Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei, People's Republic of China.
Center for Clinical Pharmacology, Shanghai Innovstone Therapeutics Limited, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2024 Jun 14;18:2273-2285. doi: 10.2147/DDDT.S461771. eCollection 2024.
OBJECTIVE: This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application. METHODS: A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (C), the areas under the plasma concentration-time curve (AUC, AUC), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated. RESULTS: Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09-103.44% for C, 94.05-103.51% for AUC, and 94.56-103.86% for AUC under fasting conditions, and 99.18-112.48% for C, 98.79-106.02% for AUC, and 98.95-105.89% for AUC under postprandial conditions, all of which were within the bioequivalence range of 80.00-125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study. CONCLUSION: The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated. CLINICAL TRIAL REGISTRATION: chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).
目的：本研究比较了空腹和餐后条件下，仿制和原研阿普米司特片在健康中国受试者中的药代动力学、安全性和生物等效性（BE），为简化新药申请提供了充分的证据。
方法：进行了一项随机、开放标签、两制剂、单剂量、两周期交叉药代动力学研究。32 名符合条件的健康中国受试者分别参加了空腹和餐后研究。在每个试验中，受试者接受单次 30mg 受试或参比阿普米司特片给药，每个周期之间有 7 天的洗脱期。每个周期中，在摄入后最多 48 小时内采集连续血样，并采用经过验证的方法测定阿普米司特的血浆浓度。采用非房室法计算主要药代动力学（PK）参数，包括最大血浆浓度（C）、血浆浓度-时间曲线下面积（AUC）。采用几何均数比及其 90%置信区间（CI）进行生物等效性分析。还评估了两种制剂的安全性。
结果：在空腹和餐后状态下，受试药物的 PK 参数与参比药物相似。空腹条件下，受试制剂与参比制剂的几何均数比的 90%CI 为 94.09%-103.44%（C）、94.05%-103.51%（AUC）和 94.56%-103.86%（AUC），餐后条件下为 99.18%-112.48%（C）、98.79%-106.02%（AUC）和 98.95%-105.89%（AUC），均在 80.00%-125.00%的生物等效范围内。两种制剂均耐受良好，研究期间均未发生严重不良事件。
结论：该试验证实，空腹和餐后状态下，仿制和原研阿普米司特片的 PK 参数在健康中国受试者中具有生物等效性，符合预定的监管标准。两种制剂均安全且耐受良好。
临床试验注册：chinaDrugtrials.org.cn，注册号 CTR20191056（2019 年 7 月 30 日）；chictr.org.cn，注册号 ChiCTR2300076806（2023 年 10 月 19 日）。
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