A Phase 2, Open-Label, Non-Comparative Clinical Trial to Study the Safety and Efficacy of Posaconazole (POS, MK-5592) in Pediatric Participants Aged 2 to Less Than 18 Years With Invasive Aspergillosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 29
- 主要终点
- Percentage of Participants Who Experience One or More Treatment-related Adverse Events (AEs)
研究概览
简要总结
This study will evaluate the safety, efficacy, and pharmacokinetics of posaconazole (POS) intravenous (IV) and oral formulations in pediatric participants 2 to <18 years of age with invasive aspergillosis (IA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Has a diagnosis of possible, probable, or proven IA per modified 2008/2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) disease definitions
- •Has one or more of pre-defined risks as per modified 2008 EORTC/MSG disease definitions
- •Has a central line (e.g., central venous catheter, peripherally-inserted central catheter) in place or planned to be in place prior to beginning IV study treatment.
- •Has clinical symptoms consistent with an acute episode of IA, defined as duration of clinical syndrome of <30 days.
- •Participants weigh at least 10 kg, and may be of any race/ethnicity.
- •During the intervention period and for at least 30 days after the last dose of study treatment, males agree to be abstinent from heterosexual intercourse or use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
- •Female is not pregnant or breastfeeding, and is not a woman of child bearing potential (WOCBP) or is a WOCBP using a highly effective contraceptive method. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
排除标准
- •Has chronic (≥30 days' duration) IA, relapsed/recurrent IA, or refractory IA that has not responded to prior antifungal treatment.
- •Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis
- •Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study treatment 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 prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of time of first dose of study treatment.
- •Has known hereditary fructose intolerance.
- •Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
- •Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
- •Is on artificial ventilation at the time of first dose of study treatment.
- •Has received any treatment prohibited by the protocol.
- •Has enrolled previously in the current study and been discontinued.
- •Is not expected, in the opinion of the investigator, to survive for at least 1 month after the initiation of study treatment.
研究组 & 干预措施
Posaconazole
On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation.
干预措施: Posaconazole IV (Drug)
Posaconazole
On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation.
干预措施: Posaconazole PFS (Drug)
Posaconazole
On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation.
干预措施: Posaconazole tablet (Drug)
结局指标
主要结局
Percentage of Participants Who Experience One or More Treatment-related Adverse Events (AEs)
时间窗: Up to 14 days after treatment (up to Day 102)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Treatment-related AEs were determined by the investigator to be related to the drug. The 95% confidence interval (CI) was based on the exact binomial method by Clopper- Pearson.
次要结局
- Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 6(Up to week 6)
- Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 12(Up to Week 12)
- Percentage of Participants Who Have a Relapse of Invasive Aspergillosis (IA) at Any Point After Achieving Favorable Global Clinical Response(Up to 28 days post-treatment (up to Day 116))
- Average Plasma Concentration (Cavg) of POS by Age Cohorts(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Minimum Plasma Concentration (Cmin) of POS by Age Cohorts(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Maximum Plasma Concentration (Cmax) of POS by Age Cohorts(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Age Cohorts(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Time to Reach Cmax (Tmax) of POS by Age Cohorts(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Average Plasma Concentration (Cavg) of POS by Formulation(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Minimum Plasma Concentration (Cmin) of POS by Formulation(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Maximum Plasma Concentration (Cmax) of POS by Formulation(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Percentage of Participants With Different Categories of Palatability After Last Day of Treatment With the POS PFS Formulation(Last day of PFS treatment (Day 85))
- Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Formulation(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Time to Reach Cmax (Tmax) of POS by Formulation(Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12)
- Percentage of Participants With Different Categories of Palatability After First Day of Treatment With the POS PFS Formulation(First day of PFS treatment (Day 8))