The Effect of Food on Doravirine Bioavailability: Results from Two Pharmacokinetic Studies in Healthy Subjects

Background and Objective Doravirine is a novel non-nucleoside reverse transcriptase inhibitor being developed for the treatment of HIV-1. In two open-label, single-dose, randomized, two-period, crossover trials, the bioavailability of doravirine administered alone or in a fixed-dose combination (FDC) was determined under fed and fasted conditions. Methods Doravirine 100 mg alone or with lamivudine and tenofovir disoproxil fumarate (each 300 mg) were administered to healthy subjects fasted or 30 min after a high-fat, high-calorie breakfast. Twenty-eight subjects, aged 26–55 years, enrolled (doravirine, n = 14; FDC, n = 14). The sequence of fed/fasted treatment was randomized (1:1). Pharmacokinetic data were analyzed as geometric mean ratios (GMRs) with 90% confidence intervals. Results Doravirine area under the plasma concentration–time curve (AUC) from time zero to infinity (fed/fasted GMRs: alone 1.16 [1.06–1.26]; FDC 1.10 [1.02–1.20]), AUC from time zero to the last measurement (GMRs: alone 1.18 [1.08–1.29]; FDC 1.10 [1.01–1.20]), and plasma concentration 24 h after administration (GMRs: alone 1.36 [1.19–1.55]; FDC 1.26 [1.13–1.41]) values increased in the fed versus fasted state when administered alone or as the FDC; the magnitude was not clinically meaningful. Doravirine maximum achieved concentration was similar after fed or fasted administration for both doravirine alone and FDC (GMRs: alone 1.03 [0.89–1.19]; FDC 0.95 [0.80–1.12]). The pharmacokinetics of tenofovir and lamivudine in the FDC were also slightly altered by administration with food; the changes were not clinically meaningful. Conclusions All treatments were generally well tolerated. Food had no clinically meaningful effect on doravirine 100 mg alone or as part of an FDC.