Center of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing 100853, People's Republic of China.
Livzon MabPharm Inc, Zhuhai, Guangdong 519045, People's Republic of China.
Drug Des Devel Ther. 2020 Jan 29;14:435-444. doi: 10.2147/DDDT.S235064. eCollection 2020.
To evaluate the pharmacokinetics (PK), bioequivalence and safety profile of the recombinant human chorionic gonadotropin (r-hCG) injection formulation LZM003 (test drug) comparing with that of Ovidrel (reference drug) in healthy Chinese subjects.
This is a randomized, single-blind, single-dose, two-arm and two-period crossover Phase I study. Subjects were randomized evenly to a single dose of LZM003 or reference drug injected subcutaneously, with a 10-day or longer between-treatment washout period. PK parameters, anti-drug antibodies (ADAs), and adverse events (AEs) were assessed. The primary PK endpoints were area under the curve (AUC) of the concentration-time curve from zero to last quantifiable concentration (AUC), AUC from zero to infinity (AUC), and peak concentration (C). Bioequivalence was determined by assessing whether the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of LZM003 to reference drug fell within predefined margins of 80% -125%.
Forty-eight subjects (24 males and 24 females) were enrolled and one subject withdrew for personal reasons. Mean values of primary PK parameters were similar (p > 0.05) between LZM003 and the reference drug. The 90% CIs for primary PK endpoints' GMR of LZM003 to reference drug ranged between 0.9144 and 1.1845, which were within bioequivalence margins of 80-125%. Incidence of AEs was similar (p > 0.05) between the two groups. Neither LZM003 nor reference drug produced anti-drug antibody (ADA) in healthy subjects.
LZM003 and reference drug were bioequivalent. The PK and safety assessments were similar (p > 0.05) between the two formulations in healthy Chinese subjects.
ChiCTR-IIR-16010158 (http://www.chictr.org.cn).
December 15, 2016.
评价健康中国受试者中重组人绒毛膜促性腺激素（rhCG）注射液 LZM003（试验药物）与 Ovidrel（参比药物）的药代动力学（PK）、生物等效性和安全性特征。
这是一项随机、单盲、单剂量、两臂、两周期交叉的 I 期研究。受试者随机均分为单次皮下注射 LZM003 或参比药物，两治疗期之间有 10 天或更长的洗脱期。评估 PK 参数、抗药物抗体（ADA）和不良事件（AE）。主要 PK 终点为从零到最后可量化浓度的浓度-时间曲线下面积（AUC）、从零到无穷大的 AUC（AUC）和峰浓度（C）。通过评估 LZM003 与参比药物的几何均数比值（GMR）的 90%置信区间（CI）是否落在 80%-125%的预设范围内来确定生物等效性。
共纳入 48 名受试者（24 名男性和 24 名女性），1 名受试者因个人原因退出。LZM003 与参比药物的主要 PK 参数的平均值相似（p>0.05）。LZM003 与参比药物主要 PK 终点 GMR 的 90%CI 范围在 0.9144 至 1.1845 之间，均在 80%-125%的生物等效性范围内。两组的 AE 发生率相似（p>0.05）。LZM003 和参比药物在健康受试者中均未产生抗药物抗体（ADA）。
LZM003 和参比药物具有生物等效性。在健康中国受试者中，两种制剂的 PK 和安全性评估相似（p>0.05）。
ChiCTR-IIR-16010158（http://www.chictr.org.cn）。
2016 年 12 月 15 日。
