Clinical trial NCT01715909: A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection
Official title: An Open-Label, Randomized, Adaptive, Two-Arm, Multicenter Trial to Evaluate Pharmacokinetics And Pharmacodynamics of Two Doses of Oseltamivir (Tamiflu®) in The Treatment Of Influenza in Immunocompromised Children Less Than 13 Years 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: 2012-10-29
Enrollment: 20
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label, randomized, adaptive, 2-arm, multicenter study will evaluate the pharmacokinetics and pharmacodynamics of oseltamivir (Tamiflu) in immunocompromised children, less than (\<) 13 years of age, with confirmed influenza infection. Participants will be randomized to receive either the standard dose or triple dose of oseltamivir orally daily for a minimum of 5 days and up to 20 days. Infants \<1 year of age will be randomized to the standard dose arm only.


Eligibility criteria: Inclusion Criteria:

* Male or female children, \<13 years of age
* Rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR), or viral culture positive for influenza
* Immunocompromised
* Symptoms/signs suggestive of influenza like illness (ILI)
* Less than or equal to (\</=) 96 hours between onset of ILI and first dose of study drug

Exclusion Criteria:

* Clinical evidence of severe hepatic impairment
* Infants with post-menstrual age (PMA) \<36 weeks
* Clinical evidence of significant renal impairment
* Allergy to oseltamivir or excipients
* Hereditary fructose intolerance
* Received anti-viral treatment with activity against influenza (for example amantadine, rimantadine, oseltamivir, laninamivir, peramivir, zanamivir, and ribavirin) or probenecid medication within 2 weeks prior to randomization

Primary outcomes:
measure: Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Steady State AUC0-12 of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Maximum Plasma Concentration (Cmax) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Cmax of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Trough Plasma Concentration (Ctrough) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
measure: Ctrough of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
measure: Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing
timeFrame: From randomization to negative PCR/culture test result (up to Day 50)
Secondary outcomes:
measure: Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS)
timeFrame: From randomization to resolution of all influenza symptoms (up to Day 50)
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to Day 50
measure: Number of Participants With Influenza Associated Complications
timeFrame: Baseline up to Day 50
measure: Number of Participants With Viral Resistance
timeFrame: Baseline up to Day 50
measure: Half-life (t1/2) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: t1/2 of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Time to Maximum Concentration (Tmax) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Tmax of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Elimination Rate Constant (Ke) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Ke of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Apparent Volume of Distribution (V/F) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: V/F of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Apparent Clearance (CL/F) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: CL/F of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Time to Last Measurable Concentration (Tlast) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Tlast of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Last Measurable Concentration (Clast) of Oseltamivir
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
measure: Clast of Oseltamivir Carboxylate
timeFrame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Child Hosp; Pediatric Pulmonary Division
state: California
city: Aurora
country: United States
facility: The Children's Hospital; Pediatric Infectious Diseases
state: Colorado
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: PR
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: RS
city: Sao Paulo
country: Brazil
facility: Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
state: SP
city: São Paulo
country: Brazil
facility: Casa de Saúde Santa Marcelina
state: SP
city: Ottawa
country: Canada
facility: Children'S Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital For Sick Children; Infectious Disease Dept
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Montreal Children's Hospital; Oncology
state: Quebec
city: Viña del Mar
country: Chile
facility: Hospital Dr. Gustavo Fricke
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
city: Cali
country: Colombia
facility: Fundacion Clinica Valle de Lili, Department Rheumatology
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt
city: München
country: Germany
facility: Dr. Von Haunersches Kinderspital
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin
city: Athens
country: Greece
facility: Childrens Regional Hospital Aglaia Kyriakou
city: Athens
country: Greece
facility: Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel; Pediatrics Department
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center; Multiple Sclerosis Center
city: Tel Aviv
country: Israel
facility: The Dana Children's Hospital
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1
state: Lombardia
city: Monza
country: Italy
facility: ASST DI MONZA; Divisione Malattie Infettive
state: Lombardia
city: Mexico
country: Mexico
facility: Instituto Nacional de Pediatria; Departmento de Neurologia
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Olsztyn
country: Poland
facility: Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego
city: Zabrze
country: Poland
facility: Medical University of Silesia; Department of Pediatric Hematology and Oncology
city: Cape Town
country: South Africa
facility: Tygerberg Hospital; Rheumatology
city: Johannesburg
country: South Africa
facility: WWCT Lakeview Hospital
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: