Bioequivalence evaluation of two formulations of tenofovir alafenamide tablets in healthy subjects under fasting and fed conditions

Abstract

Purpose: To evaluate the bioequivalence and safety of two formulations of 25 mg tenofovir alafenamide tablets in Chinese healthy male and female subjects under fed and fasting conditions. Patients and Methods: This was a randomized, open-label, single-center, crossover study consisting of a fasting trial with two periods and a fed trial with four periods. In total, 42 healthy subjects were enrolled in the fasting trial and 32 healthy subjects were enrolled in the fed trial. In each period, blood samples for pharmacokinetic analysis were collected until 72 hours post-dose. The plasma concentrations of tenofovir alafenamide and tenofovir were measured and noncompartmental analysis was used to determine pharmacokinetic para-meters. Throughout the entire study, subjects’ safety was monitored by assessment of physical examinations, vital signs, 12-lead electrocardiography, clinical laboratory para-meters, and treatment emergent adverse events (TEAEs). Results: Forty subjects completed the fasting trial and 32 subjects completed the fed trial. The 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t, AUC0-∞, and Cmax for the two formulations were within 80.00% to 125.00%, which met the bioequiva-lence acceptance criteria. The study drugs were well tolerated by all subjects. Conclusion: This study demonstrated that the test formulation of 25 mg tenofovir alafena-mide tablets was bioequivalent to the formulation marketed under the brand name VEMLIDY® in healthy Chinese male and female subjects under fasting and fed conditions.