Effects of Ensitrelvir on the Pharmacokinetics of Combined Oral Contraceptives (Ethinyl Estradiol/Drospirenone) in Healthy Adult Women: A Phase 1 Fixed-Sequence, Multiple-Dose, Drug–Drug Interaction Study

BACKGROUND AND OBJECTIVE: Ensitrelvir has shown cytochrome P450 3A (CYP3A) inhibitory/induction potential in in vitro studies. This open-label, fixed-sequence Phase 1 study evaluated potential drug-drug interactions between ensitrelvir and a combined oral contraceptive (COC) containing ethinyl estradiol (EE) and drospirenone in healthy women of childbearing age. METHODS: ) assessed using noncompartmental methods. Treatment-emergent adverse events (TEAEs) were recorded for safety assessments. RESULTS: was higher on day 24 versus day 20 and comparable with that reported previously. Treatment-emergent adverse events occurred in 58.3% of participants, none of which were severe, serious, or led to treatment discontinuation. CONCLUSION: Ensitrelvir has no clinically meaningful effect on the pharmacokinetics of EE and drospirenone, and the combination was well tolerated. These findings support the co-administration of ensitrelvir with COCs in clinical practice. TRIAL REGISTRATION: NCT06775730.