Dong Ruihua, Chen Jingcheng, Guo Nini, Yang Yingying, Wu Jingxuan, Wang Xiaoru, Song Yuqin, Zhang Xueyuan
Phase I Clinical Trial Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Clinical Department, CSPC Zhongqi Pharmaceutical Technology (SJZ) Co., LTD., Shijiazhuang, Hebei Province, People's Republic of China.
Drug Des Devel Ther. 2024 Dec 3;18:5529-5539. doi: 10.2147/DDDT.S481481. eCollection 2024.
To evaluate the safety and pharmacokinetics of olaparib tablet test formulation (T) and reference formulation (R) in healthy Chinese male subjects.
This was a single-dose, randomized-sequence, two-way crossover study including three parts: part A: a safety exploration design in lower dose (n = 14, 100 mg), part B: a pivotal comparative pharmacokinetic (PK) trial under fast condition (n = 44, 150 mg) and part C: a pivotal comparative PK trial under food condition (n = 44, 150 mg). Blood samples were collected for 72 hours and the PK parameters of C, AUC and AUC were used to evaluate PK differences.
PK analysis of the two olaparib formulations showed that the Geometric Least Squares Mean (GLSM) ratio 90% confidence intervals for pivotal fasting C, AUC and AUC were 94.82-108.97%, 92.94-104.28%, and 92.81-103.85%, respectively, and pivotal fed C, AUC, and AUC were 82.78-100.97%, 91.59-104.67%, and 92.17-104.76%, respectively. The 90% confidence interval of the two preparations, C, AUC, and AUC, all fall within the equivalent range of 80-125%. Both olaparib tablet formulations were well tolerated, with no serious adverse events (SAE) or adverse events (AE) causing withdrawal occurred.
Two types of olaparib tablets were bioequivalent under both fasting and fed condition, and were generally well tolerated in healthy Chinese male subjects.
评估奥拉帕利片试验制剂（T）和参比制剂（R）在健康中国男性受试者中的安全性和药代动力学。
这是一项单剂量、随机序列、双向交叉研究，包括三个部分：A部分：低剂量（n = 14，100 mg）安全性探索设计；B部分：禁食条件下的关键比较药代动力学（PK）试验（n = 44，150 mg）；C部分：进食条件下的关键比较PK试验（n = 44，150 mg）。采集血样72小时，采用C、AUC和AUC的PK参数评估PK差异。
两种奥拉帕利制剂的PK分析显示，关键禁食状态下C、AUC和AUC的几何最小二乘均值（GLSM）比90%置信区间分别为94.82 - 108.97%、92.94 - 104.28%和92.81 - 103.85%，关键进食状态下C、AUC和AUC分别为82.78 - 100.97%、91.59 - 104.67%和92.17 - 104.76%。两种制剂的C、AUC和AUC的90%置信区间均落在80 - 125%的等效范围内。两种奥拉帕利片制剂耐受性良好，未发生严重不良事件（SAE）或导致停药的不良事件（AE）。
两种类型的奥拉帕利片在禁食和进食条件下均具有生物等效性，且在健康中国男性受试者中总体耐受性良好。
