Influenza
Conditions
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.
Interventions
DRUGOseltamivir 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.
DRUGOseltamivir 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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Viral Shedding by Culture or RT-PCR | 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 | 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) | 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 | 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). |
| Pharmacokinetics | Days 1, 3 | — |
| Percentage of Participants Who Had a Fever During the Study | 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 | 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 | 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 | Days 1, 11, 15, 30 | Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills. |
| Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | 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). |
Countries
Denmark, France, Hungary, Italy, Lithuania, Poland, Romania, Spain, United States
Participant flow
Pre-assignment details
This study included a 5 day treatment period and an optional extension. Participants were considered to have completed treatment if they completed the 5-day course of treatment (IV and/or oral).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| 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. | 53 |
| 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. | 15 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Admin/Other (did not switch to oral) | 6 | 2 | 2 |
| Overall Study | Adverse Event | 4 | 4 | 2 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Failure to return | 0 | 2 | 0 |
| Overall Study | No reason specified | 0 | 0 | 2 |
| Overall Study | Refused treatment/ Did not Cooperate | 1 | 1 | 0 |
| Overall Study | Violation criteria | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Oseltamivir (TAMIFLU®) 100 mg | Oseltamivir (TAMIFLU®) 200 mg | Oseltamivir Open Label | Total |
|---|---|---|---|---|
| Age Continuous | 44.8 years STANDARD_DEVIATION 16.68 | 44.3 years STANDARD_DEVIATION 18.09 | 66.9 years STANDARD_DEVIATION 18.28 | 47.4 years STANDARD_DEVIATION 18.93 |
| Sex: Female, Male Female | 25 Participants | 27 Participants | 8 Participants | 60 Participants |
| Sex: Female, Male Male | 25 Participants | 26 Participants | 7 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 48 | 18 / 51 | 10 / 14 |
| serious Total, serious adverse events | 9 / 48 | 5 / 51 | 7 / 14 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death
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.
Time frame: Up to 30 days
Population: Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | Death | 1 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: IV dose | 24 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: Oral dose | 10 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs off treatment | 13 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: IV dose | 3 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: Oral dose | 2 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs off treatment | 5 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: IV dosing | 3 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: Oral dose | 1 Partipants |
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal off treatment | 0 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: Oral dose | 1 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: IV dose | 27 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | Death | 1 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: Oral dose | 0 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: IV dose | 4 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal off treatment | 0 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: IV dosing | 3 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: Oral dose | 9 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs off treatment | 1 Partipants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs off treatment | 13 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: IV dosing | 2 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs off treatment | 5 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: IV dose | 2 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs on treatment: Oral dose | 2 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal on treatment: Oral dose | 1 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | SAEs off treatment | 3 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | Death | 3 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs leading to withdrawal off treatment | 0 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: IV dose | 11 Partipants |
| Oseltamivir Open Label | Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death | AEs on treatment: Oral dose | 4 Partipants |
Secondary
Change From Baseline in Influenza Titer by Culture at 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).
Time frame: Baseline, Day 4
Population: Participants from the Intent-to-treat Influenza Infected population with data available for analysis. Only participants with positive influenza results are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Change From Baseline in Influenza Titer by Culture at Day 4 | -1.38 log10 TCID50 | Standard Deviation 1.92 |
| Oseltamivir (TAMIFLU®) 200 mg | Change From Baseline in Influenza Titer by Culture at Day 4 | -2.19 log10 TCID50 | Standard Deviation 1.186 |
| Oseltamivir Open Label | Change From Baseline in Influenza Titer by Culture at Day 4 | -3.00 log10 TCID50 | Standard Deviation 0.75 |
Secondary
Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at 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).
Time frame: Baseline, Day 4
Population: Participants from the Intent-to-Treat Infected population with data available for analysis. Only participants with positive influenza results are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu A (n=14, 14, 5) | -1.04 log 10 copies/mL | Standard Deviation 1.412 |
| Oseltamivir (TAMIFLU®) 100 mg | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu B (n=3, 5, 1) | -0.70 log 10 copies/mL | Standard Deviation 1.459 |
| Oseltamivir (TAMIFLU®) 200 mg | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu B (n=3, 5, 1) | -1.51 log 10 copies/mL | Standard Deviation 0.262 |
| Oseltamivir (TAMIFLU®) 200 mg | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu A (n=14, 14, 5) | -1.30 log 10 copies/mL | Standard Deviation 0.883 |
| Oseltamivir Open Label | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu B (n=3, 5, 1) | -2.27 log 10 copies/mL | — |
| Oseltamivir Open Label | Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 | Flu A (n=14, 14, 5) | -1.53 log 10 copies/mL | Standard Deviation 0.93 |
Secondary
Number of Participants With Viral Resistance
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.
Time frame: 30 days
Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Number of Participants With Viral Resistance | 1 Participants |
| Oseltamivir (TAMIFLU®) 200 mg | Number of Participants With Viral Resistance | 1 Participants |
| Oseltamivir Open Label | Number of Participants With Viral Resistance | 0 Participants |
Secondary
Percentage of Participants Who Had a Fever During the Study
Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).
Time frame: Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108
Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 96 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Baseline | 23 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 84 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 24 | 7 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 12 | 7 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 48 | 3 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 36 | 3 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 72 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 60 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants Who Had a Fever During the Study | Hour 108 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 84 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 36 | 3 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 48 | 6 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 60 | 6 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Baseline | 19 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 12 | 9 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 24 | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 72 | 3 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 96 | 3 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants Who Had a Fever During the Study | Hour 108 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 60 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 48 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 84 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 72 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 36 | 20 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 108 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 12 | 10 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Baseline | 20 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 96 | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants Who Had a Fever During the Study | Hour 24 | 0 Percentage of participants |
Secondary
Percentage of Participants With Influenza Symptoms
Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.
Time frame: Days 1, 11, 15, 30
Population: Intent-to-Treat population included all treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Influenza Symptoms | Day 15 | 51 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Influenza Symptoms | Day 30 | 33 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Influenza Symptoms | Day 11 | 63 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Influenza Symptoms | Day 1 | 100 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Influenza Symptoms | Day 11 | 64 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Influenza Symptoms | Day 15 | 44 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Influenza Symptoms | Day 30 | 26 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Influenza Symptoms | Day 1 | 100 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Influenza Symptoms | Day 30 | 64 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Influenza Symptoms | Day 1 | 93 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Influenza Symptoms | Day 15 | 64 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Influenza Symptoms | Day 11 | 79 Percentage of participants |
Secondary
Percentage of Participants With Viral Shedding by Culture
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.
Time frame: Days 1, 4, 6, 11, 15, 30
Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 1 (n=29, 30, 10) | 76 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 4 (n=28, 28, 10) | 14 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 6 (n=22, 28, 8) | 5 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 11 (n=22, 26, 8) | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 15 (n=17, 24, 7) | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture | Day 30 (n=22, 28, 6) | 5 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 30 (n=22, 28, 6) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 1 (n=29, 30, 10) | 80 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 11 (n=22, 26, 8) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 15 (n=17, 24, 7) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 4 (n=28, 28, 10) | 29 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture | Day 6 (n=22, 28, 8) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 4 (n=28, 28, 10) | 30 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 6 (n=22, 28, 8) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 30 (n=22, 28, 6) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 11 (n=22, 26, 8) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 1 (n=29, 30, 10) | 90 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture | Day 15 (n=17, 24, 7) | 14 Percentage of participants |
Secondary
Percentage of Participants With Viral Shedding by Culture or RT-PCR
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).
Time frame: Days 1, 4, 6, 11, 15 and 30
Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 1 (n=29, 30, 10) | 90 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 11 (n=22, 26, 8) | 9 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 15 (n=17, 24, 7) | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 30 (n=22, 28, 6) | 5 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 4 (n=28, 28, 10) | 64 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 6 (n=22, 28, 8) | 41 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 30 (n=22, 28, 6) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 6 (n=22, 28, 8) | 36 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 11 (n=22, 26, 8) | 15 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 1 (n=29, 30, 10) | 97 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 4 (n=28, 28, 10) | 75 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 15 (n=17, 24, 7) | 8 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 30 (n=22, 28, 6) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 15 (n=17, 24, 7) | 14 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 1 (n=29, 30, 10) | 90 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 4 (n=28, 28, 10) | 60 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 6 (n=22, 28, 8) | 63 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Culture or RT-PCR | Day 11 (n=22, 26, 8) | 13 Percentage of participants |
Secondary
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
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).
Time frame: Days 1, 4, 6, 11, 15 and 30
Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 15 (n=17, 24, 7) | 0 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 4 (n=28, 28, 10) | 64 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 30 (n=22, 28, 6) | 5 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 6 (n=22, 28, 8) | 41 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 11 (n=22, 26, 8) | 9 Percentage of participants |
| Oseltamivir (TAMIFLU®) 100 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 1 (n=29, 30, 10) | 86 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 1 (n=29, 30, 10) | 93 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 15 (n=17, 24, 7) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 11 (n=22, 26, 8) | 12 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 6 (n=22, 28, 8) | 36 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 30 (n=22, 28, 6) | 4 Percentage of participants |
| Oseltamivir (TAMIFLU®) 200 mg | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 4 (n=28, 28, 10) | 71 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 30 (n=22, 28, 6) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 1 (n=29, 30, 10) | 90 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 4 (n=28, 28, 10) | 60 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 11 (n=22, 26, 8) | 13 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 15 (n=17, 24, 7) | 0 Percentage of participants |
| Oseltamivir Open Label | Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Day 6 (n=22, 28, 8) | 63 Percentage of participants |
Secondary
Pharmacokinetics
Time frame: Days 1, 3
Secondary
Time to Resolution of Fever for Participants Who Had a Fever at Baseline
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.
Time frame: Baseline, Up to 30 Days
Population: Participants from the Intent-to-Treat Infected population, all treated participants with confirmed influenza infection by culture or RT-PCR, who had a fever at Baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir (TAMIFLU®) 100 mg | Time to Resolution of Fever for Participants Who Had a Fever at Baseline | 11.8 Hours |
| Oseltamivir (TAMIFLU®) 200 mg | Time to Resolution of Fever for Participants Who Had a Fever at Baseline | 18.6 Hours |
| Oseltamivir Open Label | Time to Resolution of Fever for Participants Who Had a Fever at Baseline | 47.7 Hours |