Pharmacokinetic and Pharmacodynamic Equivalence of Biosimilar and Reference Ultra-Rapid Lispro: A Comparative Clamp Study in Healthy Volunteers

IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Sergei Noskov, Ekaterina Koksharova, Anna Arefeva, Veniamin Banko, Kseniia Radaeva, Iuliia Matvienko, Maria Gefen, Igor Makarenko, Roman Drai
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Abstract

Ultra-rapid insulin lispro is an innovative insulin analogue designed to achieve rapid onset and short duration of action, aimed at optimizing glycemic control in patients with diabetes. This was a double-blind, randomized, 2-period, crossover clamp study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD), along with safety profiles, of a potential biosimilar ultra-rapid insulin lispro compared to the reference product in healthy White men. A total of 35 healthy volunteers completed hyperinsulinemic euglycemic clamp procedures across both study periods. Blood samples were collected at predefined intervals up to 8 hours to assess PK parameters. Plasma glucose levels were monitored every 5 minutes during the 8-hour clamps, with adjustments to the glucose infusion rate to maintain the target range. Insulin quantification in plasma was conducted using a validated enzyme-linked immunosorbent assay method. PD assessment was based on glucose infusion rate profiles during both clamps. Geometric mean ratios for maximum plasma concentration and area under the concentration-time curve from insulin administration to the last measurable concentration for the test and reference drugs fell within the bioequivalence range of 80%-125%. Furthermore, the investigational drugs demonstrated comparable PK/PD profiles of insulin lispro. Both formulations exhibited similar safety profiles primarily characterized by mild injection site reactions.

生物仿制药和参比超快速利斯普罗在健康志愿者体内的药代动力学和药效学等效性比较研究。
超快速胰岛素lispro是一种创新的胰岛素类似物,旨在实现快速起效和短时间的作用,旨在优化糖尿病患者的血糖控制。这是一项双盲,随机,2期,交叉钳夹研究,以评估潜在的生物仿制药超快速胰岛素lispro与参考产品在健康白人男性中的药代动力学(PK)和药效学(PD)以及安全性。在两个研究期间,共有35名健康志愿者完成了高胰岛素正糖钳夹手术。每隔8小时采集血液样本以评估PK参数。在8小时钳夹期间每5分钟监测一次血糖水平,并调整葡萄糖输注速率以维持目标范围。血浆胰岛素定量采用经验证的酶联免疫吸附测定法。PD评估是基于两个钳夹期间的葡萄糖输注速率谱。从胰岛素给药到试验药物和参比药物的最后可测浓度,最大血浆浓度和浓度-时间曲线下面积的几何平均比值均在80%-125%的生物等效性范围内。此外,研究药物显示出与胰岛素利斯普罗相当的PK/PD谱。两种制剂均表现出相似的安全性,主要特点是注射部位反应轻微。
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来源期刊
CiteScore
3.70
自引率
10.00%
发文量
154
期刊介绍: Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.
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