Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial

ABSTRACT

Background

Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects.

Research design and methods

Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. 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 the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study.

Conclusion

The study shows that the two drugs had similar bioequivalence and safety.

Clinical trial registration

DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076

KEYWORDS:

• GLP-1
• liraglutide
• pharmacokinetics
• safety
• type 2 diabetes

Acknowledgments

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. provided the drugs (liraglutide and Victoza®). Thanks to all enrolled participants, investigators, and people who contributed to this study. Thanks to Yicheng Zhao (Changchun University of Chinese Medicine) and graduate student Xinran Ren (Jilin University) for assistance in drafting the manuscript.

Declaration of interest

Z Xu and J Xue are employees of Chia Tai Tianqing Pharmaceutical Group Co. Ltd. X Chen is an employee of Ansiterui Medical Technology Consulting Co. Ltd. The authors have no other 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 apart from those disclosed.

Data availability statement

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. All data related to this study were interpreted by the staff with complete independence from the sponsor.

Reviewer disclosures

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

Ethics statement

The authors state that the trial was approved by the Ethics Committee of Affiliated Hospital of Changchun University of Chinese Medicine (Number: CCZYFYLL2019 review-019). The ethics approval process of this study met the requirements of good documentation practice, the Declaration of Helsinki, and the relevant domestic laws and regulations. All subjects agreed to participate in the trial and signed an informed consent form after being fully informed about the trial.

Author contributions

Z Xu, Z Liu and H Yang were involved in the conception and design of the trial; Y Wang, J Xue, T Chang, Y Cui, Y Cheng, G Liu, W Wang, Y Zhou, S Yu, Q Ren, W Yang, X Qu, J Chen and X Chen performed the research. Q Deng edited the paper and drew the figures. H Yang finally approved of the version. X Wang lead the revision of the manuscript and participated in some statistics. All authors agreed to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2023.2188192

Additional information

Funding

This work was supported by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd, Jiangsu, China, funding number: phase I 2019-12. The founder helped pay for this study and had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.