Li Zhongping, Liu Min, Tao Yi, Wan Lei, Chen Yuan, Zhu Mingxue, Zhao Hongtao, Tang Chengyong
Phase I Clinical Trial Center, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China.
Office of Academic Research, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Pharmaceutics. 2025 Mar 25;17(4):418. doi: 10.3390/pharmaceutics17040418.
The aim of this study was to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of two insulin glargine preparations in healthy Chinese male subjects. Forty healthy Chinese male subjects were enrolled in this randomized, open, two-sequence, four-period, single-dose, crossover study and were randomly divided into RTRT or TRTR (first-period injection of test preparation, second-period injection of reference preparation, third-period injection of test preparation, fourth-period injection of reference preparation) groups. A 24 h euglycemic clamp test measured GIR. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). WinNonLin calculated PD/PK parameters and the equivalence of the two preparations was testified by SAS9.2. The average concentration of C-peptide was lower than the baseline and the blood glucose was close to the targeted value in each sequence. PK parameters c of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL, and the AUC were 9.782 and 10.436 h·ng·mL, respectively. PD parameters GIR were 42.748 and 45.279 mg·kg·min, and AUC were 2.924 and 3.096 h·mg·kg·min, respectively. There was no clinically significant adverse reaction observed during the experiment. The glucose clamp has been established and bioequivalence between test preparation and reference preparation has been demonstrated.
本研究旨在评估两种甘精胰岛素制剂在健康中国男性受试者中的药代动力学（PK）、药效学（PD）及安全性。40名健康中国男性受试者参与了这项随机、开放、双序列、四周期、单剂量交叉研究，并被随机分为RTRT或TRTR组（第一周期注射试验制剂，第二周期注射参比制剂，第三周期注射试验制剂，第四周期注射参比制剂）。通过24小时正常血糖钳夹试验测量葡萄糖输注率（GIR）。在试验期间采集血浆甘精胰岛素浓度和C肽，并采用高效液相色谱-串联质谱法（HPLC-MS/MS）和酶联免疫吸附测定法（ELISA）进行分析。WinNonLin计算PD/PK参数，并通过SAS9.2验证两种制剂的等效性。各序列中C肽平均浓度均低于基线，血糖接近目标值。试验制剂和参比制剂甘精胰岛素的PK参数c分别为0.580和0.614 ng·mL，AUC分别为9.782和10.436 h·ng·mL。PD参数GIR分别为42.748和45.279 mg·kg·min，AUC分别为2.924和3.096 h·mg·kg·min。实验期间未观察到具有临床意义的不良反应。已建立葡萄糖钳夹试验，并证明试验制剂与参比制剂具有生物等效性。
