Liu Hui, Cao Haiyan, Li Ting, Chen Xinlei, Yu Hongling, Sun Jingfang, Yu Yerong
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.
Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.
Drug Des Devel Ther. 2025 Apr 11;19:2863-2871. doi: 10.2147/DDDT.S500347. eCollection 2025.
B01711 is a biosimilar of insulin degludec/insulin aspart (IDegAsp 70/30). This randomized, open-label, single-dose, crossover, phase I study aimed to evaluate the pharmacokinetics (PK) and safety of B01711 compared to its original product (Ryzodeg) in healthy Chinese volunteers.
The study was conducted between April and August 2022, this study included 32 participants (22 males and 10 females) who received subcutaneous injections of both B01711 and Ryzodeg, with a ≥14-day washout period between treatments. All participants completed the study without any dropouts. Blood samples were collected at pre-defined intervals for PK analysis.
The primary PK parameters included the area under the curve (AUC) of insulin degludec (IDeg) from 0 to 24 hours (AUC), AUC of insulin aspart (IAsp) from 0 to the time of the last measurable value (AUC), and the peak concentration of IAsp (C). PK equivalence would be established if the 90% confidence intervals (CIs) of least squares (LS) mean ratios of log-transformed values of primary PK endpoints for B01711 compared with Ryzodeg fell within the range of 80.0% to 125.0%. Safety was monitored throughout the study. The LS-mean ratios and corresponding 90% CIs were 106.1% (101.9%, 110.5%) for AUC; 103.9% (100.2%, 107.6%) for AUC; and 110.1% (101.0%, 119.9%) for C. Two treatment-emergent adverse events (TEAEs) were reported in two subjects (6.3%) in the B01711 group, and seven TEAEs were reported in seven subjects (21.9%) in the Ryzodeg group. The most common TEAE was a decrease in hemoglobin. The adverse events (AEs) of hypokalemia and hypoglycemia were identified as treatment-related AEs (TRAEs) and all TRAEs were mild.
This study demonstrated the PK equivalence of the two drugs and confirmed that both were well-tolerated.
B01711是德谷胰岛素/门冬胰岛素（IDegAsp 70/30）的生物类似药。这项随机、开放标签、单剂量、交叉的I期研究旨在评估在中国健康志愿者中，B01711与其原研产品（Ryzodeg）相比的药代动力学（PK）和安全性。
该研究于2022年4月至8月进行，纳入32名参与者（22名男性和10名女性），他们接受了B01711和Ryzodeg的皮下注射，治疗间隔期≥14天。所有参与者均完成研究，无一人退出。在预先设定的时间点采集血样进行PK分析。
主要PK参数包括0至24小时德谷胰岛素（IDeg）的曲线下面积（AUC）、0至最后可测值时间的门冬胰岛素（IAsp）的AUC以及IAsp的峰浓度（C）。如果B01711与Ryzodeg相比，主要PK终点的对数转换值的最小二乘（LS）均值比的90%置信区间（CI）落在80.0%至125.0%范围内，则可确定PK等效性。在整个研究过程中监测安全性。AUC的LS均值比及相应的90%CI为106.1%（101.9%，110.5%）；AUC为103.9%（100.2%，107.6%）；C为110.1%（101.0%，119.9%）。B01711组有2名受试者（6.3%）报告了2例治疗中出现的不良事件（TEAE），Ryzodeg组有7名受试者（21.9%）报告了7例TEAE。最常见的TEAE是血红蛋白降低。低钾血症和低血糖不良事件被确定为治疗相关不良事件（TRAEs），所有TRAEs均为轻度。
本研究证明了两种药物的PK等效性，并证实两者耐受性良好。
