaluated in the multiple ascending dose phase.
Results: No dose-related trends were observed in orthostatic systolic and diastolic blood pressure or heart rate after rimegepant administration. Rimegepant was rapidly absorbed with the median time of maximum observed plasma concentration from 1-3.5 hours. Rimegepant showed a more than dose-proportional increase in exposure from 25-1500 mg following a single dose and from 75-600 mg/day following multiple doses.
Conclusions: Rimegepant was safe and generally well tolerated at single oral doses up to 1500 mg and multiple doses up to 600 mg/day for 14 days in healthy participants in this study. Median terminal half-life ranged from 8-12 hours across the wide range of single doses studied.
Keywords: Migraine; calcitonin gene-related peptide; gepants; pharmacokinetics.