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 (AUC0‐24), maximum plasma concentration (Cmax), 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: AUC0‐24, 1.03; Cmax, 1.02; and C24, 1.06; S‐methadone: AUC0‐24, 1.03; Cmax, 1.01; and C24, 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC0‐inf and Cmax 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.