An open-label, Phase 1 study to evaluate the drug-drug interaction between ulonivirine and the combined oral contraceptive levonorgestrel/ethinyl estradiol in female participants without HIV

Abstract

ABSTRACT Ulonivirine is a non-nucleoside reverse transcriptase inhibitor in development as an oral, once-weekly treatment for HIV-1 in combination with investigational islatravir. The effect of ulonivirine on the pharmacokinetics of an oral contraceptive, levonorgestrel (LNG)/ethinyl estradiol (EE) was evaluated in females without HIV. In this Phase 1 study (MK-8507-009), postmenopausal or oophorectomized females received a single dose of LNG/EE (0.1 mg/0.02 mg), followed by a 5-day washout period. Participants then received ulonivirine 400 mg once-weekly for 3 weeks, and LNG/EE was co-administered with the third dose. Blood samples were collected for pharmacokinetics analysis. Safety and tolerability were monitored by clinical and laboratory assessments. Twenty adults (90% White; 100% Hispanic or Latina) were enrolled (median age, 56 years; range, 47–66 years). Two participants discontinued for reasons considered unrelated to ulonivirine. The geometric mean ratios ([LNG/EE + ulonivirine]/[LNG/EE]; 90% CI) for plasma AUC0-inf of LNG and EE were 0.88 (0.84–0.93) and 0.85 (0.82–0.89). Maximum plasma concentration of LNG and EE decreased (26% and 20%, respectively) with LNG/EE + ulonivirine versus LNG/EE alone. Ulonivirine pharmacokinetics were similar for LNG/EE + ulonivirine and LNG/EE alone. Four participants (20%) experienced ≥1 adverse event: 2 (10%) after administration of LNG/EE alone and 2 (10.5%) after co-administration of LNG/EE + ulonivirine. All adverse events were mild and considered unrelated to study intervention. Co-administration of ulonivirine 400 mg once-weekly with a single dose of LNG/EE had no clinically meaningful effect on the pharmacokinetics of LNG or EE in females without HIV and was generally well tolerated.