Pharmacokinetics of Posaconazole in Children With Chronic Granulomatous Disease (CGD) (iPOD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT00799071
First received: November 26, 2008
Last updated: May 30, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Chronic Granulomatous Disease
Drug: posaconazole (PSZ)
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Posaconazole trough levels [ Time Frame: Day 10; 20; 30 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • adverse events monitoring [ Time Frame: entire study ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: February 2009
Study Completion Date: August 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: posaconazole
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has CGD, rendering him/her at risk for invasive fungal infections hence requiring antifungal prophylaxis.
  • Patient is at least 2 years of age and younger than 17 years of age on the day of the first dosing.
  • Parents or legal representative, and children where appropriate, willing and able to give informed consent.

Exclusion Criteria:

  • Patient is suspected of an invasive fungal infection.
  • Therapy with any medicinal product for which an effect on PSZ is expected. If patient is undergoing therapy with any medicinal product which may be effected by PSZ, the patient is included on condition that the investigator judges that the effects are not clinically relevant. This should be clearly recorded.
  • Documented history of sensitivity/idiosyncrasy to PSZ.
  • Results of serum biochemistry and hematology testing are not higher than 3x the upper limit of normal. If the results exceed these limits, the patient is included on condition that the investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
  • Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
  • Relevant history or presence of cardiovascular disorder or renal and hepatic disorder.
  • History of or current abuse of drugs, alcohol or recreational substances.
  • Participation in a trial with an investigational drug within 60 days prior to the first dose.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00799071

Locations
Netherlands
Radboud University Medical Centre Nijmegen
Nijmegen, Gelderland, Netherlands
AMC
Amsterdam, Netherlands
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: David M Burger, PharmD PhD Radboud University Medical Centre Nijmegen
  More Information

Additional Information:
No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT00799071     History of Changes
Other Study ID Numbers: UMCN-AKF 08.01
Study First Received: November 26, 2008
Last Updated: May 30, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
prophylaxis
CGD
pharmacokinetics

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Granuloma
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Posaconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014