A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza

Tracking Information
First Submitted Date ICMJE	January 14, 2010
First Posted Date ICMJE	January 15, 2010
Results First Submitted Date	August 28, 2013
Results First Posted Date	November 1, 2013
Last Update Posted Date	November 1, 2013
Study Start Date ICMJE	January 2010
Actual Primary Completion Date	September 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 28, 2013)	Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death [ Time Frame: Up to 30 days ]; Safety was assessed by adverse events (AEs) as measured by the collection of AEs, vital signs, electrocardiograms and laboratory parameters. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. On treatment = AEs that started between the day of first dose and within 2 days after the last dose. Off treatment = AEs that started more than 2 days after the last dose of study drug.
Original Primary Outcome Measures ICMJE; (submitted: January 14, 2010)	Safety: AEs, vital signs, electrocardiograms, laboratory parameters [ Time Frame: AEs, vital signs: throughout study; electrocardiograms: days 1, 3, end of study; laboratory parameters: days 1, 3, after last intravenous infusion, end of study ]
Change History	Complete list of historical versions of study NCT01050257 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 28, 2013)	Pharmacokinetics [ Time Frame: Days 1, 3 ]; Percentage of Participants With Viral Shedding by Culture or RT-PCR [ Time Frame: Days 1, 4, 6, 11, 15 and 30 ]Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture [log10 median tissue culture infective dose (TCID50) > 0.5) or detection by RT-PCR (log 10 copies/mL).; Percentage of Participants With Viral Shedding by Culture [ Time Frame: Days 1, 4, 6, 11, 15, 30 ]Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture=log10 median tissue culture infective dose (TCID50) > 0.5.; Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) [ Time Frame: Days 1, 4, 6, 11, 15 and 30 ]Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by detection by RT-PCR (log 10 copies/mL).; Change From Baseline in Influenza Titer by Culture at Day 4 [ Time Frame: Baseline, Day 4 ]Nasal and throat swabs collected at Baseline and Day 4 were sent to a laboratory for analysis. Viral influenza titer (amount of virus present) was determined by culture. A log 10 median tissue culture infective dose (TCID50) > 0.5= Positive culture. A negative change from Baseline indicated improvement (less virus present).; Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 [ Time Frame: Baseline, Day 4 ]Nasal and throat swabs were collected at Baseline and Day 4 and were sent to a central laboratory for analysis. Influenza Viral titers (amount of virus present) were determined by RT-PCR for Flu A and Flu B and were reported in log 10 copies/milliliter (mL). A negative change from Baseline indicated improvement (less virus present).; Percentage of Participants Who Had a Fever During the Study [ Time Frame: Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108 ]Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).; Time to Resolution of Fever for Participants Who Had a Fever at Baseline [ Time Frame: Baseline, Up to 30 Days ]Fever was defined as a temperature of ≥ 37.8 C (degrees Celsius). Resolution of fever was a temperature ≤ 37.2 for at least 21.5 hours.; Number of Participants With Viral Resistance [ Time Frame: 30 days ]Nasal and Throat swabs were collected on Days 1, 4, 6, 11, 15 and 30 and were sent to a central laboratory for testing. Viral resistance was determined by phenotypic and genotypic testing.; Percentage of Participants With Influenza Symptoms [ Time Frame: Days 1, 11, 15, 30 ]Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.
Original Secondary Outcome Measures ICMJE; (submitted: January 14, 2010)	Pharmacokinetics [ Time Frame: Days 1, 3 ]; Viral load and shedding [ Time Frame: Days 1, 4, 6, 11 ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza
Official Title ICMJE	A Multicenter Study of the Safety of Oseltamivir Administered Intravenously for the Treatment of Influenza in Patients Aged Greater Than or Equal to 13 Years
Brief Summary	This partially randomized, multi-center parallel-group study will evaluate the safety, pharmacokinetics and the effect on viral load and viral shedding of Tamiflu (Oseltamivir) in patients with influenza. Adult and adolescent patients will be randomized to receive either 100 mg or 200 mg of study drug intravenously every 12 hours. Investigators and patients are blinded to knowledge of the assigned dose of Tamiflu. There is an option to convert to oral Tamiflu after 6 intravenous infusions. The anticipated time on study treatment is 5 days, with an optional treatment extension of a further 5 days, if necessary. There will be a non-randomized, open-label treatment group for patients with moderate/severe renal impairment or renal failure. Intravenous dose levels and frequency will be adjusted appropriately to their renal situation.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Influenza
Intervention ICMJE	Drug: Oseltamivir IV Oseltamivir IV infusions over 2 hours two times a day (every 12 hours) for 5 days for patients with moderate renal impairment. Patients with severe renal impairment received once daily dosing and patients on renal replacement therapy received dose/frequency according to protocol. Other Name: TAMIFLU®; Drug: Oseltamivir Oral Oseltamivir (TAMIFLU®) capsules taken orally for 5 days. Twice daily (every 12 hours) for patients with moderate renal impairment, once daily for patients with severe renal impairment and dose frequency according to protocol for patients on renal replacement therapy. Other Name: TAMIFLU®
Study Arms	Experimental: Oseltamivir (TAMIFLU®) 100 mg Oseltamivir (TAMIFLU®) 100 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 75 mg oral oseltamivir twice daily to complete the 5 days of treatment. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days. Interventions: Drug: Oseltamivir IV Drug: Oseltamivir Oral; Experimental: Oseltamivir (TAMIFLU®) 200 mg Oseltamivir (TAMIFLU®) 200 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 150 mg oral oseltamivir twice daily for 5 days. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days. Interventions: Drug: Oseltamivir IV Drug: Oseltamivir Oral; Experimental: Oseltamivir Open Label Moderate/Severe renal impaired participants received open label oseltamivir IV or oseltamivir capsules at reduced doses for 5 days as per protocol. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug as per protocol. Interventions: Drug: Oseltamivir IV Drug: Oseltamivir Oral
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 25, 2013)	118
Original Estimated Enrollment ICMJE; (submitted: January 14, 2010)	200
Actual Study Completion Date	September 2012
Actual Primary Completion Date	September 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adult and adolescent patients, 13 years of age and older; Diagnosis of influenza; ≤ 144 hours between the onset of influenza-like illness and first dose of study drug Non-randomized, open-label treatment group: Patients with moderate/severe renal impairment or renal failure with creatinine clearance 10-60 mL/min Exclusion Criteria: Clinical evidence of severe hepatic decompensation at the time of randomization; Acute ischemia or significant arrhythmia
Sex/Gender	Sexes Eligible for Study: All
Ages	13 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Denmark, France, Hungary, Italy, Lithuania, Poland, Romania, Spain, United States
Removed Location Countries	Canada, Germany
Administrative Information
NCT Number ICMJE	NCT01050257
Other Study ID Numbers ICMJE	NV25118
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Hoffmann-La Roche
Study Sponsor ICMJE	Hoffmann-La Roche
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Clinical Trials Hoffmann-La Roche
PRS Account	Hoffmann-La Roche
Verification Date	August 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP