Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02358499
Recruitment Status : Completed
First Posted : February 9, 2015
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
Dwight Yin, Children's Mercy Hospital Kansas City

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.

Condition or disease Intervention/treatment Phase
Fungal Infections Drug: Posaconazole Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children
Actual Study Start Date : January 2015
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).
Drug: 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.
Other Name: Noxafil




Primary Outcome Measures :
  1. Area under the plasma concentration versus time curve (AUC) of Posaconazole Injection [ Time Frame: Predose on Day 1 up to 96 hours postdose ]
    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.

  2. Maximum Concentration (Cmax) of Posaconazole Injection [ Time Frame: Predose on Day 1 up to 96 hours postdose ]
    Blood samples for the assessment of Cmax will be collected predose on Day 1 and then at prespecified time points up 96 hours postdose.

  3. Time of maximum concentration (Tmax) [ Time Frame: Predose on Day 1 up to 96 hours postdose ]
    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.

  4. Terminal half-life (t1/2) [ Time Frame: Predose on Day 1 up to 96 hours postdose ]
    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.


Secondary Outcome Measures :
  1. Number of Participants with Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to Day 4 ]
    AEs are any unfavorable and unintended signs, symptom, or disease temporally associated with the use of a study drug, whether or nor considered related to this study drug. Treatment-emergent AEs are any event not present before starting study drug treatment or any event that was present before treatment that worsened in either intensity or frequency after exposure to study drug.

  2. Number of Participants with Treatment-Related AEs [ Time Frame: Up to Day 4 ]
    AEs are any unfavorable and unintended signs, symptom, or disease temporally associated with the use of a study drug, whether or nor considered related to this study drug. Treatment-related AEs are considered by the investigator to be related to the study drug.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02358499


Locations
Layout table for location information
United States, Missouri
Children's Mercy Hospital Kansas City
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Investigators
Layout table for investigator information
Principal Investigator: Dwight E Yin, MD, MPH Children's Mercy Hospital Kansas City
Layout table for additonal information
Responsible Party: Dwight Yin, MD, MPH, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT02358499    
Other Study ID Numbers: 1490413
First Posted: February 9, 2015    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Dwight Yin, Children's Mercy Hospital Kansas City:
triazoles
fungi
transplantation, hematopoietic stem cell
leukemia
pediatrics
pharmacokinetics
bone marrow failure syndrome
Additional relevant MeSH terms:
Layout table for MeSH terms
Mycoses
Posaconazole
Antifungal Agents
Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs