Clinical trial NCT01053663: A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Influenza
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-01-21
Enrollment: 9
Sex: ALL
Maximum age (years): 365
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 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.


Eligibility criteria: 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

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: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
timeFrame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
measure: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
timeFrame: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
measure: Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1
timeFrame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2
timeFrame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4
timeFrame: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Secondary outcomes:
measure: Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
timeFrame: Baseline, Days 1, 3, 4, 6, 15
measure: Number of Participants With Oseltamivir Resistance Mutation
timeFrame: Up to Day 30
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
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: Omaha
country: United States
state: Nebraska
city: Morristown
country: United States
state: New Jersey
city: New Brunswick
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: Providence
country: United States
state: Rhode Island
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
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
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.