A Double-Blind, Randomized, Stratified Multi-Center Trial Evaluating Conventional and Double Dose Oseltamivir in the Treatment of Immunocompromised Patients With Influenza
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 208
- 主要终点
- Percentage of Participants With Tissue Rejection or Graft Versus Host Disease (GVHD)
研究概览
简要总结
This 2-arm study will investigate the safety and tolerability of oseltamivir for the treatment of influenza in immunocompromised participants and characterize the effects of oseltamivir in immunocompromised participants on the development of resistant influenza virus. Eligible immunocompromised participants with laboratory-confirmed influenza will be randomized to receive either conventional dose (30 milligrams [mg] to 75 mg twice daily orally [po], depending on age and weight) or double dose (60 mg-150 mg twice daily po depending on age and weight) olseltamivir for 10 days. Nasal and throat swabs will be taken, and safety evaluations made, at intervals during the study. The anticipated time on study medication is 10 days and the anticipated time on study is 40 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
- •Immunocompromised participants with primary or secondary immunodeficiency
- •Symptoms suggestive of influenza-like illness
- •Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
排除标准
- •Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization
- •Antiviral treatment for influenza in 2 weeks prior to randomization
- •Severe hepatic impairment
- •Any current renal replacement therapy
- •Any gastrointestinal disorders which may interfere with the absorption of oseltamivir
- •Participation in a study with an investigational drug from 4 weeks prior to study start until study end
研究组 & 干预措施
Conventional dose
Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 30 to 75 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 75 mg twice daily for adults/adolescents greater than or equal to (>/=) 13 years old or placebo-matched to oseltamivir twice daily over 10 days.
干预措施: oseltamivir (Drug)
Conventional dose
Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 30 to 75 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 75 mg twice daily for adults/adolescents greater than or equal to (>/=) 13 years old or placebo-matched to oseltamivir twice daily over 10 days.
干预措施: placebo (Other)
Double dose
Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 60 to 150 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 150 mg twice daily for adults/adolescents (>/=13 years old) or placebo matched to oseltamivir twice daily over 10 days.
干预措施: oseltamivir (Drug)
Double dose
Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 60 to 150 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 150 mg twice daily for adults/adolescents (>/=13 years old) or placebo matched to oseltamivir twice daily over 10 days.
干预措施: placebo (Other)
结局指标
主要结局
Percentage of Participants With Tissue Rejection or Graft Versus Host Disease (GVHD)
时间窗: Baseline up to Day 40
The percentage of transplant patients in the safety population who experienced tissue rejection and/or GvHD is reported.
Percentage of Participants With Adverse Events
时间窗: Baseline up to Day 40
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants Who Developed Viral Resistance to Oseltamivir
时间窗: Baseline up to Day 40
Resistance was defined as the presence of oseltamivir resistance mutations in viruses isolated from nasopharyngeal swab samples, identified by sequencing of the neuraminidase (NA) and hemagglutinin (HA) genes (genotypic resistance) and/or determination of the oseltamivir concentration at which the response is reduced by half (IC50) in an NA inhibition assay (phenotypic resistance). Reported are post-baseline phenotypic and genotypic resistance in adults \>/= 18 years and children and adolescents \<18 years in the modified Intent-to-Treat infected (mITTi) population.
次要结局
- Percentage of Participants With Persistent Viral Shedding(Baseline to Day 11 (EOT))
- Percentage of Participants Who Developed Secondary Illness(Baseline up to Day 40)
- Percentage of Participants Who Initiated Antibiotic Treatment(Baseline up to Day 40)
- Percentage of Participants Hospitalized(Baseline up to Day 40)
- Duration of Hospitalization(Baseline up to Day 40)
- Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics : Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) at Steady State of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Time to Maximum Concentration (Tmax) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Time to Resolution (TTR) of All Clinical Influenza Symptoms(Baseline up to Day 40)
- Total Symptom Score Area Under the Efficacy Curve (AUE)(Baseline up to Day 40)
- Time to Cessation of Viral Shedding by RT-PCR(Baseline up to Day 40)
- Time to Resolution of Fever(Baseline up to Day 40)
- Change From Baseline in Viral Load Assessed by Culture(Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.)
- Percentage of Participants With Viral Shedding Assessed by Culture Over Time(Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.)
- Time to Cessation of Viral Shedding by Cell Culture(Baseline up to Day 40)
- Change From Baseline in Viral Load Assessed by Reverse Transcription Polymerase Chain Reaction (RT-PCR)(Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.)
- Percentage of Participants With Viral Shedding Assessed by RT-PCR Over Time(Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.)
- Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics : AUC0-12 at Steady State of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adults(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Cmax of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Ctrough of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Tmax of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Clearance (CL/F), of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)
- Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adolescents and Children(Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose)