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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 : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Children's Mercy Hospital Kansas City

Tracking Information
First Submitted Date  ICMJE January 29, 2015
First Posted Date  ICMJE February 9, 2015
Last Update Posted Date December 22, 2020
Actual Study Start Date  ICMJE January 2015
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2015)
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2015)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children
Official Title  ICMJE Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Fungal Infections
Intervention  ICMJE 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
Study Arms  ICMJE 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).
Intervention: Drug: Posaconazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 14, 2020)		 31
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2015)		 40
Actual Study Completion Date  ICMJE December 31, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02358499
Other Study ID Numbers  ICMJE 1490413
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Children's Mercy Hospital Kansas City
Original Responsible Party Dwight Yin, Children's Mercy Hospital Kansas City, MD, MPH
Current Study Sponsor  ICMJE Children's Mercy Hospital Kansas City
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dwight E Yin, MD, MPH Children's Mercy Hospital Kansas City
PRS Account Children's Mercy Hospital Kansas City
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP