A randomized, open-label, single-dose, two-cycle crossover study to evaluate the bioequivalence and safety of lenvatinib and Lenvima® in Chinese healthy subjects

ABSTRACT

Background

Lenvatinib is a tyrosine kinase receptor inhibitor that inhibits vascular and endothelial growth factor receptor kinase activity. This study evaluated the bioequivalence and safety of lenvatinib with Lenvima® .

Research design and methods

The fasting and postprandial groups were two independent trials. Subjects were randomly divided into two sequences at a ratio of 1:1 for two-cycle crossover administration. Subjects took 10 mg lenvatinib or Lenvima® once per cycle. The wash-out period was 14 days. Detected the plasma drug concentrations and assessed the bioequivalence of two drugs. Besides, we evaluated the safety of the drugs throughout the trial.

Results

In the fasting state, the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 99.89%, 102.98% and 103.19%, respectively. The 90% CIs were all within 80%-125%. In the postprandial state, the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 98.96%, 94.25% and 95.27%, respectively. The 90% CIs were all within 80%-125%. All results met the bioequivalence criteria. Both drugs had good safety and tolerance in this trial.

Conclusion

This study showed that lenvatinib and Lenvima® had similar bioequivalence and safety in healthy Chinese subjects under fasting and postprandial conditions.

Clinical trial registration

This trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191172)

KEYWORDS:

• Bioequivalence
• biosimilars
• lenvatinib
• safety
• thyroid cancer
• VEGF

Supplementry material

Supplemental data for this article can be accessed here.

Acknowledgments

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. provided the drugs (lenvatinib and reference lenvatinib). Thanks to all enrolled participants, investigators, and people who contributed to this study.

Data availability statement

We confirm that the figures and tables in the manuscript are original and have not been published before. The data that support the findings of this study are available 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. The information about the trial can obtain from http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtmlApproved No. of ethic committee are CCZYFYLL2017 review-024 and CCZYFYLL2017 review-024-1.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This work was supported by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd, Jiangsu, China. funding number: phase I 2019-013. 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.