Results of biosimilar assessing of insulin aspart preparations of Russian and foreign production using the hyperinsulinemic euglycemic clamp method and studying the use of a new ultra-fast-acting Russian biosimilar in pumps

Abstract

Introduction. Ultra-fast-acting insulin aspart has great potential for improving postprandial glycemia in patients with type 1 and type 2 diabetes mellitus due to its pharmacological characteristics. The development and production of biosimilars are increasing the availability of modern insulins for patients.Aim. To evaluate the comparability of the pharmacokinetics and pharmacodynamics profiles of insulin aspart GP40311 (tested biosimilar of domestic production) and the reference drug (produced in Denmark) under conditions of a hyperinsulinemic euglycemic clamp in healthy volunteers. To evaluate the stability of a new ultrafast-acting biosimilar when used for continuous subcutaneous infusion in insulin pumps.Materials and methods. Double-blind, randomized, crossover study assessing the pharmacokinetics, pharmacodynamics and safety of the tested biosimilar GP40311 of domestic production and the reference drug produced in Denmark, in the form of a solution for intravenous and subcutaneous administration of 100 IU/ml, the study was conducted under conditions of a hyperinsulinemic euglycemic clamp with the participation of 36 healthy volunteers. A study of the stability, dosing accuracy and tendency to catheter occlusion of a domestic drug for continuous subcutaneous infusion was carried out using several types of insulin pumps using the gravimetric method for 72 hours. Dosing accuracy was determined at the minimum and maximum bolus dose, stability was assessed by pH and quantitative insulin content aspart. The quantitative content of insulin and impurities was assessed by high-performance liquid chromatography.Results and discission. The 90% confidence interval for the ratio of geometric mean values of the main parameters of pharmacokinetics (AUCins.0-t and Cins.max) of insulin aspart test and reference drugs corresponded to the acceptable values of 80.00– 125.00%, which indicated their biosimilarity. When assessing PD, the comparability of action parameters is shown. The safety of the study drugs is comparable. Domestic insulin aspart met the specification standards when used for continuous subcutaneous infusion according to physicochemical parameters: pH, quantitative determination of insulin aspart, impurity content. The accuracy of dosing and the absence of occlusions in systems for 72 hours when using the drug in pumps have been established.Conclusion. The study drugs were found to be biosimilar and equally safe. Domestic insulin aspart meets specification standards and can be used in various types of pumps.