Influenza
Conditions
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.
Interventions
DRUGOseltamivir
Participants will receive standard dose (30 to 75 milligrams \[mg\]) or triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for \</= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (\>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| Ctrough of Oseltamivir Carboxylate | Pre-dose (within 30 minutes prior to administration) 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) |
Secondary
| Measure | Time frame |
|---|---|
| Tmax 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 |
| Ke of Oseltamivir Carboxylate | 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 |
| 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 |
| 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) |
| 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 |
| 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 |
| Tlast 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 |
| Clast 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 |
| Number of Participants With Adverse Events | Baseline up to Day 50 |
| Number of Participants With Influenza Associated Complications | Baseline up to Day 50 |
| Number of Participants With Viral Resistance | Baseline up to Day 50 |
| 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 |
| 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 |
| 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 |
Countries
Belgium, Brazil, Canada, Chile, Colombia, Finland, Germany, Greece, Israel, Italy, Mexico, Poland, South Africa, Spain, United States
Outcome results
None listed