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

Influenza, Human Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545532
• Other study ID #: NV20234
• Secondary ID: 2006-002468-24
• Status: Completed
• Phase: Phase 3
• Start date: February 4, 2008
• Est. completion date: May 2, 2017

Study information

• Verified date: June 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: May 2, 2017
• Est. primary completion date: May 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• Influenza, Human

Intervention

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:
• placebo
Placebo matched to oseltamivir po twice daily for 10 days

Locations

Country	Name	City	State
Argentina	Hospital General de Agudos Juan Antonio Fernandez; infectología	Buenos Aires
Argentina	Instituto Medico Platense	Buenos Aires
Argentina	Hospital General de Agudos Dr. Ignacio Pirovano	Ciudad Autonoma Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma Buenos Aires
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Hospital de Niños Dr. Orlando Alassia	Santa Fe
Belgium	Onze Lieve Vrouwziekenhuis Aalst	Aalst
Belgium	UZ Brussel	Brussel
Belgium	Hospital Erasme; Neurologie	Bruxelles
Belgium	Institut Jules Bordet	Bruxelles
Brazil	Fiocruz - Fundação Oswaldo Cruz	Rio de Janeiro	RJ
Brazil	Hospital Alemao Oswaldo Cruz; Oncologia	Sao Paulo	SP
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Brazil	Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos	Sao Paulo	SP
Brazil	Iop - Graacc - Unifesp	Sao Paulo	SP
Bulgaria	UMHA - Sv. Georgi; Clinic of Nephrology & Haemodialysis	Plovdiv
Bulgaria	UMHAT Sv. Georgi, EAD; Clinic of Infectious Diseases	Plovdiv
Bulgaria	Mhat Alexandrovska Ead ; Clinic of Nephrology & Transplantation, Uni Hospital	Sofia
Bulgaria	Specialized Hospital for children with oncohaematologica Diseases; Dept. Of Transplantations	Sofia
Canada	St Paul'S	Saskatoon	Saskatchewan
Canada	Uni of Manitoba; Faculty of Medicine	Winnipeg	Manitoba
Chile	Hospital Dr. Sotero del Rio	Santiago
Chile	Hospital Luis Calvo Mackenna; Unidad de Investigacion	Santiago
Chile	Centro de Investigaciones Clinicas Viña del Mar	Viña Del Mar Valparaiso
Colombia	Infectologos Asociados	Barranquilla
Colombia	Simedics Ips	Bogota
Colombia	Centro de Investigaciones Clinicas S.A.S	Cali
Colombia	Fundacion Cardiovascular de Colombia - Instituto del Corazón	Floridablanca
Czechia	Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika	Brno
Czechia	Fakultni Nemocnice; Hemato-Oncology	Plzen
Czechia	The Institute of Hematology and Blood Transfusion Transplantation Unit; Hematology and Blood Transf	Praha
Czechia	Fakultni nemocnice v Motole; Klinika detske hematologie a onkologie UK 2.LF	Praha 5
Czechia	KASMED, s.r.o.; Alergologie a klinicka imunologie	Tabor
Czechia	Revmatologicka Ambulance-Terezin	Terezin
Czechia	Revmatologicka ambulance	Zlin
Estonia	North Estonia medical Centre; Hematology	Tallinn
Estonia	West Tallinn Central Hospital; Nephrology	Tallinn
Estonia	Tartu Uni Clinics; Clinic of Surgery & Internal Medicine Dept of Nephrology	Tartu
Estonia	Tartu Uni Hospital; Hematology - Oncology Clinic	Tartu
Estonia	Tartu University Hospital; Department of Infectious Diseases	Tartu
France	Centre Hospitalier de la Croix Rousse	Lyon
France	Hopital Europeen Georges Pompidou; Service de Nephrologie	Paris
France	Hopital Robert Debre; Pediatric Hematology Dept	Paris
France	Hopital Saint Louis; Service de Nephrologie - Transplantation	Paris
France	Hopital Rangueil; Nephrologie	Toulouse
France	CHRU Bretonneau	Tours
Germany	Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie	Aachen
Germany	Charite - Campus Virchow Klinikum; Abteilung fuer Chirurgie	Berlin
Germany	Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung	Essen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	UNI-Klinikum Heidelberg Chirurgische Klinik	Heidelberg
Germany	Ludwig-Maximilian-Universitaetsklinik; Med. Poliklinik/Infektiologie	Muenchen
Germany	Ludwig-Maximilians-Universitaet; Medizinische Klinik und Poliklinik IV	Muenchen
Germany	Universitaetsklinikum Muenster; Paedriatrische Haematologie und Onkologie	Muenster
Guatemala	CERICAP	Ciudad de Guatemala
Guatemala	Clinica Familiar Luis Angel Garcia	Ciudad de Guatemala
Guatemala	Unidad Nacional de Oncologia Pediatrica	Guatemala
Guatemala	Centro de Investigaciones Pediatricas	Guatemala City
Guatemala	Hospital Roosevelt Guatemala; Clinica de Infecciosas	Guatemala City
Hungary	Fov.Onk.Egyesitett Szt. Istvan es Szt Laszlo Korh.-Rend.Int.	Budapest
Hungary	Debreceni Egyetem, Orvos- és Egészségtudományi Centrum;	Debrecen
Hungary	Petz Aladar Megyei Korhaz; Hematologia	Gyor
Hungary	Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza	Gyula
Hungary	Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek	Gyula
Hungary	Pecsi Tudomanyegyetem	Pecs
Hungary	University of Szeged; Transplantation Department	Szeged
Hungary	Fejer Megyei Szent Gyorgy Korhaz	Szekesfehervar
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int.	Szolnok
Hungary	Veszprem Megyei Csolnoky Ferenc Korhaz Nonprofit Zrt.	Veszprem
Israel	Rambam Health Care Campus; Hematology	Haifa
Israel	Hadassah University Hospital - Ein Kerem; BMT & Cancer Immunotherapy Dept.	Jerusalem
Israel	Rabin MC- Belinson campus	Petach Tikva
Israel	Rabin Medical Center-Golda Campus - Hasharon; Department of Transplantation	Petach Tikva
Israel	Rabin Medical Center; Liver Inst.	Petach Tikva
Israel	Chaim Sheba Medical Center; Hematology BMT & CBB	Ramat Gan
Israel	Sourasky MC; Transplant Unit	Tel Aviv
Israel	Chaim Sheba MC; Pediatric Hematology Oncology	Tel Hashomer
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Dipartimento Malattie Infettive	Brescia	Lombardia
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico; Clinica Pediatica De Macchi	Milano	Molise
Italy	ASST DI MONZA; Divisione Malattie Infettive	Monza	Lombardia
Italy	Azienda Ospedaliera; Divisione Malattie Infettive E Tropicali	Parma	Emilia-Romagna
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia	Lombardia
Italy	I.N.M.I. L. Spallanzani IRCCS	Roma	Lazio
Italy	POLICLINICO Universitatio A.Gemelli, Div. Chirurgia Generale e Trapianti d'Organo	Roma	Lazio
Latvia	Children`s Clinical University Hospital	Riga
Latvia	Latvia Transplantation Center P. Stradina Hospital; Transplantation	Riga
Lithuania	Kaunas Clinics Public Institution; Clinic of Nephrology	Kaunas
Lithuania	Klaipeda University Hospital; Public Institution	Klaipeda
Lithuania	Siauliai Republican Hospital Public Institution	Siauliai
Lithuania	Republican Tuberculosis and Infectious Diseases University H	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinic	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center	Vilnius
Mexico	Phylaxis Clinical Research S de RL de CV	Cuautitlan Izcalli
Mexico	Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde; Infectología piso 7	Guadalajara
Mexico	Centro de Investigacion Clínica GRAMEL S.C	Mexico
Mexico	INER- Instituto Nacional de Enfermedades Respiratorias"Ismae	Mexico
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador; Infectologia	Mexico
Mexico	Hospital Universitario de Monterrey; Infectologia	Monterrey
Mexico	Hospital de Especialidades del Centro Medico Puerta de Hierr	Zapopan
Poland	Wojewodzki Szp.Specjalistyczny im.K.Dluskiego w Bialymstoku	Bialystok
Poland	NZOZ Vitamed	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	SPZOZ Szpital Uniw W Krakowie	Krakow
Poland	SPZOZ Uniwersytecki Szp Klin; nr1 im.N.Barlickiego UM	Lodz
Poland	SPSK nr 2 Pomorskiej Akademii Medycznej w Szczecinie	Szczecin
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka, Klinika Nefrologii, Transp. Nerek i Nadcisnienia Tetniczego	Warszawa
Poland	Szpital Dzieciatka Jezus-Centrum Lecezenia Obrazen; Dpt of Transplantation Medicine & Nephrology	Warszawa
Poland	ALL-MED Specjalistyczna Opieka Medyczna	Wroclaw
Poland	SP Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw
Romania	Institutul de Urologie Si Transplant Renal Fundeni	Bucharest
South Africa	Josha Research	Bloemfontein
South Africa	Dr V Naidoo Private Practice	Durban
South Africa	Govind U	Durban
South Africa	Londisizwe Research Centre	Durban
South Africa	Sebastian Peter	Durban
South Africa	Newtown Clinical Research	Johannesburg
South Africa	Soweto CTC - Dr Mushwana site	Johannesburg
South Africa	Soweto CTC - Dr Phoshoko site	Johannesburg
South Africa	Mzansi Ethical Research Centre	Middelburg
South Africa	Be Part Yoluntu Centre	Paarl
South Africa	Global Clinical Trials Port Elizabeth	Port Elizabeth
South Africa	Emmed Research	Pretoria
South Africa	Kalafong Hospital; Pathology	Pretoria
South Africa	Synexus Clinical Research Centres SA Stanza Bopape	Pretoria
South Africa	Soweto Clinical Trial Centre	Soweto
South Africa	Tygerberg Hospital Pediatrics and Child Health	Tygerberg; Cape Town
South Africa	Welkom Clinical Trial Centre	Welkom
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Departamento de Enfermedades Infecciosas	Barcelona
Spain	Hospital Universitari de Bellvitge; Servicio de Nefrologia	Hospitalet de Llobregat	Barcelona
Spain	Hospital Clinico San Carlos; Servicio de Nefrologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Universitario 12 de Octubre; HIV Unit	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Pediatria	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Enfermedades Infecciosas	Madrid
Spain	Hospital Universitario La Paz; Hepatología y Trasplantes	Madrid
Spain	Hospital Universitario la Paz; Servicio de Enfermedades Infecciosas - HIV unit	Madrid
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	LA Coruña
Switzerland	Universitätsspital Zürich; Klinik für Nephrologie	Zürich
Ukraine	Institute of Nephrology AMS; Dept of Nephrology & dialysis	Kiev
Ukraine	Ukrainian Pediatric Specialized Hospital of Ministry of Health of Ukraine Dept of BMT	Kiev
Ukraine	Lugansk Regional Clinical Hospital; Chair of Therapy Faculty of Postgr.Ed	Lugnansk
Ukraine	Zaporozhye State Medical University; Dept of Transplantology	Zaporozhye
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Manchester Royal Infirmary; Renal Transplant Unit	Manchester
United Kingdom	Nottingham City Hospital; Transplant Unit	Nottingham
United States	Uni of Michigan Medical Center; Internal Medicine/ Infectious Disease	Ann Arbor	Michigan
United States	EMORY UNIVERSITY; Bone Marrow & Stem Cell Transplant Center	Atlanta	Georgia
United States	Piedmont Hospital; Transplant Services	Atlanta	Georgia
United States	Medical College of Georgia; Medicine/ Nephrology	Augusta	Georgia
United States	University of Colorado; Kidney Transplant Center Office of Dr. Laurence Chan	Aurora	Colorado
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Uni of Alabama At Birmingham; Division of Nephrology	Birmingham	Alabama
United States	University of Alabama at Birmingham; Pediatric Nephrology	Birmingham	Alabama
United States	Brigham & Women'S Hospital	Boston	Massachusetts
United States	Providence Clinical Research	Burbank	California
United States	Our Lady of Lourdes Medical Center; Transplant Dept	Camden	New Jersey
United States	Medical University of South Carolina; Pediatric Cardiology	Charleston	South Carolina
United States	DJL Clinical Research PLLC	Charlotte	North Carolina
United States	Northwestern Memorial Hospital; Divison of Infectious Diseases/ Dept of Medicine	Chicago	Illinois
United States	Rush Uni Medical Center; Medicine/ Section of Infectious Diseases	Chicago	Illinois
United States	University of Chicago; Infectious Disease	Chicago	Illinois
United States	Uni of Cincinnati Medical Center; Nephrology & Hypertension	Cincinnati	Ohio
United States	Cleveland Clinic Foundation; Infectious Disease	Cleveland	Ohio
United States	Baylor University Medical Center Transplant Administration	Dallas	Texas
United States	Children'S Medical Center of Dallas	Dallas	Texas
United States	Sammons Cancer Center-Baylor University; Blood & Marrow Transplantation	Dallas	Texas
United States	UT Southwestern Medical Center; Pediatrics Dept.	Dallas	Texas
United States	Henry Ford Health System; Gastroenterology	Detroit	Michigan
United States	Karmanos Cancer Inst. ; Hudson Webber; Cancer Research Building	Detroit	Michigan
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M.D Anderson Cancer Center; Infectious Diseases, Infection Control, and Employee Health	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	Beals Institute PC	Lansing	Michigan
United States	AIDS Research Alliance	Los Angeles	California
United States	UCLA Medical center Medicine/Nephrology	Los Angeles	California
United States	Texas Tech University Health Sciences Center; Department of Urology	Lubbock	Texas
United States	Novant Health Pulmonary and Critical Care	Matthews	North Carolina
United States	Long Island Jewish/North Shore Hospital	New Hyde Park	New York
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Mount Sinai Medical Center; Division of Liver Diseases	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	Nazih Zuhdi Transplant Inst. ; Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Omega Research Consultants	Orlando	Florida
United States	Drexel University; College of Medicine	Philadelphia	Pennsylvania
United States	Uni of Pennsylvania; Infectious Diseases	Philadelphia	Pennsylvania
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Children'S Hospital of Pittsburgh; Infectious Disease	Pittsburgh	Pennsylvania
United States	Duke University Health Systems	Raleigh	North Carolina
United States	University of California Davis Health System	Sacramento	California
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	All Children'S Hospital; Pediatric Blood & Marrow Transplant Program	Saint Petersburg	Florida
United States	University of Utah Health Science Center Gastroenterology	Salt Lake City	Utah
United States	University of Texas Health Science Center Transplant center	San Antonio	Texas
United States	CALIFORNIA PACIFIC MEDICAL CENTER; Office of Dr. Venkat Peddi	San Francisco	California
United States	Kendall South Medical Center Inc.	South Miami	Florida
United States	Western New England Renal & Transplant Associates, P.C.	Springfield	Massachusetts
United States	Vita Research Solutions, Inc	Tamarac	Florida
United States	University of South Florida	Tampa	Florida
United States	Scott and White Division of Nephrology Dept of Medicine	Temple	Texas
United States	Toledo Hospital	Toledo	Ohio
United States	New England Research Associates	Trumbull	Connecticut
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  Estonia,  France,  Germany,  Guatemala,  Hungary,  Israel,  Italy,  Latvia,  Lithuania,  Mexico,  Poland,  Romania,  South Africa,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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	Baseline up to Day 40
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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