Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia

Journal Article

© 2014 American Society for Microbiology All Rights Reserved. Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of 500 ng/ml and 2,500 ng/ml in > 90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for 28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.) Copyright

Full Text

Duke Authors

Cited Authors

  • Duarte, RF; López-Jiménez, J; Comely, OA; Laverdiere, M; Helfgott, D; Haider, S; Chandrasekar, P; Langston, A; Perfect, J; Ma, L; Van Lersel, MLPS; Connelly, N; Kartsonis, N; Waskin, H

Published Date

  • October 1, 2014

Published In

Volume / Issue

  • 58 / 10

Start / End Page

  • 5758 - 5765

Electronic International Standard Serial Number (EISSN)

  • 1098-6596

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/AAC03050-14

Citation Source

  • Scopus