Zhang Hong, Wu Min, Zhu Xiaoxue, Li Cuiyun, Li Xiaojiao, Sun Jixuan, Liu Chengjiao, Liu Quan, Wei Wei, Niu Junqi, Ding Yanhua
Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2020 Oct 8;11:01329. doi: 10.3389/fphar.2020.01329. eCollection 2020.
This study was conducted to explore the tolerance, variability, pharmacokinetics (PK), and pharmacodynamics (PD) of denosumab biosimilar (QL1206) in healthy Chinese subjects.
This is a randomized, double-blind, two-arm, parallel study performed to examine the bioequivalence of denosumab biosimilar, QL1206, with that of Xgeva (Denosumab) as a reference drug. A single dose of 120 mg/kg of the denosumab biosimilar or Xgeva was administered to the subjects, who were followed up for 134 days.
Similar PK properties as those of Xgeva were exhibited by QL1206. When compared to QL1206 with Xgeva, the 90% confidence intervals of the ratios for C, AUC, and AUC were observed to be within 80-125%. The inter-subject variability (inter-CV) ranged from 29% to 39.5%. Six and three subjects in the QL1206 and Xgeva groups were found to be positive for the ADA and negative for the NAb, respectively. The CTX1 concentration-time profiles appeared similar (about 80% decrease from 48 hours to134 days) between the QL1206 and Xgeva groups. Adverse events (AEs) were observed in 92.6% and 93.4% of subjects in the QL1206 and Xgeva groups, respectively. Reduction in blood calcium level was found to be the most common AE recorded, with an incidence of 72.8% versus 72.4% in the QL1206 and Xgeva groups, respectively.
Similar PK and PD characteristics were exhibited by QL1206 as compared to those of Xgeva. The inter-CV was slightly large. The safety profiles of denosumab biosimilars and Xgeva were found to be similar.
本研究旨在探讨地舒单抗生物类似药（QL1206）在健康中国受试者中的耐受性、变异性、药代动力学（PK）和药效动力学（PD）。
这是一项随机、双盲、双臂、平行研究，旨在检验地舒单抗生物类似药QL1206与参比药物Xgeva（地舒单抗）的生物等效性。受试者接受单次剂量120mg/kg的地舒单抗生物类似药或Xgeva治疗，并随访134天。
QL1206表现出与Xgeva相似的PK特性。与QL1206和Xgeva相比，C、AUC和AUC比值的90%置信区间在80%-125%以内。受试者间变异性（inter-CV）范围为29%至39.5%。QL1206组和Xgeva组分别有6例和3例受试者ADA检测呈阳性、NAb检测呈阴性。QL1206组和Xgeva组的CTX1浓度-时间曲线相似（从48小时到134天下降约80%）。QL1206组和Xgeva组分别有92.6%和93.4%的受试者发生不良事件（AE）。血钙水平降低是最常见的AE，QL1206组和Xgeva组的发生率分别为72.8%和72.4%。
与Xgeva相比，QL1206表现出相似的PK和PD特征。受试者间变异性稍大。地舒单抗生物类似药和Xgeva的安全性相似。
