Clinical trial NCT00988325: A Pharmacokinetic/Pharmacodynamic (PK/PD) and Safety Evaluation of Oseltamivir [Tamiflu] in the Treatment of Infants 0 to <12 Months of Age With Confirmed Flu Infection
Official title: An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Oseltamivir (Tamiflu®) in the Treatment of Infants 0 to <12 Months of Age With Confirmed Influenza Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-10-02
Enrollment: 65
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the pharmacokinetics/pharmacodynamics and safety of oseltamivir \[Tamiflu\] therapy in infants less than 1 year of age with influenza diagnosed in the 96 hours prior to the first dose. Patients age 3-12 months will receive 3 mg/kg, 1-3 months will receive 2.5 mg/kg, and birth to 1 month will receive 2 mg/kg twice a day for a total of 10 doses. Patients positive for influenza virus on Day 6 will be eligible to receive continued study treatment for an additional 10 doses (5 days). The anticipated time on study treatment is 4 weeks, and the target sample size is 65-85 male and female infants.


Eligibility criteria: Inclusion Criteria:

* infants \</=12 months of age
* laboratory confirmed diagnosis of influenza within 96 hours prior to first dose
* influenza symptoms for \</=96 hours prior to first dose

Exclusion Criteria:

* preterm infants less than 40 weeks (corrected for gestational age)
* weight less than 5th percentile for age (corrected for gestational age)
* concurrent gastrointestinal conditions that preclude enteric absorption of the drug
* bronchopulmonary dysplasia/chronic lung disease on assisted ventilation at time of enrollment
* active or uncontrolled respiratory, cardiac, hepatic, CNS or renal disease at baseline
* symptomatic inborn errors of metabolism

Primary outcomes:
measure: Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Secondary outcomes:
measure: Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Clast of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate
timeFrame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
measure: Number of Participants With Change From Baseline in Neurological Assessment Scores
timeFrame: Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30
measure: Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline
timeFrame: Days 1, 3 or 4, 6, 11, 18, and 30
measure: Number of Participants With Virus Shedding by Virus Type
timeFrame: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
measure: Time to Resolution of Fever in Participants With Fever at the Baseline
timeFrame: Days 1 to 11; Day 18; Day 30
measure: Percentage of Participants With Decline of Body Temperature to the Afebrile State
timeFrame: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
measure: Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness
timeFrame: Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
measure: Number of Participants Showing Within-patient Variability in Vital Signs
timeFrame: Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Bron
country: France
facility: Hôpital Femme Mère Enfant; Service de rhumatologie pédiatrique
city: Berlin
country: Germany
facility: CAMPUS VIRCHOW-KLINIKUM CharitéCentrum 17 Klinik f.Pädiatrie Abt.Pneumologie u.Immunologie
city: Bochum
country: Germany
facility: LWL-Klinik-Bochum
city: Worms
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Med. O. Burkhard & B. Reimann
city: Milan
country: Italy
facility: Fondazione Ospedale Maggiore Policlinico
state: Lombardia
city: Bydgoszcz
country: Poland
facility: Vitamed
city: Bydgoszcz
country: Poland
facility: Samodzielny Publiczny Zakład Opieki; Wcześniaków I Intensywnej Terapii
city: Debica
country: Poland
facility: Zespol Opieki Zdrowotnej Debica; Oddzial Dzieciecy
city: Trzebnica
country: Poland
facility: St Hedwig Hospital In Trzebnica
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
state: La Coruña
city: Madrid
country: Spain
facility: Hospital Universitario de Getafe; Servicio de Pediatria
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rath BA, Brzostek J, Guillen S, Niranjan V, Chappey C, Rayner CR, Clinch B. Safety, virology and pharmacokinetics of oseltamivir in infants with laboratory-confirmed influenza: a Phase I/II, prospective, open-label, multicentre clinical trial. Antivir Ther. 2015;20(8):815-25. doi: 10.3851/IMP2967. Epub 2015 May 27.