Department of Nephrology, Beijing Jishuitan Hospital, Capital Medical University, No.31 Xinjiekou Dongjie Street, Beijing, China.
Drug Clinical Trial Institution, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China.
Clin Pharmacokinet. 2024 Feb;63(2):227-239. doi: 10.1007/s40262-023-01333-4. Epub 2024 Jan 6.
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.
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.
HSK7653 exposure levels including the maximum plasma concentration (C), area under the plasma concentration-time curve from zero to last time of quantifiable concentration (AUC), and area under the plasma concentration-time curve from zero to infinity (AUC) showed no significant differences related to the severity of renal impairment. Renal clearance (CL) showed a certain downtrend along with the severity of renal impairment. The CL 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.
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.
ClinicalTrials.gov Identifier: NCT05497297.
HSK7653 是一种新型的、超长效二肽基肽酶-4（DPP-4）抑制剂，有望用于 2 型糖尿病，给药方案为每 2 周一次。本试验旨在研究 HSK7653 在肾功能正常或受损的门诊患者中的药代动力学（PKs）、药效学（PDs）和安全性。
这是一项多中心、开放标签、非随机、平行对照的 I 期临床研究，调查了 42 例轻度（n=8）、中度（n=10）、重度肾功能损害（n=10）和终末期肾病（无透析，n=5）患者单次口服 HSK7653 后的药代动力学特征，并与匹配的肾功能正常患者（n=9）进行比较。在整个研究过程中评估安全性，并根据 DPP-4 抑制率评估药效学效应。
HSK7653 的暴露水平（包括最大血浆浓度 [C]、从零到最后可量化浓度的血浆浓度-时间曲线下面积 [AUC]和从零到无穷大的血浆浓度-时间曲线下面积 [AUC]）与肾功能损害的严重程度无显著差异。肾清除率（CL）随肾功能损害的严重程度呈一定下降趋势。重度肾功能损害组和终末期肾病组的 CL 基本相似。肾功能组的 DPP-4 抑制率-时间曲线图谱相似。所有组均具有良好的安全性，无严重不良事件发生。
HSK7653 是一种强效的口服 DPP-4 抑制剂，具有较长的血浆半衰期，支持每 2 周给药一次的方案。在单次给药后，中国受试者的肾功能受损似乎不会影响 HSK7653 的药代动力学和药效学特性。HSK7653 也具有良好的耐受性，随着肾功能损害的增加，不良事件发生率没有增加。这些结果表明，HSK7653 可能不需要在肾功能损害患者中进行剂量调整。
ClinicalTrials.gov 标识符：NCT05497297。
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