Cargando…
Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial
OBJECTIVE: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects. METHODS: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684881/ https://www.ncbi.nlm.nih.gov/pubmed/36417156 http://dx.doi.org/10.1007/s40259-022-00563-5 |
_version_ | 1784835385754386432 |
---|---|
author | Wu, Min Li, Xiaojiao Yang, Deming Wang, Meng Zhang, Hong Li, Cuiyun Mai, Jiajia Yang, Lizhi Qi, Yunpeng Yu, Jin-Chen Yang, Xiaolei Wang, Zhaohe Gu, Cailing Ding, Yanhua |
author_facet | Wu, Min Li, Xiaojiao Yang, Deming Wang, Meng Zhang, Hong Li, Cuiyun Mai, Jiajia Yang, Lizhi Qi, Yunpeng Yu, Jin-Chen Yang, Xiaolei Wang, Zhaohe Gu, Cailing Ding, Yanhua |
author_sort | Wu, Min |
collection | PubMed |
description | OBJECTIVE: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects. METHODS: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared. RESULTS: The results showed that the 90% confidence interval of the geometric mean ratio for primary pharmacokinetic parameters (maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity) among BAT2206 and ustekinumab (USA or European Union sourced) groups were all within the predefined equivalent interval of 80–125%. Furthermore, all the groups had similar incidences of treatment-emergent adverse events, in which the majority of cases belonged to Common Terminology Criteria for the Classification of Adverse Events Grade 1 or 2. Anti-drug antibodies were detected in 54 (20.1%) subjects, namely 24 (26.7%), 13 (14.8%), and 17 (18.9%) patients in the BAT2206, ustekinumab (European Union), and ustekinumab (USA) groups, respectively. In contrast, the incidences of positive neutralizing antibodies were similar among the three groups. CONCLUSIONS: Pharmacokinetic similarity between BAT2206 and ustekinumab (USA or European Union sourced) was confirmed. The three groups had similar safety profiles, and the investigational drugs were well tolerated by subjects. CLINICAL TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04371185). |
format | Online Article Text |
id | pubmed-9684881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-96848812022-11-28 Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial Wu, Min Li, Xiaojiao Yang, Deming Wang, Meng Zhang, Hong Li, Cuiyun Mai, Jiajia Yang, Lizhi Qi, Yunpeng Yu, Jin-Chen Yang, Xiaolei Wang, Zhaohe Gu, Cailing Ding, Yanhua BioDrugs Original Research Article OBJECTIVE: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects. METHODS: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared. RESULTS: The results showed that the 90% confidence interval of the geometric mean ratio for primary pharmacokinetic parameters (maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity) among BAT2206 and ustekinumab (USA or European Union sourced) groups were all within the predefined equivalent interval of 80–125%. Furthermore, all the groups had similar incidences of treatment-emergent adverse events, in which the majority of cases belonged to Common Terminology Criteria for the Classification of Adverse Events Grade 1 or 2. Anti-drug antibodies were detected in 54 (20.1%) subjects, namely 24 (26.7%), 13 (14.8%), and 17 (18.9%) patients in the BAT2206, ustekinumab (European Union), and ustekinumab (USA) groups, respectively. In contrast, the incidences of positive neutralizing antibodies were similar among the three groups. CONCLUSIONS: Pharmacokinetic similarity between BAT2206 and ustekinumab (USA or European Union sourced) was confirmed. The three groups had similar safety profiles, and the investigational drugs were well tolerated by subjects. CLINICAL TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04371185). Springer International Publishing 2022-11-22 2023 /pmc/articles/PMC9684881/ /pubmed/36417156 http://dx.doi.org/10.1007/s40259-022-00563-5 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Research Article Wu, Min Li, Xiaojiao Yang, Deming Wang, Meng Zhang, Hong Li, Cuiyun Mai, Jiajia Yang, Lizhi Qi, Yunpeng Yu, Jin-Chen Yang, Xiaolei Wang, Zhaohe Gu, Cailing Ding, Yanhua Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title | Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title_full | Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title_fullStr | Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title_full_unstemmed | Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title_short | Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial |
title_sort | comparison of pharmacokinetic similarity, immunogenicity, and safety of ustekinumab and bat2206 in healthy chinese male subjects in a double-blind, randomized, single-dose, parallel-group phase i trial |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684881/ https://www.ncbi.nlm.nih.gov/pubmed/36417156 http://dx.doi.org/10.1007/s40259-022-00563-5 |
work_keys_str_mv | AT wumin comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT lixiaojiao comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT yangdeming comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT wangmeng comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT zhanghong comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT licuiyun comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT maijiajia comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT yanglizhi comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT qiyunpeng comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT yujinchen comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT yangxiaolei comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT wangzhaohe comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT gucailing comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial AT dingyanhua comparisonofpharmacokineticsimilarityimmunogenicityandsafetyofustekinumabandbat2206inhealthychinesemalesubjectsinadoubleblindrandomizedsingledoseparallelgroupphaseitrial |