A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

Abstract

Doravirine is a novel non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus type 1 infection. Because of potential concomitant administration with acid‐reducing agents, a drug‐interaction trial was conducted to evaluate the potential impact of these types of medications on doravirine pharmacokinetics. In an open‐label, 3‐period, fixed‐sequence trial, healthy adult participants received the following: period 1, a single dose of doravirine 100 mg; period 2, coadministration of a single dose of doravirine 100 mg and an antacid (1600 mg aluminum hydroxide, 1600 mg magnesium hydroxide, and 160 mg simethicone); period 3, 40 mg pantoprazole once daily on days 1–5 coadministered with a single dose of doravirine 100 mg on day 5. There was a minimum 10‐day washout between periods. Plasma samples for pharmacokinetic evaluation were collected, and safety was assessed. Fourteen participants (8 male, 6 female) were enrolled, and 13 completed the trial. Geometric mean ratios (90% confidence intervals) for doravirine AUC_0‐inf, C_max, and C₂₄ for doravirine + antacid/doravirine were 1.01 (0.92–1.11), 0.86 (0.74–1.01), and 1.03 (0.94–1.12), respectively, and for doravirine + pantoprazole/doravirine were 0.83 (0.76–0.91), 0.88 (0.76–1.01), and 0.84 (0.77–0.92), respectively. Doravirine was generally well tolerated administered alone or with either of the acid‐reducing agents. Coadministration of an aluminum/magnesium‐containing antacid or pantoprazole did not have a clinically meaningful effect on doravirine pharmacokinetics, supporting the use of acid‐reducing agents with doravirine.