Choi Chungam, Yoo Byung Won, Kim Choon Ok, Hong Taegon, Jin Byung Hak, Seo Kwang-Seok, Jang Ja Yun, Park Min Soo
Department of Nuclear Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea,
Drug Des Devel Ther. 2018 Aug 1;12:2381-2387. doi: 10.2147/DDDT.S158277. eCollection 2018.
Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim is a recombinant filgrastim product tested for biosimilarity with its reference product, Neupogen. We conducted a comparative clinical trial of the 2 products.
A randomized, open-label, 2-way crossover, single-dose Phase I study was conducted for 56 healthy subjects. After a 5 and 10 μg/kg single subcutaneous administration of test and reference product, pharmacokinetic and pharmacodynamic parameters (absolute neutrophil count and CD34 cell count) were compared. During the study, safety tests and adverse event monitoring were performed.
The test and the reference products had a comparable pharmacokinetic, pharmacodynamic, and safety profile. In both 5 and 10 μg/kg dosing, the 90% CIs of the test to reference ratio for primary parameters (peak plasma concentration and area under the plasma concentration vs time curve from time 0 extrapolated to the infinite time for plasma filgrastim concentration; maximal effect and area under the time-effect curve from time 0 to time of the last quantifiable effect for absolute neutrophil count) were within the 0.8-1.25 range. In addition, safety profiles between the 2 products were similar without any serious adverse events.
This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product.
非格司亭，一种粒细胞集落刺激因子，用于治疗中性粒细胞减少症患者，包括中性粒细胞减少性发热。乐舒能是一种重组非格司亭产品，已针对其与参比产品优保津的生物相似性进行了测试。我们对这两种产品进行了一项对比临床试验。
对56名健康受试者进行了一项随机、开放标签、双向交叉、单剂量I期研究。在分别皮下单剂量给予5μg/kg和10μg/kg的受试产品和参比产品后，比较了药代动力学和药效学参数（绝对中性粒细胞计数和CD34细胞计数）。在研究过程中，进行了安全性测试和不良事件监测。
受试产品和参比产品具有可比的药代动力学、药效学和安全性特征。在5μg/kg和10μg/kg两种剂量下，主要参数（血浆峰浓度以及血浆非格司亭浓度从时间0外推至无限时间的血浆浓度-时间曲线下面积；最大效应以及绝对中性粒细胞计数从时间0至最后可量化效应时间的时间-效应曲线下面积）的受试产品与参比产品比值的90%置信区间均在0.8至1.25范围内。此外，两种产品的安全性特征相似，均未出现任何严重不良事件。
本研究提供了确凿的临床证据，证明受试非格司亭产品与其参比非格司亭产品相似。
