Open-label Phase 1 study to evaluate drug-drug interactions between ulonivirine and islatravir in adults without HIV.
Jesse C Nussbaum, Michelle M Pham, Ryan Vargo et al.
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In 30 seconds
This open-label, three-period Phase 1 study assessed pharmacokinetic interactions between ulonivirine and islatravir in 36 adults without HIV. Plasma exposure to both drugs was similar when administered together and separately: geometric mean ratios for the reported pharmacokinetic measures were within the standard bioequivalence bounds of 0.8-1.25. Intracellular islatravir-triphosphate measures were approximately 10%-21% lower with coadministration, potentially reflecting variability in peripheral blood mononuclear cell counts. Safety measures were comparable across study periods. The authors concluded that the combination showed no clinically meaningful drug-drug interaction.
Key findings
- For both drugs, coadministration-to-single-administration geometric mean ratios for reported plasma pharmacokinetic measures were within 0.8-1.25.
- Intracellular islatravir-triphosphate AUC 0-168 was approximately 21% lower with ulonivirine; AUC 0-inf, C max, and C 168 were approximately 15%, 16%, and 10% lower, respectively.
- Adverse events, laboratory results, and other safety parameters were comparable across the three study periods.
Why it matters
Drug interactions can affect exposure and tolerability when antiretroviral agents are combined. These findings provide early clinical pharmacology evidence that ulonivirine and islatravir can be coadministered without a clinically meaningful change in plasma exposure, while identifying modest reductions in intracellular islatravir-triphosphate measures for further consideration during development.
What to keep in mind
This was a Phase 1 study in adults without HIV, so it does not establish efficacy or safety of the combination in people receiving treatment for HIV.