Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

A Phase I Clinical Study of the Pharmacokinetics and Safety of Prusogliptin Tablets in Subjects with Mild to Moderate Hepatic Insufficiency and Normal Liver Function

Author(s): Huiting Zhang, Yicong Bian, Weifeng Zhao*, Liyan Miao*, Hua Zhang*, Juanjuan Cui, Xiaofang Zhang, Xueyuan Zhang and Wen Cai

Volume 25, Issue 2, 2024

Published on: 05 March, 2024

Page: [140 - 151] Pages: 12

DOI: 10.2174/0113892002288120240221111336

Price: $65

Abstract

Background: Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited.

Objectives: The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects.

Methods: According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures.

Results: After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study.

Conclusion: The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.

Keywords: Prusogliptin, DPP-4 inhibitor, hepatic impairment, phase I clinical study, pharmacokinetics, liver.

Graphical Abstract
[1]
Yeh, K.C.; Yeh, T.K.; Huang, C.Y.; Hu, C.B.; Wang, M.H.; Huang, Y.W.; Chou, L.H.; Ho, H.H.; Song, J.S.; Hsu, T.; Jiaang, W.T.; Chao, Y.S.; Chen, C.T. DBPR108, a novel dipeptidyl peptidase-4 inhibitor with antihyperglycemic activity. Life Sci., 2021, 278119574
[http://dx.doi.org/10.1016/j.lfs.2021.119574]
[2]
Li, Y.; Teng, D.; Shi, X.; Qin, G.; Qin, Y.; Quan, H.; Shi, B.; Sun, H.; Ba, J.; Chen, B.; Du, J.; He, L.; Lai, X.; Li, Y.; Chi, H.; Liao, E.; Liu, C.; Liu, L.; Tang, X.; Tong, N.; Wang, G.; Zhang, J.; Wang, Y.; Xue, Y.; Yan, L.; Yang, J.; Yang, L.; Yao, Y.; Ye, Z.; Zhang, Q.; Zhang, L.; Zhu, J.; Zhu, M.; Ning, G.; Mu, Y.; Zhao, J.; Teng, W.; Shan, Z. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ, 2020, 369, m997.
[http://dx.doi.org/10.1136/bmj.m997]
[3]
Chinese Type 2 Diabetes Prevention Guide (2020 Edition) %. J International Journal of Endocrinology and Metabolism., 2021, 41(05), 482-548.
[4]
Nauck, M.A.; Quast, D.R.; Wefers, J.; Meier, J.J. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Mol. Metab., 2021, 46(101102)101102
[http://dx.doi.org/10.1016/j.molmet.2020.101102]
[5]
Xu, J.; Ling, H.; Geng, J.; Huang, Y.; Xie, Y.; Zheng, H.; Niu, H.; Zhang, T.; Yuan, J.; Xiao, X. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes: A 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Diabetes Obes. Metab., 2022, 24(11), 2232-2240.
[http://dx.doi.org/10.1111/dom.14810]
[6]
Subrahmanyan, N.A.; Koshy, R.M.; Jacob, K.; Pappachan, J.M. Efficacy and cardiovascular safety of DPP-4 inhibitors. Curr. Drug Saf., 2021, 16(2), 154-164.
[http://dx.doi.org/10.2174/22123911MTA5pMzA20]
[7]
Wang, X.; Zheng, P.; Huang, G.; Yang, L.; Zhou, Z. Dipeptidyl peptidase-4(DPP-4) inhibitors: Promising new agents for autoimmune diabetes. Clin. Exp. Med., 2018, 18(4), 473-480.
[http://dx.doi.org/10.1007/s10238-018-0519-0]
[8]
Deacon, C.F. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol., 2020, 16(11), 642-653.
[http://dx.doi.org/10.1038/s41574-020-0399-8]
[9]
Gilbert, M.P.; Pratley, R.E. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: Review of head-to-head clinical trials. Front. Endocrinol., 2020, 11, 178.
[http://dx.doi.org/10.3389/fendo.2020.00178]
[10]
Scheen, A.J. Cardiovascular effects of new oral glucose-lowering agents. Circ. Res., 2018, 122(10), 1439-1459.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311588]
[11]
Scheen, A.J. Efficacy / safety balance of DPP-4 inhibitors versus SGLT2 inhibitors in elderly patients with type 2 diabetes. Diabetes Metab., 2021, 47(6)101275
[http://dx.doi.org/10.1016/j.diabet.2021.101275]
[12]
Provisions for Drug Registration J Gazette of the State Council of the People 's Republic of China. , 2020, 14, 40-56.
[13]
Wang, W.; Yao, J.; Guo, X.; Guo, Y.; Yan, C.; Liu, K.; Zhang, Y.; Wang, X.; Li, H.; Wen, Z.; Wang, X.; Li, S.; Xiao, X.; Liu, W.; Li, Z.; Zhang, L.; Shao, S.; Ye, S.; Qin, G.; Li, Y.; Li, F.; Zhang, X.; Li, X.; Peng, Y.; Deng, H.; Xu, X.; Zhou, L.; Huang, Y.; Cao, M.; Xia, X.; Shi, M.; Dou, J.; Yuan, J. Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial. Curr. Med. Res. Opin., 2020, 36(7), 1107-1115.
[http://dx.doi.org/10.1080/03007995.2020.1761311]
[14]
Thomas, D.; Kanefendt, F.; Schwers, S.; Unger, S.; Yassen, A.; Boxnick, S. First evaluation of the safety, pharmacokinetics, and pharmacodynamics of BAY 2433334, a small molecule targeting coagulation factor XIa. J. Thromb. Haemost., 2021, 19(10), 2407-2416.
[http://dx.doi.org/10.1111/jth.15439]
[15]
Xin, Y.; Kawashima, J.; Weng, W.; Kwan, E.; Tarnowski, T.; Silverman, J.A. Pharmacokinetics and safety of momelotinib in subjects with hepatic or renal impairment. J. Clin. Pharmacol., 2018, 58(4), 522-532.
[http://dx.doi.org/10.1002/jcph.1050]
[16]
Bai, Y.; Hu, X.; Ren, Z.; Hisai, T.; Yusa, W.; Weng, L.; Shiba, S.; Takase, T. A phase I pharmacokinetic study of lenvatinib in Chinese patients with unresectable hepatocellular carcinoma. Future Oncol., 2022, 18(22), 2413-2424.
[http://dx.doi.org/10.2217/fon-2022-0229]
[17]
Guidance for industry on pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. 2003. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacokinetics-patients-impaired-hepatic-function-study-design-data-analysis-and-impact-dosing-and

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy