Clinical trial NCT01033734: A Study of Intravenous Tamiflu (Oseltamivir) in Children With Influenza
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-12-16
Enrollment: 8
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1
timeFrame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
timeFrame: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3
timeFrame: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
timeFrame: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5
timeFrame: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1
timeFrame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2
timeFrame: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3
timeFrame: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4
timeFrame: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5
timeFrame: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Secondary outcomes:
measure: Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
timeFrame: Baseline, Day 1, 6 and 30
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Wilmington
country: United States
state: Delaware
city: Jacksonville
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: South Bend
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: Morristown
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: Stony Brook
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tyrone
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Madison
country: United States
state: Wisconsin
city: Petach Tikva
country: Israel
city: Beirut
country: Lebanon
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.