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
- 40
- 试验地点
- 27
- 主要终点
- Average concentration (Cavg) of single-dose IV POS (Panel A)
研究概览
简要总结
This study aims to estimate the pharmacokinetics (PK) of posaconazole (POS, MK-5592) intravenous (IV) and powder for oral suspension (PFS) formulations in pediatric participants <2 years of age with invasive fungal infection (IFI).
详细描述
There are 2 panels in this study. In Panel A, POS IV will be evaluated in ≥8 participants. In Panel B, both POS IV and POS PFS will be evaluated in ≥14 participants, including ≥6 who are <3 months of age and ≥5 who transition to the PFS formulation of POS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Panel A: is undergoing treatment for possible, probable, or proven 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 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 (Part B)
- •Has suspected/proven invasive candidiasis (Part B)
- •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
研究组 & 干预措施
Panel B: POS IV
Posaconazole 6 mg/kg body weight administered twice daily by IV infusion on Day 1, and then once daily from Day 2 to a maximum 84 days.
干预措施: Posaconazole IV 6 mg/kg (Drug)
Panel A: POS IV
Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1.
干预措施: Posaconazole IV 6 mg/kg (Drug)
Panel B: POS PFS
Following a minimum of 7 days IV dosing, participants as clinically able will be transitioned from POS IV to POS PFS nominal 6 mg/kg body weight based on weight bands administered on Day 8, once daily to a maximum 84 days.
干预措施: Posaconazole PFS 6 mg/kg (Drug)
结局指标
主要结局
Average concentration (Cavg) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The Cavg of IV POS is based on population PK analysis.
Maximum concentration (Cmax) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The Cmax of IV POS is based on population PK analysis.
Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The Tmax of IV POS is based on population PK analysis.
Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The AUC 0-24 of IV POS is based on population PK analysis.
Clearance (CL) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The clearance (CL) of IV POS is based on population PK analysis.
Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)
时间窗: Predose, 0.25 and 24 hours post-infusion on Day 1
The AUC0-∞ of IV POS is based on population PK analysis.
Cavg of multiple-dose IV POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The Cavg of IV POS is based on population PK analysis.
Cmax of multiple-dose IV POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The Cmax of IV POS is based on population PK analysis.
Tmax of multiple-dose IV POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The Tmax of IV POS is based on population PK analysis.
AUC0-24 of multiple-dose IV POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The AUC0-24 of IV POS is based on population PK analysis.
CL of multiple-dose IV POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The CL of IV POS is based on population PK analysis.
Cavg of multiple-dose PFS POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The Cavg of PFS POS is based on population PK analysis.
Cmax of multiple-dose PFS POS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The Cmax of PFS POS is based on population PK analysis.
AUC0-24 of multiple-dose PFSPOS (Panel B)
时间窗: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
The AUC0-24 of PFS POS is based on population PK analysis.
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)(Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12)
- Percentage of participants with an ≥ 1 adverse event (AE) [Panels A and B](Up to 98 days)
- Percentage of participants who discontinued study therapy due to an AE (Panels A and B)(Up to 84 days)
- Percentage of participants with a drug-related AE (Panels A and B)(Up to 98 days)
- Percentage of participants with all-cause mortality (ACM) [Panel B](Up to 28 days)
- Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period (Panel B)(Up to 84 days)