Comparative analysis of bioequivalence, safety, and tolerability of semaglutide (tablets): results of an open-label randomized crossover comparative study

The aim. To conduct a comparative evaluation of the physicochemical properties, biological activity, bioequivalence, and safety, including tolerability and immunogenicity, of the drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) and the drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark) when administered to healthy volunteers.

Materials and Methods. To assess the bioequivalence of the investigational drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) with a chemically synthesized active substance to the original (reference) drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark), an open-label randomized crossover comparative study (n = 110) was conducted. Patients were randomized into 4 groups: Group 1 (n = 25) — patients received the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 2 (n = 25) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 3 (n = 30) — the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 14 mg (1 tablet) for 28 days; Group 4 (n = 30) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 14 mg (1 tablet) for 28 days. The concentration of semaglutide was determined in serum samples using a pre-validated enzyme-linked immunosorbent assay (ELISA) method. The conclusion on bioequivalence of the compared drugs was made based on the assessment of 90 % confidence intervals for the ratios of geometric mean values of C_max and AUC_(0–t) parameters of semaglutide in the original units of measurement.

Results. The results of the clinical study demonstrated the bioequivalence of the investigational drug and the comparator drug. The pharmacokinetic parameters of the drugs were comparable: Based on statistical analysis, the obtained 90 % confidence intervals for the ratio of C_max,ss and AUC_(0-τ)ss values of semaglutide 3 mg were 96.57–120.94 % and 94.37–120.06 %, respectively. For the 14 mg dosage, the 90 % confidence intervals for the ratio of C_max,ss and AUC_(0-τ)ss values of semaglutide were 91.79–109.68 % and 91.47–112.80 %, respectively. The tolerability of the drugs in volunteers was noted as good. No serious adverse events were registered during the entire study. Thus, the investigational drug Semaltara®, tablets, and the comparator drug Rebelas®, tablets, have a similar safety profile, including tolerability, at both the 3 mg and 14 mg dosages.

Conclusion. The conducted study demonstrated the bioequivalence and similar safety profile, as well as tolerability of the Russian drug Semaltara® (semaglutide 3 and 14 mg, tablets, Promomed LLC, Russia) in comparison with the foreign drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark).

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