Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children

NCT ID: NCT02358499

Last Updated: 2020-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-12-31

Brief Summary

The main goal of this study is to see how the body breaks down an antifungal drug named posaconazole in children with certain cancers, blood disorders, or transplantation of bone marrow or similar blood cells. This study will also help us learn whether a child's age, genetics, or disease affect how well the body breaks down posaconazole.

Detailed Description

The purpose of this research study is to see how the body breaks down posaconazole, which has limited data in children. Posaconazole injection has been approved by the FDA for prevention or treatment of certain fungal infections in adult patients. In children, however, we don't have data on how best to give posaconazole or whether the dosing should be personalized to individual children. This study aims to determine pharmacokinetics of posaconazole aqueous solution for injection in children aged 2 through 17 years and explores differences in drug exposure by age, genetics, and disease state. Children will receive a single dose of posaconazole injection and have their blood levels of posaconazole checked. The study will also check for safety after giving the posaconazole.

Conditions

Fungal Infections

Keywords

triazoles; fungi; transplantation, hematopoietic stem cell; leukemia; pediatrics; pharmacokinetics; bone marrow failure syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Posaconazole Injection

We will give a single dose of intravenous posaconazole and collect blood samples for pharmacokinetics (PK). The study pool will be enriched by selecting participants with known sequence variations. Every effort will be made to balance age and disease state (HSCT vs. non-HSCT).

Group Type: EXPERIMENTAL

Posaconazole

Intervention Type: DRUG

Posaconazole will be given as a one time intravenous (IV) dose. The dose will take ninety (90) minutes to be infused and will be based on weight at the time of the visit.

Interventions

Posaconazole

Posaconazole will be given as a one time intravenous (IV) dose. The dose will take ninety (90) minutes to be infused and will be based on weight at the time of the visit.

Intervention Type: DRUG

Other Intervention Names

Noxafil

Eligibility Criteria

Inclusion Criteria

1. Age 2 years to under 18 years

2. Weight ≥10 kg

3. Diagnosis of any of the following: any malignancy (e.g., acute myelogenous leukemia [AML], acute lymphoblastic leukemia [ALL], lymphoma, solid tumor malignancy), hemophagocytic syndrome, bone marrow failure syndrome (e.g., myelodysplastic syndrome and aplastic anemia), hematopoietic stem cell transplantation (HSCT) recipient, or primary immune deficiency with a neutrophil or T-cell defect (e.g., chronic granulomatous disease, hyper IgE syndrome, severe combined immune deficiency).

Exclusion Criteria

1. A female subject must not be pregnant, intend to become pregnant during the study, or breastfeed

2. A subject must not be receiving any of the following medications within 24 hours before or after posaconazole infusion (or according to standard of care protocols): sirolimus, everolimus, pimozide, quinine, HMG-CoA reductase inhibitors primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin, simvastatin), ergot alkaloids (ergotamine, dihydroergotamine), methadone, astemizole, cisapride, halofantrine, salmeterol, or vincristine. Potential enrollees will be screened for additional concomitant medications that pose serious safety concerns when given concomitantly to posaconazole. Any of these medications will be an exclusion criterion, unless the concomitant medications may be held for 24 hours before and after posaconazole infusion or according to standard of care protocols

3. A subject must not be receiving any of the following medications concomitant (within 5 half-lives prior) to posaconazole infusion or PK sampling: rifampin, rifapentine, rifabutin, phenytoin, efavirenz, fosamprenavir, or cimetidine. Potential enrollees will be screened for additional concomitant medications that may affect posaconazole metabolism. Any of these medications will be an exclusion criterion, unless the concomitant medications may be held for 5 half-lives prior to posaconazole infusion and through PK sampling

4. A subject must not have moderate or severe liver dysfunction (except in chronic cases as judged by the P.I.) at Baseline, defined as:

• A subject must not have moderate or severe liver dysfunction at Baseline, defined as: Aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN), OR
• Alanine aminotransferase (ALT) > 5 times the ULN, OR
• Serum total bilirubin >2.5 times the ULN, OR

5. A subject must not have an electrocardiogram (ECG) with prolonged age, sex-adjusted QTc interval.

6. A subject must not have a history of dysrhythmia.

7. A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min/1.73 m2.

8. A subject must not have a history of Type 1 hypersensitivity or idiosyncratic reactions to azole agents.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dwight E Yin, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hospital Kansas City

Locations

Children's Mercy Hospital Kansas City

Kansas City, Missouri, United States

Countries

United States

Other Identifiers

1490413

Identifier Type: -

Identifier Source: org_study_id