A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection
- Registration Number
- NCT01715909
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label, randomized, adaptive, 2-arm, multicenter study will evaluate the pharmacokinetics and pharmacodynamics of oseltamivir (Tamiflu) in immunocompromised children, less than (\<) 13 years of age, with confirmed influenza infection. Participants will be randomized to receive either the standard dose or triple dose of oseltamivir orally daily for a minimum of 5 days and up to 20 days. Infants \<1 year of age will be randomized to the standard dose arm only.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Inclusion Criteria
- Male or female children, <13 years of age
- Rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR), or viral culture positive for influenza
- Immunocompromised
- Symptoms/signs suggestive of influenza like illness (ILI)
- Less than or equal to (</=) 96 hours between onset of ILI and first dose of study drug
Exclusion Criteria
- Clinical evidence of severe hepatic impairment
- Infants with post-menstrual age (PMA) <36 weeks
- Clinical evidence of significant renal impairment
- Allergy to oseltamivir or excipients
- Hereditary fructose intolerance
- Received anti-viral treatment with activity against influenza (for example amantadine, rimantadine, oseltamivir, laninamivir, peramivir, zanamivir, and ribavirin) or probenecid medication within 2 weeks prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oseltamivir: Standard dose Oseltamivir Participants will receive standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight. Infants \<1 year of age will receive oseltamivir at a dose of 3 milligrams per kilogram (mg/kg). Oseltamivir: Triple dose Oseltamivir Participants will receive three times the standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight and age. Infants \<1 year will receive standard dose at 3 mg/kg.
- Primary Outcome Measures
Name Time Method Steady State AUC0-12 of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Cmax of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Trough Plasma Concentration (Ctrough) of Oseltamivir Pre-dose (within 30 minutes prior to administration) on Days 3 or 4 Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing From randomization to negative PCR/culture test result (up to Day 50) Maximum Plasma Concentration (Cmax) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Ctrough of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
- Secondary Outcome Measures
Name Time Method Number of Participants With Influenza Associated Complications Baseline up to Day 50 V/F of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Half-life (t1/2) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Time to Maximum Concentration (Tmax) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Apparent Volume of Distribution (V/F) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Time to Last Measurable Concentration (Tlast) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 t1/2 of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Elimination Rate Constant (Ke) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS) From randomization to resolution of all influenza symptoms (up to Day 50) Tmax of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Apparent Clearance (CL/F) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 CL/F of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Last Measurable Concentration (Clast) of Oseltamivir Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Number of Participants With Viral Resistance Baseline up to Day 50 Ke of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Clast of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Tlast of Oseltamivir Carboxylate Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4 Number of Participants With Adverse Events Baseline up to Day 50
Trial Locations
- Locations (50)
Lucile Packard Child Hosp; Pediatric Pulmonary Division
🇺🇸Palo Alto, California, United States
The Children's Hospital; Pediatric Infectious Diseases
🇺🇸Aurora, Colorado, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
UZ Brussel
🇧🇪Brussel, Belgium
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Scroll for more (40 remaining)Lucile Packard Child Hosp; Pediatric Pulmonary Division🇺🇸Palo Alto, California, United States