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

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...
Ausführliche Beschreibung

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 ($ AUC_{0–t} $), and area under the plasma concentration–time curve from zero to infinity ($ AUC_{0–inf} $) showed no significant differences related to the severity of renal impairment. Renal clearance ($ CL_{R} $) showed a certain downtrend along with the severity of renal impairment. The $ CL_{R} $ 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. Ausführliche Beschreibung

Autor*in:	Shi, Dan [verfasserIn] Chen, Lin Li, Gexuan Wu, Nan Zhang, Fengyi Wang, Xiaofei Mu, Nan Chen, Xi Yang, Xiangyi Lu, Jia Lu, Yali Wang, Meixia Zhang, Dongliang

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Anmerkung:

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Übergeordnetes Werk:	Enthalten in: Clinical pharmacokinetics - Berlin [u.a.] : Springer, 1976, 63(2024), 2 vom: 06. Jan., Seite 227-239
Übergeordnetes Werk:	volume:63 ; year:2024 ; number:2 ; day:06 ; month:01 ; pages:227-239

Links:	Volltext

DOI / URN:	10.1007/s40262-023-01333-4

Katalog-ID:	SPR054669960