Abstract
BACKGROUND AND OBJECTIVE: Multidrug-resistant tuberculosis remains a major global health challenge, and bedaquiline has become an essential drug for its treatment. However, the high cost of the originator product Sirturo(®) limits accessibility, underscoring the need for affordable generic drugs supported by bioequivalence studies. The aim of this study was to evaluate the bioequivalence of bedaquiline fumarate tablets manufactured by Zhejiang Haizheng Pharmaceutical Co., Ltd. with the reference product Sirturo(®) under fasting and postprandial conditions in healthy Chinese subjects and to assess their pharmacokinetic profile and safety to support generic drug registration in China. METHODS: This study comprised a single-dose, open-label, randomized, crossover trial that was independently conducted under two conditions: fasting and postprandial. All subjects were randomized to receive the single-dose subject formulation and the reference formulation in two separate cycles. Plasma samples were collected at multiple timepoints after dosing and bedaquiline concentrations were determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Key pharmacokinetic parameters including maximum plasma concentration and area under the plasma concentration-time curve from time 0 to 72 h were calculated using a non-atrial model and bioequivalence was assessed using analysis of variance and 90% confidence intervals. RESULTS: A total of 40 cases were included in the fasting group and 50 healthy subjects in the postprandial group. The geometric mean ratio of the single-dose subject formulation to the reference formulation within both groups fell within the 80.00-125.00% bioequivalence range for the 90% confidence interval of maximum plasma concentration to area under the plasma concentration-time curve from time 0 to 72 h. Overall drug exposure levels (area under the plasma concentration-time curve) were higher in the postprandial state than in the fasting state, but the subject formulation remained consistent with the reference formulation. All subjects completed the study and no serious adverse events were observed. CONCLUSIONS: Bedaquiline fumarate tablets of Zhejiang Haizheng Pharmaceutical Co., Ltd. showed good bioequivalence and tolerability with Sirturo(®) under fasting and postprandial conditions, which supports its use as a generic drug in the treatment of multidrug-resistant tuberculosis. CLINICAL TRIAL REGISTRATION: ChiCTR2500105414.