A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.

Abstract

Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. People living with HIV-1 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single-dose islatravir on steady-state methadone pharmacokinetics. A nonrandomized, open-label study (NCT04568603) was conducted and included adult participants receiving methadone therapy. Participants received their standard methadone therapy and a single oral dose of islatravir 60 mg concomitantly. Blood samples were collected to determine methadone and islatravir pharmacokinetics. Fourteen participants aged 26-63 years were enrolled; 13 completed the study. The geometric mean ratios for methadone area under the concentration-time curve from time 0 to 24 hours (AUC_0-24), maximum plasma concentration (C_max), and concentration at 24 hours (C₂₄) were 1.03, 1.01, and 1.07, respectively. Similar effects were seen for the R- and S-enantiomer of methadone (R-methadone: AUC_0-24, 1.03; C_max, 1.02; and C₂₄, 1.06; S-methadone: AUC_0-24, 1.03; C_max, 1.01; and C₂₄, 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC_0-inf and C_max were 1.18 and 0.86, respectively. Coadministration of a single dose of islatravir and methadone was generally well tolerated. Single-dose islatravir did not affect steady-state methadone pharmacokinetics in a clinically meaningful way.