Acute, Uncomplicated Human Influenza
Conditions
Brief summary
The purpose of this study is to determine whether peramivir is safe and effective in the treatment of uncomplicated seasonal influenza.
Interventions
DRUGPeramivir
600 mg peramivir administered as bilateral 2-mL intramuscular injection
DRUGPlacebo
Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
Sponsors
BioCryst Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and non-pregnant female subjects age ≥18 years. * A positive Influenza A or B Rapid Antigen Test (RAT) performed with a commercially available test kit on an adequate anterior nasal specimen, in accordance with the manufacturer's instructions. A negative initial RAT should be repeated within one hour. * Presence of fever at time of screening of ≥38.0 ºC (≥100.4 ºF) taken orally, or ≥38.5 ºC (≥101.2 ºF) taken rectally. A subject self-report of a history of fever or feverishness within the 24 hours prior to screening will also qualify for enrollment in the absence of documented fever at the time of screening. * Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of at least moderate severity. * Presence of at least one constitutional symptom (myalgia \[aches and pains\], headache, feverishness, or fatigue) of at least moderate severity. * Onset of symptoms no more than 36 hours before presentation for screening. * Written informed consent.
Exclusion criteria
* Women who are pregnant or breast-feeding. * Presence of clinically significant signs of acute respiratory distress * History of severe chronic obstructive pulmonary disease (COPD) or severe persistent asthma. * History of heart failure or angina requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class III or IV functional status within the past 12 months. * Screening ECG which suggests acute ischemia or presence of medically significant dysrhythmia. * History of chronic renal impairment requiring hemodialysis and/or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance \<50 mL/min). * Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the investigator's opinion, indicates that such finding(s) could represent complications of influenza. * Current clinical evidence, including clinical signs and/or symptoms consistent with otitis, bronchitis, sinusitis and/or pneumonia, or active bacterial infection at any body site that requires therapy with oral or systemic antibiotics. * Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy which would include oral or systemic treatment with \> 10 mg prednisone or equivalent on a daily basis within 30 days of screening. * Currently receiving treatment for viral hepatitis B or viral hepatitis C. * Presence of known HIV infection with a CD4 count \<350 cell/mm3. * Current therapy with oral warfarin or other systemic anticoagulant. * Receipt of any doses of rimantadine, amantadine, zanamivir, or oseltamivir in the 7 days prior to screening. * Immunized against influenza with live attenuated virus vaccine (FluMist®) in the previous 21 days. * Immunized against influenza with inactivated virus vaccine within the previous 14 days. * Receipt of any intramuscular injection with the previous 7 days. * History of alcohol abuse or drug addiction within 1 year prior to admission in the study. * Participation in a previous study of intramuscular or intravenous peramivir or previous participation in this study. * Participation in a study of any investigational drug or device within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of Symptoms (Kaplan-Meier Estimate) | Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 | The primary efficacy endpoint was the time to alleviation of symptoms calculated as the number of hours from initiation of study drug until the start of the time period in which all 7 symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 hours - 10%) hours. Subjects with missing diary data were excluded and those who did not experience alleviation of symptoms were censored at the last observed symptom assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Influenza Virus Shedding | Baseline and Days 3, 4, 9 | Changes from Baseline in log10 TCID50/mL through Days 3, 4, and 9 were presented by treatment group for subjects with positive viral titers at Baseline (log10 TCID50/mL \>0.5). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Influenza-related Complications | 14 days | Study personnel were provided with an IRC checklist in the CRF to evaluate the subject for the presence of clinical signs and/or symptoms of the following IRCs: sinusitis, otitis, bronchitis, and pneumonia. Subjects with clinical signs and/or symptoms consistent with these conditions at Screening were not eligible for enrollment in this study. |
| Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | Baseline | Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. |
| Subject's Severity of Illness (Score*Hours) | Information collected predose on Day 1 and then once daily through Day 14 | A subject's severity of illness (area under the symptom score curve, as measured in score-hours) was assessed using available symptom score data until the time of alleviation of symptoms.The score-hours were calculated as the product of the daily symptom score times the hours to alleviation. All available data until time of alleviation were utilized. The daily symptom score was defined as the sum of the 7 symptoms of influenza recorded by the subject in the diary each day (cough; sore throat; nasal congestion; myalgia \[aches and pains\]; headache; feverishness; and fatigue), each graded on a 4-point severity scale \[0, absent; 1, mild; 2, moderate; 3, severe\]); for the composite score, individual scores were summed, with a range from 0 to 21. |
| Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | Baseline and up to 14 days | Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug. |
| Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | Baseline and up to 14 days | Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug. |
| Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | Baseline and up to 14 days | Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. |
| Time to Resolution of Fever | Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 | Time to resolution of fever was defined as the number of hours from initiation of study drug until temperature was less than 37.2 °C (99.0 °F) and no antipyretic medication had been taken for at least 12 hours. |
Countries
Australia, New Zealand, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection. | 203 |
| Peramivir 600 mg Peramivir 600 mg administered as bilateral 2-mL intramuscular injection. | 202 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study drug | 1 | 2 |
| Overall Study | Lost to Follow-up | 3 | 3 |
Baseline characteristics
| Characteristic | Peramivir 600 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35 years STANDARD_DEVIATION 12.1 | 35 years STANDARD_DEVIATION 11.3 | 35 years STANDARD_DEVIATION 11.7 |
| Body Mass Index (BMI) | 27.2 kg/m^2 STANDARD_DEVIATION 6.12 | 27.5 kg/m^2 STANDARD_DEVIATION 6.73 | 27.4 kg/m^2 STANDARD_DEVIATION 6.43 |
| Confirmed Influenza Infection Result Negative by PCR and Viral Culture | 40 participants | 28 participants | 68 participants |
| Confirmed Influenza Infection Result No Result/Sample | 2 participants | 1 participants | 3 participants |
| Confirmed Influenza Infection Result Positive by PCR and Viral Culture | 122 participants | 147 participants | 269 participants |
| Confirmed Influenza Infection Result Positive by PCR Only | 38 participants | 27 participants | 65 participants |
| Confirmed Influenza Infection Result Positive by Viral Culture Only | 0 participants | 0 participants | 0 participants |
| Current Smoking Behavior Nonsmoker | 165 participants | 166 participants | 331 participants |
| Current Smoking Behavior Smoker | 37 participants | 37 participants | 74 participants |
| Estimated Time of Onset of Symptoms at Screening 0-12 h Ago | 16 participants | 13 participants | 29 participants |
| Estimated Time of Onset of Symptoms at Screening 12-24 h Ago | 81 participants | 91 participants | 172 participants |
| Estimated Time of Onset of Symptoms at Screening 24-36 h Ago | 104 participants | 99 participants | 203 participants |
| Estimated Time of Onset of Symptoms at Screening Data Missing | 1 participants | 0 participants | 1 participants |
| Initial Composite Symptom Score | 14 units on a scale STANDARD_DEVIATION 3.9 | 14 units on a scale STANDARD_DEVIATION 4.3 | 14 units on a scale STANDARD_DEVIATION 4.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 5 participants | 8 participants |
| Race/Ethnicity, Customized Asian | 15 participants | 15 participants | 30 participants |
| Race/Ethnicity, Customized Black or African American | 61 participants | 68 participants | 129 participants |
| Race/Ethnicity, Customized Other | 17 participants | 14 participants | 31 participants |
| Race/Ethnicity, Customized White or Caucasian | 106 participants | 101 participants | 207 participants |
| Rapid Antigen Test (RAT) Results No data reported | 2 participants | 1 participants | 3 participants |
| Rapid Antigen Test (RAT) Results Positive | 200 participants | 202 participants | 402 participants |
| Sex: Female, Male Female | 102 Participants | 104 Participants | 206 Participants |
| Sex: Female, Male Male | 100 Participants | 99 Participants | 199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 202 | 31 / 200 |
| serious Total, serious adverse events | 1 / 202 | 0 / 200 |
Outcome results
Primary
Time to Alleviation of Symptoms (Kaplan-Meier Estimate)
The primary efficacy endpoint was the time to alleviation of symptoms calculated as the number of hours from initiation of study drug until the start of the time period in which all 7 symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 hours - 10%) hours. Subjects with missing diary data were excluded and those who did not experience alleviation of symptoms were censored at the last observed symptom assessment.
Time frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14
Population: The Intent-to-Treat Infected with Influenza A (ITTI-A) population included all subjects who were randomized, received study drug, and had confirmed influenza A by culture or PCR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Alleviation of Symptoms (Kaplan-Meier Estimate) | 106.9 hours |
| Peramivir 600 mg | Time to Alleviation of Symptoms (Kaplan-Meier Estimate) | 91.1 hours |
p-value: 0.22295% CI: [0.723, 1.188]Wilcoxon-Gehan test statistic
Secondary
Change in Influenza Virus Shedding
Changes from Baseline in log10 TCID50/mL through Days 3, 4, and 9 were presented by treatment group for subjects with positive viral titers at Baseline (log10 TCID50/mL \>0.5).
Time frame: Baseline and Days 3, 4, 9
Population: The Intent-to-Treat Infected Influenza A (ITTI-A) population included all subjects who were randomized, received study drug, and had confirmed influenza A infection by culture or PCR.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change in Influenza Virus Shedding | Change at Day 3 | -2.00 log10(TCID50/mL) |
| Placebo | Change in Influenza Virus Shedding | Change at Day 4 | -2.25 log10(TCID50/mL) |
| Placebo | Change in Influenza Virus Shedding | Change at Day 9 | -2.75 log10(TCID50/mL) |
| Peramivir 600 mg | Change in Influenza Virus Shedding | Change at Day 3 | -2.00 log10(TCID50/mL) |
| Peramivir 600 mg | Change in Influenza Virus Shedding | Change at Day 4 | -2.25 log10(TCID50/mL) |
| Peramivir 600 mg | Change in Influenza Virus Shedding | Change at Day 9 | -2.50 log10(TCID50/mL) |
p-value: >0.05van Elteren test
Other Pre-specified
Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50)
Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates.
Time frame: Baseline
Population: A subgroup of the Intent-to-Treat Infected Influenza A (ITTI-A) population that included all subjects who were randomized, received study drug, and had confirmed influenza A (H1N1) infection by culture or PCR. N was 113 for zanamivir susceptibility in the Placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Peramivir Susceptibility | 67.46 nM | Standard Error 54.625 |
| Placebo | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Oseltamivir Susceptibility | 983.41 nM | Standard Error 1129.29 |
| Placebo | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Zanamivir Susceptibility | 1.27 nM | Standard Error 1.131 |
| Peramivir 600 mg | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Peramivir Susceptibility | 72.27 nM | Standard Error 88.306 |
| Peramivir 600 mg | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Oseltamivir Susceptibility | 1007.29 nM | Standard Error 1425.095 |
| Peramivir 600 mg | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | A: H1N1-Baseline Zanamivir Susceptibility | 1.48 nM | Standard Error 1.686 |
Other Pre-specified
Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50)
Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug.
Time frame: Baseline and up to 14 days
Population: A subgroup of the Intent-to-Treat Infected (ITTI) population that included all subjects who were randomized, received study drug, and had confirmed influenza B infection by culture or PCR. The n reported is the number of participants who had baseline susceptibility values to zanamivir, oseltamivir, and peramivir.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Peramivir Susceptibility | 6.47 nM | Standard Error 2.442 |
| Placebo | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Oseltamivir Susceptibility | 40.98 nM | Standard Error 24.202 |
| Placebo | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Zanamivir Susceptibility | 5.78 nM | Standard Error 2.682 |
| Peramivir 600 mg | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Peramivir Susceptibility | 6.03 nM | Standard Error 3.633 |
| Peramivir 600 mg | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Oseltamivir Susceptibility | 28.72 nM | Standard Error 17.838 |
| Peramivir 600 mg | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | B: Baseline Zanamivir Susceptibility | 4.65 nM | Standard Error 2.282 |
Other Pre-specified
Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50)
Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype.
Time frame: Baseline and up to 14 days
Population: A subgroup of the Intent-to-Treat Infected Influenza A (ITTI-A) population that included all subjects who were randomized, received study drug, and had confirmed influenza A (H1N1) infection by culture or PCR. N is for fold change (participants who had baseline and last positive susceptibility values to zanamivir, oseltamivir, and peramivir).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Peramivir Susceptibility | 1.03 Fold Change from Baseline | Standard Error 0.66 |
| Placebo | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Oseltamivir Susceptibility | 1.20 Fold Change from Baseline | Standard Error 1.055 |
| Placebo | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Zanamivir Susceptibility | 3.68 Fold Change from Baseline | Standard Error 11.882 |
| Peramivir 600 mg | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Peramivir Susceptibility | 1.10 Fold Change from Baseline | Standard Error 0.677 |
| Peramivir 600 mg | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Oseltamivir Susceptibility | 1.28 Fold Change from Baseline | Standard Error 1.441 |
| Peramivir 600 mg | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | A: H1N1- Fold Change in Zanamivir Susceptibility | 2.67 Fold Change from Baseline | Standard Error 9.797 |
Other Pre-specified
Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50)
Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug.
Time frame: Baseline and up to 14 days
Population: A subgroup of the Intent-to-Treat Infected (ITTI) population that included all subjects who were randomized, received study drug, and had confirmed influenza B infection by culture or PCR. The n reported is the number for fold change (participants who had baseline and last positive susceptibility values to zanamivir, oseltamivir, and peramivir).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Peramivir Susceptibility | 1.27 Fold Change from Baseline | Standard Error 1.319 |
| Placebo | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Oseltamivir Susceptibility | 1.24 Fold Change from Baseline | Standard Error 0.819 |
| Placebo | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Zanamivir Susceptibility | 1.10 Fold Change from Baseline | Standard Error 0.737 |
| Peramivir 600 mg | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Peramivir Susceptibility | 0.92 Fold Change from Baseline | Standard Error 0.442 |
| Peramivir 600 mg | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Oseltamivir Susceptibility | 0.95 Fold Change from Baseline | Standard Error 0.374 |
| Peramivir 600 mg | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | B: Fold Change in Zanamivir Susceptibility | 0.95 Fold Change from Baseline | Standard Error 0.497 |
Other Pre-specified
Incidence of Influenza-related Complications
Study personnel were provided with an IRC checklist in the CRF to evaluate the subject for the presence of clinical signs and/or symptoms of the following IRCs: sinusitis, otitis, bronchitis, and pneumonia. Subjects with clinical signs and/or symptoms consistent with these conditions at Screening were not eligible for enrollment in this study.
Time frame: 14 days
Population: The Intent-to-Treat Infected Influenza A (ITTI-A) population included all subjects who were randomized, received study drug, and had confirmed influenza A infection by culture or PCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence of Influenza-related Complications | Sinusitis | 17 participants |
| Placebo | Incidence of Influenza-related Complications | Otitis | 2 participants |
| Placebo | Incidence of Influenza-related Complications | Bronchitis | 10 participants |
| Placebo | Incidence of Influenza-related Complications | Pneumonia | 0 participants |
| Placebo | Incidence of Influenza-related Complications | Any Influenza-Related Complication | 25 participants |
| Peramivir 600 mg | Incidence of Influenza-related Complications | Pneumonia | 3 participants |
| Peramivir 600 mg | Incidence of Influenza-related Complications | Any Influenza-Related Complication | 29 participants |
| Peramivir 600 mg | Incidence of Influenza-related Complications | Otitis | 4 participants |
| Peramivir 600 mg | Incidence of Influenza-related Complications | Sinusitis | 13 participants |
| Peramivir 600 mg | Incidence of Influenza-related Complications | Bronchitis | 15 participants |
p-value: 0.306Cochran-Mantel-Haenszel
Other Pre-specified
Subject's Severity of Illness (Score*Hours)
A subject's severity of illness (area under the symptom score curve, as measured in score-hours) was assessed using available symptom score data until the time of alleviation of symptoms.The score-hours were calculated as the product of the daily symptom score times the hours to alleviation. All available data until time of alleviation were utilized. The daily symptom score was defined as the sum of the 7 symptoms of influenza recorded by the subject in the diary each day (cough; sore throat; nasal congestion; myalgia \[aches and pains\]; headache; feverishness; and fatigue), each graded on a 4-point severity scale \[0, absent; 1, mild; 2, moderate; 3, severe\]); for the composite score, individual scores were summed, with a range from 0 to 21.
Time frame: Information collected predose on Day 1 and then once daily through Day 14
Population: The Intent-to-Treat Infected Influenza A (ITTI-A) population included all subjects who were randomized, received study drug, and had confirmed influenza A infection by culture or PCR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Subject's Severity of Illness (Score*Hours) | 777.0 score*hours |
| Peramivir 600 mg | Subject's Severity of Illness (Score*Hours) | 713.9 score*hours |
p-value: 0.421van Elteren test
Other Pre-specified
Time to Resolution of Fever
Time to resolution of fever was defined as the number of hours from initiation of study drug until temperature was less than 37.2 °C (99.0 °F) and no antipyretic medication had been taken for at least 12 hours.
Time frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14
Population: The Intent-to-Treat Infected Influenza A (ITTI-A) population included all subjects who were randomized, received study drug, and had confirmed influenza A infection by culture or PCR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Resolution of Fever | 44.7 hours |
| Peramivir 600 mg | Time to Resolution of Fever | 44.3 hours |
p-value: 0.885Wilcoxon-Gehan test statistic