Pharmacokinetics, Pharmacodynamics, and Bioequivalence of Test Insulin Glargine Versus Reference Preparation (Lantus®) in Healthy Male Volunteers—By Euglycemic Clamp Technique

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. <b>Methods:</b> 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. <b>Results:</b> 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_max of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL^-1, and the AUC_0-24h were 9.782 and 10.436 h·ng·mL^-1, respectively. PD parameters GIR_max were 42.748 and 45.279 mg·kg^-1·min^-1, and AUC_GIR,0-24h were 2.924 and 3.096 h·mg·kg^-1·min^-1, respectively. There was no clinically significant adverse reaction observed during the experiment. <b>Conclusions:</b> The glucose clamp has been established and bioequivalence between test preparation and reference preparation has been demonstrated.