Phase 1
N=65
A Pharmacokinetic/Pharmacodynamic (PK/PD) and Safety Evaluation of Oseltamivir [Tamiflu] in the Treatment of Infants 0 to <12 Months of Age With Confirmed Flu Infection
Influenza
Bottom Line
View on ClinicalTrials.gov: NCT00988325 ↗Enrolled (actual)
65
Serious AEs
6.2%
Results posted
Mar 2017
Primary outcome: Primary: Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate — 277; 194; 142; 4990 hour (h)*nanogram(ng)/milliliter (mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Tamiflu (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate |
277; 194; 142; 4990; 4920; NA | — |
| PRIMARY Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate |
80.8; 62.5; 25.2; 464; 530; 501 | — |
| PRIMARY Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate |
2.88; 2.09; 2.56; 238; 248; 169 | — |
| SECONDARY Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate |
1.08; 1.08; 1.08; 5.04; 2.88; 5.83 | — |
| SECONDARY Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate |
2.02; 2.01; 1.66; 9.45; 11.3; NA | — |
| SECONDARY Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate |
0.349; 0.338; 0.418; 0.0735; 0.0475; NA | — |
| SECONDARY 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 |
80500; 63000; 50600; 3940; 2180; NA | — |
| SECONDARY The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate |
234000; 183000; 121000; 53700; 35400; NA | — |
| SECONDARY Clast of Oseltamivir and Oseltamivir Carboxylate |
262; 176; 84.3; 3800; 4410; 3940 | — |
| SECONDARY Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate |
9.23; 8.53; 6.94; 10.11; 10.64; 10.45 | — |
| SECONDARY Number of Participants With Change From Baseline in Neurological Assessment Scores |
0; 2; 0; 0; 1; 0 | — |
| SECONDARY Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline |
228.5; 113.0; 113.0 | =0.166 |
| SECONDARY Number of Participants With Virus Shedding by Virus Type |
32; 10; 14; 20; 5; 14 | — |
| SECONDARY Time to Resolution of Fever in Participants With Fever at the Baseline |
12.0; 20.5; 24.0 | =0.059 |
| SECONDARY Percentage of Participants With Decline of Body Temperature to the Afebrile State |
36; 55; 25; 64; 45; 75 | — |
| SECONDARY Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness |
13; 12; 2; 3; 1; 0 | — |
| SECONDARY Number of Participants Showing Within-patient Variability in Vital Signs |
— | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT00988325). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.