A PROSPECTIVE, OPEN-LABEL STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY & EFFICACY OF ANIDULAFUNGIN WHEN USED TO TREAT CHILDREN WITH INVASIVE CANDIDIASIS, INCLUDING CANDIDEMIA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 70
- 试验地点
- 44
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
Prospective, open label study to assess the pharmacokinetics, safety & efficacy of anidulafungin when used to treat children (aged 1 month - <18 years) with invasive candidiasis, including candidemia (ICC).
详细描述
Prospective, open label study to assess the pharmacokinetics, safety & efficacy of anidulafungin when used to treat children (aged 1 month - < 18 years) with invasive candidiasis, including candidemia (ICC). To participate in the study, at the time of enrollment subjects must (1) have either a confirmed diagnosis of ICC or mycological evidence highly suggestive of Candida sp or (2) in infants 1 month to < 2 years only, be at high risk of candidiasis. All subjects meeting screening criteria receive IV anidulafungin. Subjects will be stratified by age (1 month - < 2 years; 2 years - < 5 years; 5 years - < 18 years). Subjects may be switched to oral fluconazole, provided that the pre-specified criteria are met. Subjects with microbiologically confirmed ICC must have a minimum total treatment duration of 14 days. The maximum allowed treatment duration of anidulafungin is 35 days; the maximum total treatment duration for the study is 49 days. At selected centers, anidulafungin pharmacokinetics will be assessed in the first 6 subjects age 1 month - < 2 years to confirm the recommended dosage regimen. A population PK-PD analysis will be performed in all other enrolled subjects. Subjects will be followed for safety through 6 week FU visit. Efficacy for subjects with confirmed ICC will be assessed at EOIVT, EOT, 2-week FU and 6-week FU visits.
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
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be either (1) at high risk for candidiasis (1 month - < 2 years ONLY) or (2) have a definitive diagnosis of invasive candidiasis/candidemia (ICC) (All age groups)
- •Male and female patients from 1 month to less than 18 years of age.
排除标准
- •Any patients with allergy to the drug; and any pregnant female or lactating.
- •Failed previous antifungal therapy or expected to live < 3 days.
- •Patients with documented or suspected Candida meningitis.
研究组 & 干预措施
Anidulafungin IV
All subjects meeting screening criteria will receive IV anidulafungin.
干预措施: Anidulafungin (Drug)
Anidulafungin IV
All subjects meeting screening criteria will receive IV anidulafungin.
干预措施: Fluconazole (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 6 weeks after EOT (up to 91 days)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after end of treatment (EOT) (up to 91 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. EOT visit defined as last day of study treatment (IV or oral).
Number of Participants With Laboratory Abnormalities
时间窗: Baseline up to 6 weeks after EOT (up to 91 days)
Criteria for laboratory abnormalities: Hematology parameters: red blood cell count: \<0.8\*lower limit of normal (LLN); reticulocytes count (absolute or percent): \<0.5\*LLN or greater than (\>) 1.5\*upper limit of normal (ULN); Platelets: \<0.5\*LLN or \>1.75\*ULN; white blood cell count: \<0.6\*LLN or \>1.5\*ULN; neutrophils (absolute or percent): \<0.8\*LLN or \>1.2\*ULN; basophils (absolute or percent): \>1.2\*ULN; lymphocytes (absolute or percent): \<0.8\*LLN or \>1.2\*ULN; monocytes (absolute or percent): \>1.2\*ULN. Serum Chemistry parameters: sodium: \<0.95\*LLN or \>1.05\*ULN, potassium, chloride, bicarbonate, calcium: \<0.9\*LLN or \>1.1\*ULN; magnesium: \>1.1\*ULN or \<0.9\*LLN; BUN (blood urea nitrogen): \>1.3\* ULN, creatinine: \>1.3\*ULN; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase : \>3.0\*ULN ; total bilirubin: \>1.5\*ULN; albumin: \<0.8\*LLN or \>1.2\*ULN and glucose: \<0.6\*LLN or \>1.5\*ULN.EOT visit defined as last day of study treatment (IV or oral).
次要结局
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup(Day 1: 0 to 2 hours post dose; Day 3 and Day 9:pre-dose; Day 5: 0 to 3 hours post dose; Day 7: 6 to 12 hours and 24 hours delayed post-dose)
- Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup(Day 2: Just prior to the start of infusion, 2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion)
- Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin(Sparse Sampling:Day 1:0-2 hr after end of infusion (EOI); Day3&9:pre-dose;Day 5:0-3hr post EOI; Day 7:6-12hr after EOI.For 1st 6 infants:< 2 years:Day 1:2 minutes before EOI; Day 2:pre infusion, 2 minutes before EOI, 6, 12,24 hours after start of infusion)
- Number of Participants With Global Response(End of intravenous treatment (EOIVT) (maximum of 35 days), EOT (maximum of 49 days), during 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days))
- Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup(Day 1: 0 to 2 hours post dose; Day 3 and Day 9:pre-dose; Day 5: 0 to 3 hours post dose; Day 7: 6 to 12 hours delayed post-dose)
- Number of Participants With Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)(Baseline to EOIVT (maximum of 35 days))
- Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup(Day 2: Just prior to the start of infusion, 2 minutes before the end of infusion, 6, 12, and 24 hours after the start of infusion)
- Number of Participants With Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)(Baseline to End of intravenous treatment (EOIVT) (maximum of 35 days))
- Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)(EOIVT (maximum of 35 days) and EOT (maximum of 49 days))
- Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin(Sparse Sampling:Day 1:0-2 hr after end of infusion (EOI); Day3&9:pre-dose;Day 5:0-3hr post EOI; Day 7:6-12hr after EOI.For 1st 6 infants:< 2 years:Day 1:2 minutes before EOI; Day 2:pre infusion, 2 minutes before EOI, 6, 12,24 hours after start of infusion)
- Percentage of Participants With New Infection(During 2 week follow-up (up to 63 days) and 6 week follow-up (up to 91 days) after EOT)
- All-Cause Mortality - Number of Participants Who Died During Overall Study Treatment Period and Follow-Up Visits(Overall treatment period (up to 49 days); during 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days))
- Percentage of Participants With Relapsed Response(During 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days))