Influenza
Conditions
Brief summary
This randomized, double-blind, multi-center study of Tamiflu (Oseltamivir) will evaluate the efficacy against viral activity, the effectiveness in resolving the disease symptoms, and the safety and tolerability in patients with influenza. Patients with (H1N1) 2009 influenza strain or influenza A are eligible for this study. Patients will be randomized to one of four treatment regimens. Patients will receive oral doses of either 75 mg (adults) or 150 mg (adults) of study drug twice daily for 5 or 10 consecutive days. The dose will be body weight-adjusted for pediatric patients.
Interventions
DRUGOseltamivir
Oseltamivir capsules for participants ≥ 13 years.
DRUGPlacebo
Matching placebo provided as capsules and as a suspension.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pediatric, adolescent and adult patients \>/=1 year of age * Fever \>/=37.8 degrees C or at least one respiratory symptom (cough, coryza, sore throat, or rhinitis) * Positive rapid diagnostic test for pandemic (H1N1) 2009 virus or influenza A in the 24 hours prior to the first dose of study drug * \</=96 hours between onset of influenza-like illness and first dose of oseltamivir
Exclusion criteria
* Currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or hemofiltration * History of chronic renal failure or clinical suspicion of renal failure at baseline * Clinical evidence of hepatic compensation at the time of randomization * Known HIV infection * Vaccination with live attenuated influenza vaccine (LAIV) in the two weeks prior to first dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cessation of Viral Shedding | Day 1 to Day 40 | The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Baseline and Days 3, 6, 8, 11, 15 and 40 | Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory. |
| Change From Baseline in Influenza Titer Measured by Viral Culture | Baseline, Days 2 through 15 | Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells). |
| Number of Participants With Development of Oseltamivir-Resistant Influenza Virus | 40 days | The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed. |
| Time to Resolution of Fever | Day 1 through Day 40 | Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time. |
| Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Baseline and Days 3, 6, 8, 11, 15 and 40 | Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory. |
| Time to Alleviation of All Clinical Symptoms - Adults | Day 1 to Day 40 | Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment. |
| Number of Participants Who Developed Secondary Illnesses During the Study | Day 1 through Day 40 | The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study. |
| Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics | Day 1 through Day 40 | The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics. |
| Time to Alleviation of All Clinical Symptoms - Children | Day 1 to Day 40 | Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oseltamivir Standard Dose 5 Days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment. | 26 |
| Oseltamivir Standard Dose 10 Days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days. | 26 |
| Oseltamivir High Dose 5 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment. | 25 |
| Oseltamivir High Dose 10 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days. | 24 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse event/internal illness | 0 | 1 | 0 | 1 |
| Overall Study | Failed to return | 0 | 0 | 1 | 0 |
| Overall Study | Refused treatment | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew consent | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Oseltamivir Standard Dose 5 Days | Total | Oseltamivir High Dose 10 Days | Oseltamivir High Dose 5 Days | Oseltamivir Standard Dose 10 Days |
|---|---|---|---|---|---|
| Age, Customized 13 to ≤18 years | 3 participants | 13 participants | 3 participants | 5 participants | 2 participants |
| Age, Customized >18 years | 16 participants | 61 participants | 15 participants | 13 participants | 17 participants |
| Age, Customized 1 to <13 years | 7 participants | 27 participants | 6 participants | 7 participants | 7 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 4 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants | 10 participants | 4 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized White | 23 participants | 86 participants | 20 participants | 20 participants | 23 participants |
| Race/Ethnicity, Customized White/Black | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 13 Participants | 54 Participants | 12 Participants | 14 Participants | 15 Participants |
| Sex: Female, Male Male | 13 Participants | 47 Participants | 12 Participants | 11 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 26 | 5 / 26 | 3 / 25 | 6 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 25 | 0 / 24 |
Outcome results
Primary
Time to Cessation of Viral Shedding
The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.
Time frame: Day 1 to Day 40
Population: ITT infected (ITTI) Population, including all patients randomized who received at least one dose of study medication with laboratory confirmation of pandemic (H1N1) 2009 influenza infection, excluding patients infected with oseltamivir-resistant influenza A H1N1 H275Y at baseline and patients not shedding virus at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Time to Cessation of Viral Shedding | 65.6 hours |
| Oseltamivir Standard Dose 10 Days | Time to Cessation of Viral Shedding | 70.8 hours |
| Oseltamivir High Dose 5 Days | Time to Cessation of Viral Shedding | 58.1 hours |
| Oseltamivir High Dose 10 Days | Time to Cessation of Viral Shedding | 74.1 hours |
Secondary
Change From Baseline in Influenza Titer Measured by Viral Culture
Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells).
Time frame: Baseline, Days 2 through 15
Population: ITTI
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 9 (n=19, 18, 14, 16) | -3.24 Log10 TCID50 | Standard Deviation 1.478 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 8 (n=19, 18, 15, 17) | -3.18 Log10 TCID50 | Standard Deviation 1.457 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 5 (n=19, 18, 16, 17) | -3.00 Log10 TCID50 | Standard Deviation 1.656 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 2 (n=19, 18, 15, 17) | -1.82 Log10 TCID50 | Standard Deviation 1.457 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 7 (n=19, 18, 16, 17) | -3.22 Log10 TCID50 | Standard Deviation 1.469 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 6 (n=19, 18, 15, 17) | -3.22 Log10 TCID50 | Standard Deviation 1.488 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 3.74 Log10 TCID50 | Standard Deviation 1.478 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 13 (n=19, 18, 16, 15) | -3.17 Log10 TCID50 | Standard Deviation 1.458 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 12 (n=19, 18, 15, 15) | -3.11 Log10 TCID50 | Standard Deviation 1.669 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 3 (n=19, 18, 15, 17) | -2.38 Log10 TCID50 | Standard Deviation 1.67 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 15 (n=18, 17, 14, 15) | -3.14 Log10 TCID50 | Standard Deviation 1.456 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 11 (n=19, 16, 16, 15) | -3.22 Log10 TCID50 | Standard Deviation 1.469 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 10 (n=19, 18, 15, 16) | -3.21 Log10 TCID50 | Standard Deviation 1.463 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 4 (n=19, 18, 15, 17) | -3.18 Log10 TCID50 | Standard Deviation 1.511 |
| Oseltamivir Standard Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 14 (n=18, 18, 15, 15) | -3.17 Log10 TCID50 | Standard Deviation 1.488 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 15 (n=18, 17, 14, 15) | -3.50 Log10 TCID50 | Standard Deviation 1.25 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 4.06 Log10 TCID50 | Standard Deviation 1.235 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 2 (n=19, 18, 15, 17) | -1.17 Log10 TCID50 | Standard Deviation 1.138 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 3 (n=19, 18, 15, 17) | -2.18 Log10 TCID50 | Standard Deviation 1.221 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 4 (n=19, 18, 15, 17) | -3.29 Log10 TCID50 | Standard Deviation 1.129 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 5 (n=19, 18, 16, 17) | -3.43 Log10 TCID50 | Standard Deviation 1.14 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 6 (n=19, 18, 15, 17) | -3.56 Log10 TCID50 | Standard Deviation 1.235 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 7 (n=19, 18, 16, 17) | -3.53 Log10 TCID50 | Standard Deviation 1.218 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 8 (n=19, 18, 15, 17) | -3.56 Log10 TCID50 | Standard Deviation 1.235 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 9 (n=19, 18, 14, 16) | -3.53 Log10 TCID50 | Standard Deviation 1.218 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 10 (n=19, 18, 15, 16) | -3.50 Log10 TCID50 | Standard Deviation 1.26 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 11 (n=19, 16, 16, 15) | -3.42 Log10 TCID50 | Standard Deviation 1.524 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 12 (n=19, 18, 15, 15) | -3.47 Log10 TCID50 | Standard Deviation 1.289 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 13 (n=19, 18, 16, 15) | -3.43 Log10 TCID50 | Standard Deviation 1.248 |
| Oseltamivir Standard Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 14 (n=18, 18, 15, 15) | -3.56 Log10 TCID50 | Standard Deviation 1.235 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 14 (n=18, 18, 15, 15) | -3.55 Log10 TCID50 | Standard Deviation 1.334 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 4.14 Log10 TCID50 | Standard Deviation 1.338 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 12 (n=19, 18, 15, 15) | -3.63 Log10 TCID50 | Standard Deviation 1.385 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 10 (n=19, 18, 15, 16) | -3.55 Log10 TCID50 | Standard Deviation 1.334 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 2 (n=19, 18, 15, 17) | -1.97 Log10 TCID50 | Standard Deviation 1.584 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 15 (n=18, 17, 14, 15) | -3.55 Log10 TCID50 | Standard Deviation 1.401 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 9 (n=19, 18, 14, 16) | -3.57 Log10 TCID50 | Standard Deviation 1.381 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 13 (n=19, 18, 16, 15) | -3.64 Log10 TCID50 | Standard Deviation 1.338 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 6 (n=19, 18, 15, 17) | -3.45 Log10 TCID50 | Standard Deviation 1.53 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 3 (n=19, 18, 15, 17) | -2.95 Log10 TCID50 | Standard Deviation 1.286 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 5 (n=19, 18, 16, 17) | -3.45 Log10 TCID50 | Standard Deviation 1.453 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 4 (n=19, 18, 15, 17) | -3.33 Log10 TCID50 | Standard Deviation 1.368 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 7 (n=19, 18, 16, 17) | -3.58 Log10 TCID50 | Standard Deviation 1.331 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 11 (n=19, 16, 16, 15) | -3.64 Log10 TCID50 | Standard Deviation 1.338 |
| Oseltamivir High Dose 5 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 8 (n=19, 18, 15, 17) | -3.65 Log10 TCID50 | Standard Deviation 1.385 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 4 (n=19, 18, 15, 17) | -3.76 Log10 TCID50 | Standard Deviation 0.859 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 8 (n=19, 18, 15, 17) | -4.04 Log10 TCID50 | Standard Deviation 0.746 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 15 (n=18, 17, 14, 15) | -4.10 Log10 TCID50 | Standard Deviation 0.653 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 9 (n=19, 18, 14, 16) | -4.08 Log10 TCID50 | Standard Deviation 0.688 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 3 (n=19, 18, 15, 17) | -2.88 Log10 TCID50 | Standard Deviation 1.296 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 10 (n=19, 18, 15, 16) | -4.14 Log10 TCID50 | Standard Deviation 0.652 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 14 (n=18, 18, 15, 15) | -4.10 Log10 TCID50 | Standard Deviation 0.653 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 11 (n=19, 16, 16, 15) | -4.08 Log10 TCID50 | Standard Deviation 0.632 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 2 (n=19, 18, 15, 17) | -1.15 Log10 TCID50 | Standard Deviation 1.425 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 12 (n=19, 18, 15, 15) | -4.10 Log10 TCID50 | Standard Deviation 0.653 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 5 (n=19, 18, 16, 17) | -3.91 Log10 TCID50 | Standard Deviation 0.765 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 6 (n=19, 18, 15, 17) | -3.99 Log10 TCID50 | Standard Deviation 0.726 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 13 (n=19, 18, 16, 15) | -4.10 Log10 TCID50 | Standard Deviation 0.653 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Day 7 (n=19, 18, 16, 17) | -4.04 Log10 TCID50 | Standard Deviation 0.746 |
| Oseltamivir High Dose 10 Days | Change From Baseline in Influenza Titer Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 4.54 Log10 TCID50 | Standard Deviation 0.746 |
Secondary
Number of Participants Who Developed Secondary Illnesses During the Study
The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study.
Time frame: Day 1 through Day 40
Population: ITTI population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Sinusitis | 0 participants |
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Otitis media | 0 participants |
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Any secondary illness | 1 participants |
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Pneumonia | 0 participants |
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Bronchitis | 1 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Pneumonia | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Sinusitis | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Any secondary illness | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Otitis media | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Bronchitis | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Pneumonia | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Bronchitis | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Otitis media | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Sinusitis | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Any secondary illness | 0 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Sinusitis | 2 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Otitis media | 0 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Bronchitis | 0 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Pneumonia | 0 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses During the Study | Any secondary illness | 2 participants |
Secondary
Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics
The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics.
Time frame: Day 1 through Day 40
Population: ITTI population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics | 0 participants |
| Oseltamivir High Dose 5 Days | Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics | 0 participants |
| Oseltamivir High Dose 10 Days | Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics | 2 participants |
Secondary
Number of Participants With Development of Oseltamivir-Resistant Influenza Virus
The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed.
Time frame: 40 days
Population: ITTI Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Number of Participants With Development of Oseltamivir-Resistant Influenza Virus | 0 participants |
| Oseltamivir Standard Dose 10 Days | Number of Participants With Development of Oseltamivir-Resistant Influenza Virus | 1 participants |
| Oseltamivir High Dose 5 Days | Number of Participants With Development of Oseltamivir-Resistant Influenza Virus | 1 participants |
| Oseltamivir High Dose 10 Days | Number of Participants With Development of Oseltamivir-Resistant Influenza Virus | 0 participants |
Secondary
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction
Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory.
Time frame: Baseline and Days 3, 6, 8, 11, 15 and 40
Population: ITTI
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Baseline (n=19, 18, 16, 17) | 89 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 11 (n=18, 18, 15, 14) | 5 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 3 (n=19, 17, 15, 15) | 79 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 40 (n=16, 15, 16, 14) | 5 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 6 (n=19, 17, 16, 15) | 26 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 8 (n=18, 17, 15, 15) | 11 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 15 (n=18, 14, 15, 12) | 6 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 8 (n=18, 17, 15, 15) | 11 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 6 (n=19, 17, 16, 15) | 28 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 11 (n=18, 18, 15, 14) | 6 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 40 (n=16, 15, 16, 14) | 6 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 3 (n=19, 17, 15, 15) | 83 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 8 (n=18, 17, 15, 15) | 13 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 3 (n=19, 17, 15, 15) | 69 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 6 (n=19, 17, 16, 15) | 50 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 11 (n=18, 18, 15, 14) | 25 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 40 (n=16, 15, 16, 14) | 6 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 6 (n=19, 17, 16, 15) | 47 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 40 (n=16, 15, 16, 14) | 0 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 15 (n=18, 14, 15, 12) | 6 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 3 (n=19, 17, 15, 15) | 76 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 11 (n=18, 18, 15, 14) | 18 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction | Day 8 (n=18, 17, 15, 15) | 12 percentage of participants |
Secondary
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture
Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory.
Time frame: Baseline and Days 3, 6, 8, 11, 15 and 40
Population: ITTI
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 11 (n=18, 18, 15, 14) | 5 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 3 (n=19, 17, 15, 15) | 37 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 40 (n=16, 15, 16, 14) | 5 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 6 (n=19, 17, 15, 15) | 0 percentage of participants |
| Oseltamivir Standard Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 8 (n=18, 17, 15, 15) | 5 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 8 (n=18, 17, 15, 15) | 0 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 6 (n=19, 17, 15, 15) | 0 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 11 (n=18, 18, 15, 14) | 11 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 40 (n=16, 15, 16, 14) | 11 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 3 (n=19, 17, 15, 15) | 61 percentage of participants |
| Oseltamivir Standard Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 8 (n=18, 17, 15, 15) | 0 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 3 (n=19, 17, 15, 15) | 44 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 6 (n=19, 17, 15, 15) | 6 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 11 (n=18, 18, 15, 14) | 0 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir High Dose 5 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 40 (n=16, 15, 16, 14) | 0 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 6 (n=19, 17, 15, 15) | 12 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 40 (n=16, 15, 16, 14) | 12 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 15 (n=18, 14, 15, 12) | 0 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 3 (n=19, 17, 15, 15) | 53 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Baseline (n=19, 18, 16, 17) | 100 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 11 (n=18, 18, 15, 14) | 0 percentage of participants |
| Oseltamivir High Dose 10 Days | Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture | Day 8 (n=18, 17, 15, 15) | 6 percentage of participants |
Secondary
Time to Alleviation of All Clinical Symptoms - Adults
Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time frame: Day 1 to Day 40
Population: ITTI population including adults only (\>12 years old).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Time to Alleviation of All Clinical Symptoms - Adults | 140.0 hours |
| Oseltamivir Standard Dose 10 Days | Time to Alleviation of All Clinical Symptoms - Adults | 181.8 hours |
| Oseltamivir High Dose 5 Days | Time to Alleviation of All Clinical Symptoms - Adults | 146.8 hours |
| Oseltamivir High Dose 10 Days | Time to Alleviation of All Clinical Symptoms - Adults | 94.9 hours |
Secondary
Time to Alleviation of All Clinical Symptoms - Children
Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time frame: Day 1 to Day 40
Population: ITTI population including children only (ages 1 - 12 years).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Time to Alleviation of All Clinical Symptoms - Children | 176.8 hours |
| Oseltamivir Standard Dose 10 Days | Time to Alleviation of All Clinical Symptoms - Children | 127.7 hours |
| Oseltamivir High Dose 5 Days | Time to Alleviation of All Clinical Symptoms - Children | 118.8 hours |
| Oseltamivir High Dose 10 Days | Time to Alleviation of All Clinical Symptoms - Children | 123.1 hours |
Secondary
Time to Resolution of Fever
Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time.
Time frame: Day 1 through Day 40
Population: ITTI population with fever at Baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir Standard Dose 5 Days | Time to Resolution of Fever | 19.3 hours |
| Oseltamivir Standard Dose 10 Days | Time to Resolution of Fever | 35.5 hours |
| Oseltamivir High Dose 5 Days | Time to Resolution of Fever | 24.9 hours |
| Oseltamivir High Dose 10 Days | Time to Resolution of Fever | 20.0 hours |