Trial Outcomes & Findings for A Study of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Influenza Infection (NCT NCT01527110)

NCT ID: NCT01527110

Last Updated: 2018-02-22

Results Overview

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 SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalised ratio \>1.5. The grading of AEs and SAE's for 3/4 (3= severe, 4= potentially life threatening ) and its classification as potentially drug-related was done based on the investigator's judgment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 21 participants
• Primary outcome timeframe: Start of treatment (Day 1) up to follow-up (Day 33)
• Results posted on: 2018-02-22

Participant Flow

The study was planned on 20 male or female participants, aged 16 years or older years, across 6 centers of Japan from 11 January 2012 to 29 March 2013.

A total of 21 hospitalized Japanese participants with laboratory confirmed influenza were enrolled to receive intravenous (IV) zanamivir 600 milligram (mg) twice daily (BID) for 5 days. The course was extended for up to 5 additional days based on ongoing viral shedding or clinical symptoms requiring treatment.

Participant milestones

Measure	Zanamivir 600 mg BID Eligible participants \>=18 years and adolescents \>=50 kilogram (kg) with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 minutes (min) for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated creatinine clearance (CLcr) with the initial dose corresponding to a CLcr of \> =80 milliliter per min (mL/min) for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Overall Study STARTED	21
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Zanamivir 600 mg BID Eligible participants \>=18 years and adolescents \>=50 kilogram (kg) with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 minutes (min) for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated creatinine clearance (CLcr) with the initial dose corresponding to a CLcr of \> =80 milliliter per min (mL/min) for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Overall Study Adverse Event

1

Baseline Characteristics

A Study of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Influenza Infection

Baseline characteristics by cohort

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Age, Continuous	67.3 Years STANDARD_DEVIATION 23.58 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	21 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Start of treatment (Day 1) up to follow-up (Day 33)

Population: Safety Population comprised of all participants who received at least one dose of IV zanamivir.

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 SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalised ratio >1.5. The grading of AEs and SAE's for 3/4 (3= severe, 4= potentially life threatening ) and its classification as potentially drug-related was done based on the investigator's judgment.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any AE	13 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any drug-related AE	3 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any grade 3 and grade 4 AE	2 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any grade 3 and grade 4 drug -related AE	1 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE AE leading to discontinuation of study drug	0 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE AE leading to discontinuation from study	1 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any SAE	4 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any drug-related SAE	1 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any death	1 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any fatal AE	1 Participants
Number of Participants With Any Adverse Event (AE), Drug-related AE, Grade 3 and Grade 4 AE, Grade 3 and 4 Drug-related AE , AE Leading to Discontinuation of Study Drug or From Study, Serious AE (SAE), Drug-related SAE, Fatal AE and Drug-related Fatal AE Any drug-related fatal AE	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 5

Population: Safety Population

The reference ranges for clinical chemistry parameters were ALT 5 to 45 international units per litre [IU/L]), ALP 100 to 325 IU/L, creatine kinase 60 to 270 IU/L and AST 10 to 40 IU/L. The baseline assessments were referred to assessments at Day 1. Assessments were done at Day 1, 3 and 5.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALT, Baseline, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALT, Day 3, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALT, Day 5, high	4 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALP, Baseline, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALP, Day 3, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment ALP, Day 5, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment AST, Baseline, high	6 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment AST, Day 3, high	6 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment AST, Day 5, high	5 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Baseline, high	12 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Baseline, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Day 3, high	5 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Day 3, low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Day 5, high	1 Participants
Number of Participants With Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Creatine Kinase and Aspartate Amino Transferase (AST) Outside the Normal Reference Range at Any Time During Treatment Creatine kinase, Day 5, low	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 5

Population: Safety Population

The reference ranges for clinical chemistry parameters were creatinine 41.548 - 69.836 micromole per litre (µmol/L), direct bilirubin 0 to 5.13 µmol/L and total bilirubin 3.42 to 20.52 µmol/L. The baseline assessments were referred to assessments at Day 1. Assessments were done at Day 1, 3 and 5.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Baseline, high	8 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Baseline, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Day 3, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Day 3, low	4 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Day 5, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Creatinine, Day 5, low	5 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Baseline, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Baseline, low	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Day 3, high	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Day 3, low	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Day 5, high	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Direct bilirubin, Day 5, low	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Baseline, high	1 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Baseline, low	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Day 3, high	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Day 3, low	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Day 5, high	0 Participants
Number of Participants With Clinical Chemistry Parameters of Creatinine, Direct Bilirubin and Total Bilirubin Outside the Normal Reference Range at Any Time During Treatment Total bilirubin, Day 5, low	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 5

Population: Safety Population

The reference ranges for clinical chemistry parameters were calcium 2.0958 to 2.5948 millimole per litre (mmol/L), carbon dioxide content/ bicarbonate 19.2 to 27.1 mmol/L, chloride 98 to 108 mmol/L, magnesium 0.7809 to 1.0275 mmol/L, potassium 3.5 to 5 mmol/L, sodium 137 to 147 mmol/L and urea/BUN 2.856 to 8.211 mmol/L. The baseline assessments were referred to assessments at Day 1. Assessments were done at Day 1, 3 and 5.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Calcium, Baseline, low	9 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Calcium, Day 3, low	10 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Calcium, Day 5, low	10 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Carbon dioxide content/bicarbonate, Baseline, high	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Carbon dioxide content/bicarbonate, Baseline, low	6 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Carbon dioxide content/bicarbonate, Day 3, low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Carbon dioxide content/bicarbonate, Day 5, high	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Carbon dioxide content/bicarbonate, Day 5, low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Chloride, Baseline, high	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Chloride, Baseline, low	5 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Chloride, Day 3, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Chloride, Day 3, low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Baseline, high	5 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Baseline, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Day 3, high	3 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Day 3, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Day 5, high	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Urea/ BUN, Day 5, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Magnesium, Baseline, low	6 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Magnesium, Day 3, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Magnesium, Day 5, low	3 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Sodium, Baseline, low	8 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Sodium, Day 3, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Sodium, Day 5, low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Potassium, Baseline, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Potassium, Day 3, low	2 Participants
Number of Participants With Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/ Bicarbonate, Chloride, Magnesium, Potassium, Sodium and Urea/ Blood Urea Nitrogen (BUN) Outside the Normal Reference Range at Any Time During Treatment Potassium, Day 5, low	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 5

Population: Safety Population

The reference ranges for clinical chemistry parameters were albumin 38 to 53 grams per liter (g/L) and total protein 67 to 83 g/L. The baseline assessments were referred to assessments at Day 1. Assessments were done at Day 1, 3 and 5.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Albumin, Baseline, low	10 Participants
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Albumin, Day 3, low	12 Participants
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Albumin, Day 5, low	12 Participants
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Total protein, Baseline, low	15 Participants
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Total protein, Day 3, low	17 Participants
Number of Participants With Clinical Chemistry Parameters of Albumin and Total Protein Outside the Normal Reference Range at Any Time During Treatment Total protein, Day 5, low	17 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 5

Population: Safety Population

The reference ranges for hematology parameters were basophils 0 to 2 percentage (%), eosinophils 0 to 8%, lymphocytes 18 to 49%, monocytes 2 to 10%, total neutrophils 40 to 75%, platelet count 140 to 340 giga cells per liter (GI/L), WBC count 3.3 to 9 GI/L, hemoglobin 135 to 175 g/L and haematocrit 0.397 to 0.524 ratio. The baseline assessments were referred to assessments at Day 1. Assessments were done at Day 1, 3, and 5.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hemoglobin, Baseline, low	11 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hemoglobin, Day 3, low	11 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hemoglobin, Day 5, low	10 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hematocrit, Baseline, low	11 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hematocrit, Day 3, low	10 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Hematocrit, Day 5, low	10 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Lymphocytes, Baseline, low	18 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Lymphocytes, Day 3, high	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Lymphocytes, Day 3, low	7 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Lymphocytes, Day 5, high	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Lymphocytes, Day 5, low	4 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Monocytes, Baseline, high	7 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Monocytes, Baseline, low	1 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Monocytes, Day 3, high	8 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Monocytes, Day 5, high	5 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Total neutrophils, Baseline, high	14 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Total neutrophils, Day 3, high	7 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Total neutrophils, Day 3, low	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Total neutrophils, Day 5, high	4 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Total neutrophils, Day 5, low	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Platelet Count, Baseline, low	6 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Platelet Count, Day 3, low	5 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment Platelet Count, Day 5, low	4 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Baseline, high	5 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Baseline, low	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Day 3, high	3 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Day 3, low	2 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Day 5, high	1 Participants
Number of Participants With Hematology Parameters of Basophiles, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell(WBC) Count, Hemoglobin and Hematocrit Outside the Normal Reference Range at Any Time During Treatment WBC count, Day 5, low	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Albumin and total protein were measured at Baseline , Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Albumin and Total Protein at the Indicated Time Points Albumin, Day 3	-3.2 g/L Standard Deviation 2.69
Mean Change From Baseline in Albumin and Total Protein at the Indicated Time Points Albumin, Day 5	-2.6 g/L Standard Deviation 3.20
Mean Change From Baseline in Albumin and Total Protein at the Indicated Time Points Total protein, Day 3	-4.1 g/L Standard Deviation 3.18
Mean Change From Baseline in Albumin and Total Protein at the Indicated Time Points Total protein, Day 5	-3.1 g/L Standard Deviation 4.84

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety population. The number of participants available at that particular time point were used for analysis.

ALT, ALP, creatine kinase and AST were measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points ALT, Day 3	0.2 IU/L Standard Deviation 7.16
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points ALT, Day 5	3.1 IU/L Standard Deviation 23.48
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points ALP, Day 3	-37.1 IU/L Standard Deviation 34.62
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points ALP, Day 5	-27.9 IU/L Standard Deviation 50.49
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points Creatine kinase, Day 3	-44.8 IU/L Standard Deviation 131.71
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points Creatine kinase, Day 5	-192.7 IU/L Standard Deviation 236.46
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points AST, Day 3	-0.5 IU/L Standard Deviation 11.95
Mean Change From Baseline in ALT, ALP, Creatine Kinase and AST at the Indicated Time Points AST, Day 5	-0.2 IU/L Standard Deviation 28.80

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Creatinine, direct bilirubin and total bilirubin were measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Creatinine, Day 3	-14.6351 µmol/L Standard Deviation 20.56740
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Creatinine, Day 5	-19.2024 µmol/L Standard Deviation 26.79556
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Direct bilirubin, Day 3	-0.950 µmol/L Standard Deviation 1.7812
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Direct bilirubin, Day 5	-0.475 µmol/L Standard Deviation 1.9280
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Total bilirubin, Day 3	-3.040 µmol/L Standard Deviation 4.1289
Mean Change From Baseline in Creatinine, Direct Bilirubin and Total Bilirubin at the Indicated Time Points Total bilirubin, Day 5	-1.520 µmol/L Standard Deviation 4.0589

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Calcium, potassium, chloride, magnesium, carbon dioxide content/bicarbonate, sodium and urea/BUN were measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Calcium, Day 3	-0.037 mmol/L Standard Deviation 0.0942
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Calcium, Day 5	0.019 mmol/L Standard Deviation 0.1163
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Potassium, Day 3	-0.01 mmol/L Standard Deviation 0.342
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Potassium, Day 5	0.02 mmol/L Standard Deviation 0.483
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Chloride, Day 3	3.6 mmol/L Standard Deviation 3.27
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Chloride, Day 5	3.3 mmol/L Standard Deviation 3.44
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Magnesium, Day 3	0.073 mmol/L Standard Deviation 0.0941
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Magnesium, Day 5	0.039 mmol/L Standard Deviation 0.0803
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Carbon dioxide content/bicarbonate, Day 3	0.54 mmol/L Standard Deviation 2.249
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Carbon dioxide content/bicarbonate, Day 5	1.37 mmol/L Standard Deviation 2.557
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Sodium, Day 3	2.4 mmol/L Standard Deviation 3.60
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Sodium, Day 5	2.8 mmol/L Standard Deviation 3.70
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Urea/BUN, Day 3	0.1388 mmol/L Standard Deviation 2.42482
Mean Change From Baseline in Sodium, Calcium, Potassium, Chloride, Magnesium, Carbon Dioxide Content/Bicarbonate and Urea/BUN at the Indicated Time Points Urea/BUN, Day 5	-1.4280 mmol/L Standard Deviation 1.69672

PRIMARY outcome

Timeframe: Baseline, Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Percentages of basophils, eosinophils, lymphocytes, monocytes and total neutrophils were measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Basophils, Day 3	-0.04 Percent of blood cells Standard Deviation 0.370
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Basophils, Day 5	-0.08 Percent of blood cells Standard Deviation 0.448
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Eosinophils, Day 3	1.57 Percent of blood cells Standard Deviation 2.061
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Eosinophils, Day 5	2.26 Percent of blood cells Standard Deviation 2.099
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Lymphocytes, Day 3	15.26 Percent of blood cells Standard Deviation 14.123
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Lymphocytes, Day 5	18.60 Percent of blood cells Standard Deviation 13.821
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Monocytes, Day 3	0.16 Percent of blood cells Standard Deviation 4.145
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Monocytes, Day 5	-0.19 Percent of blood cells Standard Deviation 4.961
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Total neutrophils, Day 3	-16.95 Percent of blood cells Standard Deviation 16.483
Mean Change From Baseline in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils at the Indicated Time Points Total neutrophils, Day 5	-20.59 Percent of blood cells Standard Deviation 17.469

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

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

WBC and platelet counts were measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Counts of WBC and Platelets at the Indicated Time Points Platelet count, Day 3	-1.6 GI/L Standard Deviation 15.87
Mean Change From Baseline in Counts of WBC and Platelets at the Indicated Time Points Platelet count, Day 5	14.3 GI/L Standard Deviation 28.75
Mean Change From Baseline in Counts of WBC and Platelets at the Indicated Time Points WBC count, Day 3	-1.76 GI/L Standard Deviation 2.780
Mean Change From Baseline in Counts of WBC and Platelets at the Indicated Time Points WBC count, Day 5	-1.82 GI/L Standard Deviation 2.560

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Hemoglobin was measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Hemoglobin at the Indicated Time Points Day 3	-4.9 g/L Standard Deviation 9.10
Mean Change From Baseline in Hemoglobin at the Indicated Time Points Day 5	-3.6 g/L Standard Deviation 9.82

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

Hematocrit was measured at Baseline, Day 3 and Day 5 during the treatment period. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change Baseline in Hematocrit at the Indicated Time Points Day 3	-0.0127 Ratio Standard Deviation 0.02849
Mean Change Baseline in Hematocrit at the Indicated Time Points Day 5	-0.0088 Ratio Standard Deviation 0.03347

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

The reference ranges for clinical chemistry parameters were ALT 5 to 45 IU/L, ALP 100 to 325 IU/L, creatine kinase 60 to 270 IU/L, AST 10 to 40 IU/L, creatinine 41.548 to 69.836 µmol/L, direct bilirubin 0 to 5.13 µmol/L, total bilirubin 3.42 to 20.52 µmol/L, calcium 2.0958 to 2.5948 mmol/L, CO2/ bicarbonate 19.2 to 27.1 mmol/L, chloride 98 to 108 mmol/L, magnesium 0.7809 to 1.0275 mmol/L, potassium 3.5 to 5 mmol/L, sodium 137 to 147 mmol/L and urea/ BUN 2.856 to 8.211 mmol/L. The baseline assessments were referred to assessments at Day 1. Number of participants with shifts between normal range (NR) high, within NR and NR low values in hematology parameters from baseline (Day 1) at Day 3 and Day 5 is reported.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Albumin, Day 3, within NR to NR low	5 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Albumin, Day 5, within NR to NR low	5 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period AST, Day 3, within NR to NR high	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period AST, Day 5, within NR to NR high	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Calcium, Day 3, within NR to NR low	4 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Calcium, Day 5, within NR to NR low	4 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatine Kinase, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatine Kinase, Day 5, NR high to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatine Kinase, Day 5, within NR to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Chloride, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period CO2 content/Bicarbonate,Day 5,within NR to NR high	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatinine, Day 3, within NR to NR low	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatinine, Day 5, NR high to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Creatinine, Day 5, within NR to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Potassium, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Potassium, Day 5, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Magnesium, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Total Protein, Day 3, within NR to NR low	5 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Total Protein, Day 5, within NR to NR low	4 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Urea/BUN, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Clinical Chemistry Over Period Urea/BUN, Day 5, within NR to NR low	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 3 and Day 5

Population: Safety Population. The number of participants available at that particular time point were used for analysis.

The reference ranges for hematology parameters were basophils 0 to 2%, eosinophils 0 to 8%, lymphocytes 18 to 49%, monocytes 2 to 10%, total neutrophils 40 to 75%, platelet count 140 to 340 GI/L, WBC count 3.3 to 9 GI/L, hemoglobin 135 to 175 g/L and haematocrit 0.397 to 0.524 ratio. The baseline assessments were referred to assessments at Day 1. Number of participants with shifts between NR high, within NR and NR low values in hematology parameters from baseline (Day 1) at Day 3 and Day 5 is reported.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Hemoglobin, Day 3, within NR to NR low	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Hemoglobin, Day 5, within NR to NR low	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Hematocrit, Day 3, within NR to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Hematocrit, Day 5, within NR to NR low	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Lymphocytes, Day 3, NR low to NR high	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Lymphocytes, Day 5, NR low to NR high	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Monocytes, Day 3, within NR to NR high	3 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Monocytes, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Monocytes, Day 5, within NR to NR high	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Monocytes, Day 5, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Total Neutrophils, Day 3, NR high to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Total Neutrophils, Day 3, within NR to NR low	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period Total Neutrophils, Day 5, NR high to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period WBC count, Day 3, within NR to NR high	1 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period WBC count, Day 3, within NR to NR low	2 Participants
Number of Participants With Toxicity Shifts From Baseline in Hematology Parameters Over Period WBC count, Day 5, within NR to NR low	2 Participants

PRIMARY outcome

Timeframe: Day 1, Day 3 and Day 5

Population: Safety Population

The normal reference ranges for clinical chemistry and hematology parameters were ALT 5 to 45 IU/L, ALP 100 to 325 IU/L, creatine kinase 60 to 270 IU/L, AST 10 to 40 IU/L, creatinine 41.548 to 69.836 µmol/L, direct bilirubin 0 to 5.13 µmol/L, total bilirubin 3.42 to 20.52 µmol/L, calcium 2.0958 to 2.5948 mmol/L, CO2/ bicarbonate 19.2 to 27.1 mmol/L, chloride 98 to 108 mmol/L, magnesium 0.7809 to 1.0275 mmol/L, potassium 3.5 to 5 mmol/L, sodium 137 to 147 mmol/L, urea/ BUN 2.856 to 8.211 mmol/L, basophils 0 to 2%, eosinophils 0 to 8%, lymphocytes 18 to 49%, monocytes 2 to 10%, total neutrophils 40 to 75%, platelet count 140 to 340 GI/L, WBC count 3.3 to 9 GI/L, hemoglobin 135 to 175 g/L and haematocrit 0.397 to 0.524 ratio. Participants with treatment emergent toxicities for grade 3 (severe) and grade 4 (potentially life threatening) were assessed at Day 1, Day 3 and Day 5. Classification of the toxicities as potentially drug-related was done based on the investigator's judgment.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants of Treatment Emergent Toxicities in Clinical Chemistry and Hematology Over Period Hemoglobin decrease	1 Participants
Number of Participants of Treatment Emergent Toxicities in Clinical Chemistry and Hematology Over Period Hypokalaemia	1 Participants

PRIMARY outcome

Timeframe: Baeline (Day 1) to Day 6

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

Vital sign of HR was assessed three times daily during the treatment period/hospitalization at Day 1, Day 2, Day 3, Day 4, Day 5 and Day 6. The baseline assessments were referred to assessments at Day 1. Maximum value in a day is reported where a 'day' is defined as a 24 h period (Treatment Day).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Heart Rate (HR) of Participants Over Period Baseline (Day 1)	84.4 Beats/min Standard Deviation 18.76
Mean Heart Rate (HR) of Participants Over Period Day 2	86.3 Beats/min Standard Deviation 19.70
Mean Heart Rate (HR) of Participants Over Period Day 3	80.3 Beats/min Standard Deviation 15.88
Mean Heart Rate (HR) of Participants Over Period Day 4	77.3 Beats/min Standard Deviation 13.35
Mean Heart Rate (HR) of Participants Over Period Day 5	73.2 Beats/min Standard Deviation 10.96
Mean Heart Rate (HR) of Participants Over Period Day 6	80.3 Beats/min Standard Deviation 10.20

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 6

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

Vital signs of SBP and DBP were assessed three times daily during the treatment period/hospitalization at Day 1, Day 2, Day 3, Day 4, Day 5 and Day 6. The baseline assessments were referred to assessments at Day 1. Minimum value in a day for SBP is reported where a 'day' is defined as a 24 h period (Treatment Day). DBP is measured at the same time as minimum SBP.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Baseline (Day 1)	122.5 Millimeter of mercury (mmHg) Standard Deviation 20.38
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Day 2	106.3 Millimeter of mercury (mmHg) Standard Deviation 18.49
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Day 3	110.7 Millimeter of mercury (mmHg) Standard Deviation 17.74
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Day 4	114.2 Millimeter of mercury (mmHg) Standard Deviation 24.42
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Day 5	116.1 Millimeter of mercury (mmHg) Standard Deviation 18.95
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period SBP, Day 6	117.8 Millimeter of mercury (mmHg) Standard Deviation 20.13
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Baseline (Day 1)	71.0 Millimeter of mercury (mmHg) Standard Deviation 12.61
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Day 2	59.0 Millimeter of mercury (mmHg) Standard Deviation 8.95
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Day 3	63.9 Millimeter of mercury (mmHg) Standard Deviation 11.61
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Day 4	65.2 Millimeter of mercury (mmHg) Standard Deviation 13.91
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Day 5	66.2 Millimeter of mercury (mmHg) Standard Deviation 12.54
Mean Systolic and Diastolic Blood Pressure (SBP and DBP) of Participants Over Period DBP, Day 6	70.5 Millimeter of mercury (mmHg) Standard Deviation 16.19

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 6

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

Vital signs of OS was assessed three times daily during the treatment period/hospitalization at Day 1, Day 2, Day 3, Day 4, Day 5 and Day 6. The baseline assessments were referred to assessments at Day 1. Minimum value in a day is reported, where a 'day' is defined as a 24 h period (Treatment Day).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Oxygen Saturation (OS) of Participants Over Period Baseline (Day 1)	95.6 Percent oxygen saturation Standard Deviation 2.87
Mean Oxygen Saturation (OS) of Participants Over Period Day 2	94.1 Percent oxygen saturation Standard Deviation 3.61
Mean Oxygen Saturation (OS) of Participants Over Period Day 3	95.0 Percent oxygen saturation Standard Deviation 3.05
Mean Oxygen Saturation (OS) of Participants Over Period Day 4	94.2 Percent oxygen saturation Standard Deviation 2.96
Mean Oxygen Saturation (OS) of Participants Over Period Day 5	94.8 Percent oxygen saturation Standard Deviation 2.71
Mean Oxygen Saturation (OS) of Participants Over Period Day 6	94.6 Percent oxygen saturation Standard Deviation 4.76

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 6

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

Vital signs of RR was assessed three times daily during the treatment period/hospitalization at Day 1, Day 2, Day 3, Day 4, Day 5 and Day 6. The baseline assessments were referred to assessments at Day 1. Maximum value in a day is reported, where a 'day' was defined as a 24 h period (Treatment Day).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Respiratory Rate (RR) of Participants Over Period Baseline (Day 1)	22.9 Breaths/min Standard Deviation 6.50
Mean Respiratory Rate (RR) of Participants Over Period Day 2	22.3 Breaths/min Standard Deviation 5.15
Mean Respiratory Rate (RR) of Participants Over Period Day 3	21.7 Breaths/min Standard Deviation 4.73
Mean Respiratory Rate (RR) of Participants Over Period Day 4	21.4 Breaths/min Standard Deviation 5.27
Mean Respiratory Rate (RR) of Participants Over Period Day 5	21.2 Breaths/min Standard Deviation 5.25
Mean Respiratory Rate (RR) of Participants Over Period Day 6	21.1 Breaths/min Standard Deviation 5.96

PRIMARY outcome

Timeframe: Baseline (Day 1) to Day 6

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

Vital signs of temperature was assessed three times daily during the treatment period/hospitalization at Day 1, Day 2, Day 3, Day 4, Day 5 and Day 6. The baseline assessments were referred to assessments at Day 1. Maximum value in a day is reported, where a'day' was defined as a 24 h period (Treatment Day).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Temperature of Participants Over Period Baseline (Day 1)	37.75 Degrees celcius (C) Standard Deviation 0.908
Mean Temperature of Participants Over Period Day 2	37.54 Degrees celcius (C) Standard Deviation 0.688
Mean Temperature of Participants Over Period Day 3	37.01 Degrees celcius (C) Standard Deviation 0.591
Mean Temperature of Participants Over Period Day 4	36.77 Degrees celcius (C) Standard Deviation 0.451
Mean Temperature of Participants Over Period Day 5	36.67 Degrees celcius (C) Standard Deviation 0.457
Mean Temperature of Participants Over Period Day 6	36.81 Degrees celcius (C) Standard Deviation 0.556

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Day 4

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

12-lead ECG assessments were obtained at Baseline (Day 1) and Day 4 of the treatment period. On Baseline (Day 1), 2 baseline ECGs were obtained prior to study drug infusion. On Day 4, 2 ECGs were obtained, 1 ECG just prior to study drug infusion and 1 ECG at the end of infusion. Overall ECG findings were summarized with regard to visits at Day 1 (pre-dose [ECG 1 and ECG 2]) and Day 4 (pre-dose and 30-min post dose).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Abnormal Clinically Significant Electrocardiograph (ECG) Findings Over Period Baseline (Day 1), pre-dose, ECG 1	1 Participants
Number of Participants With Abnormal Clinically Significant Electrocardiograph (ECG) Findings Over Period Baseline (Day 1), pre-dose, ECG 2	1 Participants
Number of Participants With Abnormal Clinically Significant Electrocardiograph (ECG) Findings Over Period Day 4, pre-dose	1 Participants
Number of Participants With Abnormal Clinically Significant Electrocardiograph (ECG) Findings Over Period Day 4, 30 min post-dose	1 Participants

PRIMARY outcome

Timeframe: Baseline ( pre-dose Day 1) and Day 4

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

12-lead ECG assessments were obtained at Baseline (Day 1) and Day 4 of the treatment period. On Baseline (Day 1), 2 baseline ECGs were obtained. On Day 4, 2 ECGs were obtained, 1 ECG just prior to study drug infusion and 1 ECG at the end of infusion. Overall ECG findings were summarized at Day 1 (ECG 1 and ECG 2) and Day 4 (pre-dose and 30-min post dose).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Percentage of Participants With Abnormal Clinically Significant ECG Findings Over Period Baseline (Day 1), pre-dose, ECG 1	5 % of participants
Percentage of Participants With Abnormal Clinically Significant ECG Findings Over Period Baseline (Day 1), pre-dose, ECG 2	5 % of participants
Percentage of Participants With Abnormal Clinically Significant ECG Findings Over Period Day 4, pre-dose	6 % of participants
Percentage of Participants With Abnormal Clinically Significant ECG Findings Over Period Day 4, 30 min post-dose	6 % of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: Intent-to-Treat Exposed (ITT-E) Population comprised of all participants who receive at least one dose of IV zanamivir. Only those participants available at the specified time points were analyzed.

Absence of fever, improved respiratory status, OS, HR and SBP was defined according to clinical response criteria as: temperature, <= 36.6 degree C-axilla or <= 37.2 degree C-oral or <= 37.7 degree C-rectal and tympanic, without the use of antipyretics within 8 hour; OS of >= 95%; respiratory status of return to pre-morbid oxygen requirement (participants with chronic oxygen use) or need for supplemental oxygen (administered by any modality) to no need for supplemental oxygen or RR <=24 breaths/min without supplemental oxygen; HR <=100 beats/min; SBP of >=90 mmHg without inotropic support within 8 hour. For OS, participants with a history of chronic hypoxia (without supplemental oxygen) satisfied normalization criteria for OS if the value without supplemental oxygen was <=2% from participants historical OS and waiver for participants with a history of chronic supplemental oxygen requirement with baseline OS <95% with supplemental oxygen, recorded within 12 months prior to enrolment.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Median Time to Absence of Fever, Improved Respiratory Status, Improved OS, Improved HR and Improved SBP Over Period Absence of fever	24.900 hour Interval 9.5 to 82.33
Median Time to Absence of Fever, Improved Respiratory Status, Improved OS, Improved HR and Improved SBP Over Period Improved respiratory status	35.140 hour Interval 3.83 to 331.77
Median Time to Absence of Fever, Improved Respiratory Status, Improved OS, Improved HR and Improved SBP Over Period Improved OS	11.170 hour Interval 3.0 to 49.6
Median Time to Absence of Fever, Improved Respiratory Status, Improved OS, Improved HR and Improved SBP Over Period Improved HR	6.630 hour Interval 2.5 to 24.0
Median Time to Absence of Fever, Improved Respiratory Status, Improved OS, Improved HR and Improved SBP Over Period Improved SBP	11.865 hour Interval 2.97 to 16.5

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants available at that particular time point were used for analysis.

Clinical response was defined as resolution of at least 4 of the 5 vital signs within the respective resolution criteria of temperature <= 36.6 degree C-axilla or <= 37.2 degree C-oral or <= 37.7 degree C-rectal/ tympanic, without the use of antipyretics within 8 hour; OS of >= 95%; respiratory status of return to pre-morbid oxygen requirement (participants with chronic oxygen use) or need for supplemental oxygen (administered by any modality) to no need for supplemental oxygen or RR <= 24 breaths/min without supplemental oxygen; HR <=100 beats/min; SBP of >= 90 mmHg without inotropic support within 8 h, maintained for at least 24 hour, or hospital discharge, which ever occurred first. Participants discharged from hospital due to clinical improvement/resolution were considered to have met the clinical response endpoint at the time of hospital discharge and were not required to have documented resolution of at least 4 response criteria i.e. achieved success at the time of discharge.

Outcome measures

Measure

Zanamivir 600 mg BID n=20 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Median Time to Clinical Response Over Period

85.050 hour Interval 12.67 to 530.37

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants available at that particular time point were used for analysis.

Pre-morbid functional status was defined as the best functional status in the 4 weeks prior to enrolment and status at Baseline (Day 1). The participants were assessed on a 3-point scale by activity level (bed rest, limited ambulation or unrestricted) recorded in thee electronic case report form (eCRF). For participants who were unable to communicate their pre-morbid functional status, the information was requested from another close member of the household or close family member.

Outcome measures

Measure

Zanamivir 600 mg BID n=16 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Median Time to Return to Pre-morbid Level of Activity Over Period

87.645 hour Interval 21.0 to 714.62

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

The non-invasive ventilator support includes modalities of machine-assisted: continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP). The invasive ventilator support included modalities of machine-assisted: extra corporeal membrane oxygenation (ECMO) and endotracheal mechanical ventilation. Participants with and without use of modality of invasive, non-invasive ventilatory support and oxygen supplementation was assessed from Baseline (Day 1) to Day 33 (follow-up).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Invasive and non-invasive ventilatory support, no	18 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Invasive and non-invasive ventilatory support, yes	3 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period CPAP	1 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period BiPAP	1 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period ECMO	0 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Endotracheal mechanical ventilation	2 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Oxygen supplementation, no	10 Participants
Number of Participants With and Without Use of Modality of Invasive, Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Oxygen supplementation, yes	11 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants with use of modality of invasive and non-invasive ventilatory support (3) and oxygen supplementation (11) were analysed.

The non-invasive ventilator support includes modalities of machine-assisted: CPAP and BiPAP. The invasive ventilator support included modalities of machine-assisted: ECMO and endotracheal mechanical ventilation. Participants with use of modality of invasive, non-invasive ventilatory support and oxygen supplementation was assessed from Baseline (Day 1) to Day 33 (follow-up).

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Median Duration of Use of Invasive and Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Invasive and non-invasive ventilatory support	62.330 hour Interval 17.35 to 109.08
Median Duration of Use of Invasive and Non-invasive Ventilatory Support and Oxygen Supplementation Over Period Oxygen supplementation	46.250 hour Interval 0.0 to 238.75

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

The duration of ICU stay was assessed from the first day of dosing (Day 1) up to Day 33 (follow-up). Duration in ICU was captured from the eCRF. If the duration in ICU was missing, then the data was set to 0.

Outcome measures

Measure

Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Median Duration of Intensive Care Unit (ICU) Stay for the Participants Over Period

0.0 Days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants available at that particular time point were used for analysis.

The duration of hospital stay was assessed from the first day of dosing (Day 1) up to Day 33 (follow-up). The duration was calculated as duration in hospital = date/time of discharge - date/time of 1st day of dosing.

Outcome measures

Measure

Zanamivir 600 mg BID n=20 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Median Duration of Hospital Stay for the Participants Over Period

138.215 hour Interval 65.17 to 530.37

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants available at that particular time point were used for analysis.

IC50 value is defined as the concentration of zanamivir required to achieve half maximal inhibition of the influenza viral enzyme neuraminidase of influenza A and B to prevent the release and spread of influenza virus in the respiratory tract. Susceptibility analyses were performed on nasopharyngeal swabs collected on Baseline (Day 1) up to Day 33 (follow-up) depending on the extend of continuation of treatment and duration of hospitalization. Endotracheal aspirates were used in participants who were intubated. Data is categorized for participants with influenza A/H3N2 and influenza B.

Outcome measures

Measure	Zanamivir 600 mg BID n=18 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean 50% Inhibitory Concentration (IC50) for Phenotypes of Influenza for the Measure of Viral Susceptibility to Zanamivir at All Visits Influenzavirus A/H3N2, at all visits	2.04 Nanomole per liter (nmol/L) Standard Deviation 0.275
Mean 50% Inhibitory Concentration (IC50) for Phenotypes of Influenza for the Measure of Viral Susceptibility to Zanamivir at All Visits Influenzavirus B, at all visits	8.85 Nanomole per liter (nmol/L) Standard Deviation 1.277

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants with Influenza A/H3N2 (17) and Influenzavirus B (3) were used for analysis.

A total of 30 neuraminidase gene sequences (23 influenza A/H3N2, 5 influenza B and 2 negative) from 21 participants were obtained from 76 samples. There were no resistance associated neuraminidase mutations or mutations in the neuraminidase active site identified in viruses isolated during this study. Therefore the frequency of resistance emergence to zanamivir could not be determined.

Outcome measures

Measure	Zanamivir 600 mg BID n=20 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With or Without Treatment Emergent Resistance or Suspected Treatment Emergent Resistance to Zanamivir Over Period Influenza A/H3N2, resistence or suspected	0 Participants
Number of Participants With or Without Treatment Emergent Resistance or Suspected Treatment Emergent Resistance to Zanamivir Over Period Influenza A/H3N2, without resistence	17 Participants
Number of Participants With or Without Treatment Emergent Resistance or Suspected Treatment Emergent Resistance to Zanamivir Over Period Influenzavirus B, resistence or suspected	0 Participants
Number of Participants With or Without Treatment Emergent Resistance or Suspected Treatment Emergent Resistance to Zanamivir Over Period Influenzavirus B, without resistence	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

Influenza symptoms were assessed at Baseline (pre-dose): the presence of the following symptoms were recorded: nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea and vomiting. The investigator assessed and recorded influenza symptoms based on interview with the participants. In cases where participants were not able to communicate their symptoms, in participants ventilated and/or sedated, the investigator recorded those signs/symptoms as 'unable to assess'.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants of Clinical Symptoms of Influenza Over Period Cough	20 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Dyspnea	15 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Nausea	2 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Diarrhea	6 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Feverishness	19 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Fatigue	16 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Sore throat	7 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Headache	10 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Nasal symptoms	13 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Myalgias	8 Participants
Number of Participants of Clinical Symptoms of Influenza Over Period Anorexia	15 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

Influenza symptoms were assessed at Baseline (pre-dose) and throughout the study period as presence of the following symptoms were recorded: nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea and vomiting. The investigator assessed and recorded influenza symptoms based on interview with the participants. In cases where participants were not able to communicate their symptoms, in participants ventilated and/or sedated, the investigator recorded those signs/symptoms as 'unable to assess'.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Median Duration of Clinical Symptoms of Influenza Over Period Cough	7.0 Days Interval 1.0 to 25.0
Median Duration of Clinical Symptoms of Influenza Over Period Dyspnea	1.0 Days Interval 1.0 to 3.0
Median Duration of Clinical Symptoms of Influenza Over Period Nausea and vomiting	1.0 Days Interval 1.0 to 1.0
Median Duration of Clinical Symptoms of Influenza Over Period Diarrhea	2.0 Days Interval 1.0 to 23.0
Median Duration of Clinical Symptoms of Influenza Over Period Feverishness	3.0 Days Interval 1.0 to 30.0
Median Duration of Clinical Symptoms of Influenza Over Period Fatigue	3.0 Days Interval 1.0 to 11.0
Median Duration of Clinical Symptoms of Influenza Over Period Sore throat	2.0 Days Interval 1.0 to 3.0
Median Duration of Clinical Symptoms of Influenza Over Period Headache	1.5 Days Interval 1.0 to 3.0
Median Duration of Clinical Symptoms of Influenza Over Period Nasal symptoms	2.0 Days Interval 1.0 to 30.0
Median Duration of Clinical Symptoms of Influenza Over Period Myalgias	2.0 Days Interval 1.0 to 3.0
Median Duration of Clinical Symptoms of Influenza Over Period Anorexia	2.0 Days Interval 1.0 to 8.0

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

The details of complications of influenza like bacterial pneumonia, pneumothorax, pleural effusion, acute respiratory distress syndrome (ARDS), myositis, encephalitis, myocarditis and associated antibiotic use were assessed from Baseline (Day 1) to Day 33 (follow-up). Participants with complications of influenza, with associated use of antibiotics as " associated antibiotic use yes" and without associated use of antibiotics as "associated antibiotic use no" were categorized.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Number of Participants With Complications of Influenza and Associated Use of Antibiotics Over Period Complications of influenza	11 Participants
Number of Participants With Complications of Influenza and Associated Use of Antibiotics Over Period Associated antibiotic use, no	0 Participants
Number of Participants With Complications of Influenza and Associated Use of Antibiotics Over Period Associated antibiotic use, yes	11 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. The number of participants available at that particular time point were used for analysis.

Virologic improvement was defined as a 2 log drop in viral load or sustained undetectable viral ribonucleic acid (RNA), on 2 successive occasions as measured by quantitative reverse transcriptase - polymerase chain reaction (RT-PCR) from nasopharyngeal samples. Assessment was done from Baseline (Day 1) up to Day 33 (follow-up).

Outcome measures

Measure

Zanamivir 600 mg BID n=19 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.

Median Time to Virologic Improvement Over Period

3.0 Days Interval 2.0 to 5.0

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

Quantitative RT-PCR and quantitative viral culture was carried out on nasopharyngeal swabs collected from Baseline (Day 1) up to Day 33 (follow-up) depending on the extend of continuation of treatment and duration of hospitalization of the participants. Undetectable RNA concentrations were below the level of quantification.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period BASELINE (DAY 1)	5 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period DAY 2	5 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period DAY 3	5 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period DAY 4	19 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period DAY 5	19 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period DAY 6	29 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence Cultivable Virus From Samples Obtained From Nasopharyngeal Samples Over Period LAST DAY	38 % of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population.

Quantitative RT-PCR and quantitative viral culture was carried out on lower respiratory samples (endotracheal aspirates) collected on Baseline (Day 1) up to Day 33 (follow-up) depending on the extend of continuation of treatment and duration of hospitalization. Endotracheal aspirates were used in participants who were intubated. Undetectable RNA concentrations were below the level of quantification.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Percentage of Participants With Undetectable Viral RNA and Absence of Cultivable Virus in Lower Respiratory Samples Over Period BASELINE (DAY 1)	0 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence of Cultivable Virus in Lower Respiratory Samples Over Period DAY 2	0 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence of Cultivable Virus in Lower Respiratory Samples Over Period DAY 3	0 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence of Cultivable Virus in Lower Respiratory Samples Over Period DAY 4	0 % of participants
Percentage of Participants With Undetectable Viral RNA and Absence of Cultivable Virus in Lower Respiratory Samples Over Period DAY 5	0 % of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 33 (follow-up)

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

Quantitative RT-PCR and quantitative viral culture was carried out on nasopharyngeal swabs collected on Baseline (Day 1) up to Day 33 (follow-up) depending on the extend of continuation of treatment and duration of hospitalization.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Median Time to no Detectable Viral RNA by Quantitative RT-PCR and Viral Culture From Nasopharyngeal Samples Over Period Viral RNA by quantitative RT-PCR	5.5 Days Interval 4.0 to 7.0
Median Time to no Detectable Viral RNA by Quantitative RT-PCR and Viral Culture From Nasopharyngeal Samples Over Period Quantitative viral culture	3.0 Days Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 33 (follow-up)

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

Quantitative RT-PCR was carried out on nasopharyngeal swabs collected on Day 1 up to Day 33 (last day) depending on the extend of continuation of treatment and duration of hospitalization. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value. Analysis was done for participants with positive Influenza A RNA and Influenza B RNA. Data is presented for Day 3, Day 5 and last day.

Outcome measures

Measure	Zanamivir 600 mg BID n=20 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza A RNA, Day 3	-2.53 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.683
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza A RNA, Day 5	-3.77 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.759
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza A RNA, Last Day (Day 33)	-4.13 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.938
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza B RNA, Day 3	-2.01 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.973
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza B RNA, Day 5	-3.73 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.712
Mean Change From Baseline in Quantitative Viral Load Measured by RT-PCR From Nasopharyngeal Swabs Positive at Baseline Over Period Influenza B RNA, Last Day (Day 33)	-4.43 Logarithmic base 10 (log 10) copies/mL Standard Deviation 1.630

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 33 (follow-up)

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

Quantitative viral culture as 50 % tissue culture infectious dose (TCID50) defined as median tissue culture infective dose is that amount of a pathogenic agent that produces pathological change in 50% of cell cultures inoculated. It was carried out on nasopharyngeal swabs collected on Day 1 up to Day 33 (last day) depending on the extend of continuation of treatment and duration of hospitalization. The baseline assessments were referred to assessments at Day 1. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value. Any undetectable viral load values were calculated as x.x Log10 TCID50: x.x Log10 (1.5 or 7.5 was the lower or upper limit of quantification in TCID50). Data is presented for Day 3, Day 5 and last day.

Outcome measures

Measure	Zanamivir 600 mg BID n=21 Participants Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Mean Change From Baseline in Quantitative Viral Load Measured by Viral Culture From Nasopharyngeal Swabs Over Period Day 3	-2.10 LOG TCID50/mL Standard Deviation 1.981
Mean Change From Baseline in Quantitative Viral Load Measured by Viral Culture From Nasopharyngeal Swabs Over Period Day 5	-2.23 LOG TCID50/mL Standard Deviation 1.989
Mean Change From Baseline in Quantitative Viral Load Measured by Viral Culture From Nasopharyngeal Swabs Over Period Last Day (Day 33)	-2.14 LOG TCID50/mL Standard Deviation 1.958

Adverse Events

Zanamivir 600 mg BID

Serious events: 4 serious events

Other events: 4 other events

Deaths: 1 deaths

Serious adverse events

Measure	Zanamivir 600 mg BID n=21 participants at risk Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Infections and infestations Pneumonia bacterial	4.8% 1/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.
Infections and infestations Respiratory tract infection	4.8% 1/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.
Endocrine disorders Hyperthyroidism	4.8% 1/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.
Investigations Haemoglobin decreased	4.8% 1/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.

Other adverse events

Measure	Zanamivir 600 mg BID n=21 participants at risk Eligible participants \>=18 years and adolescents \>=50 kg with normal renal function were administered an initial dose of IV zanamivir is 600 mg followed by BID maintenance dose administered at a constant rate over approximately 30 min for 5 days. The standard dosage for adolescent participants \<50 kg was 12 mg/kg. The BID maintenance dose regimen began 12 hours after starting the initial dose infusion. Participants with renal impairment received an adjusted dose based on calculated CLcr with the initial dose corresponding to a CLcr of \> =80 mL/min for adults and for adolescent participants \> = 50 kg (i.e. 600 mg) or to the appropriate weight-based dose corresponding to a CLcr \> = 80 mL/min for adolescent participants \<50 kg (i.e. 12 mg/kg). There was a delay of 24 to 48 hours after the initial dose before the BID maintenance dose regimen was initiated for participants with severe renal impairment.
Gastrointestinal disorders Diarrhoea	19.0% 4/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.
General disorders Pyrexia	9.5% 2/21 • Up to Day 33 Safety Population was used which comprised of all participants who received at least one dose of IV zanamivir.

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