Genetic Variation and Variability in Posaconazole Pharmacokinetics in Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration versus time curve (AUC) of Posaconazole Injection
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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 m
- •A subject must not have a history of Type 1 hypersensitivity or idiosyncratic reactions to azole agents.
研究组 & 干预措施
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).
干预措施: Posaconazole (Drug)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC) of Posaconazole Injection
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- Number of Participants with Treatment-Related AEs(Up to Day 4)
- Number of Participants with Treatment-Emergent Adverse Events (AEs)(Up to Day 4)