Double-blind, randomized, phase I trial comparing the pharmacokinetics and safety of agalsidase beta bioanaloguer (Fabagal®) and the original drug (Fabrazim®) in healthy volunteers

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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, 119021

Aleksey 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, 390029

Yuliya 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, 390026

Pavel 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, 390029

Elena 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, 390029

Mikhail S. Khmelevsky

OOO RPA Petrovax Pharm

Email: moiseev_s_v@staff.sechenov.ru

Clinical Research Specialist

Russian Federation, 38, 12 Presnenskaya embankment, Moscow, 123112

Maksim 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, 123112

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2. Figure. Average pharmacokinetic profiles (concentration-time) of agalsidase beta on linear (left) and semi-logarithmic (right) scales when using the study drug (ISU303, Fagabal®) and the comparator drug (Fabrazim®). Vertical lines – 95% CI

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