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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: oseltamivir [Tamiflu]

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 19202
• Lebanon
  • Beirut, Lebanon, 11-236
• United States
  • California
    • Los Angeles, California, United States, 90095
    • Oakland, California, United States, 94609-1809
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Delaware
    • Wilmington, Delaware, United States, 19803
  • Florida
    • Jacksonville, Florida, United States, 32209
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Indiana
    • South Bend, Indiana, United States, 46601
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
    • Boston, Massachusetts, United States, 02118
    • Boston, Massachusetts, United States, 02115
    • Springfield, Massachusetts, United States, 01199
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Minnesota
    • Duluth, Minnesota, United States, 55805
  • Nebraska
    • Omaha, Nebraska, United States, 68131
  • New Jersey
    • Morristown, New Jersey, United States, 07960
  • New York
    • Bronx, New York, United States, 10461
    • Brooklyn, New York, United States, 11203
    • New York, New York, United States, 10016
    • Stony Brook, New York, United States, 11794-8161
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Durham, North Carolina, United States, 27705
    • Raleigh, North Carolina, United States, 27610
  • Ohio
    • Akron, Ohio, United States, 44308
    • Cleveland, Ohio, United States, 44106
    • Dayton, Ohio, United States, 45404
    • Toledo, Ohio, United States, 43606
    • Toledo, Ohio, United States, 43608
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Tyrone, Pennsylvania, United States, 16686
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
  • South Carolina
    • Charleston, South Carolina, United States, 29524
  • Texas
    • Houston, Texas, United States, 77030
  • Virginia
    • Richmond, Virginia, United States, 23298
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm	Drug: oseltamivir [Tamiflu]; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Munoz FM, Anderson EJ, Deville JG, Clinch B, Kamal MA. Pharmacokinetics and safety of intravenous oseltamivir in infants and children in open-label studies. Int J Clin Pharmacol Ther. 2015 Jul;53(7):531-40. doi: 10.5414/CP202307.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 15, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Estimate): August 24, 2016
• Last Update Submitted That Met QC Criteria: July 13, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: NP25139