Endocrine Abstracts

Introduction: Rapid-acting insulins is widely used in the treatment of either type 1 diabetes mellitus, or type 2 diabetes mellitus. A mealtime injection of rapid-acting insulin, such as insulin aspart, allow the diabetic patients to control the levels of post-prandial glucose. The clinical development plan of the insulin biosimilarsusually contains pharmacology studies to evaluate pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety of the investigational products.

To demonstrate Insulin Aspart, solution for intravenous and subcutaneous administration, 100 U/ml (GEROPHARM, Russia) and NovoRapid Penfill, solution for intravenous and subcutaneous administration, 100 U/ml (Novo Nordisk, Denmark) have comparable PK/PD profiles hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers has been performed.

Methods: 26 healthy male Caucasian volunteers aged between 18 to 50 years were subjected in a randomized, double-blind, crossover study of the comparative pharmacokinetics of the two different formulations of insulin aspart: Insulin Aspart, GEROPHARM (test drug, T) and NovoRapid Penfill, Novo Nordisk (reference drug, R). Subjects who met the inclusion/non-inclusion criteria underwent the procedure of HECfollowing the subcutaneous injections either T (0.3 IU/kg) or R (0.3 IU/kg) in the abdomen region. After the performed injections of insulin aspart, the levels of plasma glucose were monitored every 5 minutes for 8 hours. The adjustment of the glucose infusion rates was based on the blood glucose measurements. This data was used to evaluate the PD profiles of investigational drugs. Regular blood samplingwas performed during the study. The insulin concentrations in the blood samples of the subjects were determined using avalidated ELISA method. The results of the analytic procedures were used to calculate the PK parameters of insulin aspart and fit the concentration-time curves. The clinical study was approved by The Ministry of Health of the Russian Federation, as well as by the independent local ethical committees (NCT04184466).

Results: The confidence intervals for the ratio of the geometric mean of Insulin Aspart (GEROPHARM) for C_ins and AUC_ins-t were 110.51–124.02% and 102.12–110.24% respectively; for GIR_max and AUC_GIR0-t – 94.35–117.53% and 91.09–113.84%. Both PK and PD parameters were well within 80–125% limits for establishing comparability between two formulations of insulin aspart.

Conclusions: Our data demonstrated, thatInsulin Aspart (GEROPHARM) and NovoRapid Penfill (NovoNordisk) have comparable PK and PD profiles in healthy subjects in HEC paradigm. Thus, in this clinical trial the high level of similarity of R and T formulations of insulin aspart was experimentally confirmed.