Trial Outcomes & Findings for A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza (NCT NCT01231620)

Last Updated: 2018-10-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

626 participants

Primary outcome timeframe

Up to 42 days

Results posted on

2018-10-15

Participant Flow

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)

Participant milestones

Participant milestones
Measure	IV Zanamivir 300 mg Participants \>=16 years of age received intravenous (IV) zanamivir 300 milligrams (mg) twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Overall Study STARTED	201	209	205
Overall Study COMPLETED	175	178	166
Overall Study NOT COMPLETED	26	31	39

Reasons for withdrawal

Reasons for withdrawal
Measure	IV Zanamivir 300 mg Participants \>=16 years of age received intravenous (IV) zanamivir 300 milligrams (mg) twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Overall Study Physician Decision	3	5	10
Overall Study Death	12	14	11
Overall Study Adverse Event	2	2	1
Overall Study Withdrawal by Subject	6	6	8
Overall Study Lost to Follow-up	3	4	9

Baseline Characteristics

A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.	Total n=615 Participants Total of all reporting groups
Age, Continuous	55.2 Years STANDARD_DEVIATION 18.88 • n=5 Participants	57.3 Years STANDARD_DEVIATION 17.39 • n=7 Participants	55.9 Years STANDARD_DEVIATION 18.7 • n=5 Participants	56.2 Years STANDARD_DEVIATION 18.32 • n=4 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	86 Participants n=7 Participants	117 Participants n=5 Participants	285 Participants n=4 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	123 Participants n=7 Participants	88 Participants n=5 Participants	330 Participants n=4 Participants
Race/Ethnicity, Customized African American or African Heritage	12 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Central South Asian	10 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	38 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	12 Participants n=5 Participants	18 Participants n=7 Participants	13 Participants n=5 Participants	43 Participants n=4 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	6 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White - Arabic or North African	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized White -White or Caucasian or European	150 Participants n=5 Participants	162 Participants n=7 Participants	154 Participants n=5 Participants	466 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Time to Clinical Response (TTCR) in Participants With Confirmed Influenza	5.87 Days Interval 0.12 to 99.9	5.14 Days Interval 0.23 to 99.9	5.63 Days Interval 0.03 to 99.9

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Percentage of Participants With Respiratory Improvement	77 Percentage of participants	78 Percentage of participants	74 Percentage of participants

SECONDARY outcome

Timeframe: On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days)

Population: IPP Population

The number of participants who died on or before Day 14, Day 28, and the End of Study Visit were summarized.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	8 Participants	5 Participants
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	9 Participants	9 Participants
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	12 Participants	10 Participants
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	4 Participants	4 Participants
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	5 Participants	5 Participants
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	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: IPP population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Transferring	2 Days Interval 2.0 to 38.0	2 Days Interval 2.0 to 31.0	2 Days Interval 2.0 to 40.0
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Continence	2 Days Interval 2.0 to 35.0	2 Days Interval 2.0 to 33.0	2 Days Interval 2.0 to 31.0
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 Interval 2.0 to 38.0	2 Days Interval 2.0 to 37.0	2.5 Days Interval 2.0 to 57.0
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Bathing	2 Days Interval 2.0 to 38.0	2 Days Interval 2.0 to 37.0	2 Days Interval 2.0 to 57.0
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Dressing	2 Days Interval 2.0 to 38.0	2 Days Interval 2.0 to 40.0	2 Days Interval 2.0 to 57.0
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Toileting	2 Days Interval 2.0 to 38.0	2 Days Interval 2.0 to 31.0	2 Days Interval 2.0 to 40.0
Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score Feeding	2 Days Interval 2.0 to 29.0	2 Days Interval 2.0 to 32.0	2 Days Interval 2.0 to 36.0

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	138 Participants	130 Participants
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	133 Participants	126 Participants
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	135 Participants	126 Participants
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	136 Participants	130 Participants
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	140 Participants	133 Participants
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	143 Participants	139 Participants
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	148 Participants	144 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population. Participants succeeded in pre-morbid functional status were analyzed.

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).

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=138 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=137 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=135 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale	5 Days Interval 2.0 to 34.0	4 Days Interval 2.0 to 31.0	4 Days Interval 1.0 to 57.0

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Clinical Symptoms of Influenza Myalgias	115 Participants	117 Participants	114 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Anorexia	102 Participants	112 Participants	123 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Cough	151 Participants	150 Participants	157 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Diarrhea	64 Participants	57 Participants	66 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Dyspnea	143 Participants	145 Participants	152 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Fatigue	144 Participants	144 Participants	148 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Feverishness	138 Participants	145 Participants	136 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Headache	104 Participants	102 Participants	103 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Nasal symptoms (rhinorrhea, congestion)	118 Participants	123 Participants	122 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Nausea	57 Participants	51 Participants	77 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Sore throat	94 Participants	115 Participants	97 Participants
Number of Participants With the Indicated Clinical Symptoms of Influenza Vomiting	27 Participants	23 Participants	45 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time of Duration of Clinical Symptoms of Influenza Cough	14 Days Interval 1.0 to 39.0	13 Days Interval 1.0 to 46.0	15 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Headache	3 Days Interval 1.0 to 33.0	3 Days Interval 1.0 to 33.0	4 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Anorexia	5 Days Interval 1.0 to 39.0	3 Days Interval 1.0 to 46.0	5 Days Interval 1.0 to 55.0
Median Time of Duration of Clinical Symptoms of Influenza Diarrhea	3 Days Interval 1.0 to 29.0	2 Days Interval 1.0 to 28.0	3 Days Interval 1.0 to 23.0
Median Time of Duration of Clinical Symptoms of Influenza Dyspnea	7 Days Interval 1.0 to 40.0	6 Days Interval 1.0 to 43.0	8 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Fatigue	11 Days Interval 1.0 to 41.0	11 Days Interval 1.0 to 44.0	12 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Feverishness	2 Days Interval 1.0 to 28.0	2 Days Interval 1.0 to 29.0	2.5 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Myalgias	4 Days Interval 1.0 to 39.0	3 Days Interval 1.0 to 34.0	4 Days Interval 1.0 to 56.0
Median Time of Duration of Clinical Symptoms of Influenza Nasal symptoms	6 Days Interval 1.0 to 34.0	4 Days Interval 1.0 to 43.0	5.5 Days Interval 1.0 to 35.0
Median Time of Duration of Clinical Symptoms of Influenza Nausea	3 Days Interval 1.0 to 34.0	2 Days Interval 1.0 to 24.0	2 Days Interval 1.0 to 28.0
Median Time of Duration of Clinical Symptoms of Influenza Sore throat	3 Days Interval 1.0 to 28.0	2 Days Interval 1.0 to 36.0	3 Days Interval 1.0 to 35.0
Median Time of Duration of Clinical Symptoms of Influenza Vomiting	2 Days Interval 1.0 to 19.0	1 Days Interval 1.0 to 11.0	1 Days Interval 1.0 to 20.0

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population

The number of participants with complications of influenza and associated antibiotic use were summarized

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With Complications of Influenza and Associated Antibiotic Use Any complication of influenza	34 Participants	33 Participants	41 Participants
Number of Participants With Complications of Influenza and Associated Antibiotic Use Associated use of any antibiotic	22 Participants	16 Participants	29 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation Day 1, SOD	96 Participants	103 Participants	87 Participants
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	29 Participants	37 Participants
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	0 Participants	1 Participants
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	31 Participants	37 Participants
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	135 Participants	131 Participants
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	37 Participants	50 Participants
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	0 Participants	0 Participants
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	25 Participants	27 Participants
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	29 Participants	39 Participants
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	137 Participants	128 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation Oxygen Supplementation	4.4 Days Interval 0.0 to 38.0	4.2 Days Interval 0.0 to 43.0	3.7 Days Interval 0.0 to 36.0
Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation Ventilator Support	9 Days Interval 0.0 to 38.0	5.2 Days Interval 0.0 to 36.0	8.2 Days Interval 0.0 to 36.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay Hospitalization	10 Days Interval 1.0 to 108.0	8 Days Interval 2.0 to 64.0	9 Days Interval 1.0 to 58.0
Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay Hospitalization while on study	8 Days Interval 1.0 to 39.0	6 Days Interval 1.0 to 43.0	7 Days Interval 1.0 to 39.0
Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay Hospitalization-ICU	8 Days Interval 1.0 to 41.0	7.5 Days Interval 1.0 to 36.0	8 Days Interval 1.0 to 36.0
Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay ICU Duration Modified	7 Days Interval 1.0 to 39.0	6 Days Interval 1.0 to 36.0	7 Days Interval 1.0 to 36.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure Oxygen Saturation	5.3 Days Interval 0.0 to 30.0	5.6 Days Interval 0.0 to 32.0	4.5 Days Interval 0.0 to 25.0
Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure Respiratory status	3.5 Days Interval 0.0 to 31.0	3.6 Days Interval 0.0 to 32.0	2.8 Days Interval 0.0 to 21.0
Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure Fever	1.6 Days Interval 0.0 to 34.0	0.8 Days Interval 0.0 to 14.0	1.5 Days Interval 0.0 to 31.0
Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure Heart rate	0.4 Days Interval 0.0 to 28.0	0.4 Days Interval 0.0 to 21.0	0.5 Days Interval 0.0 to 24.0
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 Interval 0.0 to 23.0	0.3 Days Interval 0.0 to 14.0	0.3 Days Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Median Time to Virologic Improvement Influenza A/H1N1	3 Days Interval 2.0 to 13.0	3 Days Interval 2.0 to 34.0	3 Days Interval 2.0 to 34.0
Median Time to Virologic Improvement Influenza A and B	3 Days Interval 2.0 to 34.0	3 Days Interval 2.0 to 35.0	3 Days Interval 2.0 to 34.0
Median Time to Virologic Improvement Influenza A/H3N2	3 Days Interval 2.0 to 8.0	3 Days Interval 2.0 to 35.0	3 Days Interval 2.0 to 11.0
Median Time to Virologic Improvement Influenza B	5 Days Interval 2.0 to 34.0	3 Days Interval 2.0 to 21.0	3 Days Interval 2.0 to 12.0

SECONDARY outcome

Timeframe: 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.

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 .

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline Day 5	-2.51 log10 TCID50/mL Interval -5.5 to 0.0	-2.26 log10 TCID50/mL Interval -5.3 to 0.0	-2.26 log10 TCID50/mL Interval -5.3 to 2.0
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline Day 8	-1.64 log10 TCID50/mL Interval -5.5 to 0.0	-2.01 log10 TCID50/mL Interval -4.3 to -0.3	-2.26 log10 TCID50/mL Interval -4.3 to 0.0
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline Day 3	-2.01 log10 TCID50/mL Interval -5.0 to 0.8	-2.01 log10 TCID50/mL Interval -4.8 to 1.3	-2.01 log10 TCID50/mL Interval -5.3 to 2.8
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline Day 10	-3.76 log10 TCID50/mL Interval -5.5 to -0.3	-0.3 log10 TCID50/mL Interval -1.3 to -0.3	-2.26 log10 TCID50/mL Interval -3.8 to -1.3
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline Day 11	-3.01 log10 TCID50/mL Interval -5.5 to -0.3	-0.3 log10 TCID50/mL Interval -0.3 to -0.3	-2.26 log10 TCID50/mL Interval -3.8 to -1.3
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline S/R Day 5	—	-4.3 log10 TCID50/mL Interval -4.3 to -4.3	-3.0 log10 TCID50/mL Interval -3.0 to -3.0
Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline S/R Day 6	-2.5 log10 TCID50/mL Interval -2.5 to -2.5	-4.3 log10 TCID50/mL Interval -4.3 to -4.3	0.0 log10 TCID50/mL Interval 0.0 to 0.0

SECONDARY outcome

Population: IPP Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles)

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline Day 11	-3.58 log10 vp/mL Interval -4.9 to -0.6	-2.6 log10 vp/mL Interval -3.1 to 1.7	-3.29 log10 vp/mL Interval -4.9 to -1.0
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 Interval -5.2 to -5.2	-5.4 log10 vp/mL Interval -5.4 to -5.4	-3.84 log10 vp/mL Interval -4.0 to -3.7
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline Day 3	-1.5 log10 vp/mL Interval -5.4 to 2.2	-1.83 log10 vp/mL Interval -4.9 to 2.0	-1.75 log10 vp/mL Interval -6.0 to 2.8
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline Day 5	-2.51 log10 vp/mL Interval -5.8 to 3.2	-2.71 log10 vp/mL Interval -6.2 to 3.1	-2.73 log10 vp/mL Interval -6.3 to 2.3
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline Day 8	-2.38 log10 vp/mL Interval -4.4 to 1.0	-3.16 log10 vp/mL Interval -5.5 to -0.3	-1.78 log10 vp/mL Interval -5.7 to 1.1
Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline Day 10	-2.75 log10 vp/mL Interval -6.0 to -0.9	-3.03 log10 vp/mL Interval -3.5 to 1.5	-2.63 log10 vp/mL Interval -4.6 to 0.9
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 Interval -3.8 to -3.8	-5.7 log10 vp/mL Interval -5.7 to -5.7

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	0 Participants	0 Participants
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	2 Participants	2 Participants
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	4 Participants	2 Participants
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	1 Participants	0 Participants
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	1 Participants	3 Participants
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	—	1 Participants
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	4 Participants	1 Participants
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	2 Participants	0 Participants
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	1 Participants	3 Participants
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	0 Participants	2 Participants
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	0 Participants	0 Participants
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
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	—	1 Participants
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	—	—
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	1 Participants	3 Participants
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	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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 Interval 1.0 to 34.0	3 Days Interval 1.0 to 35.0	4 Days Interval 1.0 to 57.0
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 Interval 2.0 to 34.0	4 Days Interval 2.0 to 35.0	4 Days Interval 2.0 to 57.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: IPP Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	0 Participants	0 Participants
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	7 Participants	5 Participants
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	4 Participants	0 Participants
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	1 Participants	2 Participants
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	1 Participants	1 Participants
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	0 Participants	1 Participants
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	0 Participants	0 Participants
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	0 Participants	2 Participants
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	0 Participants	1 Participants
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	1 Participants	0 Participants
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	0 Participants	0 Participants
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	1 Participants	0 Participants
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	0 Participants	1 Participants
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	1 Participants	0 Participants
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	0 Participants	2 Participants
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	0 Participants	2 Participants
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	2 Participants	0 Participants
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	0 Participants	2 Participants
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	0 Participants	2 Participants
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	1 Participants	0 Participants
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	0 Participants	0 Participants
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	0 Participants	0 Participants
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	1 Participants	0 Participants
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	0 Participants	1 Participants
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	1 Participants	0 Participants
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	0 Participants	1 Participants
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	0 Participants	0 Participants
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	0 Participants	1 Participants
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	1 Participants	4 Participants
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	1 Participants	3 Participants
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	0 Participants	2 Participants
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	0 Participants	0 Participants
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	0 Participants	1 Participants
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	0 Participants	1 Participants
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	0 Participants	1 Participants
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	0 Participants	0 Participants
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	0 Participants	0 Participants
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	1 Participants	0 Participants
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	0 Participants	0 Participants
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	0 Participants	1 Participants
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	0 Participants	0 Participants
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	21 Participants	21 Participants
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	8 Participants	11 Participants
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	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment	25 Participants	22 Participants	35 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With Any Severe or Grade 3/4 AE	39 Participants	45 Participants	44 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: Safety Population

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE	8 Participants	10 Participants	11 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: Safety Population

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE	14 Participants	16 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 42 days

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE	5 Participants	3 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: Safety Population. Only the participants available at the time of assessment were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypokalemia G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Albumin G1	12 Participants	18 Participants	15 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Albumin G2	32 Participants	43 Participants	40 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Albumin G3	1 Participants	5 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Albumin G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALP G1	10 Participants	15 Participants	9 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALP G2	0 Participants	4 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALP G3	0 Participants	2 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALP G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALT G1	13 Participants	10 Participants	12 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALT G2	2 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALT G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days ALT G4	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days AST G1	23 Participants	27 Participants	19 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days AST G2	8 Participants	8 Participants	6 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days AST G3	2 Participants	0 Participants	2 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days AST G4	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Total Bilirubin G1	5 Participants	2 Participants	2 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Total Bilirubin G2	3 Participants	2 Participants	3 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Total Bilirubin G3	1 Participants	2 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Total Bilirubin G4	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatine Kinase G1	10 Participants	11 Participants	6 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatine Kinase G2	3 Participants	3 Participants	6 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatine Kinase G3	1 Participants	2 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatine Kinase G4	1 Participants	1 Participants	2 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days CO2 G1	34 Participants	43 Participants	47 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days CO2 G2,	4 Participants	9 Participants	6 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days CO2 G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days CO2 G4	0 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatinine G1	6 Participants	5 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatinine G2	11 Participants	7 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatinine G3	8 Participants	7 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Creatinine G4	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Magnesium G1	14 Participants	14 Participants	15 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Magnesium G2,	7 Participants	9 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Magnesium G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Magnesium G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypercalcemia G1	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypercalcemia G2	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypercalcemia G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypercalcemia G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyperkalemia G1	0 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyperkalemia G2	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyperkalemia G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyperkalemia G4	1 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypernatremia G1	4 Participants	10 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypernatremia G2	1 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypernatremia G3	0 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypernatremia G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypocalcemia G1	43 Participants	48 Participants	40 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypocalcemia G2	26 Participants	39 Participants	42 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypocalcemia G3	7 Participants	8 Participants	8 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypocalcemia G4	0 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypokalemia G1	16 Participants	12 Participants	21 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypokalemia G2	1 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hypokalemia G3	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyponatremia G1	42 Participants	34 Participants	26 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyponatremia G2	2 Participants	2 Participants	4 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyponatremia G3	0 Participants	2 Participants	0 Participants
Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days Hyponatremia G4	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: Safety Population. Only the participants available at the time of assessment were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Hemoglobin G1	28 Participants	25 Participants	28 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Hemoglobin G2	11 Participants	19 Participants	13 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Hemoglobin G3	14 Participants	10 Participants	8 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Hemoglobin G4	0 Participants	4 Participants	1 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Lymphocytes G1	8 Participants	18 Participants	10 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Lymphocytes G2	11 Participants	15 Participants	11 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Lymphocytes G3	16 Participants	21 Participants	18 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Lymphocytes G4	18 Participants	19 Participants	14 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Neutrophils G1	2 Participants	2 Participants	3 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Neutrophils G2	2 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Neutrophils G3	0 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Neutrophils G4	1 Participants	0 Participants	3 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Platelets G1	8 Participants	22 Participants	21 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Platelets G2	18 Participants	12 Participants	16 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Platelets G3	4 Participants	3 Participants	2 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Platelets G4	2 Participants	1 Participants	2 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Leukocytes G1	3 Participants	2 Participants	1 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Leukocytes G2	3 Participants	5 Participants	3 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Leukocytes G3	0 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days Leukocytes G4	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: Safety population. Only the participants available at the time of assessment were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Albumin, G3	6 Participants	3 Participants	4 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Albumin, G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities ALP, G3	0 Participants	2 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities ALP, G4	1 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities ALT, G3	2 Participants	2 Participants	4 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities ALT, G4	0 Participants	2 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities AST, G3	2 Participants	4 Participants	5 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities AST, G4	1 Participants	2 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Total Bilirubin, G3	2 Participants	2 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Total Bilirubin, G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Creatine Kinase, G3	2 Participants	3 Participants	2 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Creatine Kinase, G4	3 Participants	1 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Carbon Dioxide, G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Carbon Dioxide, G4	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Creatinine, G3	3 Participants	6 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Creatinine, G4	3 Participants	2 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Magnesium, G3	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Magnesium, G4	0 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypercalcemia, G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypercalcemia, G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hyperkalemia, G3	2 Participants	0 Participants	1 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hyperkalemia, G4	1 Participants	5 Participants	3 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypernatremia, G3	0 Participants	1 Participants	5 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypernatremia, G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypocalcemia, G3	10 Participants	7 Participants	8 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypocalcemia, G4	2 Participants	4 Participants	4 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypokalemia, G3	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hypokalemia, G4	0 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hyponatremia, G3	1 Participants	0 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities Hyponatremia G4	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 42 days

Population: Safety Population. Only the participants available at the time of assessment were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=201 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=209 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=205 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Hemoglobin, G3	29 Participants	24 Participants	26 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Hemoglobin, G4	2 Participants	5 Participants	8 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Lymphocytes, G3	6 Participants	5 Participants	11 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Lymphocytes, G4	3 Participants	14 Participants	7 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Total Neutrophils, G3	1 Participants	2 Participants	2 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Total Neutrophils, G4	4 Participants	4 Participants	3 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Platelet count, G3	4 Participants	4 Participants	5 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Platelet count, G4	3 Participants	3 Participants	2 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Leukocytes Count, G3	1 Participants	1 Participants	0 Participants
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities Leukocytes Count, G4	2 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and during the study

Population: This end point was not analyzed

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 4

Population: Safety Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	IV Zanamivir 300 mg n=197 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=208 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=203 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	121 Participants	99 Participants
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	86 Participants	102 Participants
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	4 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Adverse Events

Intravenous (IV) Zanamivir 300mg Twice Daily

Serious events: 38 serious events

Other events: 17 other events

Deaths: 15 deaths

Intravenous (IV) Zanamivir 600mg Twice Daily

Serious events: 33 serious events

Other events: 26 other events

Deaths: 15 deaths

Oral Oseltamivir 75mg Twice Daily

Serious events: 38 serious events

Other events: 24 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Intravenous (IV) Zanamivir 300mg Twice Daily n=201 participants at risk 300mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily	Intravenous (IV) Zanamivir 600mg Twice Daily n=209 participants at risk 600mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily	Oral Oseltamivir 75mg Twice Daily n=205 participants at risk 75mg oral oseltamivir twice daily plus intravenous placebo zanamivir twice daily
Gastrointestinal disorders Diarrhoea	5.0% 10/201 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.	7.2% 15/209 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.	6.8% 14/205 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.
Gastrointestinal disorders Constipation	3.5% 7/201 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.	6.2% 13/209 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.	4.9% 10/205 • From the start of study drug until follow-up (up to 42 days). Safety population was used to assess adverse events.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	IV Zanamivir 300 mg n=163 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=162 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg n=163 Participants Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
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	0.5 Scores on the scale Standard Deviation 0.837	-0.08 Scores on the scale Standard Deviation 3.029
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	0.19 Scores on the scale Standard Deviation 0.439	0.14 Scores on the scale Standard Deviation 0.409
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	0.16 Scores on the scale Standard Deviation 0.422	0.23 Scores on the scale Standard Deviation 0.439
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	0.07 Scores on the scale Standard Deviation 0.309	0.08 Scores on the scale Standard Deviation 0.382
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	-0.5 Scores on the scale Standard Deviation 0.707	0.25 Scores on the scale Standard Deviation 0.463
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	0.17 Scores on the scale Standard Deviation 0.416	0.19 Scores on the scale Standard Deviation 0.395
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	0.93 Scores on the scale Standard Deviation 1.782	0.78 Scores on the scale Standard Deviation 1.837
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	-3.0 Scores on the scale Standard Deviation 4.243	0.75 Scores on the scale Standard Deviation 1.165
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	1.72 Scores on the scale Standard Deviation 2.342	1.98 Scores on the scale Standard Deviation 2.142
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	0.19 Scores on the scale Standard Deviation 0.429	0.18 Scores on the scale Standard Deviation 0.438
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	0.0 Scores on the scale Standard Deviation 0.0	0.0 Scores on the scale Standard Deviation 0.426
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	-0.5 Scores on the scale Standard Deviation 0.707	0.0 Scores on the scale Standard Deviation 0.0
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	0.34 Scores on the scale Standard Deviation 0.505	0.39 Scores on the scale Standard Deviation 0.507
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	0.21 Scores on the scale Standard Deviation 0.438	0.14 Scores on the scale Standard Deviation 0.427
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	0.0 Scores on the scale Standard Deviation 0.0	-0.08 Scores on the scale Standard Deviation 0.515
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	-0.5 Scores on the scale Standard Deviation 0.707	0.13 Scores on the scale Standard Deviation 0.354
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	0.37 Scores on the scale Standard Deviation 0.515	0.41 Scores on the scale Standard Deviation 0.494
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	0.33 Scores on the scale Standard Deviation 0.516	0.08 Scores on the scale Standard Deviation 0.515
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	-0.5 Scores on the scale Standard Deviation 0.707	0.0 Scores on the scale Standard Deviation 0.535
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	0.32 Scores on the scale Standard Deviation 0.514	0.37 Scores on the scale Standard Deviation 0.484
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	0.23 Scores on the scale Standard Deviation 0.451	0.17 Scores on the scale Standard Deviation 0.41
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	0.17 Scores on the scale Standard Deviation 0.408	0.08 Scores on the scale Standard Deviation 0.515
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	-0.5 Scores on the scale Standard Deviation 0.707	0.25 Scores on the scale Standard Deviation 0.463
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	0.36 Scores on the scale Standard Deviation 0.526	0.4 Scores on the scale Standard Deviation 0.492
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	0.05 Scores on the scale Standard Deviation 0.314	0.07 Scores on the scale Standard Deviation 0.374
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	0.0 Scores on the scale Standard Deviation 0.0	-0.08 Scores on the scale Standard Deviation 0.669
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	-0.5 Scores on the scale Standard Deviation 0.707	0.13 Scores on the scale Standard Deviation 0.354
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	0.0 Scores on the scale Standard Deviation 0.0	-0.08 Scores on the scale Standard Deviation 0.669

Measure	IV Zanamivir 300 mg n=180 Participants Participants \>=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5-10 days.	IV Zanamivir 600 mg n=187 Participants Participants \>=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5-10 days	Oral Oseltamivir 75 mg Participants \>=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5-10 days.
Serum Concentration of IV Zanamivir CL <15, Day 1, 30 min	14454.6 microgram/Liter (mcg/L) Standard Deviation NA Data not collected	26410.8 microgram/Liter (mcg/L) Standard Deviation 21335.43	—
Serum Concentration of IV Zanamivir CL <15, Day 4, pre-dose	293.2 microgram/Liter (mcg/L) Standard Deviation NA Data not collected	9635.6 microgram/Liter (mcg/L) Standard Deviation 8270.67	—
Serum Concentration of IV Zanamivir CL <15, Day 4, 30 min	1329.4 microgram/Liter (mcg/L) Standard Deviation NA Data not collected	19828.9 microgram/Liter (mcg/L) Standard Deviation NA Data not available	—
Serum Concentration of IV Zanamivir CL <15, Day 4, 11-12 hr	605.1 microgram/Liter (mcg/L) Standard Deviation NA Data not collected	15459.1 microgram/Liter (mcg/L) Standard Deviation NA Data not available	—
Serum Concentration of IV Zanamivir CL 15-<30, Day 13, 30 min	20403.3 microgram/Liter (mcg/L) Standard Deviation 11623.28	41102.8 microgram/Liter (mcg/L) Standard Deviation 13884.08	—
Serum Concentration of IV Zanamivir CL 15-<30, Day 4, pre-dose	5906.4 microgram/Liter (mcg/L) Standard Deviation 7167.87	4995.6 microgram/Liter (mcg/L) Standard Deviation 1966.72	—
Serum Concentration of IV Zanamivir CL 15-<30, Day 4, 30 min	13636.4 microgram/Liter (mcg/L) Standard Deviation 14029.44	13378 microgram/Liter (mcg/L) Standard Deviation 2581.36	—
Serum Concentration of IV Zanamivir CL 15-<30, Day 4, 11-12 hr	7600.3 microgram/Liter (mcg/L) Standard Deviation 8061.65	4953.4 microgram/Liter (mcg/L) Standard Deviation 2232.16	—
Serum Concentration of IV Zanamivir CL 30-<50, Day 1, 30 min	18756.8 microgram/Liter (mcg/L) Standard Deviation 12806.43	42467.3 microgram/Liter (mcg/L) Standard Deviation 14574.82	—
Serum Concentration of IV Zanamivir CL 30-<50, Day 4, pre-dose	2094.8 microgram/Liter (mcg/L) Standard Deviation 1300.99	7637.4 microgram/Liter (mcg/L) Standard Deviation 7212.1	—
Serum Concentration of IV Zanamivir CL 30-<50, Day 4, 30 min	12334.4 microgram/Liter (mcg/L) Standard Deviation 12121.18	159292.1 microgram/Liter (mcg/L) Standard Deviation 473267.3	—
Serum Concentration of IV Zanamivir CL 30-<50, Day 4, 11-12 hr	2932.5 microgram/Liter (mcg/L) Standard Deviation 2425.81	19549.2 microgram/Liter (mcg/L) Standard Deviation 40577.76	—
Serum Concentration of IV Zanamivir CL 50-<80, Day 1, 30 min	19146.7 microgram/Liter (mcg/L) Standard Deviation 8853.11	49666.1 microgram/Liter (mcg/L) Standard Deviation 111785.9	—
Serum Concentration of IV Zanamivir CL 50-<80, Day 4, pre-dose	2793.3 microgram/Liter (mcg/L) Standard Deviation 4694.43	13107.7 microgram/Liter (mcg/L) Standard Deviation 33768.61	—
Serum Concentration of IV Zanamivir CL 50-<80, Day 4, 30 min	31541.3 microgram/Liter (mcg/L) Standard Deviation 93381	22220.4 microgram/Liter (mcg/L) Standard Deviation 10064.83	—
Serum Concentration of IV Zanamivir CL 50-<80, Day 4, 11-12 hr	1345.9 microgram/Liter (mcg/L) Standard Deviation 1122.18	22623.9 microgram/Liter (mcg/L) Standard Deviation 57663.24	—
Serum Concentration of IV Zanamivir CL >=80, Day 1, 30 min,	18561.7 microgram/Liter (mcg/L) Standard Deviation 10332.14	35139.2 microgram/Liter (mcg/L) Standard Deviation 17693.85	—
Serum Concentration of IV Zanamivir CL >=80, Day 4, pre-dose	2342.6 microgram/Liter (mcg/L) Standard Deviation 6672.12	19379.8 microgram/Liter (mcg/L) Standard Deviation 105056.3	—
Serum Concentration of IV Zanamivir CL >=80, Day 4, 30 min	21580.7 microgram/Liter (mcg/L) Standard Deviation 22062.69	75255.1 microgram/Liter (mcg/L) Standard Deviation 167670.6	—
Serum Concentration of IV Zanamivir CL >=80, Day 4, 11-12 hr	2036.2 microgram/Liter (mcg/L) Standard Deviation 4412.75	19428.7 microgram/Liter (mcg/L) Standard Deviation 142284.7	—
Serum Concentration of IV Zanamivir Missing, Day 1, 30 min	—	41109.7 microgram/Liter (mcg/L) Standard Deviation 3831.74	—