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.
Brief Title
A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza
Categories
Completion Date
Completion Date Type
Actual
Conditions
Influenza
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
13 Years
NCT Id
NCT01050257
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
NV25118
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death
Outcome Time Frame
Up to 30 days
Secondary Outcomes
Outcome Time Frame
Days 1, 3
Outcome Measure
Pharmacokinetics
Outcome Description
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).
Outcome Time Frame
Days 1, 4, 6, 11, 15 and 30
Outcome Measure
Percentage of Participants With Viral Shedding by Culture or RT-PCR
Outcome Description
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.
Outcome Time Frame
Days 1, 4, 6, 11, 15, 30
Outcome Measure
Percentage of Participants With Viral Shedding by Culture
Outcome Description
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).
Outcome Time Frame
Days 1, 4, 6, 11, 15 and 30
Outcome Measure
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
Outcome Description
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).
Outcome Time Frame
Baseline, Day 4
Outcome Measure
Change From Baseline in Influenza Titer by Culture at Day 4
Outcome Description
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).
Outcome Time Frame
Baseline, Day 4
Outcome Measure
Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4
Outcome Description
Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).
Outcome Time Frame
Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108
Outcome Measure
Percentage of Participants Who Had a Fever During the Study
Outcome Description
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.
Outcome Time Frame
Baseline, Up to 30 Days
Outcome Measure
Time to Resolution of Fever for Participants Who Had a Fever at Baseline
Outcome Description
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.
Outcome Time Frame
30 days
Outcome Measure
Number of Participants With Viral Resistance
Outcome Description
Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.
Outcome Time Frame
Days 1, 11, 15, 30
Outcome Measure
Percentage of Participants With Influenza Symptoms
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
13
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Riska
Investigator Email
priska@montefiore.org
Investigator Phone
718-020-6494