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Cancer Chemotherapy and Pharmacology

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Open Access 01-10-2020 | Pharmacokinetics | Clinical Trial Report

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Authors: Donghoon Shin, Yoon Jung Lee, Jihye Choi, Dahyoung Lee, Minjeong Park, Magdalena Petkova

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2020

Abstract

Purpose

To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US).

Methods

In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUC_inf) and to the last quantifiable concentration (AUC_last), and maximum observed serum concentration (C_max). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated.

Results

The 90% CIs for the geometric LSMean ratios of AUC_inf, AUC_last and C_max were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUC_inf, 88.65%, 89.08% and 100.49% for AUC_last and 99.59%, 101.15% and 101.56% for C_max, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected.

Conclusion

This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US.

Clinicaltrials.gov identifier

NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

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Title: A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers
Authors: Donghoon Shin
Yoon Jung Lee
Jihye Choi
Dahyoung Lee
Minjeong Park
Magdalena Petkova
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Keywords: Pharmacokinetics
Bevacizumab
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04144-7

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