Abstract
Background and Objective
Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM.
Methods
Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10.
Results
Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by −0.3, −1.0 and −1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were −0.8, −0.9 and −1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred.
Conclusions
The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.
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Funding
This study was sponsored by Jiangsu Hengrui Medicine Co., Ltd.
Conflict of interest
Haiyan Liu, Yan-Ping Liu, Ying Chen, Minquan Wang, Jia Li and Huaqiong Shen were full-time employees of Jiangsu Hengrui Medicine Co., Ltd., when the study was conducted. All other authors have no conflicts of interest.
Ethical approval
The study was conducted in accordance with Good Clinical Practice as defined by the International Conference on Harmonisation, and Chinese State Food and Drug Administration, and Declaration of Helsinki. The study protocol and all amendments were reviewed and approved by the Clinical Research Ethics Committee of Chengdu Military General Hospital and Xijing Hospital.
Informed consent
All subjects were informed of the nature and purpose of the study, and gave written consent to participate before any screening procedures.
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Yong, X., Wen, A., Liu, X. et al. Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus. Clin Drug Investig 36, 195–202 (2016). https://doi.org/10.1007/s40261-015-0366-7
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DOI: https://doi.org/10.1007/s40261-015-0366-7