Affiliation:
1. Certara USA Princeton New Jersey USA
2. Navitas Data Sciences Pottstown Pennsylvania USA
3. Biohaven Pharmaceuticals New Haven Connecticut USA
Abstract
AbstractObjectiveTo assess the effect of single and multiple doses of rimegepant 75 mg dose on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol (EE)/norgestimate (NGM) in healthy females of childbearing potential or non‐menopausal females with tubal ligation.BackgroundFemales of childbearing age experience the highest prevalence of migraine and frequently inquire about the concomitant use of anti‐migraine medications and contraceptives. Rimegepant, a calcitonin gene–related peptide receptor antagonist, demonstrated efficacy and safety for treating an acute migraine attack and preventing migraine.MethodsThis open‐label, single‐center, phase 1, drug–drug interaction study explored the effects of rimegepant 75 mg daily dose on the pharmacokinetics of an oral contraceptive containing EE/NGM 0.035 mg/0.25 mg in healthy females of childbearing potential or non‐menopausal females with tubal ligation. During cycles 1 and 2, participants received EE/NGM once daily for 21 days followed by placebo tablets with inactive ingredients for 7 days. Rimegepant was administered during only cycle 2 for 8 days, from days 12 through 19. The primary endpoint was the effect of single and multiple doses of rimegepant on the pharmacokinetics of EE and norelgestromin (NGMN), an active metabolite of NGM, at steady state, including area under the concentration‐time curve for 1 dosing interval (AUC0−τ,ss) and maximum observed concentration (Css[max]).ResultsThe study enrolled 25 participants, with pharmacokinetic data assessed for 20 participants. A single 75 mg dose of rimegepant co‐administered with EE/NGM increased exposures of EE and NGMN by ≤16% (geometric mean ratio [GMR], 1.03; 90% confidence interval [CI], 1.01–1.06; and GMR, 1.16; 90% CI, 1.13–1.20, respectively). After 8 days of co‐administering EE/NGM with rimegepant, EE pharmacokinetic parameters, AUC0−τ,ssandCss(max), increased by 20% (GMR, 1.20; 90% CI, 1.16–1.25) and 34% (GMR, 1.34; 90% CI, 1.23–1.46), respectively, and NGMN pharmacokinetic parameters increased by 46% (GMR, 1.46; 90% CI, 1.39–1.52) and 40% (GMR, 1.40; 90% CI, 1.30–1.51), respectively.ConclusionsThe study identified modest elevations in overall EE and NGMN exposures after multiple doses of rimegepant, but these elevations are unlikely to be clinically relevant in healthy females with migraine.
Subject
Neurology (clinical),Neurology
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献