Abstract Details

Title Absence of Clinically Significant Drug Interactions With Coadministration of Atogepant and an Ethinyl Estradiol/Levonorgestrel 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 13-019

Objective To assess the drug-interaction potential of atogepant and the combination oral contraceptive, Nordette^®-28 (ethinyl estradiol [EE]/levonorgestrel [LNG]).

Background The incidence of migraine is higher among females than males and peaks during reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene?related peptide receptor in development for preventing migraine, 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 atogepant (60 mg) on single-dose PK of EE 0.03 mg/LNG 0.15 mg in healthy postmenopausal or oophorectomized adult females. In period 1, subjects received a single dose of EE/LNG followed by a 7-day washout. In period 2, they received atogepant once daily on days 1-17; an oral dose of EE/LNG was coadministered with atogepant on day 14. Plasma PK parameters included AUC_0-inf and C_max of EE and LNG calculated as geometric mean ratios (GMRs; with/without atogepant). Lack of an effect of atogepant on EE/LNG PK values was confirmed if all GMR 90% CIs were within (0.80, 1.25). Safety and tolerability were assessed.

Results Of 26 subjects aged 45-64 years, 1 discontinued due to moderate pneumonia and ligament sprain unrelated to study drugs; 2 discontinued for personal reasons. The 90% CIs for the GMRs were within (0.80, 1.25) for the AUC_0-inf and C_max of EE and the C_max of LNG, but not the AUC_0-inf of LNG (GMR: 1.19; 90% CI: 1.13, 1.26). Adverse events were mild to moderate and resolved by study end.

Conclusions Coadministration of multiple doses of atogepant and a single dose of EE/LNG did not substantially alter the PK of EE; the ~19% increase in plasma AUC_0-inf of LNG is not anticipated to be clinically significant. Coadministration of atogepant and EE/LNG 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
	No disclosure on file
Kwan-hong C. Min, MD, PhD (Neurologic Insight LLC)	No disclosure on file

��ɫ��

��ɫ��