title: 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: Catalan Institute of Oncology, Barcelona, Spain rduarte@iconcologia.net.
authors: Rafael F
authors: RF
authors: Duarte
authors: Hospital Ramón y Cajal, Madrid, Spain.
authors: Javier
authors: J
authors: López-Jiménez
authors: First Department of Internal Medicine, ZKS Köln, BMBF 01KN1106, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors: Oliver A
authors: OA
authors: Cornely
authors: Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors: Michel
authors: M
authors: Laverdiere
authors: New York-Presbyterian/Weill Cornell Medical Center, New York, New York, USA.
authors: David
authors: D
authors: Helfgott
authors: Juravinski Hospital, Hamilton, Ontario, Canada.
authors: Shariq
authors: S
authors: Haider
authors: Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
authors: Pranatharthi
authors: P
authors: Chandrasekar
authors: Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
authors: Amelia
authors: A
authors: Langston
authors: Duke University Medical Center, Durham, North Carolina, USA.
authors: John
authors: J
authors: Perfect
authors: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors: Lei
authors: L
authors: Ma
authors: MSD, Oss, Netherlands.
authors: Marlou L P S
authors: ML
authors: van Iersel
authors: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors: Nancy
authors: N
authors: Connelly
authors: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors: Nicholas
authors: N
authors: Kartsonis
authors: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors: Hetty
authors: H
authors: Waskin
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D009503:Neutropenia / Q000382:microbiology*; D013607:Tablets / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D013607:Tablets; D014230:Triazoles; C101425:posaconazole