A Study of Oseltamivir (Tamiflu) for Treatment of Influenza in Immunocompromised Participants.

A Double-Blind, Randomized, Stratified Multi-Center Trial Evaluating Conventional and Double Dose Oseltamivir in the Treatment of Immunocompromised Patients With Influenza

This 2-arm study will investigate the safety and tolerability of oseltamivir for the treatment of influenza in immunocompromised participants and characterize the effects of oseltamivir in immunocompromised participants on the development of resistant influenza virus. Eligible immunocompromised participants with laboratory-confirmed influenza will be randomized to receive either conventional dose (30 milligrams [mg] to 75 mg twice daily orally [po], depending on age and weight) or double dose (60 mg-150 mg twice daily po depending on age and weight) olseltamivir for 10 days. Nasal and throat swabs will be taken, and safety evaluations made, at intervals during the study. The anticipated time on study medication is 10 days and the anticipated time on study is 40 days.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Drug: oseltamivir; Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1202
    • Hospital General de Agudos Juan Antonio Fernandez; infectología
  • Buenos Aires, Argentina
    • Instituto Medico Platense
  • Ciudad Autonoma Buenos Aires, Argentina, 1426
    • Instituto Médico Especializado Alexander Fleming
  • Ciudad Autonoma Buenos Aires, Argentina, 1430
    • Hospital General de Agudos Dr. Ignacio Pirovano
  • La Plata, Argentina, 1725
    • Hospital Italiano de La Plata
  • Santa Fe, Argentina, S3000CII
    • Hospital de Niños Dr. Orlando Alassia
• Belgium
  • Aalst, Belgium, 9300
    • Onze Lieve Vrouwziekenhuis Aalst
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1070
    • Hospital Erasme; Neurologie
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21040-360
      • Fiocruz - Fundação Oswaldo Cruz
  • SP
    • Sao Paulo, SP, Brazil, 01323-020
      • Hospital Alemao Oswaldo Cruz; Oncologia
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP
    • Sao Paulo, SP, Brazil, 04023-062
      • Iop - Graacc - Unifesp
    • Sao Paulo, SP, Brazil, 04038-002
      • Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHA - Sv. Georgi; Clinic of Nephrology & Haemodialysis
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sv. Georgi, EAD; Clinic of Infectious Diseases
  • Sofia, Bulgaria, 1431
    • Mhat Alexandrovska Ead ; Clinic of Nephrology & Transplantation, Uni Hospital
  • Sofia, Bulgaria, 1527
    • Specialized Hospital for children with oncohaematologica Diseases; Dept. Of Transplantations
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 6518
      • Uni of Manitoba; Faculty of Medicine
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7M 0Z9
      • St Paul'S
• Chile
  • Santiago, Chile, 8207257
    • Hospital Dr. Sótero del Río
  • Santiago, Chile, 7500539
    • Hospital Luis Calvo Mackenna; Unidad de Investigacion
  • Viña Del Mar Valparaiso, Chile, 2520000
    • Centro de Investigaciones Clinicas Vina Del Mar
• Colombia
  • Barranquilla, Colombia
    • Infectologos Asociados
  • Bogota, Colombia
    • Simedics Ips
  • Cali, Colombia
    • Centro de Investigaciones Clinicas S.A.S
  • Floridablanca, Colombia
    • Fundacion Cardiovascular de Colombia - Instituto del Corazón
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
  • Plzen, Czechia, 300 00
    • Fakultni Nemocnice; Hemato-Oncology
  • Praha, Czechia, 12820
    • The Institute of Hematology and Blood Transfusion Transplantation Unit; Hematology and Blood Transf
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole; Klinika detske hematologie a onkologie UK 2.LF
  • Tabor, Czechia, 390 01
    • KASMED, s.r.o.; Alergologie a klinicka imunologie
  • Terezin, Czechia, 411 55
    • Revmatologicka Ambulance-Terezin
  • Zlin, Czechia, 760 01
    • Revmatologicka ambulance
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia medical Centre; Hematology
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital; Nephrology
  • Tartu, Estonia, 51014
    • Tartu Uni Hospital; Hematology - Oncology Clinic
  • Tartu, Estonia, 51014
    • Tartu Uni Clinics; Clinic of Surgery & Internal Medicine Dept of Nephrology
  • Tartu, Estonia, 51014
    • Tartu University Hospital; Department of Infectious Diseases
• France
  • Lyon, France, 69317
    • Centre Hospitalier de la Croix Rousse
  • Paris, France, 75019
    • Hopital Robert Debre; Pediatric Hematology Dept
  • Paris, France, 75475
    • Hopital Saint Louis; Service de Nephrologie - Transplantation
  • Paris, France, 75908
    • Hopital Europeen Georges Pompidou; Service de Nephrologie
  • Toulouse, France, 31059
    • Hopital Rangueil; Nephrologie
  • Tours, France, 37044
    • CHRU Bretonneau
• Germany
  • Aachen, Germany, 52057
    • Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie
  • Berlin, Germany, 13353
    • Charite - Campus Virchow Klinikum; Abteilung fuer Chirurgie
  • Essen, Germany, 45122
    • Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • UNI-Klinikum Heidelberg Chirurgische Klinik
  • Muenchen, Germany, 80336
    • Ludwig-Maximilian-Universitaetsklinik; Med. Poliklinik/Infektiologie
  • Muenchen, Germany, 80336
    • Ludwig-Maximilians-Universitaet; Medizinische Klinik und Poliklinik IV
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster; Paedriatrische Haematologie und Onkologie
• Guatemala
  • Ciudad de Guatemala, Guatemala, 01001
    • Clinica Familiar Luis Angel Garcia
  • Ciudad de Guatemala, Guatemala, 01009
    • CERICAP
  • Guatemala, Guatemala
    • Unidad Nacional De Oncologia Pediatrica
  • Guatemala City, Guatemala, 1015
    • Centro de Investigaciones Pediátricas
  • Guatemala City, Guatemala
    • Hospital Roosevelt Guatemala; Clinica de Infecciosas
• Hungary
  • Budapest, Hungary, 1096
    • Fov.Onk.Egyesitett Szt. Istvan es Szt Laszlo Korh.-Rend.Int.
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem, Orvos- és Egészségtudományi Centrum;
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Korhaz; Hematologia
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
  • Gyula, Hungary, 5703
    • Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek
  • Pecs, Hungary, 7624
    • Pecsi Tudomanyegyetem
  • Szeged, Hungary, 6720
    • University of Szeged; Transplantation Department
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Korhaz
  • Szolnok, Hungary, 5000
    • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.
  • Veszprem, Hungary, 8200
    • Veszprem Megyei Csolnoky Ferenc Korhaz Nonprofit Zrt.
• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus; Hematology
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital - Ein Kerem; BMT & Cancer Immunotherapy Dept.
  • Petach Tikva, Israel, 49100
    • Rabin MC- Belinson campus
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center-Golda Campus - Hasharon; Department of Transplantation
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center; Liver Inst.
  • Ramat Gan, Israel, 52662
    • Chaim Sheba Medical Center; Hematology BMT & CBB
  • Tel Aviv, Israel, 64239
    • Sourasky MC; Transplant Unit
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba MC; Pediatric Hematology Oncology
• Italy
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • Azienda Ospedaliera; Divisione Malattie Infettive E Tropicali
  • Lazio
    • Roma, Lazio, Italy, 00168
      • POLICLINICO Universitatio A.Gemelli, Div. Chirurgia Generale e Trapianti d'Organo
    • Roma, Lazio, Italy, RM 00149
      • I.N.M.I. L. Spallanzani IRCCS
  • Lombardia
    • Brescia, Lombardia, Italy, 25126
      • ASST DEGLI SPEDALI CIVILI DI BRESCIA; Dipartimento Malattie Infettive
    • Monza, Lombardia, Italy, 20052
      • ASST DI MONZA; Divisione Malattie Infettive
    • Pavia, Lombardia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
  • Molise
    • Milano, Molise, Italy, 20122
      • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico; Clinica Pediatica De Macchi
• Latvia
  • Riga, Latvia, LV-1002
    • Latvia Transplantation Center P. Stradina Hospital; Transplantation
  • Riga, Latvia, LV-1004
    • Children's Clinical University Hospital
• Lithuania
  • Kaunas, Lithuania, 50009
    • Kaunas Clinics Public Institution; Clinic of Nephrology
  • Klaipeda, Lithuania, 92288
    • Klaipeda University Hospital; Public Institution
  • Siauliai, Lithuania, 76231
    • Siauliai Republican Hospital Public Institution
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinic
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center
  • Vilnius, Lithuania, 8117
    • Republican Tuberculosis and Infectious Diseases University H
• Mexico
  • Cuautitlan Izcalli, Mexico, 54769
    • Phylaxis Clinical Research S de RL de CV
  • Guadalajara, Mexico, 44280
    • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde; Infectología piso 7
  • Mexico, Mexico, 03720
    • Centro de Investigacion Clínica GRAMEL S.C
  • Mexico, Mexico, 14080
    • INER- Instituto Nacional de Enfermedades Respiratorias"Ismae
  • Mexico, Mexico, 14000
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador; Infectologia
  • Monterrey, Mexico, 64040
    • Hospital Universitario de Monterrey; Infectologia
  • Zapopan, Mexico, 45116
    • Hospital de Especialidades del Centro Medico Puerta de Hierr
• Poland
  • Bialystok, Poland, 15-540
    • Wojewodzki Szp.Specjalistyczny im.K.Dluskiego w Bialymstoku
  • Bydgoszcz, Poland, 85-079
    • NZOZ Vitamed
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 31-501
    • SPZOZ Szpital Uniw W Krakowie
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szp Klin; nr1 im.N.Barlickiego UM
  • Szczecin, Poland, 70-111
    • SPSK nr 2 Pomorskiej Akademii Medycznej w Szczecinie
  • Warszawa, Poland, 02-006
    • Szpital Dzieciatka Jezus-Centrum Lecezenia Obrazen; Dpt of Transplantation Medicine & Nephrology
  • Warszawa, Poland, 04-730
    • Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego
  • Wroclaw, Poland, 50-445
    • ALL-MED Specjalistyczna Opieka Medyczna
  • Wroclaw, Poland, 50-367
    • SP Szpital Kliniczny Nr 1 we Wroclawiu
• Romania
  • Bucharest, Romania, 022328
    • Institutul de Urologie Si Transplant Renal Fundeni
• South Africa
  • Bloemfontein, South Africa, 9301
    • Josha Research
  • Durban, South Africa, 4001
    • Londisizwe Research Centre
  • Durban, South Africa, 4001
    • Sebastian Peter
  • Durban, South Africa, 4092
    • Dr V Naidoo Private Practice
  • Durban, South Africa, 4096
    • Govind U
  • Johannesburg, South Africa, 2113
    • Newtown Clinical Research
  • Johannesburg, South Africa, 1818
    • Soweto CTC - Dr Phoshoko site
  • Johannesburg, South Africa, 1983
    • Soweto CTC - Dr Mushwana site
  • Middelburg, South Africa, 1055
    • Mzansi Ethical Research Centre
  • Paarl, South Africa, 7626
    • Be Part Yoluntu Centre
  • Port Elizabeth, South Africa, 6020
    • Global Clinical Trials Port Elizabeth
  • Pretoria, South Africa, 0084
    • Emmed Research
  • Pretoria, South Africa, 0002
    • Kalafong Hospital; Pathology
  • Pretoria, South Africa, 0112
    • Synexus Clinical Research Centres SA Stanza Bopape
  • Soweto, South Africa, 1818
    • Soweto Clinical Trial Centre
  • Tygerberg; Cape Town, South Africa, 7505
    • Tygerberg Hospital Pediatrics and Child Health
  • Welkom, South Africa, 9460
    • Welkom Clinical Trial Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Departamento de Enfermedades Infecciosas
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos; Servicio de Nefrologia
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Enfermedades Infecciosas
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; HIV Unit
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Pediatria
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Hepatología y Trasplantes
  • Madrid, Spain, 28046
    • Hospital Universitario la Paz; Servicio de Enfermedades Infecciosas - HIV unit
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge; Servicio de Nefrologia
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Hospital Clinico Universitario de Santiago
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich; Klinik für Nephrologie
• Ukraine
  • Kiev, Ukraine, 01135
    • Ukrainian Pediatric Specialized Hospital of Ministry of Health of Ukraine Dept of BMT
  • Kiev, Ukraine, 04050
    • Institute of Nephrology AMS; Dept of Nephrology & dialysis
  • Lugnansk, Ukraine, 91045
    • Lugansk Regional Clinical Hospital; Chair of Therapy Faculty of Postgr.Ed
  • Zaporozhye, Ukraine, 69600
    • Zaporozhye State Medical University; Dept of Transplantology
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • University Hospitals Bristol NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary; Renal Transplant Unit
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Transplant Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham; Pediatric Nephrology
    • Birmingham, Alabama, United States, 35233
      • Uni of Alabama At Birmingham; Division of Nephrology
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Los Angeles, California, United States, 90015
      • AIDS Research Alliance
    • Los Angeles, California, United States, 90095
      • UCLA Medical center Medicine/Nephrology
    • Sacramento, California, United States, 95817
      • University of California Davis Health System
    • San Francisco, California, United States, 94115
      • CALIFORNIA PACIFIC MEDICAL CENTER; Office of Dr. Venkat Peddi
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado; Kidney Transplant Center Office of Dr. Laurence Chan
  • Connecticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health System
  • Florida
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants
    • Saint Petersburg, Florida, United States, 33701
      • All Children'S Hospital; Pediatric Blood & Marrow Transplant Program
    • South Miami, Florida, United States, 33143
      • Kendall South Medical Center Inc.
    • Tamarac, Florida, United States, 33319
      • Vita Research Solutions, Inc
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital; Transplant Services
    • Atlanta, Georgia, United States, 30322
      • EMORY UNIVERSITY; Bone Marrow & Stem Cell Transplant Center
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia; Medicine/ Nephrology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital; Divison of Infectious Diseases/ Dept of Medicine
    • Chicago, Illinois, United States, 60612
      • Rush Uni Medical Center; Medicine/ Section of Infectious Diseases
    • Chicago, Illinois, United States, 60655
      • University of Chicago; Infectious Disease
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women'S Hospital
    • Springfield, Massachusetts, United States, 01107
      • Western New England Renal & Transplant Associates, P.C.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0378
      • Uni of Michigan Medical Center; Internal Medicine/ Infectious Disease
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Inst. ; Hudson Webber; Cancer Research Building
    • Detroit, Michigan, United States, 48210
      • Wayne State University School of Medicine
    • Detroit, Michigan, United States, 48202-2689
      • Henry Ford Health System; Gastroenterology
    • Lansing, Michigan, United States, 48917
      • Beals Institute PC
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Wash Uni. Sch. Of Med
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Our Lady of Lourdes Medical Center; Transplant Dept
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New Hyde Park, New York, United States, 11042
      • Long Island Jewish/North Shore Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center; Division of Liver Diseases
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research PLLC
    • Matthews, North Carolina, United States, 28105
      • Novant Health Pulmonary and Critical Care
    • Raleigh, North Carolina, United States, 27609
      • Duke University Health Systems
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Uni of Cincinnati Medical Center; Nephrology & Hypertension
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Infectious Disease
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-4481
      • Nazih Zuhdi Transplant Inst. ; Integris Baptist Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University; College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Uni of Pennsylvania; Infectious Diseases
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children'S Hospital of Pittsburgh; Infectious Disease
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina; Pediatric Cardiology
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center; Pediatrics Dept.
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center Transplant Administration
    • Dallas, Texas, United States, TX 75246
      • Sammons Cancer Center-Baylor University; Blood & Marrow Transplantation
    • Houston, Texas, United States, 77005
      • The Methodist Hospital
    • Houston, Texas, United States, 77030
      • M.D Anderson Cancer Center; Infectious Diseases, Infection Control, and Employee Health
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center; Department of Urology
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center Transplant center
    • Temple, Texas, United States, 76508
      • Scott and White Division of Nephrology Dept of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Science Center Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
• Immunocompromised participants with primary or secondary immunodeficiency
• Symptoms suggestive of influenza-like illness
• Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding

Exclusion Criteria:

• Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization
• Antiviral treatment for influenza in 2 weeks prior to randomization
• Severe hepatic impairment
• Any current renal replacement therapy
• Any gastrointestinal disorders which may interfere with the absorption of oseltamivir
• Participation in a study with an investigational drug from 4 weeks prior to study start until study end

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional dose; Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 30 to 75 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 75 mg twice daily for adults/adolescents greater than or equal to (>/=) 13 years old or placebo-matched to oseltamivir twice daily over 10 days.	Drug: oseltamivir; Dose ranging between 30 to 150 mg orally administered as syrup or capsules (depending on participant's age and weight) po twice daily for 10 days; Other Names: Tamiflu; Other: placebo; Placebo matched to oseltamivir po twice daily for 10 days
Experimental: Double dose; Immunocompromised participants will receive oseltamivir syrup at a dose ranging from 60 to 150 mg based on body weight, twice daily for children (1 to 12 years old) and oseltamivir capsules 150 mg twice daily for adults/adolescents (>/=13 years old) or placebo matched to oseltamivir twice daily over 10 days.	Drug: oseltamivir; Dose ranging between 30 to 150 mg orally administered as syrup or capsules (depending on participant's age and weight) po twice daily for 10 days; Other Names: Tamiflu; Other: placebo; Placebo matched to oseltamivir po twice daily for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline up to Day 40
Percentage of Participants Who Developed Viral Resistance to Oseltamivir	Resistance was defined as the presence of oseltamivir resistance mutations in viruses isolated from nasopharyngeal swab samples, identified by sequencing of the neuraminidase (NA) and hemagglutinin (HA) genes (genotypic resistance) and/or determination of the oseltamivir concentration at which the response is reduced by half (IC50) in an NA inhibition assay (phenotypic resistance). Reported are post-baseline phenotypic and genotypic resistance in adults >/= 18 years and children and adolescents <18 years in the modified Intent-to-Treat infected (mITTi) population.	Baseline up to Day 40
Percentage of Participants With Tissue Rejection or Graft Versus Host Disease (GVHD)	The percentage of transplant patients in the safety population who experienced tissue rejection and/or GvHD is reported.	Baseline up to Day 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resolution (TTR) of All Clinical Influenza Symptoms	TTR of all clinical influenza symptoms was defined as the time from treatment initiation to the start of the 24-hour period in which all 7 influenza symptoms had scores </= 1 (mild) and remained </=1 for at least 21.5 hours. . Reported are TTRs in adults >/= 18 years, adults and adolescents >/= 13 years and children <13 years in the mITTi population.	Baseline up to Day 40
Total Symptom Score Area Under the Efficacy Curve (AUE)	The overall extent and severity of illness was quantified by the AUE of the total symptom scores over the duration of illness, i.e., from the start of treatment to the time symptoms first alleviated. Total symptom scores were calculated from the sum of seven individual symptom scores with each individual symptom scored from 0 (healthy) to 3 (worst sickness) and a maximum total symptom score of 21. The AUE of these average scores was then calculated for each participant using the trapezoidal rule (the trapezoidal rule calculates the area under any curve by adding up all trapezoids under such a curve). A larger area indicates more severe disease. In this study participants were treated for 10 days. If a participant had scored 21 on every visit then AUE would have been 21 score x 10 days x 24 hours/day =5040 score x hours units, which is the highest possible score. The lowest possible score is 0. Reported are results for adults >/= 18 years in the mITTi population.	Baseline up to Day 40
Time to Resolution of Fever	Fever was defined as temperature >/= 37.8 degrees Celsius at any time point during the study. TTR of fever was determined in Adults >/= 18 years, Adults and adolescents >/= 13 years and Children < 13 years of the mITTi population.	Baseline up to Day 40
Change From Baseline in Viral Load Assessed by Culture	Nasopharyngeal swab samples were cultured in Madin-Darby Canine Kidney cells. Culture supernatants were harvested after 2 weeks, or after a full-blown cytopathic effect was observed. Presence of infectious viruses in the cell culture supernatants (viral titer), expressed as log10 50% Tissue Culture Infectious Dose/milliliter (TCID50/mL), was determined by hemagglutination assay using turkey erythrocytes for H1 and B viruses or by detection of the virus nucleoprotein (NP) using ELISA for H3 viruses. A value of < 0.5 log10 TCID50/mL was interpreted as negative. Data are reported for adults >/= 18 years and adolescents and children < 18 years.	Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Percentage of Participants With Viral Shedding Assessed by Culture Over Time	Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the percentage of participants with viral shedding over time in adults >/= 18 years and adolescents and children < 18 years.	Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Time to Cessation of Viral Shedding by Cell Culture	Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the time to cessation of viral shedding over time in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Change From Baseline in Viral Load Assessed by Reverse Transcription Polymerase Chain Reaction (RT-PCR)	Nasopharyngeal swab samples were tested for influenza A and B RNA using semi-quantitative RT-PCR specific for influenza A and B matrix gene, respectively, after viral RNA isolation. Cycle threshold (Ct) value was determined for each sample. Conversion of Ct values into viral load, expressed as log10 virus particles/mL (vp/mL), was obtained using external standard curves ran in parallel in all RT-PCR experiments. A value of < 2.6 log10 vp/mL for Flu A strains and < 3.0 log10 vp/mL for Flu B strains was interpreted as a negative result. Data are reported for adults >/= 18 years and adolescents and children < 18 years.	Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Percentage of Participants With Viral Shedding Assessed by RT-PCR Over Time	Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the percentage of subjects with viral shedding over time in adults >/= 18 years and adolescents and children < 18 years.	Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Time to Cessation of Viral Shedding by RT-PCR	Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the time to cessation of viral shedding over time in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Percentage of Participants With Persistent Viral Shedding	Persistent shedding was defined as a viral load reduction <1 log10 vp/mL at end of treatment compared with baseline. Reported is the percentage of participants with persistent viral shedding at end of treatment in adults >/= 18 years and adolescents and children < 18 years.	Baseline to Day 11 (EOT)
Percentage of Participants Who Developed Secondary Illness	Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with at least one event in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Percentage of Participants Who Initiated Antibiotic Treatment	Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with secondary illness, who initiated antibiotic treatment, in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Percentage of Participants Hospitalized	Reported is the percentage of participants, who required hospitalization at any time between treatment initiation and the end of the study period, in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Duration of Hospitalization	Reported is the duration of hospitalization at any time between treatment initiation and the end of the study period, in adults >/= 18 years and adolescents and children < 18 years.	Baseline up to Day 40
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Oseltamivir in Adults	Reported here are oseltamivir Cmax data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir in Adults	Reported here are oseltamivir Ctrough data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics : Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) at Steady State of Oseltamivir in Adults	AUC0-12 was reported at steady state as nanograms per hour per milliliter. (ng*hr/mL). Reported here are oseltamivir AUC0-12 data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Pharmacokinetics: Time to Maximum Concentration (Tmax) of Oseltamivir in Adults	Reported here are oseltamivir tmax data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adults	Reported here are oseltamivir ke data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adults	Reported here are oseltamivir CL/F data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adults	Reported here are oseltamivir Vc/F data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate Cmax data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate Ctrough data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics : AUC0-12 at Steady State of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate AUC0-12 data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate tmax data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adults	Reported here are oxeltamivir carboxylate ke data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate CL/F data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adults	Reported here are oseltamivir carboxylate Vc/F data for adults >/= 18 years.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Cmax of Oseltamivir in Adolescents and Children	Reported here are oseltamivir Cmax data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Ctrough of Oseltamivir in Adolescents and Children	Reported here are oseltamivir Ctrough data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir in Adolescents and Children	AUC0-12 will be reported at steady state as ng*hr/mL. Reported here are oseltamivir AUC0-12 data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Pharmacokinetics: Tmax of Oseltamivir in Adolescents and Children	Reported here are oseltamivir data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate Cmax data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate Ctrough data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir Carboxylate in Adolescents and Children	AUC0-12 will be reported at steady state as ng*hr/mL. Reported here are oseltamivir carboxylate AUC0-12 data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate tmax data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adolescents and Children	Reported here are oseltamivir ke data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adolescents and Children	Reported here are oseltamivir CL/F data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adolescents and Children	Reported here are oseltamivir Vc/F data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate ke data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Clearance (CL/F), of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate CL/F data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adolescents and Children	Reported here are oseltamivir carboxylate Vc/F data for adolescents and children < 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.	Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Mitha E, Krivan G, Jacobs F, Nagler A, Alrabaa S, Mykietiuk A, Kenwright A, Le Pogam S, Clinch B, Vareikiene L. Safety, Resistance, and Efficacy Results from a Phase IIIb Study of Conventional- and Double-Dose Oseltamivir Regimens for Treatment of Influenza in Immunocompromised Patients. Infect Dis Ther. 2019 Dec;8(4):613-626. doi: 10.1007/s40121-019-00271-8. Epub 2019 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2008
• Primary Completion (Actual): May 2, 2017
• Study Completion (Actual): May 2, 2017

Study Registration Dates

• First Submitted: October 16, 2007
• First Submitted That Met QC Criteria: October 16, 2007
• First Posted (Estimate): October 17, 2007

Study Record Updates

• Last Update Posted (Actual): July 12, 2018
• Last Update Submitted That Met QC Criteria: June 15, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: NV20234; 2006-002468-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No