A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.
<h4>Purpose</h4>This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizuma...
Guardado en:
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/45bef64f51cc46f89c05d51ff1082315 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:45bef64f51cc46f89c05d51ff1082315 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:45bef64f51cc46f89c05d51ff10823152021-12-02T20:08:05ZA randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab.1932-620310.1371/journal.pone.0248222https://doaj.org/article/45bef64f51cc46f89c05d51ff10823152021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0248222https://doaj.org/toc/1932-6203<h4>Purpose</h4>This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizumab (NCT03390673).<h4>Methods</h4>In this randomized, double-blind, 3-way parallel group, single-dose comparative PK study, healthy male subjects were randomized to receive a single 1 mg/kg intravenous dose of HD204, EU-sourced bevacizumab or US-sourced bevacizumab. PK parameters were calculated using non-compartmental methods. PK equivalence was determined using the pre-defined equivalence margin of 0.8-1.25 in terms of AUC(0-∞) for the pairwise comparisons.<h4>Findings</h4>Baseline demographics for the 119 randomized subjects were similar across the three groups. The 90% CIs for the ratio of the geometric means of HD204 to US-sourced bevacizumab, HD204 to EU-sourced bevacizumab, and EU-sourced to US-sourced bevacizumab were all within the interval of 80% to 125% for AUC0-inf, thus demonstrating equivalency in the PK properties for all three treatment groups. Similarly, the ratio of the geometric means for AUC0-last and Cmax were all within the 80% and 125% margins, supporting the robustness of the primary findings. All other PK parameters, including the half-life (t1⁄2) clearance (CL), volume of distribution (Vd) and time of maximum concentration (tmax), were comparable. There was no difference between the 3 treatment arms in terms of vital signs, laboratory tests and adverse events. None of the subjects treated with HD204 had positive ADA results.<h4>Implications</h4>HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT03390673).Martin DemarchiPierre ColiatPhilippe BarthelemyRoland SchottMeher BenAbdelghaniMichael KimJocelyn Chung Shii HiiPeggy FeyaertsFelicia Rui Xia AngMarie Paule DerdeFilip DeforceThierry PetitChris SchwabeChris WynneLisa Soyeon ParkXavier PivotPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0248222 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Martin Demarchi Pierre Coliat Philippe Barthelemy Roland Schott Meher BenAbdelghani Michael Kim Jocelyn Chung Shii Hii Peggy Feyaerts Felicia Rui Xia Ang Marie Paule Derde Filip Deforce Thierry Petit Chris Schwabe Chris Wynne Lisa Soyeon Park Xavier Pivot A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
description |
<h4>Purpose</h4>This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizumab (NCT03390673).<h4>Methods</h4>In this randomized, double-blind, 3-way parallel group, single-dose comparative PK study, healthy male subjects were randomized to receive a single 1 mg/kg intravenous dose of HD204, EU-sourced bevacizumab or US-sourced bevacizumab. PK parameters were calculated using non-compartmental methods. PK equivalence was determined using the pre-defined equivalence margin of 0.8-1.25 in terms of AUC(0-∞) for the pairwise comparisons.<h4>Findings</h4>Baseline demographics for the 119 randomized subjects were similar across the three groups. The 90% CIs for the ratio of the geometric means of HD204 to US-sourced bevacizumab, HD204 to EU-sourced bevacizumab, and EU-sourced to US-sourced bevacizumab were all within the interval of 80% to 125% for AUC0-inf, thus demonstrating equivalency in the PK properties for all three treatment groups. Similarly, the ratio of the geometric means for AUC0-last and Cmax were all within the 80% and 125% margins, supporting the robustness of the primary findings. All other PK parameters, including the half-life (t1⁄2) clearance (CL), volume of distribution (Vd) and time of maximum concentration (tmax), were comparable. There was no difference between the 3 treatment arms in terms of vital signs, laboratory tests and adverse events. None of the subjects treated with HD204 had positive ADA results.<h4>Implications</h4>HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT03390673). |
format |
article |
author |
Martin Demarchi Pierre Coliat Philippe Barthelemy Roland Schott Meher BenAbdelghani Michael Kim Jocelyn Chung Shii Hii Peggy Feyaerts Felicia Rui Xia Ang Marie Paule Derde Filip Deforce Thierry Petit Chris Schwabe Chris Wynne Lisa Soyeon Park Xavier Pivot |
author_facet |
Martin Demarchi Pierre Coliat Philippe Barthelemy Roland Schott Meher BenAbdelghani Michael Kim Jocelyn Chung Shii Hii Peggy Feyaerts Felicia Rui Xia Ang Marie Paule Derde Filip Deforce Thierry Petit Chris Schwabe Chris Wynne Lisa Soyeon Park Xavier Pivot |
author_sort |
Martin Demarchi |
title |
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
title_short |
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
title_full |
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
title_fullStr |
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
title_full_unstemmed |
A randomized phase I study comparing the pharmacokinetics of a bevacizumab (HD204) biosimilar to European Union- and United States of America-sourced bevacizumab. |
title_sort |
randomized phase i study comparing the pharmacokinetics of a bevacizumab (hd204) biosimilar to european union- and united states of america-sourced bevacizumab. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/45bef64f51cc46f89c05d51ff1082315 |
work_keys_str_mv |
AT martindemarchi arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT pierrecoliat arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT philippebarthelemy arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT rolandschott arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT meherbenabdelghani arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT michaelkim arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT jocelynchungshiihii arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT peggyfeyaerts arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT feliciaruixiaang arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT mariepaulederde arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT filipdeforce arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT thierrypetit arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT chrisschwabe arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT chriswynne arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT lisasoyeonpark arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT xavierpivot arandomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT martindemarchi randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT pierrecoliat randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT philippebarthelemy randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT rolandschott randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT meherbenabdelghani randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT michaelkim randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT jocelynchungshiihii randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT peggyfeyaerts randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT feliciaruixiaang randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT mariepaulederde randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT filipdeforce randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT thierrypetit randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT chrisschwabe randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT chriswynne randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT lisasoyeonpark randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab AT xavierpivot randomizedphaseistudycomparingthepharmacokineticsofabevacizumabhd204biosimilartoeuropeanunionandunitedstatesofamericasourcedbevacizumab |
_version_ |
1718375236805591040 |