培格非格司亭-cbqv 与培格非格司亭在健康受试者中的药代动力学和药效学等效性。
Pharmacokinetic and Pharmacodynamic Equivalence of Pegfilgrastim-cbqv and Pegfilgrastim in Healthy Subjects.
机构信息
Coherus BioSciences, Redwood City, CA, USA.
出版信息
Adv Ther. 2020 Oct;37(10):4291-4307. doi: 10.1007/s12325-020-01459-y. Epub 2020 Aug 13.
INTRODUCTION
Pegfilgrastim-cbqv was developed as a biosimilar of pegfilgrastim, a pegylated form of recombinant human granulocyte colony-stimulating factor approved for decreasing febrile neutropenia-associated infection in patients receiving myelosuppressive drugs. This multicenter, randomized, single-blind, partial-reference-replicated, three-sequence crossover study assessed pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv and pegfilgrastim in healthy subjects.
METHODS
One hundred twenty-two subjects were randomized to one of three treatment sequences; each included one dose of pegfilgrastim-cbqv and two doses of pegfilgrastim separated by ≥ 28 days. The primary pharmacokinetic end points were area under the curve (AUC) from 0 to infinity (AUC) and maximum concentration (C). The primary pharmacodynamic end points were maximum absolute neutrophil count (ANC) and ANC AUC from time 0 to the last measurable observation (ANC AUC). Pharmacokinetic and pharmacodynamic bioequivalences were demonstrated if the 90% CI for the geometric mean ratio (GMR) of pegfilgrastim-cbqv to pegfilgrastim was within 80-125% for the primary end points.
RESULTS
Pharmacokinetic bioequivalence criteria were met for C (GMR 105.0; 90% CI 95.5-115.4) and AUC (GMR 97.5; 90% CI 88.6-107.2). Pharmacodynamic bioequivalence criteria were met for ANC (GMR 99.6; 90% CI 96.2-103.2) and ANC AUC (GMR 96.7; 90% CI 92.2-101.4). Adverse events occurred in 76.0%, 76.6%, and 73.1% of subjects for pegfilgrastim-cbqv, first pegfilgrastim, and second pegfilgrastim dosing periods across treatment sequences, respectively. Investigators found no drug-related serious adverse events.
CONCLUSION
This study established pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv to pegfilgrastim. The treatments displayed similar safety profiles, including immunogenicity, with no unexpected safety findings.
CLINICAL TRIALS REGISTRATION
ClinicalTrials.gov, NCT02650973, February 2016.
简介
Pegfilgrastim-cbqv 是一种 pegfilgrastim 的生物类似药，pegfilgrastim 是一种聚乙二醇化的重组人粒细胞集落刺激因子，用于降低接受骨髓抑制药物治疗的患者中性粒细胞减少症相关感染的发热发生率。这项多中心、随机、单盲、部分参照复制、三序列交叉研究评估了 pegfilgrastim-cbqv 和 pegfilgrastim 在健康受试者中的药代动力学和药效学生物等效性。
方法
122 名受试者按治疗顺序随机分为三组；每组包括一次 pegfilgrastim-cbqv 剂量和两次 pegfilgrastim 剂量，间隔时间≥28 天。主要药代动力学终点为从 0 到无穷大（AUC）的曲线下面积（AUC）和最大浓度（C）。主要药效学终点为最大绝对中性粒细胞计数（ANC）和从时间 0 到最后一次可测量观察（ANC AUC）的 ANC AUC。如果 pegfilgrastim-cbqv 与 pegfilgrastim 的几何均数比值（GMR）的 90%置信区间（CI）在 80%-125%范围内，则认为药代动力学和药效学等效。
结果
C（GMR 105.0；90%CI 95.5-115.4）和 AUC（GMR 97.5；90%CI 88.6-107.2）符合药代动力学等效标准。ANC（GMR 99.6；90%CI 96.2-103.2）和 ANC AUC（GMR 96.7；90%CI 92.2-101.4）符合药效学等效标准。在治疗顺序中，分别有 76.0%、76.6%和 73.1%的受试者在 pegfilgrastim-cbqv、第一 pegfilgrastim 和第二 pegfilgrastim 给药期间发生不良事件。研究者未发现与药物相关的严重不良事件。
结论
本研究确立了 pegfilgrastim-cbqv 与 pegfilgrastim 的药代动力学和药效学等效性。两种治疗方法的安全性特征相似，包括免疫原性，无意外安全性发现。
临床试验注册
ClinicalTrials.gov，NCT02650973，2016 年 2 月。
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