NNRTI MK-8507 does not alter the pharmacokinetics of the combined oral contraceptive levonorgestrel/ethinyl estradiol


BACKGROUND: Every week, ~5500 young women aged 15'24 years become infected with HIV worldwide. Hormonal contraceptives are widely used and highly effective in this population, but many antiretrovirals (ARV) have clinically meaningful drug-drug interactions (DDI) with hormonal contraceptives. MK-8507 is a highly potent oral non-nucleoside reverse transcriptase inhibitor in development for once weekly (QW) administration for treatment of HIV-1 infection. MK-8507 does not inhibit or induce major CYP enzymes and is not expected to alter the pharmacokinetics (PK) of hormonal contraceptives. This clinical study evaluated the DDI of multiple dose MK-8507 with the combination oral contraceptive levonorgestrel (LNG)/ethinyl estradiol (EE).
METHODS: An open-label, 2-period, fixed-sequence DDI study in healthy postmenopausal or oopherectomized females was conducted. In Period 1, a single dose of LNG 0.1 mg/EE 0.02 mg was given followed by a 5-day washout. In Period 2, MK-8507 400 mg was administered once weekly for 3 weeks; a single dose of LNG 0.1 mg/EE 0.02 mg was given concomitantly with the 3rd dose of MK-8507. PK samples were collected for evaluation of LNG, EE, and MK-8507.
RESULTS: Twenty participants aged 47-66 were enrolled; 18 completed. The PK of EE and LNG were not meaningfully altered by co-administration with MK-8507. The geometric mean ratios (GMRs) (90% confidence intervals (CIs)) for LNG AUC0-inf and Cmax of LNG/EE given with MK-8507 compared to LNG/EE alone were 0.88 (0.84, 0.93) and 0.74 (0.66, 0.83), respectively; for EE the GMRs (90% CI) for AUC0-inf and Cmax were 0.85 (0.82, 0.90) and 0.80 (0.74, 0.85), respectively. Co-administration of all three drugs was generally well tolerated.
CONCLUSIONS: The results of this study support use of hormonal contraceptives in people living with HIV receiving MK-8507.