Abstract
Objective
Afatinib is an oral, irreversible ErbB family blocker. It binds covalently to the kinase domains of epidermal growth factor (EGFR), HER2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation. Our trial compared the bioequivalence and safety between afatinib produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Giotrif® produced by Boehringer Ingelheim.
Methods
Healthy Chinese subjects (N = 36) were randomly divided into two groups at a ratio of 1:1. There was a single dose per period of afatinib and Giotrif®. The washout was set as 14 days. Plasma drug concentrations of afatinib and Giotrif® were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial.
Results
The geometric mean ratios (GMRs) of Cmax, AUC0−t, and AUC0−∞ for afatinib and Giotrif® were 102.80%, 101.83%, and 101.58%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both drugs showed a good safety profile during the trial.
Conclusion
This study showed that afatinib was bioequivalent to Giotrif® in healthy Chinese subjects with well safety.
Chinese Clinical trial registry
This trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20171160).
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Date availability statement
We confirm that the figures and tables in the manuscript are original and not previously published. Data supporting the findings of this study may be obtained from the corresponding author upon reasonable request but remain subject to all applicable legal requirements to protect the confidentiality of the study participants’ personal information.
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Acknowledgements
Chia Tai Tianqing Pharmaceutical Group Co., Ltd. provided the drugs (afatinib and Giotrif®). Thanks to all enrolled participants, investigators, and people who contributed to this study.
Funding
This work was supported by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd, Nanjing, China. Funding number: phase I 2017-041. The founder helps pay for this study and has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Contributions
GL and HY were involved in the conception and design of the trial. JX, YW, ZL, XL, XQ, ZQ, LS, MC, YW, XC, JY, DQ, LL and LZ, performed the research. YZ led the draft of the manuscript and participated in some statistics. QD, ZS and KX drafted the manuscript, figures and participated in some statistics. HY finally approved of the version. All authors agreed to be accountable for all aspects of the work.
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Conflict of interest
All data related to this study were interpreted by the trial staff with complete independence from the sponsor. Jinling Xue and Li Xue are employees of Chia Tai Tianqing Pharmaceutical Group Co.,Ltd; Guangwen Liu, Yanli Wang, Zhengzhi Liu, Xinyao Qu, Zhaojing Qu, Linlin Sun, Mingming Cao, Ying Wang, Lixiu, Zhang, Haimiao Yang are employees of Affiliated Hospital of Changchun University of Chinese Medicine. Qiaohuan Deng, Zhengjie Su and Kaibo Xu are graduate students of Affiliated Hospital of Changchun University of Chinese Medicine. Xuesong Chen, Jing Yu, Dongmei Qu, Lang Liu are employees of Ansiterui Medical Technology Consulting Co.,Ltd. Jilin, China. Yicheng Zhao is an employee of Puheng Technology Co., Ltd. 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.
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Liu, G., Xue, J., Wang, Y. et al. A randomized, open-label, two-cycle, two-crossover phase I clinical trial comparing the bioequivalence and safety of afatinib and Giotrif® in healthy Chinese subjects. J Cancer Res Clin Oncol 149, 2585–2593 (2023). https://doi.org/10.1007/s00432-022-04148-1
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DOI: https://doi.org/10.1007/s00432-022-04148-1