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

NCT ID: NCT00799071

Last Updated: 2020-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2010-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Granulomatous Disease

Keywords

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prophylaxis CGD pharmacokinetics

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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posaconazole

posaconazole as antifungal prophylaxis

Group Type EXPERIMENTAL

posaconazole (PSZ)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Noxafil

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David M Burger, PharmD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Centre Nijmegen

Locations

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Radboud University Medical Centre Nijmegen

Nijmegen, Gelderland, Netherlands

Site Status

AMC

Amsterdam, , Netherlands

Site Status

Countries

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United Kingdom Netherlands

References

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Welzen ME, Bruggemann RJ, Van Den Berg JM, Voogt HW, Gilissen JH, Pajkrt D, Klein N, Burger DM, Warris A. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease. Pediatr Infect Dis J. 2011 Sep;30(9):794-7. doi: 10.1097/INF.0b013e3182195808.

Reference Type RESULT
PMID: 21772229 (View on PubMed)

Related Links

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http://journals.lww.com/pidj/Abstract/2011/09000/A_Twice_Daily_Posaconazole_Dosing_Algorithm_for.18.aspx

Pediatr Infect Dis J. 2011 Sep;30(9):794-7. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease.

Other Identifiers

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UMCN-AKF 08.01

Identifier Type: -

Identifier Source: org_study_id