Absence of Clinically Significant Drug Interactions With Coadministration of Ubrogepant and an Ethinyl Estradiol/Norgestimate Oral Contraceptive in Healthy Female Subjects: A Phase 1 Pharmacokinetic Analysis (P1.10-018)

Objective: To assess the drug-interaction potential of ubrogepant and the commonly used oral contraceptive, Ortho-Cyclen® (ethinyl estradiol [EE]/norgestimate [NGM]). Background: Migraine incidence is higher among females than males and peaks during reproductive years, when contraceptive medication use is common. Ubrogepant, a novel, oral calcitonin gene–related peptide receptor antagonist in development for acute treatment of migraine attacks, is thus likely to be used by women taking oral contraceptives. Design/Methods: This phase 1, open-label, single-center, 2-period, fixed-sequence study examined the effect of multiple-dose ubrogepant (50 mg) on single-dose PK of a monophasic, combination oral contraceptive (EE 0.035 mg/NGM 0.25 mg) in healthy postmenopausal or oophorectomized adult females. In period 1, subjects received a single oral dose of EE/NGM followed by a 7-day washout. In period 2, they received oral ubrogepant once daily on days 1–14; an oral dose of EE/NGM was coadministered with ubrogepant on day 10. Plasma PK parameters included AUC0–inf and Cmax of EE and norelgestromin (NGMN), a major pharmacologically active metabolite of NGM (with/without ubrogepant). Lack of effect of ubrogepant on EE/NGM PK values was confirmed if all 90% CIs for the geometric mean ratios (GMRs) were within (0.80, 1.25). Safety and tolerability were assessed. Results: Of 22 subjects aged 44–66 years, 1 discontinued due to mild vomiting related to ubrogepant. 90% CIs for the GMRs were within (0.80, 1.25) for the AUC0–inf and Cmax of NGMN and the AUC0–inf of EE, but not the Cmax of EE (0.74 [0.69, 0.79]). Most (18/21) drug-related adverse events were related to ubrogepant and were mild. Conclusions: Coadministration of multiple doses of ubrogepant and a single dose of EE/NGM did not substantially alter NGMN PK. The reduction in plasma Cmax of EE (~26%) is unlikely to be clinically meaningful. Coadministration of ubrogepant and EE/NGM was safe and generally well tolerated. Disclosure: Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck \u0026 Co, Inc. Dr. Palcza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Sharp \u0026 Dohme Corp., a subsidiary of Merck \u0026 Co., Inc. Dr. Xu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck \u0026 Co., Inc. Dr. Xu holds stock and/or stock options in Merck \u0026 Co., Inc. Dr. Thornton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Sharp \u0026 Dohme Corp., a subsidiary of Merck \u0026 Co. Inc. Dr. Thornton holds stock and/or stock options in Merck Sharp \u0026 Dohme Corp. a subsidiary of Merck \u0026 Co., Inc. Dr. Ankrom has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck \u0026 Co, Inc.. Dr. Ankrom holds stock and/or stock options in Merck \u0026 Co, Inc., which sponsored research in which Dr. Ankrom was involved as an investigator. Dr. Jakate has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Jakate holds stock and/or stock options in Allergan plc. Dr. Marcantonio has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck \u0026 Co., Inc. Dr. Marcantonio holds stock and/or stock options in Merck.