Abstract Details

Title 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

Topic Headache

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-018

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 AUC_0-inf and C_max 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 AUC_0-inf and C_max of NGMN and the AUC_0-inf of EE, but not the C_max 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 C_max of EE (~26%) is unlikely to be clinically meaningful. Coadministration of ubrogepant and EE/NGM was safe and generally well tolerated.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Abhijeet Jakate, PhD (Allergan Plc)	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��