A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza

Phase 1

Terminated

Brief Summary: This open-label study will assess the pharmacokinetics and safety of oseltamivir \[Tamiflu\] in 3 cohorts of infants, aged 0-30 days, 31-90 days and 91-\<365 days with influenza infection. Patients will receive 10 doses of intravenous oseltamivir \[Tamiflu\] therapy over 5 or 6 days. Optional oral therapy with oseltamivir \[Tamiflu\] may be considered following the intravenous dose associated with pharmacokinetic blood sampling. Evidence of continued virus shedding at day 6 can allow for up to 5 additional days (10 doses) of oral or intravenous administration. Anticipated time on study drug is 5-11 days. Target sample size is \<50 patients.

Recruitment & Eligibility

Inclusion Criteria

Infant patients
Date of birth to date of enrollment is <1 year
Diagnosis of influenza
Duration of influenza symptoms </=96 hours prior to first dose
- Parent/guardian willing to have patient receive intravenous therapy for 3 or 4 days (5 or 6 doses of study drug)

Exclusion Criteria

Date of conception to date of birth + date of birth to enrollment is <36 weeks
Creatinine clearance <30 mL/min/1.73m2
Patients receiving any form of renal replacement therapy at baseline
Clinical evidence of severe hepatic decompensation at the time of enrollment
Patients taking probenecid medication within 1 week prior to study day 1 or during the study

Arm && Interventions

Group	Intervention	Description
1	Tamiflu	-

Primary Outcome Measures

Name	Time	Method
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4	Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4	Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2

Secondary Outcome Measures

Name	Time	Method
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Number of Participants With Oseltamivir Resistance Mutation	Up to Day 30	Resistance was assessed by neuraminidase (NA) and hemagglutinin (HA) genes sequencing analysis, using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values	Baseline, Days 1, 3, 4, 6, 15	IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either ≥5 times change in the NAI IC50 visit value from the Reference value at a visit or ≥5 times change in the NAI IC50 Visit value from the Baseline value.
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4