Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection

Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection:

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 (C_avg) and percentage of participants with steady-state C_avg (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 C_avg was 1610 ng/ml (% coefficient of variation [%CV] 42.8%) in the intensive PK subgroup (n = 20). All participants achieved a steady-state C_avg > 500 ng/ml. Predicted C_avg (pC_avg) was 1770 ng/ml (%CV 33.7%) in the total population (n = 64); 92.2% of participants had pC_avg 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.