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

Abstract

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.).

• Authors: Rafael F Duarte, Javier López-Jiménez, Oliver A Cornely, Michel Laverdiere, David Helfgott, Shariq Haider, Pranatharthi Chandrasekar, Amelia Langston, John Perfect, Lei Ma, Marlou L P S van Iersel, Nancy Connelly, Nicholas Kartsonis, Hetty Waskin
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 10 Pg. 5758-65 (Oct 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 25049247 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antifungal Agents
• Tablets
• Triazoles
• posaconazole

Topics

• Antifungal Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Mycoses (prevention & control)
• Neutropenia (microbiology)
• Tablets (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Triazoles (administration & dosage, pharmacokinetics, therapeutic use)