A Phase 2, Open-Label, Single-Arm, Sequential-Panel Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Posaconazole (POS, MK-5592) Intravenous and Powder for Oral Suspension Formulations in Pediatric Participants From Birth to Less Than 2 Years of Age With Possible, Probable, or Proven Invasive Fungal Infection
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
研究概览
简要总结
To estimate the pharmacokinetics (PK) of posaconazole (POS) intravenous (IV) and powder for oral suspension (PFS) in participants <2 years of age (Panels A and B).
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Panel A: Is undergoing treatment for possible, probable, or proven invasive fungal infection (IFI) known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (which can include candidiasis)
- •Panel B: has an investigator-assessed diagnosis of possible, probable, or proven IFI known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (and cannot include candidiasis)
- •Has a central line (eg, central venous catheter, peripherally-inserted central catheter) in place or planned to be in place before beginning IV study intervention
- •Has a body weight of ≥500 g
- •The participant (or legally acceptable representative) has provided documented informed consent for the study.
排除标准
- •Has received POS within 30 days before Day 1
- •Has enrolled previously in the current study and been discontinued
- •Has QTc prolongation at screening >500 msec
- •Has significant liver dysfunction
- •Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days
- •Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
- •Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- •Has known or suspected active COVID-19 infection
- •Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used
- •Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT interval (QT) prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention
- •Has received any listed prohibited medications within the specified timeframes before the start of study intervention
- •Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Panel B)
- •Has suspected/proven invasive candidiasis (Panel B)
结局指标
主要结局
Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)
Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)
Clearance (CL) of single-dose IV POS (Panel A)
Clearance (CL) of single-dose IV POS (Panel A)
Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)
Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)
Cavg of multiple-dose IV POS (Panel B)
Cavg of multiple-dose IV POS (Panel B)
Average concentration (Cavg) of single-dose IV POS (Panel A)
Average concentration (Cavg) of single-dose IV POS (Panel A)
Maximum concentration (Cmax) of single-dose IV POS (Panel A)
Maximum concentration (Cmax) of single-dose IV POS (Panel A)
Cmax of multiple-dose IV POS (Panel B)
Cmax of multiple-dose IV POS (Panel B)
Tmax of multiple-dose IV POS (Panel B)
Tmax of multiple-dose IV POS (Panel B)
AUC0-24 of multiple-dose IV POS (Panel B)
AUC0-24 of multiple-dose IV POS (Panel B)
CL of multiple-dose IV POS (Panel B)
CL of multiple-dose IV POS (Panel B)
Cavg of multiple-dose PFS (Panel B)
Cavg of multiple-dose PFS (Panel B)
Cmax of multiple-dose PFS (Panel B)
Cmax of multiple-dose PFS (Panel B)
AUC0-24 of multiple-dose PFS (Panel B)
AUC0-24 of multiple-dose PFS (Panel B)
次要结局
- Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B only)
- Percentage of participants with ≥1 adverse events (AEs) [Panels A and B]
- Percentage of participants with ≥1 drug-related AEs (Panels A and B)
- Percentage of participants discontinuing from study treatment due to AE(s) (Panels A and B)
- Percentage of participants with all-cause mortality through 28 days (Panel B)
- Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period [Panel B]
研究者
Stephen Holden
Scientific
Merck Sharp & Dohme LLC