Results of a phase I open randomized comparative crossover clinical trial to assess the safety and pharmacokinetics of Glurazyme® (imiglucerase) in comparison with the reference product in healthy volunteers

Background. Currently, the main treatment for Gaucher disease is enzyme replacement therapy. Recombinant glucocerebrosidase (imiglu-cerase) is the first biotechnological drug for enzyme replacement therapy with proven clinical efficacy and safety for the treatment of patients of different ages with Gaucher disease type 1 and type 3, used in clinical practice since 1994. In Russia, within the framework of the “Pharma 2020” pharmaceutical industry development strategy, the first biosimilar of imiglucerase, the drug Glurazyme®, was developed. The obtained results of preclinical studies became the basis for a phase I randomized comparative crossover clinical trial.

The objective of the study was to assess the short-term safety and pharmacokinetic parameters of Glurazyme® in comparison with the Cerezyme® after a single intravenous administration to healthy volunteers.

Materials and methods. 23 healthy volunteers aged 18—45 years were included in a 3-stage clinical trial. The study during the 1^st and 2^nd stages was open, randomized, comparative, crossover. At the 1^st stage, volunteers from the 1^st group received the Glurazyme®, from the 2^nd group — the Cerezyme® once in doses of 30 U/kg. At the 2^nd stage, Cerezyme® was administered to the 1^st group, Glurazyme® - to the 2^nd group once at doses of 30 U/kg. After the end of the 1^st and 2^nd stages, the 3^rd stage was carried out for the 3rd group (n = 5) with the administration of the test drug once at a dose of 60 U/kg.

Results. For all studied pharmacokinetic parameters, after administration of the test and reference drugs in doses of 30 U/kg, 90 % confidence interval was in the range from 80 to 125 %, which indicates the pharmacokinetic compared drugs equivalence. A total of 6 adverse events of mild and moderate severity were recorded. Of these, 4 adverse events were noted after administration of the study drug and were not associated with its administration. A comparative analysis of safety assessment parameters in this study (frequency and severity of adverse events, physical examination of healthy volunteers with an assessment of vital signs, laboratory tests, electrocardiography) did not reveal intergroup differences.

Conclusion. The pharmacokinetic equivalence of the Glurazyme® and the reference drug in a dose of 30 U/kg has been established. A nonlinear dependence of the main pharmacokinetic parameters on studied drug administered dose was revealed. Safety and the absence of adverse reactions after a single injection of the study drug are shown.

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