Peking University People's Hospital, Beijing, China.
The First Affiliated Hospital of Soochow University, Suzhou, China.
Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22.
This study characterized the multidose pharmacokinetic (PK) characteristics of posaconazole tablets used as prophylactic antifungal therapy in Chinese patients with acute myelogenous leukemia (AML) at risk for invasive fungal infection (IFI).
Participants in this open-label, single-arm, phase 1b study received posaconazole 300 mg twice daily on day 1 and then once daily for up to 28 days. In the intensive PK sampling subgroup, posaconazole was administered under fasting conditions on days 1 and 8, and blood samples were regularly collected over 24 h. Trough PK sampling was conducted in all participants on days 1, 2, 3, 8, 14, 21, and 28 without regard for food intake. Population PK characteristics were predicted using PK modeling. Primary endpoints were steady-state average concentration (C) and percentage of participants with steady-state C (predicted and observed) > 500 ng/ml. Treatment safety and efficacy were secondary endpoints.
Sixty-five adult Chinese participants were enrolled. On day 8, steady-state arithmetic mean C was 1610 ng/ml (% coefficient of variation [%CV] 42.8%) in the intensive PK subgroup (n = 20). All participants achieved a steady-state C > 500 ng/ml. Predicted C (pC) was 1770 ng/ml (%CV 33.7%) in the total population (n = 64); 92.2% of participants had pC values ≥ 500 ng/ml (n = 59). The posaconazole tablet safety profile was consistent with that of the oral formulation, and the IFI rate was 3%.
In Chinese AML patients, the posaconazole 300-mg tablet provided PK data comparable with those of previous studies and was generally well tolerated and efficacious.
ClinicalTrials.gov, NCT02387983.
本研究旨在描述接受泊沙康唑片剂预防治疗的中国急性髓细胞白血病（AML）侵袭性真菌感染（IFI）高危患者的多剂量药代动力学（PK）特征。
本开放标签、单臂、1b 期研究中，参与者在第 1 天接受泊沙康唑 300mg 每日 2 次，然后每日 1 次，最多持续 28 天。在密集 PK 采样亚组中，第 1 天和第 8 天禁食时给予泊沙康唑，并在 24 小时内定期采集血样。所有参与者在第 1、2、3、8、14、21 和 28 天进行谷浓度 PK 采样，不考虑饮食摄入情况。采用 PK 模型预测群体 PK 特征。主要终点为稳态平均浓度（C）和稳态 C（预测和观察值）>500ng/ml 的参与者比例。治疗安全性和疗效为次要终点。
共纳入 65 例成年中国参与者。在密集 PK 采样亚组中（n=20），第 8 天稳态算术平均 C 为 1610ng/ml（%变异系数[CV]42.8%）。所有参与者均达到稳态 C>500ng/ml。在总人群（n=64）中，预测 C（pC）为 1770ng/ml（%CV 33.7%）；92.2%的参与者 pC 值≥500ng/ml（n=59）。泊沙康唑片剂的安全性特征与口服制剂一致，IFI 发生率为 3%。
在中国 AML 患者中，泊沙康唑 300mg 片剂提供的 PK 数据与既往研究相似，且通常具有良好的耐受性和疗效。
ClinicalTrials.gov，NCT02387983。
