Effects of rimegepant 75 mg daily on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate in healthy female participants

Abstract

Objective To 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. Background Females 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. Methods This 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]). Results The 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,ss and Css(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. Conclusions The 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.

The Pharmacokinetics, Safety, and Tolerability of Rimegepant 75 mg Are Similar in Elderly and Nonelderly Adults: A Phase 1, Open‐Label, Parallel‐Group, Single‐Dose Study

“…The key findings from this study included the following: rimegepant exposure (AUC) was approximately 5% higher in elderly participants than in nonelderly subjects, which was accompanied by a 5% decrease in C max for the elderly group; mean elimination (t 1/2el ) of rimegepant was somewhat longer in the elderly compared with nonelderly participants (15 vs 10 hours, respectively), although overall exposures were similar; and a single oral 75‐mg dose of rimegepant was safe and well tolerated in all participants, regardless of age. The overall results of this study for both elderly and nonelderly adults are generally consistent with prior pharmacokinetic data reported for rimegepant 21,23‐25,27,39 …”