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.