Russian development for drug independence in endocrinology: comparative analysis of bioequivalence, safety and tolerability of the first domestic liraglutide

Abstract

Liraglutide is one of the analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently a priority treatment for diseases such as type 2 diabetes mellitus (mono- and combination therapy), obesity and overweight in the presence of at least one concomitant disease.The aim of the work was to assess the bioequivalence and comparability of the safety and tolerability profile of the drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) and the drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark) after a single dose in healthy volunteers.Materials and methods. This study was an open-label, randomized, crossover comparative study to evaluate pharmacokinetic parameters, safety, tolerability and immunogenicity. The study comprised 26 healthy volunteers, 26 of whom were included in the bioequivalence assessment population. The study consisted of 2 periods, in each of which the volunteers received either the test drug (liraglutide at a single dose of 0.6 mg) or the reference drug (liraglutide at a single dose of 0.6 mg) once. The washout period between each dose was 7 days. Blood plasma samples were taken to determine the concentration of liraglutide in the range from 0 to 72 hours in each study period. Liraglutide concentrations were determined using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to liraglutide in the blood serum samples was carried out using a microplate photometer and ready-made ELISA kits pre-validated by the manufacturer. The conclusion about the equivalence of the compared drugs was made based on the ratio of the parameters Cmax, AUC0→t and AUC0→t of the studied drug in relation to the reference one.Results. The pharmacokinetic parameters of the drugs were comparable to each other. The resulting 90% confidence intervals for the ratio of the values of Cmax, AUC0-t and AUC0-∞ of the Russian test and reference drug were 87.18–110.46, 84.40–104.11 and 86.69–103.22% respectively, which satisfied the criteria for assessing bioequivalence. The tolerability of the drugs in the volunteers was notified as good. The incidence of adverse events was comparable for the test and reference drugs. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to russian produced liraglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.Conclusion. During the study, the pharmacokinetic equivalence of the test and reference drugs was confirmed. The Russian drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) in comparison with a foreign drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark).