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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir in the Treatment of Infants Less Than One Year of Age With Influenza Infection

Conditions
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Influenza

Intervention / Treatment
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* Drug: Tamiflu


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 365 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Tamiflu<br>* 10 doses over 5 or 6 days of which the first 5 or 6 doses must be intravenous, up to 5 days (10 doses) of additional intravenously or oral treatment if virus shedding continues at day 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4 |  | Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 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. | Baseline, Days 1, 3, 4, 6, 15 | 
| Number of Participants With Oseltamivir Resistance Mutation | Resistance was assessed by neuraminidase (NA) and hemagglutinin (HA) genes sequencing analysis, using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | Up to Day 30 |