A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT‑P41 and reference denosumab in healthy males
BACKGROUND: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT‑P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes.
RESEARCH DESIGN AND METHODS: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT‑P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated.
RESULTS: Of 154 participants randomized (76 CT‑P41; 78 US-denosumab), 151 received study drug (74 CT‑P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3).
CONCLUSIONS: Following a single dose in healthy males, CT‑P41 demonstrated PK equivalence with US-denosumab.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT06037395.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Expert opinion on biological therapy - (2024) vom: 22. Feb., Seite 1-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Anhye [VerfasserIn] |
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| Links: |
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| Themen: |
Biosimilar |
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| Anmerkungen: |
Date Revised 27.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT06037395 Citation Status Publisher |
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| doi: |
10.1080/14712598.2024.2316846 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368397424 |
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| 100 | 1 | |a Kim, Anhye |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT‑P41 and reference denosumab in healthy males |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT06037395 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a BACKGROUND: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT‑P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes | ||
| 520 | |a RESEARCH DESIGN AND METHODS: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT‑P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated | ||
| 520 | |a RESULTS: Of 154 participants randomized (76 CT‑P41; 78 US-denosumab), 151 received study drug (74 CT‑P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3) | ||
| 520 | |a CONCLUSIONS: Following a single dose in healthy males, CT‑P41 demonstrated PK equivalence with US-denosumab | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov: NCT06037395 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biosimilar | |
| 650 | 4 | |a CT‑P41 | |
| 650 | 4 | |a denosumab | |
| 650 | 4 | |a immunogenicity | |
| 650 | 4 | |a pharmacodynamics | |
| 650 | 4 | |a pharmacokinetics | |
| 700 | 1 | |a Hong, Jang Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Wonsuk |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Hyounggyoon |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Jin-Gyu |e verfasserin |4 aut | |
| 700 | 1 | |a Reginster, Jean-Yves |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, SungHyun |e verfasserin |4 aut | |
| 700 | 1 | |a Bae, YunJu |e verfasserin |4 aut | |
| 700 | 1 | |a Suh, JeeHye |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sera |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, EunKyung |e verfasserin |4 aut | |
| 700 | 1 | |a Silverman, Stuart |e verfasserin |4 aut | |
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