Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects

ABSTRACT

Background

Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.

Research design & methods

We designed a clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug.

Results

32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of C_max, AUC_0-t, and AUC_0-∞ met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards.

Conclusion

The results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile.

Clinical trial registration

This trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708)

KEYWORDS:

• Bioequivalence
• chronic myeloid leukemia
• dasatinib
• pharmacokinetics
• safety

Acknowledgments

Thanks to all enrolled participants, investigators, and people who contributed to this study.

Declaration of interest

All data related to this study were interpreted by the trial staff with complete independence from the sponsor. Yanli Wang, Yingzi Cui, Guangwen Liu, Wei Yang, Zhengzhi Liu, Jiahui Chen, Qing Ren, Shuang Yu, Yang Cheng, Yannan Zhou, Wanhua Wang and Haimiao Yang are employees of Affiliated Hospital to Changchun University of Chinese Medicine; Jinling Xue is an employee of Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Qiaohuan Deng and Zhengjie Su are graduate students of Changchun University of Chinese Medicine; Yicheng Zhao is an employee of Puheng Technology Co., Ltd and Changchun University of Chinese Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest in or financial with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

H Yang and J Xue involved in the conception and designed of the trial. Y Wang, Y Cui, G Liu, W Yang, Z Liu, J Chen, Q Ren, S Yu, Y Cheng, Y Zhou, W Wang, X Chen and D Qu performed the research. Y Zhao lead the draft of the manuscript. Q Deng and Z Su drafted the paper and drew the figures; H Yang finally approved of the version. All authors agreed to be accountable for all aspects of the work.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2023.2179481

Additional information

Funding

This manuscript was funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China. Funding number is phase I 2017-038.