Double-blind, randomized, phase I trial comparing the pharmacokinetics and safety of agalsidase beta bioanaloguer (Fabagal®) and the original drug (Fabrazim®) in healthy volunteers
- Authors: Moiseev S.V.1, Shchulkin A.V.2, Abalenikhina Y.V.2, Mylnikov P.Y.2, Yakusheva E.N.2, Khmelevsky M.S.3, Macyak M.V.3
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Affiliations:
- Sechenov University
- Ryazan State Medical University N.A. Acad. I.P.Pavlov
- OOO RPA Petrovax Pharm
- Issue: Vol 15, No 3 (2023)
- Pages: 30-36
- Section: Original Articles
- URL: https://journals.eco-vector.com/2075-3594/article/view/624726
- DOI: https://doi.org/10.18565/nephrology.2023.3.30-36
- ID: 624726
Cite item
Abstract
Objective. Confirmation of the bioequivalence of agalsidase beta bioanalogue (ISU303, Fabagal®), developed by the Korean company ISU ABXIS Co., Ltd, and the original drug (Fabrazim®) and comparison of their tolerability and safety in healthy volunteers.
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.
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About the authors
Sergey V. Moiseev
Sechenov University
Email: moiseev_s_v@staff.sechenov.ru
ORCID iD: 0000-0002-7232-4640
Head of the Department of Internal, Occupational Diseases and Rheumatology, Director of the E.M.Tareev Clinic of Rheumatology, Nephrology and Occupational Pathology
Russian Federation, Bldg 4,5 11 Rossolimo st., Moscow, 119021Aleksey V. Shchulkin
Ryazan State Medical University N.A. Acad. I.P.Pavlov
Email: alekseyshulkin@rambler.ru
ORCID iD: 0000-0003-1688-0017
SPIN-code: 2754-1702
ResearcherId: N-9143-2016
Dr.Sci.(Med.), Professor at the Department of Pharmacology
Russian Federation, Blg. 2, 34 Shevchenko st., Ryazan, 390029Yuliya V. Abalenikhina
Ryazan State Medical University N.A. Acad. I.P.Pavlov
Email: moiseev_s_v@staff.sechenov.ru
ORCID iD: 0000-0003-0427-0967
SPIN-code: 4496-9027
ResearcherId: L-8965-2018
Cand.Sci. (Biol.) , Associate Professor at the Department of Biological Chemistry with the course of CLD FAPE
Russian Federation, 9 Vysokovoltnaya st., Ryazan, 390026Pavel Yu. Mylnikov
Ryazan State Medical University N.A. Acad. I.P.Pavlov
Email: dukeviperlr@gmail.com
ORCID iD: 0000-0001-7829-2494
SPIN-code: 8503-3082
Cand.Sci. (Biol.), Teaching Assistant at the Department of Pharmacology
Russian Federation, Blg. 2, 34 Shevchenko st., Ryazan, 390029Elena N. Yakusheva
Ryazan State Medical University N.A. Acad. I.P.Pavlov
Email: e.yakusheva@rzgmu.ru
ORCID iD: 0000-0001-6887-4888
SPIN-code: 2865-3080
ResearcherId: T-6343-2017
Dr.Sci. (Med.), Professor, Head of the Department of Pharmacology
Russian Federation, Blg. 2, 34 Shevchenko st., Ryazan, 390029Mikhail S. Khmelevsky
OOO RPA Petrovax Pharm
Email: moiseev_s_v@staff.sechenov.ru
Clinical Research Specialist
Russian Federation, 38, 12 Presnenskaya embankment, Moscow, 123112Maksim V. Macyak
OOO RPA Petrovax Pharm
Author for correspondence.
Email: moiseev_s_v@staff.sechenov.ru
ORCID iD: 0009-0000-8443-3257
Head of the Hospital Department
Russian Federation, 38, 12 Presnenskaya embankment, Moscow, 123112References
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