The effect of multiple doses of ubrogepant on the pharmacokinetics of an oral contraceptive in healthy women: Results of an open-label, single-center, two-period, fixed-sequence study

Abstract

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist for acute treatment of migraine. This study evaluated potential drug–drug interactions between ubrogepant and an oral contraceptive containing ethinyl estradiol (EE) and norgestimate (NGM). Methods: This open-label, single-center, two-period, fixed-sequence study enrolled healthy, postmenopausal or oophorectomized, adult women. In period 1, participants received a single oral dose of EE 0.035 mg/NGM 0.25 mg (EE-NGM) followed by a 7-day washout. In period 2, participants received oral ubrogepant 50 mg daily on days 1–14; single-dose EE-NGM was coadministered with ubrogepant on day 10. Pharmacokinetic parameters for plasma EE and norelgestromin (NGMN) were compared with and without ubrogepant. Results: Twenty-two participants aged 46–66 years were enrolled; 21 completed the study. Geometric mean ratios and 90% confidence intervals for the comparison of EE-NGM + ubrogepant to EE-NGM alone were contained within 0.80 and 1.25 for area under the plasma drug concentration–time curve (AUC) from time zero to infinity (AUC0–∞; 0.96 [0.91, 1.01]) and C max (0.91 [0.82, 1.004]) of NGMN and AUC0–∞ (0.97 [0.93, 1.01]) of EE, but not C max of EE (0.74 [0.69, 0.79]). Median t max of EE was delayed following EE-NGM + ubrogepant (3.0 h) versus EE-NGM alone (median of 1.5 h), whereas median t max of NGMN was unchanged (1.5 h). Geometric mean apparent terminal half-life (t ½) was similar with and without ubrogepant for EE (23 vs. 21 h) and NGMN (36 h both conditions). All ubrogepant-related adverse events were mild or moderate. Conclusion: Ubrogepant did not demonstrate potential for clinically meaningful drug–drug interactions with an EE-NGM oral contraceptive. Trial registration: Not applicable (phase 1 trial)