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Double-blind, randomized, phase I trial comparing the pharmacokinetics and safety of agalsidase beta bioanaloguer (Fabagal®) and the original drug (Fabrazim®) in healthy volunteers
DOI: https://dx.doi.org/10.18565/nephrology.2023.3.30-36
Moiseev S.V., Shchulkin A.V., Abalenikhina Yu.V., Mylnikov P.Yu., Yakusheva E.N., Khmelevsky M.S., Matsiyak M.V.
1) E.M. Tareev Clinic, Sechenov University, Moscow, Russia; 2) Ryazan State Medical University n.a. Acad. I.P.Pavlov, Ryazan, Russia; 3) OOO RPA Petrovax Pharm, Moscow, Russia
Material and methods. Single-center, double-blind, randomized, phase I, parallel-group, active-controlled trial enrolled 52 healthy male volunteers aged 18–45 years who were divided into two equal groups. The study (Fabagal®) and original (Fabrazim®) drugs were administered once intravenously at the recommended dose of 1 mg/kg after premedication with ibuprofen and diphenhydramine. Quantification of agalsidase beta was carried out indirectly by assessing the α-galactosidase A activity by spectrofluorimetric method using the commercial Alpha Galactosidase Activity Assay Kit manufactured by Abcam (USA). The primary criterion for assessing bioequivalence was the area under the plasma concentration-time curve from zero to infinity (AUC0-∞), the secondary criteria were the area under the plasma concentration-time curve from zero to time t (AUC0-t) and the maximum plasma concentration (Cmax). Parameters were studied using an ANOVA model for a parallel design.
Results. The mean parameters of pharmacokinetics of agalsidase beta with the infusion of the study drug (Fabagal® ) and the reference drug (Fabrazim®) were similar. The two-sided 93.92% confidence interval (CI) for the geometric mean ratio of AUC0-∞ of agalsidase beta after infusion of study drug and comparator (104.99–122.45%) was within the acceptable range of 80.00–125.00%, established for bioequivalence studies; 90% CI for the ratio of the geometric mean values of AUC0-t and Cmax were 106.25–121.54 and 99.54–112.16%, respectively, and were also within the bioequivalence limits. Side effects, deviations in the results of the physical examination, ECG, laboratory tests were not registered. Conclusion. The study confirmed the bioequivalence of the agalsidase beta bioanalogue (Fabagal®) and the original drug (Fabrazim ®) in a single intravenous injection at the recommended dose of 1 mg/kg and showed a favorable tolerability profile of the study drug in healthy volunteers.
About the Autors
Sergey V. Moiseev – Head of the Department of Internal, Occupational Diseases and Rheumatology, Director of the E/M.Tareev Clinic of Rheumatology, Nephrology and Occupational Pathology, University Clinical Hospital №3. Address: Bldg 4,5 11 Rossolimo st., Moscow, 119021. ORCID: 0000-0002-7232-4640.
Aleksey V. Shchulkin – Dr.Sci.(Med.), Professor at the Department of Pharmacology, Ryazan State Medical University n.a.Acad. I.P. Pavlov. Address: Blg. 2, 34 Shevchenko st., Ryazan, 390029. ORCID: 0000-0003-1688-0017, SPIN: 2754-1702, Researcher ID: N-9143-2016.
Yuliya V. Abalenikhina – Cand.Sci. (Biol.) , Associate Professor at the Department of Biological Chemistry with the course of CLD FAPE, Ryazan State Medical University n.a.
I.P. Pavlov. Address: 9 Vysokovoltnaya st., Ryazan, 390026. ORCID: 0000-0003-0427-0967, SPIN: 4496-9027, Researcher ID: L-8965-2018.
Pavel Yu.Mylnikov – Cand.Sci. (Biol.), Teaching Assistant at the Department of Pharmacology, Ryazan State Medical Universityn.a. Acad. I.P. Pavlov. Address: Blg. 2, 34 Shevchenko st., Ryazan, 390029. ORCID: 0000-0001-7829-2494, SPIN: 8503-3082.
Elena N. Yakusheva – Dr.Sci. (Med.), Professor, Head of the Department of Pharmacology, Ryazan State Medical University n.a. Acad. I.P. Pavlov. Address: Blg. 2, 34 Shevchenko st., Ryazan, 390029. ORCID: 0000-0001-6887-4888, SPIN: 2865-3080, Researcher ID: T-6343-2017.
Pavel O. Bochkov – Specialist in Pharmacokinetics, Center for Preclinical Studies, OOO RPA Petrovax Pharm. Address: Federation Tower Vostok, Floor 38, 12 Presnenskaya embankment, Moscow, 123112.
Mikhail S.Khmelevsky – Clinical Research Specialist, OOO RPA Petrovax Pharm. Federation Tower Vostok, Floor 38, 12 Presnenskaya embankment, Moscow, 123112. Maksim V. Matsiyak – Head of the Hospital Department, OOO RPA Petrovax Pharm. Federation Tower Vostok, Floor 38, 12 Presnenskaya embankment, Moscow, 123112. ORCID: 0009-0000-8443-3257.
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