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A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Oseltamivir
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza

Eligibility Criteria

undefined - 12 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Lucile Packard Child Hosp; Pediatric Pulmonary Division
  • The Children's Hospital; Pediatric Infectious Diseases
  • Tufts Medical Center
  • University of Minnesota
  • SUNY Upstate Medical University
  • Cincinnati Children's Hospital Medical Center
  • Seattle Children's Hospital
  • UZ Brussel
  • Cliniques Universitaires St-Luc
  • UZ Leuven Gasthuisberg
  • Hospital Erasto Gaertner
  • Hospital São Lucas da PUCRS
  • Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
  • Casa de Saúde Santa Marcelina
  • Children'S Hospital of Eastern Ontario
  • Hospital For Sick Children; Infectious Disease Dept
  • McGill University; Montreal Children's Hospital; Oncology
  • Hospital Dr. Gustavo Fricke
  • Centro Medico Imbanaco
  • Fundacion Clinica Valle de Lili, Department Rheumatology
  • Turun yliopistollinen keskussairaala
  • Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie
  • Universitatsklinikum Frankfurt
  • Dr. Von Haunersches Kinderspital
  • Universitätsklinikum Münster
  • Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin
  • Childrens Regional Hospital Aglaia Kyriakou
  • Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics
  • Rambam Medical Center
  • Hadassah University Hospital - Ein Kerem
  • Schneider Children's Medical Center of Israel; Pediatrics Department
  • The Chaim Sheba Medical Center; Multiple Sclerosis Center
  • The Dana Children's Hospital
  • Ospedale Pediatrico Bambino Gesu
  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1
  • ASST DI MONZA; Divisione Malattie Infettive
  • Instituto Nacional de Pediatria; Departmento de Neurologia
  • Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
  • Uniwersyteckie Centrum Kliniczne
  • Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology
  • Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego
  • Medical University of Silesia; Department of Pediatric Hematology and Oncology
  • Tygerberg Hospital; Rheumatology
  • WWCT Lakeview Hospital
  • Chris Hani Baragwanath Hospital
  • Hospital Sant Joan De Deu
  • Hospital Universitari Vall d'Hebron
  • Hospital General Universitario Gregorio Marañon
  • Hospital Infantil Universitario Nino Jesus
  • Hospital Universitario La Paz

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Oseltamivir: Standard dose

Oseltamivir: Triple dose

Arm Description

Participants will receive standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight. Infants <1 year of age will receive oseltamivir at a dose of 3 milligrams per kilogram (mg/kg).

Participants will receive three times the standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight and age. Infants <1 year will receive standard dose at 3 mg/kg.

Outcomes

Primary Outcome Measures

Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir
Steady State AUC0-12 of Oseltamivir Carboxylate
Maximum Plasma Concentration (Cmax) of Oseltamivir
Cmax of Oseltamivir Carboxylate
Trough Plasma Concentration (Ctrough) of Oseltamivir
Ctrough of Oseltamivir Carboxylate
Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing

Secondary Outcome Measures

Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS)
Number of Participants With Adverse Events
Number of Participants With Influenza Associated Complications
Number of Participants With Viral Resistance
Half-life (t1/2) of Oseltamivir
t1/2 of Oseltamivir Carboxylate
Time to Maximum Concentration (Tmax) of Oseltamivir
Tmax of Oseltamivir Carboxylate
Elimination Rate Constant (Ke) of Oseltamivir
Ke of Oseltamivir Carboxylate
Apparent Volume of Distribution (V/F) of Oseltamivir
V/F of Oseltamivir Carboxylate
Apparent Clearance (CL/F) of Oseltamivir
CL/F of Oseltamivir Carboxylate
Time to Last Measurable Concentration (Tlast) of Oseltamivir
Tlast of Oseltamivir Carboxylate
Last Measurable Concentration (Clast) of Oseltamivir
Clast of Oseltamivir Carboxylate

Full Information

First Posted
October 25, 2012
Last Updated
October 15, 2018
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01715909
Brief Title
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
January 22, 2014 (Actual)
Primary Completion Date
June 17, 2018 (Actual)
Study Completion Date
June 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oseltamivir: Standard dose
Arm Type
Experimental
Arm Description
Participants will receive standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight. Infants <1 year of age will receive oseltamivir at a dose of 3 milligrams per kilogram (mg/kg).
Arm Title
Oseltamivir: Triple dose
Arm Type
Experimental
Arm Description
Participants will receive three times the standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight and age. Infants <1 year will receive standard dose at 3 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
Participants will receive standard dose (30 to 75 milligrams [mg]) or triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for </= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.
Primary Outcome Measure Information:
Title
Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Steady State AUC0-12 of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Maximum Plasma Concentration (Cmax) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Cmax of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Trough Plasma Concentration (Ctrough) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
Title
Ctrough of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
Title
Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing
Time Frame
From randomization to negative PCR/culture test result (up to Day 50)
Secondary Outcome Measure Information:
Title
Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS)
Time Frame
From randomization to resolution of all influenza symptoms (up to Day 50)
Title
Number of Participants With Adverse Events
Time Frame
Baseline up to Day 50
Title
Number of Participants With Influenza Associated Complications
Time Frame
Baseline up to Day 50
Title
Number of Participants With Viral Resistance
Time Frame
Baseline up to Day 50
Title
Half-life (t1/2) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
t1/2 of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Time to Maximum Concentration (Tmax) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Tmax of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Elimination Rate Constant (Ke) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Ke of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Apparent Volume of Distribution (V/F) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
V/F of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Apparent Clearance (CL/F) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
CL/F of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Time to Last Measurable Concentration (Tlast) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Tlast of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Last Measurable Concentration (Clast) of Oseltamivir
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Title
Clast of Oseltamivir Carboxylate
Time Frame
Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

10. Eligibility

Sex
All
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Lucile Packard Child Hosp; Pediatric Pulmonary Division
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
The Children's Hospital; Pediatric Infectious Diseases
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
UZ Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Cliniques Universitaires St-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hospital Erasto Gaertner
City
Curitiba
State/Province
PR
ZIP/Postal Code
81520-060
Country
Brazil
Facility Name
Hospital São Lucas da PUCRS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04023-062
Country
Brazil
Facility Name
Casa de Saúde Santa Marcelina
City
São Paulo
State/Province
SP
ZIP/Postal Code
08270-070
Country
Brazil
Facility Name
Children'S Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Facility Name
Hospital For Sick Children; Infectious Disease Dept
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
McGill University; Montreal Children's Hospital; Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Hospital Dr. Gustavo Fricke
City
Viña del Mar
ZIP/Postal Code
2520000
Country
Chile
Facility Name
Centro Medico Imbanaco
City
Cali
Country
Colombia
Facility Name
Fundacion Clinica Valle de Lili, Department Rheumatology
City
Cali
Country
Colombia
Facility Name
Turun yliopistollinen keskussairaala
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitatsklinikum Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Dr. Von Haunersches Kinderspital
City
München
ZIP/Postal Code
80337
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Childrens Regional Hospital Aglaia Kyriakou
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Hadassah University Hospital - Ein Kerem
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Schneider Children's Medical Center of Israel; Pediatrics Department
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
The Chaim Sheba Medical Center; Multiple Sclerosis Center
City
Ramat-Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
The Dana Children's Hospital
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
ASST DI MONZA; Divisione Malattie Infettive
City
Monza
State/Province
Lombardia
ZIP/Postal Code
20052
Country
Italy
Facility Name
Instituto Nacional de Pediatria; Departmento de Neurologia
City
Mexico
ZIP/Postal Code
04530
Country
Mexico
Facility Name
Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology
City
Olsztyn
ZIP/Postal Code
10-561
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego
City
Szczecin
ZIP/Postal Code
71-242
Country
Poland
Facility Name
Medical University of Silesia; Department of Pediatric Hematology and Oncology
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Facility Name
Tygerberg Hospital; Rheumatology
City
Cape Town
ZIP/Postal Code
7500
Country
South Africa
Facility Name
WWCT Lakeview Hospital
City
Johannesburg
ZIP/Postal Code
1501
Country
South Africa
Facility Name
Chris Hani Baragwanath Hospital
City
Johannesburg
ZIP/Postal Code
2013
Country
South Africa
Facility Name
Hospital Sant Joan De Deu
City
Esplugues De Llobregas
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Infantil Universitario Nino Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
280146
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection

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