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Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function

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Abstract

Objective

HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function.

Methods

This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9). Safety was evaluated throughout the study, and the pharmacodynamic effects were assessed on the basis of a DPP-4 inhibition rate.

Results

HSK7653 exposure levels including the maximum plasma concentration (Cmax), area under the plasma concentration–time curve from zero to last time of quantifiable concentration (AUC0–t), and area under the plasma concentration–time curve from zero to infinity (AUC0–inf) showed no significant differences related to the severity of renal impairment. Renal clearance (CLR) showed a certain downtrend along with the severity of renal impairment. The CLR of the group with severe renal impairment and the group with end-stage renal disease were basically similar. The DPP-4 inhibition rate–time curve graph was similar among the renal function groups. All groups had favorable safety, and no serious adverse events occurred.

Conclusions

HSK7653 is a potent oral DPP-4 inhibitor with a long plasma half-life, supporting a dosing regimen of once every 2 weeks. Impaired renal function does not appear to impact the pharmacokinetic and pharmacodynamic properties of HSK7653 after a single administration in Chinese subjects. HSK7653 is also well tolerated without an increase in adverse events with increasing renal impairment. These results indicate that dose adjustment of HSK7653 may not be required in patients with renal impairment.

Trial Registration

ClinicalTrials.gov Identifier: NCT05497297.

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Acknowledgments

The authors thank all subjects who participated in this trial. We also acknowledge Haisco Pharmaceutical Group Co., Ltd. for support with the HSK7653.

Author information

Author notes

  1. Dan Shi, Lin Chen and Gexuan Li have contributed equally to this article.

Authors and Affiliations

  1. Department of Nephrology, Beijing Jishuitan Hospital, Capital Medical University, No.31 Xinjiekou Dongjie Street, Beijing, China

    Dan Shi, Xiaofei Wang & Dongliang Zhang

  2. Drug Clinical Trial Institution, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China

    Lin Chen

  3. Clinical Trial Institution Management Office, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China

    Gexuan Li, Nan Mu, Xi Chen, Xiangyi Yang, Jia Lu, Yali Lu & Meixia Wang

  4. Haisco Pharmaceutical Group Co., Ltd., Chengdu, China

    Nan Wu & Fengyi Zhang

Authors
  1. Dan Shi
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  2. Lin Chen
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  4. Nan Wu
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Corresponding authors

Correspondence to Meixia Wang or Dongliang Zhang.

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Funding

This work was sponsored by Haisco Pharmaceutical Group Co., Ltd.

Conflict of Interest

Nan Wu and Fengyi Zhang are employed by Haisco Pharmaceutical Group Co., Ltd. Other authors all declare no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author Contributions

Dan Shi and Gexuan Li organized the Administrative Bureau to steer the study progress. Lin Chen organized the study progresss in the Drug Clinical Trial Institution, the First Affiliated Hospital of Jinan University. Nan Wu and Fengyi Zhang designed the study protocol. Xiaofei Wang and Gexuan Li enrolled patients and did case records in Beijing Jishuitan Hospital, Capital Medical University. Nan Mu, Xi Chen, Xiangwei Yang, Jia Lu, and Yali Lu conducted the follow-up in the Phase I Research Center Ward. Nan Mu and Xi Chen were also responsible for data handling. Xiangwei Yang and Jia Lu were responsible for the judgment of data for publication. Yali Lu was responsible for statistical analysis. Meixia Wang and Dongliang Zhang were the guarantors of the entire works associated with the present study and take responsibility for the integrity of the data and the accuracy of data analysis. Dan Shi extensively contributed to the manuscript preparation. All authors reviewed and approved the manuscript before submission.

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Shi, D., Chen, L., Li, G. et al. Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function. Clin Pharmacokinet 63, 227–239 (2024). https://doi.org/10.1007/s40262-023-01333-4

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  • DOI: https://doi.org/10.1007/s40262-023-01333-4

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