Abstract：
BACKGROUND: This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab).
METHODS: In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria.
RESULTS: Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies.
CONCLUSIONS: This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.
BACKGROUND: ANZCTR number: ACTRN12621000573853.
METHODS: In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria.
RESULTS: Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies.
CONCLUSIONS: This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.
BACKGROUND: ANZCTR number: ACTRN12621000573853.
摘要：
背景：这项研究评估了BP02（拟议的曲妥珠单抗生物仿制药）与欧盟（EU-曲妥珠单抗）和美国（US-曲妥珠单抗）批准的参考曲妥珠单抗之间的药代动力学（PK）等效性。
方法：在此阶段1，双盲，平行组试验,111名健康男性志愿者以1：1：1的比例随机接受单次6-mg/kg静脉输注BP02，EU-曲妥珠单抗，或US-曲妥珠单抗，并评估78天。通过非房室方法分析血清药物浓度-时间数据。BP02与两种参考产品的PK相似性，在欧盟曲妥珠单抗和美国曲妥珠单抗之间，使用标准的80-125%生物等效性标准确定。
结果：在所有治疗组中，具有可评估的药代动力学的111名受试者的基线人口统计学相似。这三种产品的PK曲线相似。从给药时间到无穷大（AUC0-inf）的血清浓度-时间曲线下面积（AUC）比率的90％置信区间（CI），从给药时间到最后可量化浓度（AUC0-t）的AUC，在所有三个成对比较中,曲妥珠单抗的峰值血清浓度(Cmax)在80%~125%以内.所有手臂的不良事件(AE)相似，与治疗相关的不良事件报告为73.0%，73.0%,和89.2%的受试者在BP02，EU-曲妥珠单抗，和美国曲妥珠单抗组，分别。最常见的不良事件是头痛，输液相关反应,和上呼吸道感染.四名受试者-US-曲妥珠单抗组的三名和BP02组的一名-由于AE而中断了研究。除两个抗药物抗体测试阴性外,所有给药后样品。
结论：这项研究证明了BP02，EU-曲妥珠单抗之间的PK相似性，和美国曲妥珠单抗。在本研究中观察到的三种产品的安全性和免疫原性谱与先前关于曲妥珠单抗的报道一致。
背景：ANZCTR编号：ACTRN12621000573853。
方法：在此阶段1，双盲，平行组试验,111名健康男性志愿者以1：1：1的比例随机接受单次6-mg/kg静脉输注BP02，EU-曲妥珠单抗，或US-曲妥珠单抗，并评估78天。通过非房室方法分析血清药物浓度-时间数据。BP02与两种参考产品的PK相似性，在欧盟曲妥珠单抗和美国曲妥珠单抗之间，使用标准的80-125%生物等效性标准确定。
结果：在所有治疗组中，具有可评估的药代动力学的111名受试者的基线人口统计学相似。这三种产品的PK曲线相似。从给药时间到无穷大（AUC0-inf）的血清浓度-时间曲线下面积（AUC）比率的90％置信区间（CI），从给药时间到最后可量化浓度（AUC0-t）的AUC，在所有三个成对比较中,曲妥珠单抗的峰值血清浓度(Cmax)在80%~125%以内.所有手臂的不良事件(AE)相似，与治疗相关的不良事件报告为73.0%，73.0%,和89.2%的受试者在BP02，EU-曲妥珠单抗，和美国曲妥珠单抗组，分别。最常见的不良事件是头痛，输液相关反应,和上呼吸道感染.四名受试者-US-曲妥珠单抗组的三名和BP02组的一名-由于AE而中断了研究。除两个抗药物抗体测试阴性外,所有给药后样品。
结论：这项研究证明了BP02，EU-曲妥珠单抗之间的PK相似性，和美国曲妥珠单抗。在本研究中观察到的三种产品的安全性和免疫原性谱与先前关于曲妥珠单抗的报道一致。
背景：ANZCTR编号：ACTRN12621000573853。
