Header

UZH-Logo

Maintenance Infos

Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease


Cornely, Oliver A; Robertson, Michael N; Haider, Shariq; Grigg, Andrew; Geddes, Michelle; Aoun, Mickael; Heinz, Werner J; Raad, Issam; Schanz, Urs; Meyer, Ralf G; Hammond, Sarah P; Mullane, Kathleen M; Ostermann, Helmut; Ullmann, Andrew J; Zimmerli, Stefan; Van Iersel, M L P S; Hepler, Deborah A; Waskin, Hetty; Kartsonis, Nicholas A; Maertens, Johan (2017). Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. Journal of Antimicrobial Chemotherapy, 72(12):3406-3413.

Abstract

Objectives A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods Patients (N = 237) received 300 mg of posaconazole iv twice daily on day 1, followed by 300 mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400 mg twice daily or 200 mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (Cavg) and posaconazole trough levels (Cmin). Results Mean posaconazole Cmin was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state Cmin was 1090 ng/mL (day 10). Mean steady-state posaconazole Cavg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions Intravenous posaconazole at 300 mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk. Trial registry and number ClinicalTrials.gov, NCT01075984.

Abstract

Objectives A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods Patients (N = 237) received 300 mg of posaconazole iv twice daily on day 1, followed by 300 mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400 mg twice daily or 200 mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (Cavg) and posaconazole trough levels (Cmin). Results Mean posaconazole Cmin was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state Cmin was 1090 ng/mL (day 10). Mean steady-state posaconazole Cavg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions Intravenous posaconazole at 300 mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk. Trial registry and number ClinicalTrials.gov, NCT01075984.

Statistics

Citations

Dimensions.ai Metrics
1 citation in Web of Science®
1 citation in Scopus®
2 citations in Microsoft Academic
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 December 2017
Deposited On:08 Feb 2018 10:27
Last Modified:19 Feb 2018 10:53
Publisher:Oxford University Press
ISSN:0305-7453
Additional Information:Corrigendum für diesen Artikel: https://doi.org/10.1093/jac/dkx382 // J Antimicrob Chemother 2017; 72: 3406–3413, In the original published version of this article Andrew J. Ullmann’s affiliations were incorrectly given as 6 and 9. His correct affiliation is 7 (i.e. Universitätsklinikum Würzburg, Würzburg, Germany). This error has now been corrected. The authors apologize for this error.
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/jac/dkx263
PubMed ID:28961714

Download

Full text not available from this repository.
View at publisher

Get full-text in a library