Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children

NCT02358499 | Completed Phase 1 DMC

• 1 other identifier: 1490413
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Fungal Infections

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Area under the plasma concentration versus time curve (AUC) of Posaconazole Injection

  Posaconazole concentrations in the plasma will be measured after a single dose of posaconazole injection to estimate the area under the concentration-versus-time curve (AUC). Blood samples for the assessment of AUC will be collected predose on Day 1 and then at specified time points up to 96 hours postdose.

  Predose on Day 1 up to 96 hours postdose

• Maximum Concentration (Cmax) of Posaconazole Injection

  Blood samples for the assessment of Cmax will be collected predose on Day 1 and then at prespecified time points up 96 hours postdose.

  Predose on Day 1 up to 96 hours postdose

• Time of maximum concentration (Tmax)

  Blood samples for the assessment of Tmax will be collected predose on Day 1 and then at prespecified time points up to 96 hours postdose.

  Predose on Day 1 up to 96 hours postdose

• Terminal half-life (t1/2)

  Blood samples for the assessment of t1/2 will be collected predose on Day 1 and then at prespecified time points up to 96 hours postdose.

  Predose on Day 1 up to 96 hours postdose

Secondary Outcomes (2)

• Number of Participants with Treatment-Emergent Adverse Events (AEs)

  Up to Day 4

• Number of Participants with Treatment-Related AEs

  Up to Day 4

Study Arms (1)

Posaconazole Injection

EXPERIMENTAL

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).

Drug: Posaconazole

Interventions

Posaconazole 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.

Also known as: Noxafil

Posaconazole Injection

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2 years to under 18 years
• Weight ≥10 kg
• 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).

You may not qualify if:

• A female subject must not be pregnant, intend to become pregnant during the study, or breastfeed
• 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
• A subject must not have an electrocardiogram (ECG) with prolonged age, sex-adjusted QTc interval.
• A subject must not have a history of dysrhythmia.
• A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min/1.73 m2.
• A subject must not have a history of Type 1 hypersensitivity or idiosyncratic reactions to azole agents.

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead

Study Sites (1)

Children's Mercy Hospital Kansas City

Kansas City, Missouri, 64108, United States

Location

MeSH Terms

Conditions

Mycoses; Leukemia; Bone Marrow Failure Disorders

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Dwight E Yin, MD, MPH

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 9, 2015
• Study Start: January 1, 2015
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: December 22, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)