Bioequivalence Study of Bedaquiline and Sirturo - A Randomized, Open-Label, Single-Dose, Crossover Trial - Bioequivalence Under Fasting and Postprandial Conditions

Sep 28, 2026

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Multidrug-resistant tuberculosis remains a major global health challenge, and bedaquiline is central to treatment, yet access is constrained by the high cost of Sirturo®. This randomized, open-label, single-dose, crossover study compares Zhejiang Haizheng Pharmaceutical bedaquiline fumarate tablets with Sirturo® in healthy Chinese subjects under fasting and postprandial conditions. Pharmacokinetic exposure was evaluated using validated LC–MS/MS assays and 90% confidence intervals to assess bioequivalence. The study also monitored safety and tolerability to support generic registration in China.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Abstract

Background and Objective

Methods

Results

Conclusions

Key Points

Drugs in R&D (2025) 25:321–331 [https://doi.org/10.1007/s40268-025-00525-6](https://doi.org/10.1007/s40268-025-00525-6) Bioequivalence Study of Bedaquiline and Sirturo® in Healthy Chinese Subjects Under Fasting and Postprandial Conditions: A Randomized, Open‑Label, Single‑Dose, Crossover Trial Yixuan Li1 · Yi Wu2 · Shufan Cai2 · Xiangxin Huang2 · Lijun Ye2 · Lin Wang2 · Yingying Zhang1 · Ying Wang2,3,4 · Xuexia Tao2 Received: 8 July 2025 / Accepted: 28 September 2025 / Published online: 31 October 2025 © The Author(s) 2025 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 . 1 Introduction Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global public health challenge and a leading cause of death worldwide [1] . Unregulated or ineffective treatment regimens can lead to the development of drugresistant TB, with multidrug-resistant TB (MDR-TB) posing a particular clinical risk [2] . Bedaquiline, the first Extended author information available on the last page of the article diarylquinoline antimycobacterial drug, was approved by the US Food and Drug Administration (FDA) in 2012, and its clinical application has significantly improved treatment outcomes for patients with MDR-TB [3] . Bedaquiline exerts its bactericidal effect by specifically targeting the proton pump of mycobacterial ATP synthase, binding to the c subunit, thereby interfering with bacterial energy metabolism [4] . It exhibits linear pharmacokinetics after oral administration, with a time to maximum plasma

FAQs

What was the study purpose?

To evaluate the bioequivalence of bedaquiline fumarate tablets from Zhejiang Haizheng Pharmaceutical with Sirturo® under fasting and postprandial conditions, including pharmacokinetics and safety.

How was bioequivalence assessed in the trial?

Plasma samples were collected after single-dose administration in a randomized, open-label crossover design, and key PK parameters (Cmax and AUC0–72h) were analyzed with 90% confidence intervals.

What were the main findings regarding safety and tolerability?

All enrolled subjects completed the study and no serious adverse events were observed, with overall tolerability reported as good.

Sep 28, 2026

Uploaded by Connor