Bioequivalence Study of Bedaquiline Fumarate Tablets in Healthy Chinese Subjects.

Abstract

Bedaquiline fumarate tablets are a novel oral antimycobacterial drug. This study assessed the bioequivalence of a generic bedaquiline fumarate tablet compared to a reference tablet under fasting (n = 44) and fed (n = 24) conditions. Conducted as a single-center, randomized, open-label, 2-sequence, crossover trial, 68 participants were randomly assigned to receive a 100-mg dose of either the test or reference tablet, with a 42-day washout period between doses. Blood samples were collected at prespecified time points from 0 hour (before administration) to 984 hours after administration. Plasma concentrations of bedaquiline were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Safety was monitored throughout the study. Key pharmacokinetic parameters included maximum plasma concentration, area under the plasma concentration-time curve (AUC) from 0 to 72 hours, AUC from time 0 to the last measurable concentration, AUC from 0 to 336 hours, and AUC from time 0 to infinity. The 90% confidence intervals for the geometric mean ratios of the test/reference formulations for maximum plasma concentration, AUC from 0 to 72 hours, AUC from 0 to 336 hours, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity fell within the bioequivalence acceptance range of 80%-125%. confirming bioequivalence between the 2 formulations in healthy Chinese volunteers. Moreover, a high-fat diet can significantly elevate the exposure of bedaquiline. No serious adverse events occurred, and both formulations were well tolerated across all participants.