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.
Kim, Anhye; Hong, Jang Hee; Shin, Wonsuket al.
2024 • In Expert Opinion on Biological Therapy, p. 1 - 9
[en] [en] 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.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Kim, Anhye ; Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine, Seongnam, Republic of Korea
Hong, Jang Hee ; Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
Shin, Wonsuk ; Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine, Seongnam, Republic of Korea
Yoo, Hyounggyoon ; Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine, Seongnam, Republic of Korea
Jung, Jin-Gyu ; Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique ; WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Aging, Liège, Belgium ; College of Science, Kind Saud University, Riyadh, Kingdom of Saudi Arabia
Kim, SungHyun; Celltrion, Inc., Incheon, Republic of Korea
Bae, YunJu; Celltrion, Inc., Incheon, Republic of Korea
Suh, JeeHye; Celltrion, Inc., Incheon, Republic of Korea
Kim, Sera; Celltrion, Inc., Incheon, Republic of Korea
Lee, EunKyung; Celltrion, Inc., Incheon, Republic of Korea
Silverman, Stuart ; Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA ; OMC Clinical Research Center, Beverly Hills, CA, USA
Language :
English
Title :
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.
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