Universität zu Köln

Cornely, Oliver A., Duarte, Rafael F., Haider, Shariq, Chandrasekar, Pranatharthi, Helfgott, David, Lopez Jimenez, Javier, Candoni, Anna ORCID: 0000-0003-4436-1310, Raad, Issam, Laverdiere, Michel, Langston, Amelia, Kartsonis, Nicholas, Van Iersel, Marlou, Connelly, Nancy and Waskin, Hetty (2016). Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J. Antimicrob. Chemother., 71 (3). S. 718 - 727. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

Full text not available from this repository.

Abstract

This Phase 1B study showed that a single tablet of 300aEuroSmg of posaconazole, given once daily as prophylaxis to 210 patients at risk for invasive fungal disease, was as safe as that reported for posaconazole oral suspension and achieved steady-state > 500aEuroSng/mL for all but one patient.Antifungal prophylaxis with a new oral tablet formulation of posaconazole may be beneficial to patients at high risk for invasive fungal disease. A two-part (Phase 1B/3) study evaluated posaconazole tablet pharmacokinetics (PK) and safety. Patients with neutropenia following chemotherapy for haematological malignancy or recipients of allogeneic HSCT receiving prophylaxis or treatment for graft-versus-host disease received 300 mg posaconazole (as tablets) once daily (twice daily on day 1) for up to 28 days without regard to food intake. Weekly trough PK sampling was performed during therapy, and a subset of patients had sampling on days 1 and 8. C-min-evaluable subjects received a parts per thousand yen6 days of dosing, and were compliant with specified sampling timepoints. Steady-state PK parameters, safety, clinical failure and survival to day 65 were assessed. ClinicalTrials.gov, NCT01777763; EU Clinical Trials Register, EUDRA-CT 2008-006684-36. Two hundred and ten patients received 300 mg posaconazole (as tablets) once daily. Among C-min-evaluable subjects (naEuroS=aEuroS186), steady-state mean C-min was 1720 ng/mL (rangeaEuroS=aEuroS210-9140). Steady-state C-min was a parts per thousand yen700 ng/mL in 90% of subjects with 5% (10 of 186) < 500 ng/mL and 5% (10 of 186) 500-700 ng/mL. Six (3%) patients had steady-state C-min a parts per thousand yen3750 ng/mL. One patient (< 1%) had an invasive fungal infection. The most common treatment-related adverse events were nausea (11%) and diarrhoea (8%). There was no increase in adverse event frequency with higher posaconazole exposure. In patients at high risk for invasive fungal disease, 300 mg posaconazole (as tablets) once daily was well tolerated and demonstrated a safety profile similar to that reported for posaconazole oral suspension: most patients (99%) achieved steady-state pC(avg) exposures > 500 ng/mL and only one patient (< 1%) had a pC(avg) < 500 ng/mL.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Duarte, Rafael F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haider, Shariq UNSPECIFIED UNSPECIFIED UNSPECIFIED Chandrasekar, Pranatharthi UNSPECIFIED UNSPECIFIED UNSPECIFIED Helfgott, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Lopez Jimenez, Javier UNSPECIFIED UNSPECIFIED UNSPECIFIED Candoni, Anna UNSPECIFIED orcid.org/0000-0003-4436-1310 UNSPECIFIED Raad, Issam UNSPECIFIED UNSPECIFIED UNSPECIFIED Laverdiere, Michel UNSPECIFIED UNSPECIFIED UNSPECIFIED Langston, Amelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kartsonis, Nicholas UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Iersel, Marlou UNSPECIFIED UNSPECIFIED UNSPECIFIED Connelly, Nancy UNSPECIFIED UNSPECIFIED UNSPECIFIED Waskin, Hetty UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-283784
DOI:	10.1093/jac/dkv380
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	71
Number:	3
Page Range:	S. 718 - 727
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VERSUS-HOST-DISEASE; ORAL POSACONAZOLE; HEALTHY-VOLUNTEERS; EXPOSURE-RESPONSE; CANCER-PATIENTS; PROPHYLAXIS; INFECTIONS; CHEMOTHERAPY; NEUTROPENIA; FLUCONAZOLE Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28378