Open-label Phase 1 study to evaluate drug-drug interactions between ulonivirine and islatravir in adults without HIV

Abstract

ABSTRACT Ulonivirine is a non-nucleoside reverse transcriptase inhibitor in clinical development for once-weekly oral treatment of HIV-1 in combination with islatravir. This open-label, 3-period, Phase 1 study (MK-8507-016, NCT06619678) in adults without HIV evaluated the potential drug-drug interactions (DDIs) between ulonivirine and islatravir. In Period 1, participants received islatravir 2 mg on Day 1. In Period 2, participants received ulonivirine 200 mg on Days 1 and 8. In Period 3, a single dose of islatravir 2 mg was co-administered with ulonivirine 200 mg 7 days after the Day 8 dose in Period 2, followed by four doses of ulonivirine 200 mg once weekly. Thirty-six participants (58% female, 67% White, median age 43 years) were enrolled. Plasma pharmacokinetics of islatravir and ulonivirine were similar with and without coadministration. The 90% CIs for geometric mean ratios of co-administration versus single administration of islatravir (AUC0-168, 1.06 [1.02–1.09]; C168, 1.05 [0.98–1.12]; Cmax, 1.10 [1.02–1.19]) and ulonivirine (AUC0-168, 1.07 [1.05–1.09]; C168, 1.08 [1.04–1.12]; Cmax, 1.03 [0.98–1.07]) were within standard bioequivalence bounds (0.8–1.25). During Period 3 (co-administration with ulonivirine), intracellular ISL-triphosphate AUC0-168, AUC0-inf, Cmax, and C168 were approximately 21%, 15%, 16%, and 10% lower, respectively, compared with ISL alone. These differences may in part reflect variability in peripheral blood mononuclear cell counts. Adverse events, laboratory test results, and other safety parameters were comparable among all three periods. In conclusion, no clinically meaningful DDIs were observed between ulonivirine 200 mg and islatravir 2 mg, supporting continued development of this combination for HIV-1 treatment.