Pharmacokinetics of Posaconazole in Children With Chronic Granulomatous Disease (CGD) (iPOD)
The purpose of this study is to find a dose for a twice daily regimen for posaconazole (PSZ) as prophylactic treatment in children with CGD, based on the PSZ trough level.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Investigation of POsaconazole Prophylaxis in Children With Chronic Granulomatous Disease (CGD): Pharmacokinetics and Tolerability (iPOD)|
- Posaconazole trough levels [ Time Frame: Day 10; 20; 30 ] [ Designated as safety issue: No ]
- adverse events monitoring [ Time Frame: entire study ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Study Completion Date:||August 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
posaconazole as antifungal prophylaxis
Drug: posaconazole (PSZ)
Intake of PSZ oral suspension 40mg/ml twice daily with food. Starting dose is based on bodyweight. The dosage will be adjusted if the exposure is not adequate based on PSZ trough level on Day 10 and 20.
Other Name: Noxafil
At this moment itraconazole is the drug of first choice in the prophylaxis of fungal infections in children with CGD. Breakthrough fungal infections while on itra-conazole prophylaxis are described in literature indicating the need for a drug with a broader antifungal spectrum. PSZ might provide in this need. PSZ may also have a clinical safety and tolerability advantage over other antifungal agents. Because PSZ is metabolized through phase II glucuronidation it is less common to be subject to drug interactions. PSZ is known to be a CYP3A4 inhibitor, but does not inhibit other CYP enzymes, therefore it may exhibit fewer drug interactions as compared with other azole antifungal agents.
Treatment of children is still off-label use. No data have been published to date on the exposure of PSZ in children under the age of 8 or in children with CGD. There is an urgent need to study the use of PSZ in these young children. Furthermore, the current regimen for antifungal prophylaxis requires a three times daily administration of PSZ. For this specific purpose less complex dosing schedules are warranted thus defining the need to examine a twice daily schedule.
As the tolerability and pharmacokinetics are unknown in patients under the age of 8 years and only limited data are available for age groups 8 to 16 years, we propose a feasibility study of a twice daily regimen of PSZ prophylaxis in CGD patients. With this information available we can suggest a dosage for future prophylaxis in this patient group.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00799071
|Radboud University Medical Centre Nijmegen|
|Nijmegen, Gelderland, Netherlands|
|Principal Investigator:||David M Burger, PharmD PhD||Radboud University Medical Centre Nijmegen|