A Study of Intravenous Tamiflu (Oseltamivir) in Children With Influenza

Study Overview
=================
Brief Summary
-----------------
This open-label study will assess the pharmacokinetics/pharmacodynamics and safety of intravenous (iv) Tamiflu (oseltamivir) in 3 cohorts of children, aged 6-12, 3-5 and 1-2 years, with influenza infection. Patients will receive iv Tamiflu therapy for 5 days (10 doses). For patients whose conditions no longer merit continued iv dosing, therapy may be switched to oral Tamiflu to complete their prescribed course of treatment. If medically necessary, iv or oral therapy with Tamiflu may be continued for up to 5 additional days. Anticipated time on study treatment is 5 to 10 days.

Official Title
-----------------
An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir (Tamiflu) in the Treatment of Children 1 to 12 Years of Age With Influenza Infection

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Drug: oseltamivir [Tamiflu]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: children, 1-12 years of age diagnosis of influenza duration of influenza symptoms </=96 hours prior to first dose of study drug Exclusion Criteria: evidence of severe hepatic decompensation patients taking probenecid within 1 week prior to first dose of study drug

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br> | Drug: oseltamivir [Tamiflu]<br>* 5-day course (10 doses), intravenous administration, may be switched to oral administration at the discretion of the investigator; up to 5 additional days of treatment possible.<br>|

What is the study measuring?
-----------------
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 |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion. | 
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 |  | Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 |  | Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 |  | Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 |  | Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion | 
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 |  | Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 |  | Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 |  | Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 |  | Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate |  | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | 
| 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, >=5 times change in the NAI IC50 Visit value from the Baseline value. | Baseline, Day 1, 6 and 30 |