Kaiyan Liu1, Depei Wu2, Junmin Li3, Hu Chen4, Hongmei Ning4, Ting Zhao5, Haiping Dai2, Li Chen3, Eric Mangin6, Gregory A Winchell7, Hetty Waskin6, Jun Jiang6, Yanping Qiu6, Xu Min Zhao6. 1. Peking University People's Hospital, Beijing, China. liukaiyan@medmail.com.cn. 2. The First Affiliated Hospital of Soochow University, Suzhou, China. 3. Shanghai Ruijin Hospital, Beijing, China. 4. The 307th Hospital of Chinese People's Liberation Army, Beijing, China. 5. Peking University People's Hospital, Beijing, China. 6. Merck & Co., Inc., Kenilworth, NJ, USA. 7. Certara USA, Inc., Princeton, NJ, USA.
Abstract
INTRODUCTION: 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). METHODS: 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 (Cavg) and percentage of participants with steady-state Cavg (predicted and observed) > 500 ng/ml. Treatment safety and efficacy were secondary endpoints. RESULTS:Sixty-five adult Chinese participants were enrolled. On day 8, steady-state arithmetic mean Cavg was 1610 ng/ml (% coefficient of variation [%CV] 42.8%) in the intensive PK subgroup (n = 20). All participants achieved a steady-state Cavg > 500 ng/ml. Predicted Cavg (pCavg) was 1770 ng/ml (%CV 33.7%) in the total population (n = 64); 92.2% of participants had pCavg 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%. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387983.
RCT Entities:
INTRODUCTION: 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). METHODS: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 (Cavg) and percentage of participants with steady-state Cavg (predicted and observed) > 500 ng/ml. Treatment safety and efficacy were secondary endpoints. RESULTS: Sixty-five adult Chinese participants were enrolled. On day 8, steady-state arithmetic mean Cavg was 1610 ng/ml (% coefficient of variation [%CV] 42.8%) in the intensive PK subgroup (n = 20). All participants achieved a steady-state Cavg > 500 ng/ml. Predicted Cavg (pCavg) was 1770 ng/ml (%CV 33.7%) in the total population (n = 64); 92.2% of participants had pCavg 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%. CONCLUSION: In Chinese AMLpatients, the posaconazole 300-mg tablet provided PK data comparable with those of previous studies and was generally well tolerated and efficacious. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387983.
Authors: Yuqian Sun; He Huang; Jing Chen; Jianyong Li; Jun Ma; Juan Li; Yingmin Liang; Jianmin Wang; Yan Li; Kang Yu; Jianda Hu; Jie Jin; Chun Wang; Depei Wu; Yang Xiao; Xiaojun Huang Journal: Tumour Biol Date: 2014-10-08
Authors: Gopal Krishna; Allen Moton; Lei Ma; Matthew M Medlock; James McLeod Journal: Antimicrob Agents Chemother Date: 2008-12-15 Impact factor: 5.191
Authors: Changcheng Shi; Jian Ye; Yaping Xie; Rong Dong; Weizhong Jin; Linling Wang; Yingying Fang; Qiyuan Shan; Nengming Lin Journal: Front Public Health Date: 2022-05-17