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

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 6; pp. 2585 - 2593
• Main Authors: Liu, Guangwen, Xue, Jinling, Wang, Yanli, Liu, Zhengzhi, Li, Xue, Qu, Dongmei, Su, Zhengjie, Xu, Kaibo, Qu, Xinyao, Qu, Zhaojuan, Sun, Linlin, Cao, Mingming, Wang, Ying, Chen, Xuesong, Yu, Jing, Liu, Lang, Deng, Qiaohuan, Zhao, Yicheng, Zhang, Lixiu, Yang, Haimiao
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2023; Springer Nature B.V
• Subjects: Afatinib - adverse effects; Afatinib - pharmacology; Area Under Curve; Bioequivalence; Cancer Research; chemical bonding; China; Chromatography, Liquid; Clinical trials; CTR; CTR20171160; drugs; East Asian People; epidermal growth factor; Epidermal growth factor receptors; ErbB protein; ErbB-2 protein; Hematology; Humans; Internal Medicine; Liquid chromatography; Mass spectroscopy; Medicine; Medicine & Public Health; Oncology; Pharmacokinetics; protein phosphorylation; Protein-tyrosine kinase; Safety; Salvia hispanica; Statistical analysis; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency; tyrosine; China; Generic drug; Epidermal growth factor; Afatinib; Bioequivalence; Lung cancer
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-022-04148-1

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 C max , AUC 0−t , and AUC 0−∞ 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).