两种恩杂鲁胺软胶囊制剂在中国健康男性受试者中的生物等效性研究。
完整摘要 · 中文译文
恩杂鲁胺是一种口服第二代雄激素受体抑制剂，用于治疗晚期前列腺癌。本研究评估了新开发的恩杂鲁胺软胶囊（受试制剂）与参比制剂（XTANDI）在健康中国成人空腹及餐后条件下的药代动力学（PK）、生物等效性（BE）和安全性。采用单中心、随机、开放、两周期、两序列、交叉设计研究，共纳入72名男性受试者（36名空腹和36名餐后）。每名受试者接受单次口服40 mg受试制剂或参比制剂，给药间隔为34天清洗期。给药后采集血样至72小时。采用非房室模型分析法计算药代动力学参数（Cmax和AUC0-72 h）。通过几何均值比（GMRs）的90%置信区间（CIs）评估生物等效性。整个研究期间监测安全性。在空腹和餐后两种条件下，Cmax和AUC0-72 h的GMRs的90% CIs均在预先设定的80%-125%生物等效性范围内。两种制剂均表现出良好的单次给药安全性特征，未报告严重不良事件。受试恩杂鲁胺软胶囊在中国健康志愿者中与参比制剂具有生物等效性，显示出相似的药代动力学特征和安全性。本研究提供了针对中国人群的药代动力学证据，支持该仿制药在中国临床使用。
完整摘要 · 英文原文
Enzalutamide is an oral second-generation androgen receptor inhibitor used for advanced prostate cancer. This study evaluated the pharmacokinetics (PK), bioequivalence (BE), and safety of a newly developed generic enzalutamide soft capsule (test) compared with the reference product (XTANDI) in healthy Chinese adults under fasting and fed conditions. A single-center, randomized, open-label, two-period, two-sequence, crossover study was conducted in 72 male participants (36 fasting and 36 fed). Each participant received a single 40-mg dose of test or reference formulation, separated by a 34-day washout. Blood samples were collected up to 72 h post-dose. PK parameters (Cmax and AUC0-72 h) were calculated using non-compartmental analysis. BE was assessed by 90% confidence intervals (CIs) of geometric mean ratios (GMRs). Safety was monitored throughout the study. In both fasting and fed conditions, the 90% CIs of GMRs for Cmax and AUC0-72 h were within the predefined 80%-125% BE range. Both formulations exhibited a favorable single-dose safety profile, with no serious adverse events reported. The test enzalutamide soft capsule is bioequivalent to the reference product in healthy Chinese volunteers, demonstrating similar PK profiles and safety. This study provides population-specific PK evidence supporting the clinical use of the generic formulation in China.