Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children
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|ClinicalTrials.gov Identifier: NCT02358499|
Recruitment Status : Completed
First Posted : February 9, 2015
Last Update Posted : December 22, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Fungal Infections||Drug: Posaconazole||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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).
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
- 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.
- 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.
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|Ages Eligible for Study:||2 Years to 17 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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).
- A female subject must not be pregnant, intend to become pregnant during the study, or breastfeed
- 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
- 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
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.
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
|United States, Missouri|
|Children's Mercy Hospital Kansas City|
|Kansas City, Missouri, United States, 64108|
|Principal Investigator:||Dwight E Yin, MD, MPH||Children's Mercy Hospital Kansas City|
|Responsible Party:||Children's Mercy Hospital Kansas City|
|Other Study ID Numbers:||
|First Posted:||February 9, 2015 Key Record Dates|
|Last Update Posted:||December 22, 2020|
|Last Verified:||December 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
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