Influenza, Human
Conditions
Keywords
Seasonal Influenza, Pandemic, Orthomyxoviridae Infections, Influenza, Influenza A Virus, H1N1 Subtype, Enzyme Inhibitors, Influenza, seasonal, Respiratory Tract Diseases, Zanamivir, Pharmacologic Actions, Antiviral Agents, Anti-Infective Agents, H1N1, Neuraminidase inhibitor, Influenza B virus
Brief summary
The purpose of this study is to test the safety and efficacy of zanamivir given intravenously and how well it works at two different doses in hospitalized adolescents and adults with flu. Zanamivir will be compared with oseltamivir, which is used for treating flu.
Detailed description
The recent influenza pandemic has highlighted the need for alternative formulations for anti-influenza therapies. This will be an international Phase III, double-blind, double-dummy, 3-arm study to evaluate the efficacy, antiviral activity and safety of IV zanamivir 600 mg twice daily compared to oral oseltamivir 75 mg twice daily, and 600 mg IV zanamivir twice daily compared to 300 mg IV zanamivir for 5 days in hospitalized subjects with laboratory confirmed or suspected influenza infection. For a given subject, the initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms or patient characteristics as assessed by the investigator warrant further treatment. Alternatively, if the investigator considers that a subject is failing to improve clinically on their randomized treatment, the investigator can choose to initiate the switch/rescue option (600 mg IV zanamivir twice daily) on any day from Day 6 through Day 10 for up to an additional 5 days of treatment. On switching treatments, subjects complete a maximum of 14 days of treatment and are followed-up to Post-Treatment +28 Days.
Interventions
DRUGZanamivir
Zanamivir aqueous solution, 10 mg/mL, will be provided as a single use, sterile clear, colorless preparation in 20 mL clear glass vials.
DRUGPlacebo to match zanamivir
Placebo to match IV zanamivir will be provided as a normal saline solution of a matched volume.
DRUGOseltamivir
Oseltamivir will be provided as over-encapsulated 75 mg capsules.
DRUGPlacebo to match oseltamivir
Placebo to match oral oseltamivir will be provided as capsules with a common excipient of appropriate quality.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged 16 years; a female is eligible to enter and participate in the study if she is: 1. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post- menopausal); or, 2. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to use protocol specified methods of birth control while on study. * Vital signs criteria defined as 3 or more of the following at Baseline: 1. Presence of fever \[oral temperature of 38°C or equivalent\] at Baseline. However, this requirement is waived if the subject has a history of fever within in the 24 hours prior to Baseline; or, if the subject reported symptoms of feverishness at some time during the 48 hours prior to Baseline. AND at least 2 out of the following 4: 2. Oxygen saturation \<95% on room air by trans-cutaneous method or need for any supplemental oxygenation or ventilatory support, or increase in oxygen supplementation requirement of ≥2 litres for subjects with chronic oxygen dependency. For those subjects with a history of chronic hypoxia (without supplemental oxygen), an oxygen saturation of at least 3% below the patient's historical baseline oxygen saturation will satisfy this criterion. 3. Respiration rate \>24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived. 4. Heart rate \>100 beats per minute. 5. Systolic blood pressure \<90 mmHg. * Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting. * Clinical symptoms of influenza with positive influenza diagnostic test result or strong suspicion of influenza illness based on clinical symptoms and local surveillance information. * Subjects willing and able to give written informed consent to participate in the study and to adhere to the procedures stated in the protocol, or legally acceptable representative willing and able to give written informed consent on behalf of the subject for minors, unconscious adults and those incapable of consenting themselves due to their medical condition, or included as permitted by local regulatory authorities, IRB/IECs or local laws. * Severity of any medical illness that, in the Investigator's judgement, justifies hospitalization of the subject for treatment and supportive care * French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion criteria
* Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy in the period from onset of symptoms and prior to enrolment. * Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline. * Subjects who are considered to require concurrent therapy with another influenza antiviral medication. * Subjects who are known or suspected to be hypersensitive to any component of the study medications. * Subjects with creatinine clearance ≤10 mL/min who are not being treated with continuous renal replacement therapy (CRRT). * Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline * Subjects who require routine/intermittent hemodialysis or continuous peritoneal dialysis (due to inability to provide appropriate dosing schedule for oseltamivir) at Baseline. CRRT modalities are allowed. * Liver toxicity criteria based on local laboratory results obtained within 24 hours of Baseline: 1. ALT or AST 3xULN and bilirubin 2xULN 2. ALT 5xULN * Underlying chronic liver disease with evidence of severe liver impairment. * History of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject. * Females who are pregnant or are breastfeeding. * Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline. * French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Response (TTCR) in Participants With Confirmed Influenza | Up to 42 days | Clinical response is defined as the resolution of at least 4 of the 5 vital signs (temperature, oxygen saturation, respiratory status, heart rate, systolic blood pressure) within the respective resolution criteria, maintained for at least 24 hours, or hospital discharge, whichever occurred first. This analysis was performed for Influenza positive population, for those with symptom onset less than or equal to (\<=) 4 days, and for those on mechanical (mech) ventilation or in intensive care unit (ICU). 99 days is censored time for the participants who did not achieve TTCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days) | The number of participants who died on or before Day 14, Day 28, and the End of Study Visit were summarized. |
| Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Baseline (Day 1) and up to 42 days | The Katz ADL scores were collected for bathing, dressing, toileting, transferring, continence, and feeding activities and were assessed once daily during the treatment period/hospitalization and once at each post-treatment Clinic Visit. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline is defined as the difference at each time point (Day 5/6, and Day 10/11, and last day S/R if treatment was extended beyond 5 days) and the end of the study (post-treatment \[PT\] +28 Days) compared to Baseline. |
| Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Up to 42 days | Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. Median time to return to pre-morbid functional status was assessed via the Katz ADL score (bathing, dressing, toileting, transferring, continence, and feeding activities). For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent. |
| Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Up to 42 days | Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. The number of participants who returned to their pre-morbid functional status at the end of the study assessed per the Katz ADL score (bathing, dressing, toileting, transferring, continence and feeding activities) is summarized. |
| Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale | Up to 42 days | Median time to return to pre-morbid level of activity was assessed once daily during treatment/hospitalization and once at each post-treatment assessment and was measured using the 3- point scale (bed rest, limited ambulation, or unrestricted). |
| Number of Participants With the Indicated Clinical Symptoms of Influenza | Up to 42 days | Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient hospitalization and once at each post-treatment assessment. |
| Median Time of Duration of Clinical Symptoms of Influenza | Up to 42 days | Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient/hospitalization and once at each post-treatment assessment. |
| Number of Participants With Complications of Influenza and Associated Antibiotic Use | Up to 42 days | The number of participants with complications of influenza and associated antibiotic use were summarized |
| Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Up to 42 days | Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD), no supplemental oxygen (O2) or ventilation support, Respiratory support at any time (AT) on study and at Baseline (Day 1) are summarized. Data for the any time (AT) on study time point was reported. |
| Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Baseline (Day 1) and up to 42 days | Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitalization and once at each post-treatment clinic visit. |
| Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Day 1 to the end of the study (assessed up to 42 days) | Hospital duration and ICU duration was assessed from the first day of dosing. Hospital duration was calculated as the discharge date minus the admission date + 1. Hospital duration while on study was the earlier of discharge, completion, or withdrawal minus the later of the admission date or the study start date + 1. ICU duration-Modified was calculated as the original ICU duration minus ICU days prior to Study Day 1. |
| Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Baseline (Day 1) and up to 42 days | The absence of fever is defined as a non-axillary temperature recording \<=36.6 degrees Celsius axillary, \<= 37.2 degrees Celsius oral or \<= 37.7 degrees Celsius core. Respiratory Status (RS) response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), or the need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate =\<24 breaths/minute (without supplemental oxygen). Oxygen saturation response criteria: \>=95% (without supplemental oxygen). Heart rate response criteria: =\<100 beats/minute. Systolic blood pressure response criteria: \>=90 millimeters of mercury. Vital signs were assessed three times daily during the treatment period/hospitalization. Vital signs were assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit. |
| Median Time to Virologic Improvement | Baseline (Day 1) and up to 42 days | Virologic improvement is defined as a 2 log drop in viral load or sustained undetectable viral ribonucleic acid (RNA) (on two successive occasions) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples. Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Days 6, 8, 10 and on the last day of randomized treatment. For participants who utilized the Switch (S)/Rescue (R) option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Nasopharyngeal swabs were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16, and +28 day assessment. |
| Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable | Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day1, S/R Day3, S/R Day5, or S/R Day6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16 and +28Day assessment. Viral load was measured by Quantitative Virus Culture, log10 50% Tissue Culture Infectious Dose (TCID50)/milliliter (mL). Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus Baseline value . |
| Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable | Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the post-treatment +2, +5, +9, +16 and +28 day assessment. Viral load as measured by PCR. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Percentage of Participants With Respiratory Improvement | Up to 42 days | Respiratory Status (RS) is a component of TTCR. Response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), a need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate of =\<24 breaths/minute (without supplemental oxygen). Data are presented as the percentage of participants achieving respiratory improvement. |
| Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Baseline (Day 1) and up to 42 days | Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples, where available) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment). Endotracheal aspirates were collected in participants who were intubated. If treatment was continued beyond Day 5, additional samples were taken on Treatment Day 6, Day 8, Day 10, and/or the day of the last dose of randomized treatment, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R treatment. If the participant was symptomatic and hospitalized, samples were taken on the Post-treatment+2, +5, +9, +16 assessment days, and at the Post-Treatment +28 Day. Assessment of samples was done by quantitative RT-PCR. |
| Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | Baseline (Day 1) and up to 42 days | Nasopharyngeal swabs and endotracheal /BAL samples were collected for viral susceptibility analysis. Susceptibility analyses consisted of phenotyping and genotyping. Resistance mutations were detected by genotyping. Viral susceptibility to zanamivir and oral oseltamivir at Baseline and throughout treatment determined by NA and HA (gene of influenza A and B viruses) sequence analysis and NA enzyme inhibition. Number of participants with viral mutation events are summarized, this includes all resistance mutations (substitutions) i.e. those present at Baseline and those that emerged during treatment. |
| Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | Up to 42 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. All AEs were assessed by the Investigator as related or not related to the study treatment. |
| Number of Participants With Any Severe or Grade 3/4 AE | Up to 42 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of AEs. Grade 3=severe; Grade 4=potentially life threatening. |
| Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | Up to 42 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. |
| Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | Up to 42 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. |
| Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | Up to 42 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assessed by the Investigator as related or not related to the study treatment. |
| Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Baseline (Day 1) and up to 42 days | Samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), switch/rescue (S/R) Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino tranferase (AST), total bilirubin, calcium, creatine kinase, chloride, carbon dioxide content (CO2), creatinine, potassium, magnesium, sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range are summarized. |
| Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Baseline (Day 1) and up to 42 days | Blood samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), S/R Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC) count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range for the indicated hematology parameters is summarized. Baseline is defined as the pre-dose value collected on Study Day 1. |
| Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Baseline (Day 1) and up to 42 days | A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatine kinase, chloride, CO2/bicarbonate, creatinine, potassium, magnesium and sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1. |
| Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Baseline (Day 1) and up to 42 days | A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1. |
| Median Quantity of Oxygen Delivery Measured at Baseline (Day 1) and During the Study | Baseline (Day 1) and during the study | Oxygen delivery were assessed three times daily at Baseline (Day 1) and during the treatment period/hospitalization (ideally at least 6 hours apart) and once daily during inpatient/hospitalization and once at Post +5 days, +16 days, and +28 days clinic visits. The median quantity of oxygen delivery during the study was not summarized since the data was not collected in a way to accurately calculate values. Baseline is defined as the pre-dose value collected on Study Day 1. |
| Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Baseline (Day 1) and Day 4 | On Baseline/Day 1, a 12-lead ECG was obtained within approximately 24 hours prior to dosing. The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. In the original protocol ECGs were also done on Day 4, however, amendment 2 removed this requirement and therefore not all participants had Day 4 ECGs. |
| Serum Concentration of IV Zanamivir | Day 1 and Day 4 | Pharmacokinetic samples were collected at four time points to characterize peak concentration (end of infusion; C\[EOI\]) after the first dose on Day 1 and on Day 4 to characterize the pre-dose concentration (C\[0\]), the peak concentration C(EOI), and the trough concentration at 11-12 hours post-dose (C\[12\]) of zanamavir. Data was summarized by Creatinine clearance (CL) Category. The dose on Day 1 is the initial dose (unadjusted) and the dose on Day 4 is the maintenance dose. |
| Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Baseline (Day 1) and up to 42 days | Lower respiratory samples included BAL and endotracheal aspirates. Endotracheal aspirates were requested in participants (par.) who were intubated. Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment \[trt\]). Endotracheal aspirates were collected in participants who were intubated. If trt was continued beyond Day 5, additional samples were taken on Trt Day 6, Day 8, Day 10, and/or the day of the last dose of randomized trt, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R trt. If the par. was symptomatic and hospitalized, samples were taken on the Post-Trt +2, +5, +9, +16 assessment days, and at the Post-Trt \[PT\]+28 Day assessment. Assessment of samples was done by quantitative RT-PCR and viral culture. |
Countries
Australia, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Mexico, Netherlands, New Zealand, Norway, Poland, Russia, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
Male and female adult and adolescent participants \>=16 years of age hospitalized with documented influenza or suspected influenza were eligible for enrollment. A total of 626 participants were randomized, and 615 participants were included in the Intent-to-Treat Exposed (ITT-E) Population (pop)
Participants by arm
| Arm | Count |
|---|---|
| IV Zanamivir 300 mg Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days. | 201 |
| IV Zanamivir 600 mg Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days | 209 |
| Oral Oseltamivir 75 mg Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days. | 205 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 |
| Overall Study | Death | 12 | 14 | 11 |
| Overall Study | Lost to Follow-up | 3 | 4 | 9 |
| Overall Study | Physician Decision | 3 | 5 | 10 |
| Overall Study | Withdrawal by Subject | 6 | 6 | 8 |
Baseline characteristics
| Characteristic | IV Zanamivir 300 mg | IV Zanamivir 600 mg | Oral Oseltamivir 75 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 55.2 Years STANDARD_DEVIATION 18.88 | 57.3 Years STANDARD_DEVIATION 17.39 | 55.9 Years STANDARD_DEVIATION 18.7 | 56.2 Years STANDARD_DEVIATION 18.32 |
| Race/Ethnicity, Customized African American or African Heritage | 12 Participants | 4 Participants | 10 Participants | 26 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian - Central South Asian | 10 Participants | 15 Participants | 13 Participants | 38 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 12 Participants | 18 Participants | 13 Participants | 43 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 6 Participants | 4 Participants | 7 Participants | 17 Participants |
| Race/Ethnicity, Customized Mixed Race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Arabic or North African | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized White -White or Caucasian or European | 150 Participants | 162 Participants | 154 Participants | 466 Participants |
| Sex: Female, Male Female | 82 Participants | 86 Participants | 117 Participants | 285 Participants |
| Sex: Female, Male Male | 119 Participants | 123 Participants | 88 Participants | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 15 / 201 | 15 / 209 | 11 / 205 |
| other Total, other adverse events | 17 / 201 | 26 / 209 | 24 / 205 |
| serious Total, serious adverse events | 38 / 201 | 33 / 209 | 38 / 205 |
Outcome results
Primary
Time to Clinical Response (TTCR) in Participants With Confirmed Influenza
Clinical response is defined as the resolution of at least 4 of the 5 vital signs (temperature, oxygen saturation, respiratory status, heart rate, systolic blood pressure) within the respective resolution criteria, maintained for at least 24 hours, or hospital discharge, whichever occurred first. This analysis was performed for Influenza positive population, for those with symptom onset less than or equal to (\<=) 4 days, and for those on mechanical (mech) ventilation or in intensive care unit (ICU). 99 days is censored time for the participants who did not achieve TTCR.
Time frame: Up to 42 days
Population: ITT-E population comprised of all randomized participants who received at least one dose of investigational product. The Influenza positive population (IPP) is comprised of all participants in the ITT-E population with proven influenza infection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Zanamivir 300 mg | Time to Clinical Response (TTCR) in Participants With Confirmed Influenza | 5.87 Days |
| IV Zanamivir 600 mg | Time to Clinical Response (TTCR) in Participants With Confirmed Influenza | 5.14 Days |
| Oral Oseltamivir 75 mg | Time to Clinical Response (TTCR) in Participants With Confirmed Influenza | 5.63 Days |
p-value: 0.2595% CI: [-1.79, 0.75]Wilcoxon rank sum
p-value: 0.3995% CI: [-2.11, 0.97]Wilcoxon rank sum
Secondary
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline
Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day1, S/R Day3, S/R Day5, or S/R Day6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16 and +28Day assessment. Viral load was measured by Quantitative Virus Culture, log10 50% Tissue Culture Infectious Dose (TCID50)/milliliter (mL). Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus Baseline value .
Time frame: Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
Population: IPP Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -1.64 log10 TCID50/mL |
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.51 log10 TCID50/mL |
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -2.01 log10 TCID50/mL |
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -3.76 log10 TCID50/mL |
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | -2.5 log10 TCID50/mL |
| IV Zanamivir 300 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -3.01 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -0.3 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -2.01 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.26 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -2.01 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -0.3 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | S/R Day 5 | -4.3 log10 TCID50/mL |
| IV Zanamivir 600 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | -4.3 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -2.01 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -2.26 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | 0.0 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | S/R Day 5 | -3.0 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -2.26 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -2.26 log10 TCID50/mL |
| Oral Oseltamivir 75 mg | Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.26 log10 TCID50/mL |
Secondary
Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score
The Katz ADL scores were collected for bathing, dressing, toileting, transferring, continence, and feeding activities and were assessed once daily during the treatment period/hospitalization and once at each post-treatment Clinic Visit. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline is defined as the difference at each time point (Day 5/6, and Day 10/11, and last day S/R if treatment was extended beyond 5 days) and the end of the study (post-treatment \[PT\] +28 Days) compared to Baseline.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: DAY 5/6 | 0.07 Scores on the scale | Standard Deviation 0.322 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Last Day of S/R | 0.2 Scores on the scale | Standard Deviation 0.447 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 10/11 | 0.88 Scores on the scale | Standard Deviation 1.746 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Day 10/11 | 0.13 Scores on the scale | Standard Deviation 0.342 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: DAY 5/6 | 0.19 Scores on the scale | Standard Deviation 0.456 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 5/6 | 1.07 Scores on the scale | Standard Deviation 1.959 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Last Day of S/R | -0.2 Scores on the scale | Standard Deviation 0.447 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: PT + 28 DAYS | 0.43 Scores on the scale | Standard Deviation 0.498 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: PT+28 Day | 0.21 Scores on the scale | Standard Deviation 0.409 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: PT+28 Day | 0.22 Scores on the scale | Standard Deviation 0.431 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: PT+28 Day | 0.4 Scores on the scale | Standard Deviation 0.491 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Last Day of S/R | -0.2 Scores on the scale | Standard Deviation 0.447 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 5/6 | 0.07 Scores on the scale | Standard Deviation 0.331 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing:PT+28 Day | 0.42 Scores on the scale | Standard Deviation 0.495 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 10/11 | 0.13 Scores on the scale | Standard Deviation 0.342 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: Last Day of S/R | 0.2 Scores on the scale | Standard Deviation 0.447 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: DAY 5/6 | 0.28 Scores on the scale | Standard Deviation 0.505 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Day 10/11 | 0.13 Scores on the scale | Standard Deviation 0.342 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 10/11 | 0.19 Scores on the scale | Standard Deviation 0.403 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Day 10/11 | 0.19 Scores on the scale | Standard Deviation 0.403 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Day 10/11 | 0.13 Scores on the scale | Standard Deviation 0.342 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 5/6 | 0.24 Scores on the scale | Standard Deviation 0.488 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Last Day of S/R | 0.0 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Last Day of S/R | 0.2 Scores on the scale | Standard Deviation 0.447 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score PT+28 Day | 2.13 Scores on the scale | Standard Deviation 2.234 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: PT+28 Day | 0.45 Scores on the scale | Standard Deviation 0.499 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing DAY 5/6 | 0.23 Scores on the scale | Standard Deviation 0.481 |
| IV Zanamivir 300 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Last Day of S/R | 0.2 Scores on the scale | Standard Deviation 2.49 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing:PT+28 Day | 0.37 Scores on the scale | Standard Deviation 0.515 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: DAY 5/6 | 0.19 Scores on the scale | Standard Deviation 0.439 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Day 10/11 | 0.33 Scores on the scale | Standard Deviation 0.516 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: PT+28 Day | 0.32 Scores on the scale | Standard Deviation 0.514 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: DAY 5/6 | 0.23 Scores on the scale | Standard Deviation 0.451 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Day 10/11 | 0.17 Scores on the scale | Standard Deviation 0.408 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: PT+28 Day | 0.36 Scores on the scale | Standard Deviation 0.526 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: DAY 5/6 | 0.05 Scores on the scale | Standard Deviation 0.314 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Day 10/11 | 0.0 Scores on the scale | Standard Deviation 0 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: PT+28 Day | 0.16 Scores on the scale | Standard Deviation 0.422 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 5/6 | 0.07 Scores on the scale | Standard Deviation 0.309 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 10/11 | 0.0 Scores on the scale | Standard Deviation 0 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: PT+28 Day | 0.17 Scores on the scale | Standard Deviation 0.416 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 5/6 | 0.93 Scores on the scale | Standard Deviation 1.782 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 10/11 | 0.5 Scores on the scale | Standard Deviation 0.837 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Last Day of S/R | -3.0 Scores on the scale | Standard Deviation 4.243 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score PT+28 Day | 1.72 Scores on the scale | Standard Deviation 2.342 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 5/6 | 0.19 Scores on the scale | Standard Deviation 0.429 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 10/11 | 0.0 Scores on the scale | Standard Deviation 0 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: Last Day of S/R | -0.5 Scores on the scale | Standard Deviation 0.707 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: PT + 28 DAYS | 0.34 Scores on the scale | Standard Deviation 0.505 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing DAY 5/6 | 0.21 Scores on the scale | Standard Deviation 0.438 |
| IV Zanamivir 600 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Day 10/11 | 0.0 Scores on the scale | Standard Deviation 0 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: PT + 28 DAYS | 0.39 Scores on the scale | Standard Deviation 0.507 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 10/11 | -0.08 Scores on the scale | Standard Deviation 3.029 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: PT+28 Day | 0.4 Scores on the scale | Standard Deviation 0.492 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Day 10/11 | 0.08 Scores on the scale | Standard Deviation 0.515 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Last Day of S/R | 0.75 Scores on the scale | Standard Deviation 1.165 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Last Day of S/R | 0.25 Scores on the scale | Standard Deviation 0.463 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing:PT+28 Day | 0.41 Scores on the scale | Standard Deviation 0.494 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score PT+28 Day | 1.98 Scores on the scale | Standard Deviation 2.142 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: Day 10/11 | 0.08 Scores on the scale | Standard Deviation 0.515 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing DAY 5/6 | 0.14 Scores on the scale | Standard Deviation 0.427 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 5/6 | 0.18 Scores on the scale | Standard Deviation 0.438 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Transferring: DAY 5/6 | 0.17 Scores on the scale | Standard Deviation 0.41 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: DAY 5/6 | 0.14 Scores on the scale | Standard Deviation 0.409 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: DAY 10/11 | 0.0 Scores on the scale | Standard Deviation 0.426 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: PT+28 Day | 0.37 Scores on the scale | Standard Deviation 0.484 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 5/6 | 0.08 Scores on the scale | Standard Deviation 0.382 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Last Day of S/R | 0.13 Scores on the scale | Standard Deviation 0.354 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Day 10/11 | -0.08 Scores on the scale | Standard Deviation 0.669 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: PT+28 Day | 0.23 Scores on the scale | Standard Deviation 0.439 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Bathing: Last Day of S/R | 0.0 Scores on the scale | Standard Deviation 0 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: Last Day of S/R | 0.25 Scores on the scale | Standard Deviation 0.463 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Last Day of S/R | 0.13 Scores on the scale | Standard Deviation 0.354 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Toileting: Last Day of S/R | 0.0 Scores on the scale | Standard Deviation 0.535 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Feeding: PT+28 Day | 0.19 Scores on the scale | Standard Deviation 0.395 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: Day 10/11 | -0.08 Scores on the scale | Standard Deviation 0.669 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Dressing: Day 10/11 | -0.08 Scores on the scale | Standard Deviation 0.515 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Total Score Day 5/6 | 0.78 Scores on the scale | Standard Deviation 1.837 |
| Oral Oseltamivir 75 mg | Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score | Continence: DAY 5/6 | 0.07 Scores on the scale | Standard Deviation 0.374 |
Secondary
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline
Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the post-treatment +2, +5, +9, +16 and +28 day assessment. Viral load as measured by PCR. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
Population: IPP Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -2.38 log10 vp/mL |
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.51 log10 vp/mL |
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -1.5 log10 vp/mL |
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -2.75 log10 vp/mL |
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | -5.2 log10 vp/mL |
| IV Zanamivir 300 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -3.58 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -3.03 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -1.83 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.71 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -3.16 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -2.6 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | S/R Day 5 | -3.8 log10 vp/mL |
| IV Zanamivir 600 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | -5.4 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 3 | -1.75 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 11 | -3.29 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | S/R Day 6 | -3.84 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | S/R Day 5 | -5.7 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 8 | -1.78 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 10 | -2.63 log10 vp/mL |
| Oral Oseltamivir 75 mg | Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline | Day 5 | -2.73 log10 vp/mL |
Secondary
Median Quantity of Oxygen Delivery Measured at Baseline (Day 1) and During the Study
Oxygen delivery were assessed three times daily at Baseline (Day 1) and during the treatment period/hospitalization (ideally at least 6 hours apart) and once daily during inpatient/hospitalization and once at Post +5 days, +16 days, and +28 days clinic visits. The median quantity of oxygen delivery during the study was not summarized since the data was not collected in a way to accurately calculate values. Baseline is defined as the pre-dose value collected on Study Day 1.
Time frame: Baseline (Day 1) and during the study
Population: This end point was not analyzed
Secondary
Median Time of Duration of Clinical Symptoms of Influenza
Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient/hospitalization and once at each post-treatment assessment.
Time frame: Up to 42 days
Population: IPP Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Cough | 14 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Fatigue | 11 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Dyspnea | 7 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Sore throat | 3 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Feverishness | 2 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Anorexia | 5 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Vomiting | 2 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Headache | 3 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nausea | 3 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Diarrhea | 3 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Myalgias | 4 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nasal symptoms | 6 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Myalgias | 3 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nasal symptoms | 4 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nausea | 2 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Sore throat | 2 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Vomiting | 1 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Dyspnea | 6 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Fatigue | 11 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Cough | 13 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Feverishness | 2 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Anorexia | 3 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Headache | 3 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Clinical Symptoms of Influenza | Diarrhea | 2 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Vomiting | 1 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Anorexia | 5 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Cough | 15 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Diarrhea | 3 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Dyspnea | 8 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Fatigue | 12 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Feverishness | 2.5 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Headache | 4 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Myalgias | 4 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nasal symptoms | 5.5 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Nausea | 2 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Clinical Symptoms of Influenza | Sore throat | 3 Days |
Secondary
Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay
Hospital duration and ICU duration was assessed from the first day of dosing. Hospital duration was calculated as the discharge date minus the admission date + 1. Hospital duration while on study was the earlier of discharge, completion, or withdrawal minus the later of the admission date or the study start date + 1. ICU duration-Modified was calculated as the original ICU duration minus ICU days prior to Study Day 1.
Time frame: Day 1 to the end of the study (assessed up to 42 days)
Population: IPP population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization | 10 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization while on study | 8 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization-ICU | 8 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | ICU Duration Modified | 7 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | ICU Duration Modified | 6 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization | 8 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization-ICU | 7.5 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization while on study | 6 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | ICU Duration Modified | 7 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization while on study | 7 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization-ICU | 8 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay | Hospitalization | 9 Days |
Secondary
Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitalization and once at each post-treatment clinic visit.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population. Only those participants available with the indicated ventilator support or oxygen supplementation were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Ventilator Support | 9 Days |
| IV Zanamivir 300 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Oxygen Supplementation | 4.4 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Ventilator Support | 5.2 Days |
| IV Zanamivir 600 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Oxygen Supplementation | 4.2 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Ventilator Support | 8.2 Days |
| Oral Oseltamivir 75 mg | Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Oxygen Supplementation | 3.7 Days |
Secondary
Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples)
Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples, where available) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment). Endotracheal aspirates were collected in participants who were intubated. If treatment was continued beyond Day 5, additional samples were taken on Treatment Day 6, Day 8, Day 10, and/or the day of the last dose of randomized treatment, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R treatment. If the participant was symptomatic and hospitalized, samples were taken on the Post-treatment+2, +5, +9, +16 assessment days, and at the Post-Treatment +28 Day. Assessment of samples was done by quantitative RT-PCR.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population. Only those participants available at the specified time points were analyzed. Data also presented for participants positive at Baseline.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Influenza A and B | 4 Days |
| IV Zanamivir 300 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Positive at Baseline | 4 Days |
| IV Zanamivir 600 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Influenza A and B | 3 Days |
| IV Zanamivir 600 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Positive at Baseline | 4 Days |
| Oral Oseltamivir 75 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Influenza A and B | 4 Days |
| Oral Oseltamivir 75 mg | Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples) | Positive at Baseline | 4 Days |
Secondary
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score
Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. Median time to return to pre-morbid functional status was assessed via the Katz ADL score (bathing, dressing, toileting, transferring, continence, and feeding activities). For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent.
Time frame: Up to 42 days
Population: IPP population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Bathing | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Transferring | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Toileting | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Total score | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Feeding | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Continence | 2 Days |
| IV Zanamivir 300 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Dressing | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Toileting | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Total score | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Bathing | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Dressing | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Transferring | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Continence | 2 Days |
| IV Zanamivir 600 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Feeding | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Transferring | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Bathing | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Feeding | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Continence | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Toileting | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Dressing | 2 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score | Total score | 2.5 Days |
Secondary
Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale
Median time to return to pre-morbid level of activity was assessed once daily during treatment/hospitalization and once at each post-treatment assessment and was measured using the 3- point scale (bed rest, limited ambulation, or unrestricted).
Time frame: Up to 42 days
Population: IPP Population. Participants succeeded in pre-morbid functional status were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Zanamivir 300 mg | Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale | 5 Days |
| IV Zanamivir 600 mg | Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale | 4 Days |
| Oral Oseltamivir 75 mg | Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale | 4 Days |
Secondary
Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure
The absence of fever is defined as a non-axillary temperature recording \<=36.6 degrees Celsius axillary, \<= 37.2 degrees Celsius oral or \<= 37.7 degrees Celsius core. Respiratory Status (RS) response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), or the need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate =\<24 breaths/minute (without supplemental oxygen). Oxygen saturation response criteria: \>=95% (without supplemental oxygen). Heart rate response criteria: =\<100 beats/minute. Systolic blood pressure response criteria: \>=90 millimeters of mercury. Vital signs were assessed three times daily during the treatment period/hospitalization. Vital signs were assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Heart rate | 0.4 Days |
| IV Zanamivir 300 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Respiratory status | 3.5 Days |
| IV Zanamivir 300 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Fever | 1.6 Days |
| IV Zanamivir 300 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Oxygen Saturation | 5.3 Days |
| IV Zanamivir 300 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Systolic blood pressure | 0.3 Days |
| IV Zanamivir 600 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Respiratory status | 3.6 Days |
| IV Zanamivir 600 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Fever | 0.8 Days |
| IV Zanamivir 600 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Oxygen Saturation | 5.6 Days |
| IV Zanamivir 600 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Heart rate | 0.4 Days |
| IV Zanamivir 600 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Systolic blood pressure | 0.3 Days |
| Oral Oseltamivir 75 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Systolic blood pressure | 0.3 Days |
| Oral Oseltamivir 75 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Heart rate | 0.5 Days |
| Oral Oseltamivir 75 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Fever | 1.5 Days |
| Oral Oseltamivir 75 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Respiratory status | 2.8 Days |
| Oral Oseltamivir 75 mg | Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure | Oxygen Saturation | 4.5 Days |
Secondary
Median Time to Virologic Improvement
Virologic improvement is defined as a 2 log drop in viral load or sustained undetectable viral ribonucleic acid (RNA) (on two successive occasions) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples. Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Days 6, 8, 10 and on the last day of randomized treatment. For participants who utilized the Switch (S)/Rescue (R) option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Nasopharyngeal swabs were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16, and +28 day assessment.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population. Only those participants available at the specified time points were analyzed. Data presented is for participants positive at Baseline.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Zanamivir 300 mg | Median Time to Virologic Improvement | Influenza A and B | 3 Days |
| IV Zanamivir 300 mg | Median Time to Virologic Improvement | Influenza A/H1N1 | 3 Days |
| IV Zanamivir 300 mg | Median Time to Virologic Improvement | Influenza A/H3N2 | 3 Days |
| IV Zanamivir 300 mg | Median Time to Virologic Improvement | Influenza B | 5 Days |
| IV Zanamivir 600 mg | Median Time to Virologic Improvement | Influenza B | 3 Days |
| IV Zanamivir 600 mg | Median Time to Virologic Improvement | Influenza A and B | 3 Days |
| IV Zanamivir 600 mg | Median Time to Virologic Improvement | Influenza A/H3N2 | 3 Days |
| IV Zanamivir 600 mg | Median Time to Virologic Improvement | Influenza A/H1N1 | 3 Days |
| Oral Oseltamivir 75 mg | Median Time to Virologic Improvement | Influenza B | 3 Days |
| Oral Oseltamivir 75 mg | Median Time to Virologic Improvement | Influenza A/H1N1 | 3 Days |
| Oral Oseltamivir 75 mg | Median Time to Virologic Improvement | Influenza A/H3N2 | 3 Days |
| Oral Oseltamivir 75 mg | Median Time to Virologic Improvement | Influenza A and B | 3 Days |
Secondary
Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4
On Baseline/Day 1, a 12-lead ECG was obtained within approximately 24 hours prior to dosing. The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. In the original protocol ECGs were also done on Day 4, however, amendment 2 removed this requirement and therefore not all participants had Day 4 ECGs.
Time frame: Baseline (Day 1) and Day 4
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Not Clinically Significant | 97 Participants |
| IV Zanamivir 300 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Normal | 100 Participants |
| IV Zanamivir 300 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Clinically Significant | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Not Clinically Significant | 86 Participants |
| IV Zanamivir 600 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Normal | 121 Participants |
| IV Zanamivir 600 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Clinically Significant | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Normal | 99 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Clinically Significant | 7 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4 | Abnormal - Not Clinically Significant | 102 Participants |
Secondary
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
Time frame: Up to 42 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Zanamivir 300 mg | Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | 10 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | 11 Participants |
Secondary
Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study
Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. The number of participants who returned to their pre-morbid functional status at the end of the study assessed per the Katz ADL score (bathing, dressing, toileting, transferring, continence and feeding activities) is summarized.
Time frame: Up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Bathing | 135 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Transferring | 140 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Toileting | 139 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Total | 139 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Feeding | 145 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Continence | 142 Participants |
| IV Zanamivir 300 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Dressing | 138 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Toileting | 136 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Total | 138 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Bathing | 133 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Dressing | 135 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Transferring | 140 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Continence | 143 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Feeding | 148 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Transferring | 133 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Bathing | 126 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Feeding | 144 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Continence | 139 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Toileting | 130 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Dressing | 126 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study | Total | 130 Participants |
Secondary
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
Time frame: Up to 42 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Zanamivir 300 mg | Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | 14 Participants |
| IV Zanamivir 600 mg | Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | 16 Participants |
| Oral Oseltamivir 75 mg | Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | 13 Participants |
Secondary
Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit
The number of participants who died on or before Day 14, Day 28, and the End of Study Visit were summarized.
Time frame: On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days)
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: attributable | 5 Participants |
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: attributable | 5 Participants |
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: all cause | 10 Participants |
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: all cause | 5 Participants |
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: attributable | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: all cause | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: all cause | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: attributable | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: all cause | 9 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: all cause | 12 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: attributable | 6 Participants |
| IV Zanamivir 600 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: attributable | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: attributable | 6 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: all cause | 5 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: all cause | 9 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died while on-study: all cause | 10 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 14: attributable | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit | Died on or before Study Day 28: attributable | 5 Participants |
Secondary
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. All AEs were assessed by the Investigator as related or not related to the study treatment.
Time frame: Up to 42 days
Population: The Safety Population comprised of all randomized participants who received at least one dose of investigational product and assessed according to their actual treatment received, regardless of the randomization assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | 25 Participants |
| IV Zanamivir 600 mg | Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | 22 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | 35 Participants |
Secondary
Number of Participants With Any Severe or Grade 3/4 AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of AEs. Grade 3=severe; Grade 4=potentially life threatening.
Time frame: Up to 42 days
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With Any Severe or Grade 3/4 AE | 39 Participants |
| IV Zanamivir 600 mg | Number of Participants With Any Severe or Grade 3/4 AE | 45 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Any Severe or Grade 3/4 AE | 44 Participants |
Secondary
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assessed by the Investigator as related or not related to the study treatment.
Time frame: Up to 42 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | 7 Participants |
Secondary
Number of Participants With Complications of Influenza and Associated Antibiotic Use
The number of participants with complications of influenza and associated antibiotic use were summarized
Time frame: Up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Any complication of influenza | 34 Participants |
| IV Zanamivir 300 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Associated use of any antibiotic | 22 Participants |
| IV Zanamivir 600 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Associated use of any antibiotic | 16 Participants |
| IV Zanamivir 600 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Any complication of influenza | 33 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Associated use of any antibiotic | 29 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Complications of Influenza and Associated Antibiotic Use | Any complication of influenza | 41 Participants |
Secondary
Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate)
Lower respiratory samples included BAL and endotracheal aspirates. Endotracheal aspirates were requested in participants (par.) who were intubated. Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment \[trt\]). Endotracheal aspirates were collected in participants who were intubated. If trt was continued beyond Day 5, additional samples were taken on Trt Day 6, Day 8, Day 10, and/or the day of the last dose of randomized trt, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R trt. If the par. was symptomatic and hospitalized, samples were taken on the Post-Trt +2, +5, +9, +16 assessment days, and at the Post-Trt \[PT\]+28 Day assessment. Assessment of samples was done by quantitative RT-PCR and viral culture.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population. Data is presented for participants positive at Baseline. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 1 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 2 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 4 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 5 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 6 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 8 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 10 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B S/R Day 3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B S/R Day 5 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 2 Days | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 5 Days | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 9 Days | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 16 Days | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 28 Days | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 6 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 8 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 9 Days | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 10 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 16 Days | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 2 Days | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 1 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 2 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 4 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 5 Days | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 5 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 4 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 5 Days | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 1 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 2 Days | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 6 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 2 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 8 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 16 Days | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 10 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B S/R Day 1 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 9 Days | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B S/R Day 3 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B PT + 28 Days | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate) | Influenza A and B Day 5 | 2 Participants |
Secondary
Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples
Nasopharyngeal swabs and endotracheal /BAL samples were collected for viral susceptibility analysis. Susceptibility analyses consisted of phenotyping and genotyping. Resistance mutations were detected by genotyping. Viral susceptibility to zanamivir and oral oseltamivir at Baseline and throughout treatment determined by NA and HA (gene of influenza A and B viruses) sequence analysis and NA enzyme inhibition. Number of participants with viral mutation events are summarized, this includes all resistance mutations (substitutions) i.e. those present at Baseline and those that emerged during treatment.
Time frame: Baseline (Day 1) and up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:E278G/E | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:D198D/G | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222N | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:I223I/K | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/N | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142G | 18 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:I222V | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:H1N1: S183P | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S198A | 13 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/N | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S262N | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A138S | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:G248G/E | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S124G | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142K | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/I | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:Q75H | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304A/P | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294D/N | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:L194P/L | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304D | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:S245N | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247N | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:R292R/K | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: G141E | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q136Q/R | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:T325I | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294S/N | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :V152I | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:Y155H | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/G | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :L151P/L | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1: H275H/Y | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: E148G | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222S/D/N/G | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:H275Y | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:V149A | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222G | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q313R | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: M403I | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D187E | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:D199N | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2: Y155F | 5 Participants |
| IV Zanamivir 300 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :S162N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/N | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2: Y155F | 7 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:S245N | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:I222V | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294S/N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:V149A | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:D198D/G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294D/N | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:R292R/K | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:T325I | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:Y155H | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1: H275H/Y | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:H275Y | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q313R | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:D199N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:E278G/E | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142G | 21 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S198A | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A138S | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142K | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304A/P | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304D | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:L194P/L | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S124G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S262N | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:H1N1: S183P | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/N | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :S162N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D187E | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222S/D/N/G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :L151P/L | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :V152I | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q136Q/R | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247N | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/I | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: E148G | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: G141E | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: M403I | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:G248G/E | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:I223I/K | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:Q75H | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294S/N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :S162N | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q313R | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2: Y155F | 5 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D187E | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:H275Y | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: E148G | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222G | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1: H275H/Y | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:I222V | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222S/D/N/G | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:Y155H | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :L151P/L | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:T325I | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: G141E | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :V152I | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:I223I/K | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:R292R/K | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:S245N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:Q136Q/R | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:N294D/N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S124G | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304D | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A304A/P | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:L194P/L | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142K | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:Q75H | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:A138S | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:G248G/E | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S198A | 11 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:H1N1: S183P | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:S262N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H3N2:R142G | 21 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/I | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:D198D/G | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/G | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,B: M403I | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H3N2:V149A | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222D/N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:E278G/E | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:S247S/N | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | HA Gene, H1N1 :D222N | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples | NA Gene,H1N1:D199N | 0 Participants |
Secondary
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days
Samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), switch/rescue (S/R) Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino tranferase (AST), total bilirubin, calcium, creatine kinase, chloride, carbon dioxide content (CO2), creatinine, potassium, magnesium, sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range are summarized.
Time frame: Baseline (Day 1) and up to 42 days
Population: Safety Population. Only the participants available at the time of assessment were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G2 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G1 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G2 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G2 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G1 | 13 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G2 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G1 | 34 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G1 | 16 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G1 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G2, | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G2 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G2, | 7 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G1 | 6 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G1 | 14 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G2 | 11 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G1 | 42 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G3 | 8 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G1 | 12 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G3 | 7 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G1 | 10 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G2 | 26 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G1 | 23 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G1 | 43 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G2 | 8 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G3 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G2 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G2 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G1 | 5 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G1 | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G2 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G2 | 32 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G2 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G1 | 10 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G3 | 7 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G1 | 18 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G2 | 43 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G3 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G1 | 15 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G2 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G1 | 10 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G2 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G1 | 27 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G2 | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G1 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G2 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G1 | 11 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G2 | 3 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G1 | 43 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G2, | 9 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G1 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G2 | 7 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G1 | 14 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G2, | 9 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G1 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G2 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G1 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G2 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G1 | 10 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G2 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G1 | 48 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G2 | 39 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G3 | 8 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G1 | 12 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G2 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G1 | 34 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G2 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G2 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G1 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G2 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G2 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyperkalemia G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Total Bilirubin G1 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G1 | 9 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G1 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G2 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G3 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G3 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G2 | 6 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypernatremia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | AST G1 | 19 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G1 | 15 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G1 | 40 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G1 | 26 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G2 | 42 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G3 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G2 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G3 | 8 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatinine G1 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G2 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G1 | 15 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G2 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G2, | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypocalcemia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G2, | 6 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALT G1 | 12 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Magnesium G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | CO2 G1 | 47 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hyponatremia G2 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G1 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G4 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypokalemia G1 | 21 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G2 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G3 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | ALP G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G2 | 6 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Albumin G2 | 40 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Hypercalcemia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days | Creatine Kinase G1 | 6 Participants |
Secondary
Number of Participants With the Indicated Clinical Symptoms of Influenza
Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient hospitalization and once at each post-treatment assessment.
Time frame: Up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Anorexia | 102 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Cough | 151 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Diarrhea | 64 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Dyspnea | 143 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Fatigue | 144 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Feverishness | 138 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Headache | 104 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Myalgias | 115 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nasal symptoms (rhinorrhea, congestion) | 118 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nausea | 57 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Sore throat | 94 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Vomiting | 27 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Vomiting | 23 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Anorexia | 112 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Headache | 102 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nasal symptoms (rhinorrhea, congestion) | 123 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Cough | 150 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Feverishness | 145 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Sore throat | 115 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Diarrhea | 57 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Myalgias | 117 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Fatigue | 144 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Dyspnea | 145 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nausea | 51 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Dyspnea | 152 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Fatigue | 148 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nausea | 77 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Feverishness | 136 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Headache | 103 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Myalgias | 114 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Sore throat | 97 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Anorexia | 123 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Cough | 157 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Nasal symptoms (rhinorrhea, congestion) | 122 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Diarrhea | 66 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Clinical Symptoms of Influenza | Vomiting | 45 Participants |
Secondary
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days
Blood samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), S/R Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC) count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range for the indicated hematology parameters is summarized. Baseline is defined as the pre-dose value collected on Study Day 1.
Time frame: Baseline (Day 1) and up to 42 days
Population: Safety Population. Only the participants available at the time of assessment were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G2 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G4 | 18 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G2 | 11 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G2 | 11 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G1 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G3 | 14 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G2 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G1 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G3 | 16 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G4 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G1 | 8 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G3 | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G1 | 8 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G2 | 18 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G1 | 28 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G2 | 12 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G3 | 3 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G1 | 25 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G1 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G2 | 15 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G2 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G3 | 21 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G3 | 10 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G4 | 19 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G1 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G2 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G4 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G2 | 19 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G1 | 22 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G1 | 18 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G1 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G1 | 28 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G2 | 13 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G3 | 8 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Hemoglobin G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G1 | 10 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G2 | 11 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G3 | 18 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Lymphocytes G4 | 14 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G2 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Neutrophils G4 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G1 | 21 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G2 | 16 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G3 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Platelets G4 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G1 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G2 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days | Leukocytes G4 | 2 Participants |
Secondary
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
Time frame: Baseline (Day 1) and up to 42 days
Population: Safety Population. Only the participants available at the time of assessment were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G3 | 29 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G4 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G3 | 6 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G4 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G4 | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G3 | 4 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G4 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G4 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G3 | 24 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G4 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G4 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G4 | 3 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G3 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G3 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G4 | 14 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G4 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G4 | 7 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G3 | 2 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Total Neutrophils, G4 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Platelet count, G3 | 5 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G3 | 26 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Leukocytes Count, G4 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, G4 | 8 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Lymphocytes, G3 | 11 Participants |
Secondary
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities
A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatine kinase, chloride, CO2/bicarbonate, creatinine, potassium, magnesium and sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
Time frame: Baseline (Day 1) and up to 42 days
Population: Safety population. Only the participants available at the time of assessment were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G3 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G4 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G3 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G3 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G4 | 3 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G4 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G3 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G3 | 6 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G3 | 10 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia, G3 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G3 | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G3 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G4 | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G4 | 1 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G3 | 3 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G4 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G3 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G4 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G3 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G3 | 3 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G4 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G3 | 6 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G4 | 2 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G4 | 5 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G3 | 1 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G3 | 7 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G4 | 4 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G4 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia, G3 | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G3 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G3 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyperkalemia, G4 | 3 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Total Bilirubin, G3 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G3 | 5 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALP, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypernatremia, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | AST, G3 | 5 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G3 | 8 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hyponatremia, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatinine, G3 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypocalcemia, G4 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | ALT, G3 | 4 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Magnesium, G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Carbon Dioxide, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Albumin, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G4 | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypokalemia, G3 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Hypercalcemia, G4 | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities | Creatine Kinase, G3 | 2 Participants |
Secondary
Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD), no supplemental oxygen (O2) or ventilation support, Respiratory support at any time (AT) on study and at Baseline (Day 1) are summarized. Data for the any time (AT) on study time point was reported.
Time frame: Up to 42 days
Population: IPP Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: ECMO | 0 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: Endotracheal | 28 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, SOD | 96 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, No supplemental O2 or ventilation support | 32 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Respiratory Support | 34 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: ECMO | 2 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: Endotracheal | 36 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, SOD | 137 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, No supplemental O2 or ventilation sup | 138 Participants |
| IV Zanamivir 300 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Respiratory Support | 46 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, No supplemental O2 or ventilation sup | 135 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: ECMO | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: ECMO | 0 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Respiratory Support | 29 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: Endotracheal | 25 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Respiratory Support | 37 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, SOD | 137 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, SOD | 103 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: Endotracheal | 31 Participants |
| IV Zanamivir 600 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, No supplemental O2 or ventilation support | 29 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, SOD | 128 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, No supplemental O2 or ventilation support | 37 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Respiratory Support | 39 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: ECMO | 1 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, No supplemental O2 or ventilation sup | 131 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Machine-Assisted: Endotracheal | 37 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: ECMO | 0 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | AT on Study, Respiratory Support | 50 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, Machine-Assisted: Endotracheal | 27 Participants |
| Oral Oseltamivir 75 mg | Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation | Day 1, SOD | 87 Participants |
Secondary
Percentage of Participants With Respiratory Improvement
Respiratory Status (RS) is a component of TTCR. Response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), a need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate of =\<24 breaths/minute (without supplemental oxygen). Data are presented as the percentage of participants achieving respiratory improvement.
Time frame: Up to 42 days
Population: IPP Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Zanamivir 300 mg | Percentage of Participants With Respiratory Improvement | 77 Percentage of participants |
| IV Zanamivir 600 mg | Percentage of Participants With Respiratory Improvement | 78 Percentage of participants |
| Oral Oseltamivir 75 mg | Percentage of Participants With Respiratory Improvement | 74 Percentage of participants |
p-value: 0.506Wei-Johnson method
p-value: 0.41Wei-Johnson method
Secondary
Serum Concentration of IV Zanamivir
Pharmacokinetic samples were collected at four time points to characterize peak concentration (end of infusion; C\[EOI\]) after the first dose on Day 1 and on Day 4 to characterize the pre-dose concentration (C\[0\]), the peak concentration C(EOI), and the trough concentration at 11-12 hours post-dose (C\[12\]) of zanamavir. Data was summarized by Creatinine clearance (CL) Category. The dose on Day 1 is the initial dose (unadjusted) and the dose on Day 4 is the maintenance dose.
Time frame: Day 1 and Day 4
Population: Pharmacokinetic (PK) Population comprised of all participants who received IV zanamivir and underwent sparse PK sampling during the study from which one or more serum zanamivir concentrations was determined. This outcome was not analyzed for participants receiving oseltamivir 75 mg. Only the participants available at the time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, 11-12 hr | 605.1 microgram/Liter (mcg/L) | — |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, 11-12 hr | 2932.5 microgram/Liter (mcg/L) | Standard Deviation 2425.81 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, 30 min | 13636.4 microgram/Liter (mcg/L) | Standard Deviation 14029.44 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 1, 30 min | 19146.7 microgram/Liter (mcg/L) | Standard Deviation 8853.11 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, 30 min | 1329.4 microgram/Liter (mcg/L) | — |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, pre-dose | 2793.3 microgram/Liter (mcg/L) | Standard Deviation 4694.43 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, 11-12 hr | 7600.3 microgram/Liter (mcg/L) | Standard Deviation 8061.65 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, 30 min | 31541.3 microgram/Liter (mcg/L) | Standard Deviation 93381 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 13, 30 min | 20403.3 microgram/Liter (mcg/L) | Standard Deviation 11623.28 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, 11-12 hr | 1345.9 microgram/Liter (mcg/L) | Standard Deviation 1122.18 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 1, 30 min | 18756.8 microgram/Liter (mcg/L) | Standard Deviation 12806.43 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 1, 30 min, | 18561.7 microgram/Liter (mcg/L) | Standard Deviation 10332.14 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL <15, Day 1, 30 min | 14454.6 microgram/Liter (mcg/L) | — |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, pre-dose | 2342.6 microgram/Liter (mcg/L) | Standard Deviation 6672.12 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, pre-dose | 2094.8 microgram/Liter (mcg/L) | Standard Deviation 1300.99 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, 30 min | 21580.7 microgram/Liter (mcg/L) | Standard Deviation 22062.69 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, pre-dose | 5906.4 microgram/Liter (mcg/L) | Standard Deviation 7167.87 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, 11-12 hr | 2036.2 microgram/Liter (mcg/L) | Standard Deviation 4412.75 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, 30 min | 12334.4 microgram/Liter (mcg/L) | Standard Deviation 12121.18 |
| IV Zanamivir 300 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, pre-dose | 293.2 microgram/Liter (mcg/L) | — |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, 11-12 hr | 19428.7 microgram/Liter (mcg/L) | Standard Deviation 142284.7 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | Missing, Day 1, 30 min | 41109.7 microgram/Liter (mcg/L) | Standard Deviation 3831.74 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL <15, Day 1, 30 min | 26410.8 microgram/Liter (mcg/L) | Standard Deviation 21335.43 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, pre-dose | 9635.6 microgram/Liter (mcg/L) | Standard Deviation 8270.67 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, 30 min | 19828.9 microgram/Liter (mcg/L) | — |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL <15, Day 4, 11-12 hr | 15459.1 microgram/Liter (mcg/L) | — |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 13, 30 min | 41102.8 microgram/Liter (mcg/L) | Standard Deviation 13884.08 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, pre-dose | 4995.6 microgram/Liter (mcg/L) | Standard Deviation 1966.72 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, 30 min | 13378 microgram/Liter (mcg/L) | Standard Deviation 2581.36 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 15-<30, Day 4, 11-12 hr | 4953.4 microgram/Liter (mcg/L) | Standard Deviation 2232.16 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 1, 30 min | 42467.3 microgram/Liter (mcg/L) | Standard Deviation 14574.82 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, pre-dose | 7637.4 microgram/Liter (mcg/L) | Standard Deviation 7212.1 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, 30 min | 159292.1 microgram/Liter (mcg/L) | Standard Deviation 473267.3 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 30-<50, Day 4, 11-12 hr | 19549.2 microgram/Liter (mcg/L) | Standard Deviation 40577.76 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 1, 30 min | 49666.1 microgram/Liter (mcg/L) | Standard Deviation 111785.9 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, pre-dose | 13107.7 microgram/Liter (mcg/L) | Standard Deviation 33768.61 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, 30 min | 22220.4 microgram/Liter (mcg/L) | Standard Deviation 10064.83 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL 50-<80, Day 4, 11-12 hr | 22623.9 microgram/Liter (mcg/L) | Standard Deviation 57663.24 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 1, 30 min, | 35139.2 microgram/Liter (mcg/L) | Standard Deviation 17693.85 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, pre-dose | 19379.8 microgram/Liter (mcg/L) | Standard Deviation 105056.3 |
| IV Zanamivir 600 mg | Serum Concentration of IV Zanamivir | CL >=80, Day 4, 30 min | 75255.1 microgram/Liter (mcg/L) | Standard Deviation 167670.6 |