A phase-I randomized euglycemic clamp study to demonstrate the pharmacokinetic and pharmacodynamic equivalence of an insulin degludec biosimilar (B01411) with the reference product in healthy Chinese volunteers

ABSTRACT

Background

B01411 is a biosimilar candidate manufactured by Jilin Huisheng Biopharmaceutical Co. Ltd for the reference insulin degludec (Tresiba) (IDeg). This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of the two IDeg products and to assess the PK/PD similarity of B01411 compared with the reference IDeg product.

Research design & methods

A single-center, single-dose, randomized, crossover, open-labeled, phase I, euglycemic clamp study in healthy Chinese subjects to examine the bioequivalence of B01411 (0.4 U/kg) compared with the reference IDeg product. Blood samples were collected at a predefined time for the analysis of blood glucose (BG), IDeg, and C-peptide concentrations. The glucose infusion rate (GIR) was adjusted to maintain the BG at approximately 0.28 mmol/L below baseline throughout the clamp.

Results

Thirty-two subjects (20 males and 12 females) were enrolled, 31 of whom received both treatments. The 90% confidence intervals for the ratio of the least-squares geometric means for AUC_{IDeg,0–24 h}, AUC_{GIR,0–24 h}, IDeg_max, and GIR_max were all in the range of 0.80–1.25. Only one adverse event of puncture site bruising occurred once in a subject in the B01411 group.

Conclusion

B01411 exhibited a pharmacokinetic and pharmacodynamic similarity to the reference product. Both IDeg products were well tolerated.

Clinical trial registration

http://www.chinadrugtrials.org.cn/index.html#. Identifier is CTR20192122.

KEYWORDS:

• B01411
• insulin degludec
• euglycemic clamp
• pharmacokinetics
• pharmacodynamics
• healthy subjects

Declaration of interest

The author, Dejia Jia is an employee of the funder, Jilin Huisheng Biopharmaceutical Co., Ltd. Hui Liu, Ting Li, Hongling Yu, Xinlei Chen, Jiaqi Li, Huiwen Tan, Yerong Yu are employees of Sichuan University, West China Hospital. 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.

Reviewer disclosures

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

Author contribution statement

Yerong Yu is the principal investigator of this study and is responsible for the whole study management and data collection. Hui Liu and Ting Li are the study physicians of the study and are responsible for the safety evaluation of the drug in healthy subjects. Hongling Yu and Xinlei Chen contribute to drug administration and blood sample collection. Hui Liu, Ting Li, Xinlei Chen, and Hongling Yu performed the euglycemic clamp procedures. Dejia Jia is involved in the study design and data analysis. Jiaqi Li and Huiwen Tan are involved in data analysis. Hui Liu and Yerong Yu wrote the manuscript. All authors critically reviewed the manuscript and approved it for submission.

Availability of data and material

The data of the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

This manuscript was funded by Jilin Huisheng Biopharmaceutical Co., Ltd.