Evaluation of Pharmacokinetics and Safety of the Biosimilar (B01711) and Insulin Degludec/Insulin Aspart (IDegAsp, Ryzodeg) in Healthy Chinese Adults in a Randomized, Open-Label, Single-Dose, Crossover, Phase I Study.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-04-11 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S500347

Hui Liu, Haiyan Cao, Ting Li, Xinlei Chen, Hongling Yu, Jingfang Sun, Yerong Yu

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引用次数: 0

Abstract

Objective: 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.

Methods: 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.

Results: The primary PK parameters included the area under the curve (AUC) of insulin degludec (IDeg) from 0 to 24 hours (AUC_{IDeg, 0-24 h}), AUC of insulin aspart (IAsp) from 0 to the time of the last measurable value (AUC_{IAsp, 0-t}), and the peak concentration of IAsp (C_{IAsp, max}). 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_{IDeg, 0-24 h}; 103.9% (100.2%, 107.6%) for AUC_{IAsp, 0-t}; and 110.1% (101.0%, 119.9%) for C_{IAsp, max}. 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.

Conclusion: This study demonstrated the PK equivalence of the two drugs and confirmed that both were well-tolerated.

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在一项随机、开放标签、单剂量、交叉、I期研究中，评价生物类似药（B01711）和葡糖苷胰岛素/天冬氨酸胰岛素（IDegAsp, Ryzodeg）在中国健康成人中的药代动力学和安全性

目的：B01711是一种degludec/insulin aspart （IDegAsp 70/30）生物仿制药。这项随机、开放标签、单剂量、交叉、I期研究旨在评估B01711在健康中国志愿者中的药代动力学（PK）和安全性，并与原产品Ryzodeg进行比较。方法：研究于2022年4月至8月进行，该研究包括32名参与者（22名男性和10名女性），接受皮下注射B01711和Ryzodeg，两次治疗之间有≥14天的洗脱期。所有的参与者都完成了研究，没有一个人中途退出。每隔一段时间采集血样进行PK分析。结果：主要PK参数包括胰岛素葡糖苷（insulin degludec, IDeg） 0 ~ 24 h的曲线下面积（AUC）（AUCIDeg, 0 ~ 24 h）、胰岛素分离（insulin aspart, IAsp） 0 ~最后可测时间的曲线下面积（AUC）（AUCIAsp, 0 ~ t）和胰岛素分离峰浓度（CIAsp, max）。当B01711与Ryzodeg的主要PK终点对数变换值的最小二乘（LS）平均比值的90%置信区间（CIs）在80.0% ~ 125.0%之间时，可以建立PK等效。在整个研究过程中都对安全性进行了监测。0 ~ 24 h AUCIDeg的ls -平均值和相应的90% ci分别为106.1% (101.9%,110.5%)；AUCIAsp， 0-t为103.9% (100.2%,107.6%)；和110.1% (101.0%,119.9%)；B01711组报告2例治疗不良事件（teae）（6.3%）， Ryzodeg组报告7例teae（21.9%）。最常见的TEAE是血红蛋白降低。将低钾血症和低血糖不良事件（ae）确定为治疗相关ae (TRAEs)，所有TRAEs均为轻度。结论：本研究证实了两种药物的PK等效性，并证实了两种药物的良好耐受性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.