一项在健康男性中比较地舒单抗生物类似药 CT-P41 与参照地舒单抗的药代动力学、药效学、安全性和免疫原性的随机、双盲、单次剂量、1 期研究。
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.
机构信息
Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine, Seongnam, Republic of Korea.
Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
出版信息
Expert Opin Biol Ther. 2024 Jul;24(7):655-663. doi: 10.1080/14712598.2024.2316846. Epub 2024 Feb 22.
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 (AUC), AUC from time zero to the last quantifiable concentration (AUC), and maximum serum concentration (C). 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 AUC (100.4-114.7), AUC (99.9-114.3), and C (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.
背景
本研究的目的是在健康的亚洲成年男性中证明地舒单抗生物类似药 CT-P41 与美国许可的地舒单抗（US-denosumab）的药代动力学（PK）相似性和安全性，并考虑药效学（PD）结果。
研究设计和方法
这是一项双盲、两臂、平行组、I 期研究，将健康男性随机分为 CT-P41 或 US-denosumab 单次（60mg）皮下给药组（1:1）。主要终点是从零时到无穷大的浓度-时间曲线下面积（AUC）（AUC）、从零时到最后可量化浓度的 AUC（AUC）和最大血清浓度（C）。如果几何最小二乘均值（gLSM）比值的 90%置信区间（CI）在 80-125%的等效性范围内，则确定 PK 等效性。还评估了次要 PK、PD、安全性和免疫原性结果。
结果
在 154 名随机分组的参与者（76 名 CT-P41；78 名 US-denosumab）中，151 名接受了研究药物（74 名 CT-P41；77 名 US-denosumab）。组间主要和次要 PK、PD、安全性和免疫原性结果相似。AUC（100.4-114.7）、AUC（99.9-114.3）和 C（95.2-107.3）的 gLSM 比值 90%CI 在预设的等效性范围内。
结论
在健康男性中单次给药后，CT-P41 表现出与 US-denosumab 的 PK 等效性。
试验注册
ClinicalTrials.gov：NCT06037395。
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