An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Oseltamivir (Tamiflu®) in the Treatment of Infants 0 to <12 Months of Age With Confirmed Influenza Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 12
- 主要终点
- Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
研究概览
简要总结
This study will assess the pharmacokinetics/pharmacodynamics and safety of oseltamivir [Tamiflu] therapy in infants less than 1 year of age with influenza diagnosed in the 96 hours prior to the first dose. Patients age 3-12 months will receive 3 mg/kg, 1-3 months will receive 2.5 mg/kg, and birth to 1 month will receive 2 mg/kg twice a day for a total of 10 doses. Patients positive for influenza virus on Day 6 will be eligible to receive continued study treatment for an additional 10 doses (5 days). The anticipated time on study treatment is 4 weeks, and the target sample size is 65-85 male and female infants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •infants </=12 months of age
- •laboratory confirmed diagnosis of influenza within 96 hours prior to first dose
- •influenza symptoms for </=96 hours prior to first dose
排除标准
- •preterm infants less than 40 weeks (corrected for gestational age)
- •weight less than 5th percentile for age (corrected for gestational age)
- •concurrent gastrointestinal conditions that preclude enteric absorption of the drug
- •bronchopulmonary dysplasia/chronic lung disease on assisted ventilation at time of enrollment
- •active or uncontrolled respiratory, cardiac, hepatic, CNS or renal disease at baseline
- •symptomatic inborn errors of metabolism
研究组 & 干预措施
Oseltamivir 3 mg
infants 3 to <12 months
干预措施: Tamiflu (Drug)
Oseltamivir 2.5 mg
infants 1 to <3 months of age
干预措施: Tamiflu (Drug)
Oseltamivir 2 mg
infants 0 to 30 days (post natal) of age
干预措施: Tamiflu (Drug)
结局指标
主要结局
Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
时间窗: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule
Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
时间窗: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis
Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
时间窗: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis.
次要结局
- Clast of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Number of Participants With Virus Shedding by Virus Type(Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days)
- The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline(Days 1, 3 or 4, 6, 11, 18, and 30)
- Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Number of Participants With Change From Baseline in Neurological Assessment Scores(Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30)
- Number of Participants Showing Within-patient Variability in Vital Signs(Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days)
- Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate(15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1)
- Time to Resolution of Fever in Participants With Fever at the Baseline(Days 1 to 11; Day 18; Day 30)
- Percentage of Participants With Decline of Body Temperature to the Afebrile State(Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days)
- Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness(Up to 3 days after the last dose of oseltamivir (Approximately 14 days))