Effect of gender and age on the relative bioavailability of doravirine: results of a Phase I trial in healthy subjects.

BACKGROUND: Doravirine is a potent, once-daily, non-nucleoside reverse transcriptase inhibitor with a distinct resistance profile in Phase III development for the treatment of HIV-1. As doravirine may be administered to women and the elderly, we investigated the effect of gender and age in doravirine pharmacokinetics.
METHODS: In this Phase I, open-label, single-period, parallel-group investigation, doravirine 100 mg was administered to 36 healthy subjects in three groups: elderly men (n=12, 65-80 years), elderly women (n=12, 65-80 years) and young women (n=12, 18-50 years). Data for young men (n=6, 18-50 years) from a previous study were included as a comparator. Doravirine plasma pharmacokinetics and safety were assessed.
RESULTS: No clinically meaningful effect on pharmacokinetics was observed in association with gender or age. Gender effects were assessed using combined data from elderly and young men versus elderly and young women because the datasets met predefined pooling criteria. The geometric mean ratios (GMRs; women/men [90% CIs]) of doravirine AUC0-∞, Cmax and C24h were 1.20 (1.03, 1.40), 1.42 (1.23, 1.64) and 1.02 (0.84, 1.24), respectively. Age effects were assessed separately in men and women because the datasets did not meet pooling criteria. The AUC0-∞, Cmax, and C24h GMRs (elderly/young) were 0.85 (0.67, 1.10), 0.92 (0.73, 1.16), 0.81 (0.59, 1.11), respectively for men and 0.97 (0.79, 1.19), 1.18 (0.98, 1.42), 0.94 (0.72, 1.21), respectively, for women. Doravirine was well-tolerated throughout the trial.
CONCLUSIONS: Neither gender nor age affects the bioavailability of single-dose doravirine 100 mg in healthy subjects, thus supporting administration of doravirine 100 mg in elderly and adult women without dose adjustment.