Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal
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ORIGINAL RESEARCH
Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection Kaiyan Liu . Depei Wu . Junmin Li . Hu Chen . Hongmei Ning . Ting Zhao . Haiping Dai . Li Chen . Eric Mangin . Gregory A. Winchell . Hetty Waskin . Jun Jiang . Yanping Qiu . Xu Min Zhao
Received: February 20, 2020 Ó Springer Healthcare Ltd., part of Springer Nature 2020
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 Digital Features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12086820. K. Liu (&) T. Zhao Peking University People’s Hospital, Beijing, China e-mail: [email protected] D. Wu H. Dai The First Affiliated Hospital of Soochow University, Suzhou, China J. Li L. Chen Shanghai Ruijin Hospital, Beijing, China H. Chen H. Ning The 307th Hospital of Chinese People’s Liberation Army, Beijing, China E. Mangin H. Waskin J. Jiang Y. Qiu X. M. Zhao Merck & Co., Inc., Kenilworth, NJ, USA G. A. Winchell Certara USA, Inc., Princeton, NJ, USA
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 C 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. Keywords: Pharmacokinetics; Triazole antifungal
Posaconazole;
Adv Ther
Key Summary Points Why carry out this study? Data are lacking regarding the pharmacokinetic and safety outcomes of posaconazole tablets when used as antifungal prophylaxis in Chinese patients at high risk for invasive fungal infection.
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