R&D Center, GEROPHARM, Saint Petersburg, Russia.
Federal State Budgetary Educational Institution of Higher Education "A.I. Evdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
Pharmacol Res Perspect. 2023 Oct;11(5):e01125. doi: 10.1002/prp2.1125.
The pharmacodynamic (PD) similarity between GP40141, a proposed romiplostim biosimilar, and reference romiplostim was evaluated. Pharmacokinetics and safety were also assessed.
In this phase 1, randomized, double-blind, single-dose, crossover comparative study with an adaptive design, 56 healthy male volunteers were randomized 1:1 to receive a 3 ug × kg subcutaneous dose of GP40141 and reference romiplostim. The PD similarity between GP40141 and the reference romiplostim was determined using the standard equivalence criteria (80%-125%) for the area under the platelet count-time curve from time 0 to the time of the last sampling for PD (AUC ) and the maximum observed platelet count (P ).
GP40141 and the reference romiplostim exhibited similar PD profiles. 90% CI for the geometric mean ratios for the primary PD parameters (AUC P ) for GP40141 (T) and the reference romiplostim (R) were fully contained within the predefined equivalence limits of 80%-125%: 98.13%-102.42% for AUC and 97.56%-105.80% for P . The pharmacokinetic profiles of GP40141 and the reference romiplostim were well described. No adverse events were observed during the clinical trial after the administration of GP40141 and the reference romiplostim.
This study demonstrates the PD similarity of GP40141 to the reference romiplostim. Both treatments had comparable safety profiles (NCT05652595).
评估拟开发的罗米司亭生物类似药 GP40141 与参照罗米司亭的药效学（PD）相似性。同时评估了药代动力学和安全性。
这是一项采用适应性设计的、随机、双盲、单次给药、交叉比较的 1 期临床研究，共纳入 56 名健康男性志愿者，按 1:1 比例随机接受 3μg×kg-1 皮下注射剂量的 GP40141 和参照罗米司亭。采用标准等效性标准（80%-125%），以血小板计数时间曲线下面积（从 0 时间到 PD 最后一次采样时间的 AUC）和最大血小板计数（P）作为主要 PD 参数，评估 GP40141 与参照罗米司亭的 PD 相似性。
GP40141 与参照罗米司亭表现出相似的 PD 特征。GP40141（T）和参照罗米司亭（R）的主要 PD 参数（AUC P）的几何均数比值的 90%置信区间（CI）完全包含在 80%-125%的预设等效性限值内：AUC 为 98.13%-102.42%，P 为 97.56%-105.80%。GP40141 和参照罗米司亭的药代动力学特征均得到了很好的描述。在 GP40141 和参照罗米司亭给药后，临床试验期间未观察到任何不良事件。
这项研究表明 GP40141 与参照罗米司亭的 PD 相似。两种治疗方法具有相似的安全性特征（NCT05652595）。
