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Trial record 48 of 118 for:    oseltamivir

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

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ClinicalTrials.gov Identifier: NCT01231620
Recruitment Status : Completed
First Posted : November 1, 2010
Results First Posted : November 20, 2017
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Influenza, Human
Interventions Drug: Zanamivir
Drug: Placebo to match zanamivir
Drug: Oseltamivir
Drug: Placebo to match oseltamivir
Enrollment 626
Recruitment Details  
Pre-assignment Details Male and female adult and adolescent participants >=16 years of age hospitalized with documented influenza or suspected influenza were eligible for enrollment. A total of 626 participants were randomized, and 615 participants were included in the Intent-to-Treat Exposed (ITT-E) Population (pop)
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description Participants >=16 years of age received intravenous (IV) zanamivir 300 milligrams (mg) twice daily, adjusted for renal function for 5–10 days. Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Period Title: Overall Study
Started 201 209 205
Completed 175 178 166
Not Completed 26 31 39
Reason Not Completed
Physician Decision             3             5             10
Death             12             14             11
Adverse Event             2             2             1
Withdrawal by Subject             6             6             8
Lost to Follow-up             3             4             9
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg Total
Hide Arm/Group Description Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days. Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days. Total of all reporting groups
Overall Number of Baseline Participants 201 209 205 615
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 209 participants 205 participants 615 participants
55.2  (18.88) 57.3  (17.39) 55.9  (18.7) 56.2  (18.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 209 participants 205 participants 615 participants
Female
82
  40.8%
86
  41.1%
117
  57.1%
285
  46.3%
Male
119
  59.2%
123
  58.9%
88
  42.9%
330
  53.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 201 participants 209 participants 205 participants 615 participants
African American or African Heritage 12 4 10 26
American Indian or Alaskan Native 3 2 4 9
Asian - Central South Asian 10 15 13 38
Asian - East Asian Heritage 12 18 13 43
Asian - South East Asian Heritage 6 4 7 17
Native Hawaiian or Other Pacific 2 1 0 3
White - Arabic or North African 4 3 3 10
White -White or Caucasian or European 150 162 154 466
Unknown 1 0 1 2
Mixed Race 1 0 0 1
1.Primary Outcome
Title Time to Clinical Response (TTCR) in Participants With Confirmed Influenza
Hide Description Clinical response is defined as the resolution of at least 4 of the 5 vital signs (temperature, oxygen saturation, respiratory status, heart rate, systolic blood pressure) within the respective resolution criteria, maintained for at least 24 hours, or hospital discharge, whichever occurred first. This analysis was performed for Influenza positive population, for those with symptom onset less than or equal to (<=) 4 days, and for those on mechanical (mech) ventilation or in intensive care unit (ICU). 99 days is censored time for the participants who did not achieve TTCR.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E population comprised of all randomized participants who received at least one dose of investigational product. The Influenza positive population (IPP) is comprised of all participants in the ITT-E population with proven influenza infection.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
5.87
(0.12 to 99.90)
5.14
(0.23 to 99.90)
5.63
(0.03 to 99.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Zanamivir 300 mg, IV Zanamivir 600 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method Wilcoxon rank sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-1.79 to 0.75
Estimation Comments IV Zanamivir 300 mg versus IV Zanamivir 600 mg
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Zanamivir 600 mg, Oral Oseltamivir 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Wilcoxon rank sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-2.11 to 0.97
Estimation Comments Oral oseltamivir 75 mg versus IV Zanamivir 600 mg
2.Secondary Outcome
Title Percentage of Participants With Respiratory Improvement
Hide Description Respiratory Status (RS) is a component of TTCR. Response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), a need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate of =<24 breaths/minute (without supplemental oxygen). Data are presented as the percentage of participants achieving respiratory improvement.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Number
Unit of Measure: Percentage of participants
77 78 74
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IV Zanamivir 300 mg, IV Zanamivir 600 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.506
Comments [Not Specified]
Method Wei-Johnson method
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IV Zanamivir 600 mg, Oral Oseltamivir 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method Wei-Johnson method
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With All Cause and Attributable Mortality at Day 14, at Day 28, and at the End of Study Visit
Hide Description The number of participants who died on or before Day 14, Day 28, and the End of Study Visit were summarized.
Time Frame On or before Day 14, Day 28, End of Study Visit (assessed up to 42 days)
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Died on or before Study Day 14: all cause
5
   3.1%
8
   4.9%
5
   3.1%
Died on or before Study Day 28: all cause
8
   4.9%
9
   5.6%
9
   5.5%
Died while on-study: all cause
10
   6.1%
12
   7.4%
10
   6.1%
Died on or before Study Day 14: attributable
3
   1.8%
4
   2.5%
4
   2.5%
Died on or before Study Day 28: attributable
5
   3.1%
5
   3.1%
5
   3.1%
Died while on-study: attributable
5
   3.1%
6
   3.7%
6
   3.7%
4.Secondary Outcome
Title Change From Baseline in the Katz Activities of Daily Living (ADL) Score and Each ADL Activity Score
Hide Description The Katz ADL scores were collected for bathing, dressing, toileting, transferring, continence, and feeding activities and were assessed once daily during the treatment period/hospitalization and once at each post-treatment Clinic Visit. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline is defined as the difference at each time point (Day 5/6, and Day 10/11, and last day S/R if treatment was extended beyond 5 days) and the end of the study (post-treatment [PT] +28 Days) compared to Baseline.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Mean (Standard Deviation)
Unit of Measure: Scores on the scale
Total Score Day 5/6 Number Analyzed 149 participants 150 participants 139 participants
1.07  (1.959) 0.93  (1.782) 0.78  (1.837)
Total Score Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.88  (1.746) 0.5  (0.837) -0.08  (3.029)
Total Score Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
0.2  (2.49) -3.0  (4.243) 0.75  (1.165)
Total Score PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
2.13  (2.234) 1.72  (2.342) 1.98  (2.142)
Bathing: DAY 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.24  (0.488) 0.19  (0.429) 0.18  (0.438)
Bathing: DAY 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.19  (0.403) 0.0  (0.0) 0.0  (0.426)
Bathing: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
0.2  (0.447) -0.5  (0.707) 0.0  (0.0)
Bathing: PT + 28 DAYS Number Analyzed 138 participants 134 participants 120 participants
0.43  (0.498) 0.34  (0.505) 0.39  (0.507)
Dressing DAY 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.23  (0.481) 0.21  (0.438) 0.14  (0.427)
Dressing: Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.13  (0.342) 0.0  (0.0) -0.08  (0.515)
Dressing: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
0.2  (0.447) -0.5  (0.707) 0.13  (0.354)
Dressing:PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
0.42  (0.495) 0.37  (0.515) 0.41  (0.494)
Toileting: DAY 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.19  (0.456) 0.19  (0.439) 0.14  (0.409)
Toileting: Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.13  (0.342) 0.33  (0.516) 0.08  (0.515)
Toileting: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
0.2  (0.447) -0.5  (0.707) 0.0  (0.535)
Toileting: PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
0.4  (0.491) 0.32  (0.514) 0.37  (0.484)
Transferring: DAY 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.28  (0.505) 0.23  (0.451) 0.17  (0.41)
Transferring: Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.19  (0.403) 0.17  (0.408) 0.08  (0.515)
Transferring: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
0.0  (0.707) -0.5  (0.707) 0.25  (0.463)
Transferring: PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
0.45  (0.499) 0.36  (0.526) 0.4  (0.492)
Continence: DAY 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.07  (0.322) 0.05  (0.314) 0.07  (0.374)
Continence: Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.13  (0.342) 0.0  (0.0) -0.08  (0.669)
Continence: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
-0.2  (0.447) -0.5  (0.707) 0.13  (0.354)
Continence: PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
0.22  (0.431) 0.16  (0.422) 0.23  (0.439)
Feeding: Day 5/6 Number Analyzed 149 participants 150 participants 139 participants
0.07  (0.331) 0.07  (0.309) 0.08  (0.382)
Feeding: Day 10/11 Number Analyzed 16 participants 6 participants 12 participants
0.13  (0.342) 0.0  (0.0) -0.08  (0.669)
Feeding: Last Day of S/R Number Analyzed 5 participants 2 participants 8 participants
-0.2  (0.447) -0.5  (0.707) 0.25  (0.463)
Feeding: PT+28 Day Number Analyzed 138 participants 134 participants 120 participants
0.21  (0.409) 0.17  (0.416) 0.19  (0.395)
5.Secondary Outcome
Title Median Time to Return to Pre-morbid Functional Status as Measured by the Katz ADL Score and Each ADL Activity Score
Hide Description Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. Median time to return to pre-morbid functional status was assessed via the Katz ADL score (bathing, dressing, toileting, transferring, continence, and feeding activities). For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. The total score is generated by adding the scores of all six activities. A total score of 6 indicates that the participant was independent; a total score of 0 indicates that the participant was very dependent.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Total score
2
(2 to 38)
2
(2 to 37)
2.5
(2 to 57)
Bathing
2
(2 to 38)
2
(2 to 37)
2
(2 to 57)
Dressing
2
(2 to 38)
2
(2 to 40)
2
(2 to 57)
Toileting
2
(2 to 38)
2
(2 to 31)
2
(2 to 40)
Transferring
2
(2 to 38)
2
(2 to 31)
2
(2 to 40)
Continence
2
(2 to 35)
2
(2 to 33)
2
(2 to 31)
Feeding
2
(2 to 29)
2
(2 to 32)
2
(2 to 36)
6.Secondary Outcome
Title Number of Participants Who Returned to Their Pre-morbid Functional Status as Assessed Per the Katz ADL Score and Each ADL Activity Score at the End of the Study
Hide Description Pre-morbid functional status is defined as the best functional status in the 4 weeks prior to enrolment. The number of participants who returned to their pre-morbid functional status at the end of the study assessed per the Katz ADL score (bathing, dressing, toileting, transferring, continence and feeding activities) is summarized.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Total
139
  85.3%
138
  85.2%
130
  79.8%
Bathing
135
  82.8%
133
  82.1%
126
  77.3%
Dressing
138
  84.7%
135
  83.3%
126
  77.3%
Toileting
139
  85.3%
136
  84.0%
130
  79.8%
Transferring
140
  85.9%
140
  86.4%
133
  81.6%
Continence
142
  87.1%
143
  88.3%
139
  85.3%
Feeding
145
  89.0%
148
  91.4%
144
  88.3%
7.Secondary Outcome
Title Median Time to Return to the Pre-morbid Level of Activity as Measured by the 3-point Scale
Hide Description Median time to return to pre-morbid level of activity was assessed once daily during treatment/hospitalization and once at each post-treatment assessment and was measured using the 3- point scale (bed rest, limited ambulation, or unrestricted).
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population. Participants succeeded in pre-morbid functional status were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 138 137 135
Median (Full Range)
Unit of Measure: Days
5
(2 to 34)
4
(2 to 31)
4
(1 to 57)
8.Secondary Outcome
Title Number of Participants With the Indicated Clinical Symptoms of Influenza
Hide Description Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient hospitalization and once at each post-treatment assessment.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Anorexia
102
  62.6%
112
  69.1%
123
  75.5%
Cough
151
  92.6%
150
  92.6%
157
  96.3%
Diarrhea
64
  39.3%
57
  35.2%
66
  40.5%
Dyspnea
143
  87.7%
145
  89.5%
152
  93.3%
Fatigue
144
  88.3%
144
  88.9%
148
  90.8%
Feverishness
138
  84.7%
145
  89.5%
136
  83.4%
Headache
104
  63.8%
102
  63.0%
103
  63.2%
Myalgias
115
  70.6%
117
  72.2%
114
  69.9%
Nasal symptoms (rhinorrhea, congestion)
118
  72.4%
123
  75.9%
122
  74.8%
Nausea
57
  35.0%
51
  31.5%
77
  47.2%
Sore throat
94
  57.7%
115
  71.0%
97
  59.5%
Vomiting
27
  16.6%
23
  14.2%
45
  27.6%
9.Secondary Outcome
Title Median Time of Duration of Clinical Symptoms of Influenza
Hide Description Influenza clinical symptoms included nasal symptoms (rhinorrhea, congestion), feverishness, cough, myalgias, fatigue, diarrhea, anorexia, dyspnea, headache, sore throat, nausea, and vomiting. Influenza symptoms were assessed once daily during inpatient/hospitalization and once at each post-treatment assessment.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Anorexia Number Analyzed 102 participants 112 participants 123 participants
5
(1 to 39)
3
(1 to 46)
5
(1 to 55)
Cough Number Analyzed 151 participants 150 participants 157 participants
14
(1 to 39)
13
(1 to 46)
15
(1 to 56)
Diarrhea Number Analyzed 64 participants 57 participants 66 participants
3
(1 to 29)
2
(1 to 28)
3
(1 to 23)
Dyspnea Number Analyzed 143 participants 145 participants 152 participants
7
(1 to 40)
6
(1 to 43)
8
(1 to 56)
Fatigue Number Analyzed 144 participants 144 participants 148 participants
11
(1 to 41)
11
(1 to 44)
12
(1 to 56)
Feverishness Number Analyzed 138 participants 145 participants 136 participants
2
(1 to 28)
2
(1 to 29)
2.5
(1 to 56)
Headache Number Analyzed 104 participants 102 participants 103 participants
3
(1 to 33)
3
(1 to 33)
4
(1 to 56)
Myalgias Number Analyzed 115 participants 117 participants 114 participants
4
(1 to 39)
3
(1 to 34)
4
(1 to 56)
Nasal symptoms Number Analyzed 118 participants 123 participants 122 participants
6
(1 to 34)
4
(1 to 43)
5.5
(1 to 35)
Nausea Number Analyzed 57 participants 51 participants 77 participants
3
(1 to 34)
2
(1 to 24)
2
(1 to 28)
Sore throat Number Analyzed 94 participants 115 participants 97 participants
3
(1 to 28)
2
(1 to 36)
3
(1 to 35)
Vomiting Number Analyzed 27 participants 23 participants 45 participants
2
(1 to 19)
1
(1 to 11)
1
(1 to 20)
10.Secondary Outcome
Title Number of Participants With Complications of Influenza and Associated Antibiotic Use
Hide Description The number of participants with complications of influenza and associated antibiotic use were summarized
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
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Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Associated use of any antibiotic
22
  13.5%
16
   9.9%
29
  17.8%
Any complication of influenza
34
  20.9%
33
  20.4%
41
  25.2%
11.Secondary Outcome
Title Number of Participants With the Indicated Ventilation Status: Modality of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
Hide Description Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD), no supplemental oxygen (O2) or ventilation support, Respiratory support at “any time (AT) on study” and at Baseline (Day 1) are summarized. Data for the "any time (AT) on study" time point was reported.
Time Frame Up to 42 days
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IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1, Machine-Assisted: ECMO
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, Machine-Assisted: Endotracheal
28
  17.2%
25
  15.4%
27
  16.6%
Day 1, SOD
96
  58.9%
103
  63.6%
87
  53.4%
Day 1, No supplemental O2 or ventilation support
32
  19.6%
29
  17.9%
37
  22.7%
Day 1, Respiratory Support
34
  20.9%
29
  17.9%
39
  23.9%
AT on Study, Machine-Assisted: ECMO
2
   1.2%
0
   0.0%
1
   0.6%
AT on Study, Machine-Assisted: Endotracheal
36
  22.1%
31
  19.1%
37
  22.7%
AT on Study, SOD
137
  84.0%
137
  84.6%
128
  78.5%
AT on Study, No supplemental O2 or ventilation sup
138
  84.7%
135
  83.3%
131
  80.4%
AT on Study, Respiratory Support
46
  28.2%
37
  22.8%
50
  30.7%
12.Secondary Outcome
Title Median Time of Duration of Invasive and Non-invasive Ventilator Support and Oxygen Supplementation
Hide Description Ventilation status was assessed three times daily during the treatment period/hospitalization. Ventilation status was assessed once daily during inpatient/hospitalization and once at each post-treatment clinic visit.
Time Frame Baseline (Day 1) and up to 42 days
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Hide Analysis Population Description
IPP Population. Only those participants available with the indicated ventilator support or oxygen supplementation were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Ventilator Support Number Analyzed 46 participants 37 participants 50 participants
9
(0 to 38)
5.2
(0 to 36)
8.2
(0 to 36)
Oxygen Supplementation Number Analyzed 137 participants 137 participants 128 participants
4.4
(0 to 38)
4.2
(0 to 43)
3.7
(0 to 36)
13.Secondary Outcome
Title Median Time of Duration of Hospitalization and Intensive Care Unit (ICU) Stay
Hide Description Hospital duration and ICU duration was assessed from the first day of dosing. Hospital duration was calculated as the discharge date minus the admission date + 1. Hospital duration while on study was the earlier of discharge, completion, or withdrawal minus the later of the admission date or the study start date + 1. ICU duration-Modified was calculated as the original ICU duration minus ICU days prior to Study Day 1.
Time Frame Day 1 to the end of the study (assessed up to 42 days)
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IPP population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Hospitalization Number Analyzed 163 participants 162 participants 163 participants
10
(1 to 108)
8
(2 to 64)
9
(1 to 58)
Hospitalization while on study Number Analyzed 163 participants 162 participants 163 participants
8
(1 to 39)
6
(1 to 43)
7
(1 to 39)
Hospitalization-ICU Number Analyzed 72 participants 56 participants 71 participants
8
(1 to 41)
7.5
(1 to 36)
8
(1 to 36)
ICU Duration Modified Number Analyzed 70 participants 54 participants 69 participants
7
(1 to 39)
6
(1 to 36)
7
(1 to 36)
14.Secondary Outcome
Title Median Time to the Absence of Fever and Improved Respiratory Status, Oxygen Saturation, Heart Rate, and Systolic Blood Pressure
Hide Description The absence of fever is defined as a non-axillary temperature recording <=36.6 degrees Celsius axillary, <= 37.2 degrees Celsius oral or <= 37.7 degrees Celsius core. Respiratory Status (RS) response criteria included the return to the pre-morbid oxygen requirement (participants with chronic oxygen use), or the need for supplemental oxygen (administered by any modality: ventilator, non-invasive ventilation, facemask, facetent, nasal canula, etc.) to no need for supplemental oxygen, or a respiratory rate =<24 breaths/minute (without supplemental oxygen). Oxygen saturation response criteria: >=95% (without supplemental oxygen). Heart rate response criteria: =<100 beats/minute. Systolic blood pressure response criteria: >=90 millimeters of mercury. Vital signs were assessed three times daily during the treatment period/hospitalization. Vital signs were assessed once daily during inpatient/hospitization and once at each post-treatment clinic visit.
Time Frame Baseline (Day 1) and up to 42 days
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IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Fever Number Analyzed 163 participants 162 participants 163 participants
1.6
(0 to 34)
0.8
(0 to 14)
1.5
(0 to 31)
Oxygen Saturation Number Analyzed 98 participants 108 participants 99 participants
5.3
(0 to 30)
5.6
(0 to 32)
4.5
(0 to 25)
Respiratory status Number Analyzed 126 participants 126 participants 121 participants
3.5
(0 to 31)
3.6
(0 to 32)
2.8
(0 to 21)
Heart rate Number Analyzed 156 participants 148 participants 155 participants
0.4
(0 to 28)
0.4
(0 to 21)
0.5
(0 to 24)
Systolic blood pressure Number Analyzed 156 participants 156 participants 154 participants
0.3
(0 to 23)
0.3
(0 to 14)
0.3
(0 to 16)
15.Secondary Outcome
Title Median Time to Virologic Improvement
Hide Description Virologic improvement is defined as a 2 log drop in viral load or sustained undetectable viral ribonucleic acid (RNA) (on two successive occasions) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples. Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Days 6, 8, 10 and on the last day of randomized treatment. For participants who utilized the Switch (S)/Rescue (R) option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Nasopharyngeal swabs were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16, and +28 day assessment.
Time Frame Baseline (Day 1) and up to 42 days
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IPP Population. Only those participants available at the specified time points were analyzed. Data presented is for participants positive at Baseline.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Influenza A and B Number Analyzed 116 participants 122 participants 129 participants
3
(2 to 34)
3
(2 to 35)
3
(2 to 34)
Influenza A/H1N1 Number Analyzed 47 participants 42 participants 48 participants
3
(2 to 13)
3
(2 to 34)
3
(2 to 34)
Influenza A/H3N2 Number Analyzed 55 participants 58 participants 61 participants
3
(2 to 8)
3
(2 to 35)
3
(2 to 11)
Influenza B Number Analyzed 15 participants 20 participants 21 participants
5
(2 to 34)
3
(2 to 21)
3
(2 to 12)
16.Secondary Outcome
Title Change From Baseline in Quantitative Virus Culture From Nasopharyngeal Swabs Positive at Baseline
Hide Description Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day1, S/R Day3, S/R Day5, or S/R Day6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the Post-Treatment +2, +5, +9, +16 and +28Day assessment. Viral load was measured by Quantitative Virus Culture, log10 50% Tissue Culture Infectious Dose (TCID50)/milliliter (mL). Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus Baseline value .
Time Frame Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
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IPP Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: log10 TCID50/mL
Day 3 Number Analyzed 78 participants 76 participants 89 participants
-2.01
(-5.0 to 0.8)
-2.01
(-4.8 to 1.3)
-2.01
(-5.3 to 2.8)
Day 5 Number Analyzed 66 participants 69 participants 80 participants
-2.51
(-5.5 to 0.0)
-2.26
(-5.3 to 0.0)
-2.26
(-5.3 to 2.0)
Day 8 Number Analyzed 6 participants 7 participants 10 participants
-1.64
(-5.5 to 0.0)
-2.01
(-4.3 to -0.3)
-2.26
(-4.3 to 0.0)
Day 10 Number Analyzed 4 participants 3 participants 4 participants
-3.76
(-5.5 to -0.3)
-0.3
(-1.3 to -0.3)
-2.26
(-3.8 to -1.3)
Day 11 Number Analyzed 3 participants 3 participants 4 participants
-3.01
(-5.5 to -0.3)
-0.3
(-0.3 to -0.3)
-2.26
(-3.8 to -1.3)
S/R Day 5 Number Analyzed 0 participants 1 participants 1 participants
-4.3
(-4.3 to -4.3)
-3.0
(-3.0 to -3.0)
S/R Day 6 Number Analyzed 1 participants 1 participants 1 participants
-2.5
(-2.5 to -2.5)
-4.3
(-4.3 to -4.3)
0.0
(0.0 to 0.0)
17.Secondary Outcome
Title Change From Baseline Viral Load (Influenza A or B) by qPCR From Nasopharyngeal Swabs Positive at Baseline
Hide Description Nasopharyngeal swabs were collected daily from Baseline through Day 5. If randomized treatment was continued beyond Day 5, samples were taken on Treatment Day 6, Day 8, Day 10, Day 11, and the last day of randomized treatment. For participants who utilized the S/R option, samples were taken on S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6, whichever was the last day of S/R treatment. Samples were taken if the participant was symptomatic and continued to be hospitalized on the post-treatment +2, +5, +9, +16 and +28 day assessment. Viral load as measured by PCR. Baseline is defined as the pre-dose value collected on Study Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline (Day 1), Day 3, Day 5, Day 8, Day 10, Day 11 and/or last day of randomized treatment, if randomized treatment was extended beyond 5 days, and S/R Day 5/6 (up to Day 14) if applicable
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IPP Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles)
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: log10 vp/mL
Day 3 Number Analyzed 126 participants 127 participants 129 participants
-1.5
(-5.4 to 2.2)
-1.83
(-4.9 to 2.0)
-1.75
(-6.0 to 2.8)
Day 5 Number Analyzed 110 participants 114 participants 114 participants
-2.51
(-5.8 to 3.2)
-2.71
(-6.2 to 3.1)
-2.73
(-6.3 to 2.3)
Day 8 Number Analyzed 15 participants 12 participants 16 participants
-2.38
(-4.4 to 1.0)
-3.16
(-5.5 to -0.3)
-1.78
(-5.7 to 1.1)
Day 10 Number Analyzed 13 participants 6 participants 8 participants
-2.75
(-6.0 to -0.9)
-3.03
(-3.5 to 1.5)
-2.63
(-4.6 to 0.9)
Day 11 Number Analyzed 9 participants 4 participants 7 participants
-3.58
(-4.9 to -0.6)
-2.6
(-3.1 to 1.7)
-3.29
(-4.9 to -1.0)
S/R Day 5 Number Analyzed 0 participants 1 participants 1 participants
-3.8
(-3.8 to -3.8)
-5.7
(-5.7 to -5.7)
S/R Day 6 Number Analyzed 1 participants 1 participants 2 participants
-5.2
(-5.2 to -5.2)
-5.4
(-5.4 to -5.4)
-3.84
(-4.0 to -3.7)
18.Secondary Outcome
Title Number of Participants With no Detectable Viral RNA and the Absence of Cultivable Virus in Lower Respiratory Samples (Bronchoalveolar Lavage Sample [BAL], Endotracheal Aspirate)
Hide Description Lower respiratory samples included BAL and endotracheal aspirates. Endotracheal aspirates were requested in participants (par.) who were intubated. Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment [trt]). Endotracheal aspirates were collected in participants who were intubated. If trt was continued beyond Day 5, additional samples were taken on Trt Day 6, Day 8, Day 10, and/or the day of the last dose of randomized trt, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R trt. If the par. was symptomatic and hospitalized, samples were taken on the Post-Trt +2, +5, +9, +16 assessment days, and at the Post-Trt [PT]+28 Day assessment. Assessment of samples was done by quantitative RT-PCR and viral culture.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
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IPP Population. Data is presented for participants positive at Baseline. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
Influenza A and B Day 1 Number Analyzed 21 participants 17 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
Influenza A and B Day 2 Number Analyzed 17 participants 15 participants 14 participants
0
   0.0%
4
  26.7%
1
   7.1%
Influenza A and B Day 3 Number Analyzed 16 participants 10 participants 15 participants
1
   6.3%
2
  20.0%
0
   0.0%
Influenza A and B Day 4 Number Analyzed 16 participants 10 participants 15 participants
2
  12.5%
2
  20.0%
2
  13.3%
Influenza A and B Day 5 Number Analyzed 15 participants 10 participants 15 participants
3
  20.0%
4
  40.0%
2
  13.3%
Influenza A and B Day 6 Number Analyzed 14 participants 5 participants 9 participants
3
  21.4%
1
  20.0%
3
  33.3%
Influenza A and B Day 8 Number Analyzed 5 participants 3 participants 7 participants
2
  40.0%
0
   0.0%
2
  28.6%
Influenza A and B Day 10 Number Analyzed 4 participants 3 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
Influenza A and B S/R Day 1 Number Analyzed 0 participants 0 participants 1 participants
0
   0.0%
Influenza A and B S/R Day 3 Number Analyzed 1 participants 0 participants 1 participants
0
   0.0%
1
 100.0%
Influenza A and B S/R Day 5 Number Analyzed 1 participants 0 participants 0 participants
0
   0.0%
Influenza A and B PT + 2 Days Number Analyzed 9 participants 3 participants 9 participants
4
  44.4%
1
  33.3%
3
  33.3%
Influenza A and B PT + 5 Days Number Analyzed 11 participants 2 participants 6 participants
4
  36.4%
1
  50.0%
0
   0.0%
Influenza A and B PT + 9 Days Number Analyzed 5 participants 2 participants 4 participants
4
  80.0%
1
  50.0%
3
  75.0%
Influenza A and B PT + 16 Days Number Analyzed 4 participants 1 participants 3 participants
3
  75.0%
1
 100.0%
2
  66.7%
Influenza A and B PT + 28 Days Number Analyzed 1 participants 0 participants 1 participants
1
 100.0%
1
 100.0%
19.Secondary Outcome
Title Median Time to no Detectable Viral RNA and the Absence of Cultivable Virus in Any Obtained Sample (Upper and Lower Respiratory Samples)
Hide Description Upper (nasopharyngeal swabs) and lower (Endotracheal aspirates, bronchoalveolar lavage samples, where available) respiratory samples were collected daily from Baseline/Day 1 through Day 5 and Day 6 (if the last day of randomized treatment). Endotracheal aspirates were collected in participants who were intubated. If treatment was continued beyond Day 5, additional samples were taken on Treatment Day 6, Day 8, Day 10, and/or the day of the last dose of randomized treatment, if applicable, and S/R Day 1, S/R Day 3, S/R Day 5, or S/R Day 6 if the last day of S/R treatment. If the participant was symptomatic and hospitalized, samples were taken on the Post-treatment+2, +5, +9, +16 assessment days, and at the Post-Treatment +28 Day. Assessment of samples was done by quantitative RT-PCR.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population. Only those participants available at the specified time points were analyzed. Data also presented for participants positive at Baseline.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Median (Full Range)
Unit of Measure: Days
Influenza A and B Number Analyzed 114 participants 118 participants 115 participants
4
(1 to 34)
3
(1 to 35)
4
(1 to 57)
Positive at Baseline Number Analyzed 102 participants 104 participants 102 participants
4
(2 to 34)
4
(2 to 35)
4
(2 to 57)
20.Secondary Outcome
Title Number of Participants With Resistance-associated Mutations Detected in the Neuraminidase (NA) and Hemagglutinin (HA) Gene of Influenza A and B Viruses in Nasopharyngeal Swabs and Endotracheal/BAL Samples
Hide Description Nasopharyngeal swabs and endotracheal /BAL samples were collected for viral susceptibility analysis. Susceptibility analyses consisted of phenotyping and genotyping. Resistance mutations were detected by genotyping. Viral susceptibility to zanamivir and oral oseltamivir at Baseline and throughout treatment determined by NA and HA (gene of influenza A and B viruses) sequence analysis and NA enzyme inhibition. Number of participants with viral mutation events are summarized, this includes all resistance mutations (substitutions) i.e. those present at Baseline and those that emerged during treatment.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
IPP Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 163 162 163
Measure Type: Count of Participants
Unit of Measure: Participants
NA Gene,H3N2: Y155F
5
   3.1%
7
   4.3%
5
   3.1%
NA Gene,H3N2:S245N
4
   2.5%
4
   2.5%
0
   0.0%
NA Gene,H3N2:I222V
0
   0.0%
1
   0.6%
2
   1.2%
NA Gene,H3N2:N294S/N
2
   1.2%
0
   0.0%
0
   0.0%
NA Gene,H3N2:V149A
0
   0.0%
1
   0.6%
1
   0.6%
NA Gene,H3N2:D198D/G
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H3N2:G248G/E
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,H3N2:N294D/N
0
   0.0%
1
   0.6%
0
   0.0%
NA Gene,H3N2:R292R/K
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H3N2:T325I
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,H3N2:Y155H
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H1N1: H275H/Y
0
   0.0%
1
   0.6%
4
   2.5%
NA Gene,H1N1:H275Y
0
   0.0%
1
   0.6%
3
   1.8%
NA Gene,H1N1:Q313R
1
   0.6%
0
   0.0%
2
   1.2%
NA Gene,H1N1:D199N
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,H1N1:E278G/E
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H1N1:I223I/K
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H1N1:Q136Q/R
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,H1N1:S247N
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,H1N1:S247S/I
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,H1N1:S247S/N
0
   0.0%
1
   0.6%
0
   0.0%
NA Gene,B: E148G
1
   0.6%
0
   0.0%
0
   0.0%
NA Gene,B: G141E
0
   0.0%
0
   0.0%
1
   0.6%
NA Gene,B: M403I
1
   0.6%
0
   0.0%
0
   0.0%
HA Gene, H3N2:R142G
18
  11.0%
21
  13.0%
21
  12.9%
HA Gene, H3N2:S198A
13
   8.0%
8
   4.9%
11
   6.7%
HA Gene, H3N2:A138S
3
   1.8%
1
   0.6%
2
   1.2%
HA Gene, H3N2:R142K
0
   0.0%
0
   0.0%
2
   1.2%
HA Gene, H3N2:A304A/P
0
   0.0%
0
   0.0%
1
   0.6%
HA Gene, H3N2:A304D
0
   0.0%
1
   0.6%
0
   0.0%
HA Gene, H3N2:L194P/L
1
   0.6%
0
   0.0%
0
   0.0%
HA Gene, H3N2:Q75H
0
   0.0%
1
   0.6%
0
   0.0%
HA Gene, H3N2:S124G
0
   0.0%
0
   0.0%
1
   0.6%
HA Gene, H3N2:S262N
0
   0.0%
1
   0.6%
0
   0.0%
HA Gene, H3N2:H1N1: S183P
1
   0.6%
0
   0.0%
2
   1.2%
HA Gene, H1N1 :D222D/G
0
   0.0%
0
   0.0%
2
   1.2%
HA Gene, H1N1 :D222D/N
0
   0.0%
2
   1.2%
0
   0.0%
HA Gene, H1N1 :D222N
0
   0.0%
0
   0.0%
2
   1.2%
HA Gene, H1N1 :S162N
0
   0.0%
0
   0.0%
2
   1.2%
HA Gene, H1N1 :D187E
0
   0.0%
1
   0.6%
0
   0.0%
HA Gene, H1N1 :D222G
1
   0.6%
0
   0.0%
0
   0.0%
HA Gene, H1N1 :D222S/D/N/G
1
   0.6%
0
   0.0%
0
   0.0%
HA Gene, H1N1 :L151P/L
0
   0.0%
1
   0.6%
0
   0.0%
HA Gene, H1N1 :V152I
0
   0.0%
0
   0.0%
1
   0.6%
21.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
Hide Description An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. All AEs were assessed by the Investigator as related or not related to the study treatment.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population comprised of all randomized participants who received at least one dose of investigational product and assessed according to their actual treatment received, regardless of the randomization assigned.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
25
  12.4%
22
  10.5%
35
  17.1%
22.Secondary Outcome
Title Number of Participants With Any Severe or Grade 3/4 AE
Hide Description An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of AEs. Grade 3=severe; Grade 4=potentially life threatening.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
39
  19.4%
45
  21.5%
44
  21.5%
23.Secondary Outcome
Title Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
Hide Description An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
8
   4.0%
10
   4.8%
11
   5.4%
24.Secondary Outcome
Title Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
Hide Description An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
14
   7.0%
16
   7.7%
13
   6.3%
25.Secondary Outcome
Title Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
Hide Description An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. AEs that occurred during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assessed by the Investigator as related or not related to the study treatment.
Time Frame Up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
5
   2.5%
3
   1.4%
7
   3.4%
26.Secondary Outcome
Title Number of Participants With the Indicated Chemistry Laboratory Values Shifts From Baseline (Day 1) and up to 42 Days
Hide Description Samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), switch/rescue (S/R) Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino tranferase (AST), total bilirubin, calcium, creatine kinase, chloride, carbon dioxide content (CO2), creatinine, potassium, magnesium, sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range are summarized.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only the participants available at the time of assessment were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
Albumin G1 Number Analyzed 194 participants 203 participants 202 participants
12
   6.2%
18
   8.9%
15
   7.4%
Albumin G2 Number Analyzed 194 participants 203 participants 202 participants
32
  16.5%
43
  21.2%
40
  19.8%
Albumin G3 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
5
   2.5%
0
   0.0%
Albumin G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
ALP G1 Number Analyzed 194 participants 203 participants 202 participants
10
   5.2%
15
   7.4%
9
   4.5%
ALP G2 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
4
   2.0%
1
   0.5%
ALP G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
2
   1.0%
0
   0.0%
ALP G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
ALT G1 Number Analyzed 194 participants 203 participants 202 participants
13
   6.7%
10
   4.9%
12
   5.9%
ALT G2 Number Analyzed 194 participants 203 participants 202 participants
2
   1.0%
1
   0.5%
1
   0.5%
ALT G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
ALT G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
AST G1 Number Analyzed 193 participants 202 participants 202 participants
23
  11.9%
27
  13.4%
19
   9.4%
AST G2 Number Analyzed 193 participants 202 participants 202 participants
8
   4.1%
8
   4.0%
6
   3.0%
AST G3 Number Analyzed 193 participants 202 participants 202 participants
2
   1.0%
0
   0.0%
2
   1.0%
AST G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
Total Bilirubin G1 Number Analyzed 194 participants 203 participants 202 participants
5
   2.6%
2
   1.0%
2
   1.0%
Total Bilirubin G2 Number Analyzed 194 participants 203 participants 202 participants
3
   1.5%
2
   1.0%
3
   1.5%
Total Bilirubin G3 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
2
   1.0%
0
   0.0%
Total Bilirubin G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
Creatine Kinase G1 Number Analyzed 194 participants 203 participants 202 participants
10
   5.2%
11
   5.4%
6
   3.0%
Creatine Kinase G2 Number Analyzed 194 participants 203 participants 202 participants
3
   1.5%
3
   1.5%
6
   3.0%
Creatine Kinase G3 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
2
   1.0%
4
   2.0%
Creatine Kinase G4 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
1
   0.5%
2
   1.0%
CO2 G1 Number Analyzed 193 participants 202 participants 202 participants
34
  17.6%
43
  21.3%
47
  23.3%
CO2 G2, Number Analyzed 193 participants 202 participants 202 participants
4
   2.1%
9
   4.5%
6
   3.0%
CO2 G3 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
CO2 G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
1
   0.5%
0
   0.0%
Creatinine G1 Number Analyzed 194 participants 203 participants 202 participants
6
   3.1%
5
   2.5%
4
   2.0%
Creatinine G2 Number Analyzed 194 participants 203 participants 202 participants
11
   5.7%
7
   3.4%
4
   2.0%
Creatinine G3 Number Analyzed 194 participants 203 participants 202 participants
8
   4.1%
7
   3.4%
4
   2.0%
Creatinine G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
Magnesium G1 Number Analyzed 194 participants 203 participants 202 participants
14
   7.2%
14
   6.9%
15
   7.4%
Magnesium G2, Number Analyzed 194 participants 203 participants 202 participants
7
   3.6%
9
   4.4%
4
   2.0%
Magnesium G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Magnesium G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypercalcemia G1 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypercalcemia G2 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypercalcemia G3 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypercalcemia G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperkalemia G1 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
1
   0.5%
1
   0.5%
Hyperkalemia G2 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperkalemia G3 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperkalemia G4 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
0
   0.0%
1
   0.5%
Hypernatremia G1 Number Analyzed 194 participants 203 participants 202 participants
4
   2.1%
10
   4.9%
4
   2.0%
Hypernatremia G2 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
1
   0.5%
0
   0.0%
Hypernatremia G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
1
   0.5%
1
   0.5%
Hypernatremia G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypocalcemia G1 Number Analyzed 193 participants 202 participants 202 participants
43
  22.3%
48
  23.8%
40
  19.8%
Hypocalcemia G2 Number Analyzed 193 participants 202 participants 202 participants
26
  13.5%
39
  19.3%
42
  20.8%
Hypocalcemia G3 Number Analyzed 193 participants 202 participants 202 participants
7
   3.6%
8
   4.0%
8
   4.0%
Hypocalcemia G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
1
   0.5%
0
   0.0%
Hypokalemia G1 Number Analyzed 193 participants 202 participants 202 participants
16
   8.3%
12
   5.9%
21
  10.4%
Hypokalemia G2 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
1
   0.5%
1
   0.5%
Hypokalemia G3 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
0
   0.0%
0
   0.0%
Hypokalemia G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyponatremia G1 Number Analyzed 194 participants 203 participants 202 participants
42
  21.6%
34
  16.7%
26
  12.9%
Hyponatremia G2 Number Analyzed 194 participants 203 participants 202 participants
2
   1.0%
2
   1.0%
4
   2.0%
Hyponatremia G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
2
   1.0%
0
   0.0%
Hyponatremia G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
27.Secondary Outcome
Title Number of Participants With the Indicated Hematology Values Shifts From Baseline (Day 1) and up to 42 Days
Hide Description Blood samples for laboratory assessments were collected at Baseline (Day 1), Day 3, Day 5/6, Day 8, Day 10/11 (or last day of randomized treatment), S/R Day 1, S/R Day 3, and S/R Day 5/6 (last day of S/R treatment for those participants who utilized this option), Post-Treatment +2 (if hospitalized), and Post-Treatment +5, +16, and +28 Days. Hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC) count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade (G) 1=mild, G2= moderate, G3=severe and G4=potentially life threatening. The number of participants with values that were G1, G2, G3 and G4 relative to the normal range for the indicated hematology parameters is summarized. Baseline is defined as the pre-dose value collected on Study Day 1.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only the participants available at the time of assessment were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin G1 Number Analyzed 194 participants 202 participants 200 participants
28
  14.4%
25
  12.4%
28
  14.0%
Hemoglobin G2 Number Analyzed 194 participants 202 participants 200 participants
11
   5.7%
19
   9.4%
13
   6.5%
Hemoglobin G3 Number Analyzed 194 participants 202 participants 200 participants
14
   7.2%
10
   5.0%
8
   4.0%
Hemoglobin G4 Number Analyzed 194 participants 202 participants 200 participants
0
   0.0%
4
   2.0%
1
   0.5%
Lymphocytes G1 Number Analyzed 186 participants 199 participants 198 participants
8
   4.3%
18
   9.0%
10
   5.1%
Lymphocytes G2 Number Analyzed 186 participants 199 participants 198 participants
11
   5.9%
15
   7.5%
11
   5.6%
Lymphocytes G3 Number Analyzed 186 participants 199 participants 198 participants
16
   8.6%
21
  10.6%
18
   9.1%
Lymphocytes G4 Number Analyzed 186 participants 199 participants 198 participants
18
   9.7%
19
   9.5%
14
   7.1%
Neutrophils G1 Number Analyzed 193 participants 202 participants 200 participants
2
   1.0%
2
   1.0%
3
   1.5%
Neutrophils G2 Number Analyzed 193 participants 202 participants 200 participants
2
   1.0%
0
   0.0%
0
   0.0%
Neutrophils G3 Number Analyzed 193 participants 202 participants 200 participants
0
   0.0%
1
   0.5%
0
   0.0%
Neutrophils G4 Number Analyzed 193 participants 202 participants 200 participants
1
   0.5%
0
   0.0%
3
   1.5%
Platelets G1 Number Analyzed 194 participants 200 participants 198 participants
8
   4.1%
22
  11.0%
21
  10.6%
Platelets G2 Number Analyzed 194 participants 200 participants 198 participants
18
   9.3%
12
   6.0%
16
   8.1%
Platelets G3 Number Analyzed 194 participants 200 participants 198 participants
4
   2.1%
3
   1.5%
2
   1.0%
Platelets G4 Number Analyzed 194 participants 200 participants 198 participants
2
   1.0%
1
   0.5%
2
   1.0%
Leukocytes G1 Number Analyzed 194 participants 202 participants 200 participants
3
   1.5%
2
   1.0%
1
   0.5%
Leukocytes G2 Number Analyzed 194 participants 202 participants 200 participants
3
   1.5%
5
   2.5%
3
   1.5%
Leukocytes G3 Number Analyzed 194 participants 202 participants 200 participants
0
   0.0%
1
   0.5%
0
   0.0%
Leukocytes G4 Number Analyzed 194 participants 202 participants 200 participants
1
   0.5%
0
   0.0%
2
   1.0%
28.Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent (TE) Grade (G) 3/4 Clinical Chemistry Toxicities
Hide Description A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatine kinase, chloride, CO2/bicarbonate, creatinine, potassium, magnesium and sodium. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only the participants available at the time of assessment were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
Albumin, G3 Number Analyzed 194 participants 203 participants 202 participants
6
   3.1%
3
   1.5%
4
   2.0%
Albumin, G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
ALP, G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
2
   1.0%
0
   0.0%
ALP, G4 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
0
   0.0%
1
   0.5%
ALT, G3 Number Analyzed 194 participants 203 participants 202 participants
2
   1.0%
2
   1.0%
4
   2.0%
ALT, G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
2
   1.0%
1
   0.5%
AST, G3 Number Analyzed 193 participants 202 participants 202 participants
2
   1.0%
4
   2.0%
5
   2.5%
AST, G4 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
2
   1.0%
1
   0.5%
Total Bilirubin, G3 Number Analyzed 194 participants 203 participants 202 participants
2
   1.0%
2
   1.0%
1
   0.5%
Total Bilirubin, G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Creatine Kinase, G3 Number Analyzed 201 participants 209 participants 205 participants
2
   1.0%
3
   1.4%
2
   1.0%
Creatine Kinase, G4 Number Analyzed 194 participants 203 participants 202 participants
3
   1.5%
1
   0.5%
1
   0.5%
Carbon Dioxide, G3 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Carbon Dioxide, G4 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
0
   0.0%
0
   0.0%
Creatinine, G3 Number Analyzed 194 participants 203 participants 202 participants
3
   1.5%
6
   3.0%
1
   0.5%
Creatinine, G4 Number Analyzed 194 participants 203 participants 202 participants
3
   1.5%
2
   1.0%
0
   0.0%
Magnesium, G3 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
0
   0.0%
0
   0.0%
Magnesium, G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
1
   0.5%
Hypercalcemia, G3 Number Analyzed 194 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypercalcemia, G4 Number Analyzed 194 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperkalemia, G3 Number Analyzed 193 participants 202 participants 202 participants
2
   1.0%
0
   0.0%
1
   0.5%
Hyperkalemia, G4 Number Analyzed 193 participants 202 participants 202 participants
1
   0.5%
5
   2.5%
3
   1.5%
Hypernatremia, G3 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
1
   0.5%
5
   2.5%
Hypernatremia, G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypocalcemia, G3 Number Analyzed 193 participants 202 participants 202 participants
10
   5.2%
7
   3.5%
8
   4.0%
Hypocalcemia, G4 Number Analyzed 193 participants 202 participants 202 participants
2
   1.0%
4
   2.0%
4
   2.0%
Hypokalemia, G3 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypokalemia, G4 Number Analyzed 193 participants 202 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyponatremia, G3 Number Analyzed 194 participants 203 participants 202 participants
1
   0.5%
0
   0.0%
0
   0.0%
Hyponatremia G4 Number Analyzed 194 participants 203 participants 202 participants
0
   0.0%
0
   0.0%
0
   0.0%
29.Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
Hide Description A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, lymphocytes, total neutrophils, platelet count, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the pre-dose value collected on Study Day 1.
Time Frame Baseline (Day 1) and up to 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only the participants available at the time of assessment were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 201 209 205
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin, G3 Number Analyzed 194 participants 202 participants 200 participants
29
  14.9%
24
  11.9%
26
  13.0%
Hemoglobin, G4 Number Analyzed 194 participants 202 participants 200 participants
2
   1.0%
5
   2.5%
8
   4.0%
Lymphocytes, G3 Number Analyzed 186 participants 199 participants 198 participants
6
   3.2%
5
   2.5%
11
   5.6%
Lymphocytes, G4 Number Analyzed 186 participants 199 participants 198 participants
3
   1.6%
14
   7.0%
7
   3.5%
Total Neutrophils, G3 Number Analyzed 193 participants 202 participants 200 participants
1
   0.5%
2
   1.0%
2
   1.0%
Total Neutrophils, G4 Number Analyzed 193 participants 202 participants 200 participants
4
   2.1%
4
   2.0%
3
   1.5%
Platelet count, G3 Number Analyzed 194 participants 200 participants 198 participants
4
   2.1%
4
   2.0%
5
   2.5%
Platelet count, G4 Number Analyzed 194 participants 200 participants 198 participants
3
   1.5%
3
   1.5%
2
   1.0%
Leukocytes Count, G3 Number Analyzed 194 participants 202 participants 200 participants
1
   0.5%
1
   0.5%
0
   0.0%
Leukocytes Count, G4 Number Analyzed 194 participants 202 participants 200 participants
2
   1.0%
1
   0.5%
3
   1.5%
30.Secondary Outcome
Title Median Quantity of Oxygen Delivery Measured at Baseline (Day 1) and During the Study
Hide Description Oxygen delivery were assessed three times daily at Baseline (Day 1) and during the treatment period/hospitalization (ideally at least 6 hours apart) and once daily during inpatient/hospitalization and once at Post +5 days, +16 days, and +28 days clinic visits. The median quantity of oxygen delivery during the study was not summarized since the data was not collected in a way to accurately calculate values. Baseline is defined as the pre-dose value collected on Study Day 1.
Time Frame Baseline (Day 1) and during the study
Hide Outcome Measure Data
Hide Analysis Population Description
This end point was not analyzed
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
31.Secondary Outcome
Title Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) and Day 4
Hide Description On Baseline/Day 1, a 12-lead ECG was obtained within approximately 24 hours prior to dosing. The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. In the original protocol ECGs were also done on Day 4, however, amendment 2 removed this requirement and therefore not all participants had Day 4 ECGs.
Time Frame Baseline (Day 1) and Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 197 208 203
Measure Type: Count of Participants
Unit of Measure: Participants
Normal
100
  50.8%
121
  58.2%
99
  48.8%
Abnormal - Not Clinically Significant
97
  49.2%
86
  41.3%
102
  50.2%
Abnormal – Clinically Significant
5
   2.5%
4
   1.9%
7
   3.4%
32.Secondary Outcome
Title Serum Concentration of IV Zanamivir
Hide Description Pharmacokinetic samples were collected at four time points to characterize peak concentration (end of infusion; C[EOI]) after the first dose on Day 1 and on Day 4 to characterize the pre-dose concentration (C[0]), the peak concentration C(EOI), and the trough concentration at 11-12 hours post-dose (C[12]) of zanamavir. Data was summarized by Creatinine clearance (CL) Category. The dose on Day 1 is the initial dose (unadjusted) and the dose on Day 4 is the maintenance dose.
Time Frame Day 1 and Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population comprised of all participants who received IV zanamivir and underwent sparse PK sampling during the study from which one or more serum zanamivir concentrations was determined. This outcome was not analyzed for participants receiving oseltamivir 75 mg. Only the participants available at the time point were analyzed.
Arm/Group Title IV Zanamivir 300 mg IV Zanamivir 600 mg Oral Oseltamivir 75 mg
Hide Arm/Group Description:
Participants >=16 years of age received IV zanamivir 300 mg twice daily, adjusted for renal function for 5–10 days.
Participants >=16 years of age received IV zanamivir 600 mg twice daily, adjusted for renal function for 5–10 days
Participants >=16 years of age received oral oseltamvir 75 mg twice daily, adjusted for renal function for 5–10 days.
Overall Number of Participants Analyzed 180 187 0
Mean (Standard Deviation)
Unit of Measure: microgram/Liter (mcg/L)
CL <15, Day 1, 30 min Number Analyzed 1 participants 3 participants 0 participants
14454.6 [1]   (NA) 26410.8  (21335.43)
CL <15, Day 4, pre-dose Number Analyzed 1 participants 2 participants 0 participants
293.2 [1]   (NA) 9635.6  (8270.67)
CL <15, Day 4, 30 min Number Analyzed 1 participants 1 participants 0 participants
1329.4 [1]   (NA) 19828.9 [2]   (NA)
CL <15, Day 4, 11-12 hr Number Analyzed 1 participants 1 participants 0 participants
605.1 [1]   (NA) 15459.1 [2]   (NA)
CL 15-<30, Day 13, 30 min Number Analyzed 13 participants 9 participants 0 participants
20403.3  (11623.28) 41102.8  (13884.08)
CL 15-<30, Day 4, pre-dose Number Analyzed 10 participants 6 participants 0 participants
5906.4  (7167.87) 4995.6  (1966.72)
CL 15-<30, Day 4, 30 min Number Analyzed 10 participants 6 participants 0 participants
13636.4  (14029.44) 13378  (2581.36)
CL 15-<30, Day 4, 11-12 hr Number Analyzed 8 participants 5 participants 0 participants
7600.3  (8061.65) 4953.4  (2232.16)
CL 30-<50, Day 1, 30 min Number Analyzed 28 participants 18 participants 0 participants
18756.8  (12806.43) 42467.3  (14574.82)
CL 30-<50, Day 4, pre-dose Number Analyzed 12 participants 15 participants 0 participants
2094.8  (1300.99) 7637.4  (7212.1)
CL 30-<50, Day 4, 30 min Number Analyzed 12 participants 13 participants 0 participants
12334.4  (12121.18) 159292.1  (473267.3)
CL 30-<50, Day 4, 11-12 hr Number Analyzed 11 participants 13 participants 0 participants
2932.5  (2425.81) 19549.2  (40577.76)
CL 50-<80, Day 1, 30 min Number Analyzed 36 participants 49 participants 0 participants
19146.7  (8853.11) 49666.1  (111785.9)
CL 50-<80, Day 4, pre-dose Number Analyzed 31 participants 25 participants 0 participants
2793.3  (4694.43) 13107.7  (33768.61)
CL 50-<80, Day 4, 30 min Number Analyzed 32 participants 25 participants 0 participants
31541.3  (93381) 22220.4  (10064.83)
CL 50-<80, Day 4, 11-12 hr Number Analyzed 30 participants 23 participants 0 participants
1345.9  (1122.18) 22623.9  (57663.24)
CL >=80, Day 1, 30 min, Number Analyzed 93 participants 96 participants 0 participants
18561.7  (10332.14) 35139.2  (17693.85)
CL >=80, Day 4, pre-dose Number Analyzed 99 participants 107 participants 0 participants
2342.6  (6672.12) 19379.8  (105056.3)
CL >=80, Day 4, 30 min Number Analyzed 100 participants 106 participants 0 participants
21580.7  (22062.69) 75255.1  (167670.6)
CL >=80, Day 4, 11-12 hr Number Analyzed 94 participants 99 participants 0 participants
2036.2  (4412.75) 19428.7  (142284.7)
Missing, Day 1, 30 min Number Analyzed 0 participants 2 participants 0 participants
41109.7  (3831.74)
[1]
Data not collected
[2]
Data not available
Time Frame From the start of study drug until follow-up (up to 42 days).
Adverse Event Reporting Description Safety population was used to assess adverse events.
 
Arm/Group Title Intravenous (IV) Zanamivir 300mg Twice Daily Intravenous (IV) Zanamivir 600mg Twice Daily Oral Oseltamivir 75mg Twice Daily
Hide Arm/Group Description 300mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily 600mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily 75mg oral oseltamivir twice daily plus intravenous placebo zanamivir twice daily
All-Cause Mortality
Intravenous (IV) Zanamivir 300mg Twice Daily Intravenous (IV) Zanamivir 600mg Twice Daily Oral Oseltamivir 75mg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/201 (7.46%)   15/209 (7.18%)   11/205 (5.37%) 
Show Serious Adverse Events Hide Serious Adverse Events
Intravenous (IV) Zanamivir 300mg Twice Daily Intravenous (IV) Zanamivir 600mg Twice Daily Oral Oseltamivir 75mg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/201 (18.91%)   33/209 (15.79%)   38/205 (18.54%) 
Blood and lymphatic system disorders       
Anaemia  1  0/201 (0.00%)  0/209 (0.00%)  2/205 (0.98%) 
Disseminated intravascular  1  1/201 (0.50%)  0/209 (0.00%)  1/205 (0.49%) 
Neutropenia  1  0/201 (0.00%)  0/209 (0.00%)  2/205 (0.98%) 
Febrile neutropenia  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Thrombocytopenia  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Cardiac disorders       
Cardiac arrest  1  2/201 (1.00%)  1/209 (0.48%)  1/205 (0.49%) 
Cardiac failure congestive  1  1/201 (0.50%)  1/209 (0.48%)  1/205 (0.49%) 
Cardiac failure  1  1/201 (0.50%)  0/209 (0.00%)  1/205 (0.49%) 
Myocardial infarction  1  1/201 (0.50%)  1/209 (0.48%)  0/205 (0.00%) 
Angina pectoris  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Atrial fibrillation  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Bradycardia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Cardio-respiratory arrest  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Cardiogenic shock  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Cardiomyopathy  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Myocardial ischaemia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Myocarditis  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Tachycardia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Gastrointestinal disorders       
Gastrointestinal haemorrhage  1  0/201 (0.00%)  1/209 (0.48%)  1/205 (0.49%) 
General disorders       
Multi-organ failure  1  2/201 (1.00%)  2/209 (0.96%)  2/205 (0.98%) 
Catheter site haemorrhage  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Hyperthermia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Pyrexia  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Drug-induced liver injury  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Liver injury  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Immune system disorders       
Anti-neutrophil cytoplasmic antibody  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Infections and infestations       
Pneumonia  1  7/201 (3.48%)  1/209 (0.48%)  4/205 (1.95%) 
Septic shock  1  4/201 (1.99%)  1/209 (0.48%)  2/205 (0.98%) 
Sepsis  1  1/201 (0.50%)  1/209 (0.48%)  1/205 (0.49%) 
Bronchitis  1  2/201 (1.00%)  0/209 (0.00%)  0/205 (0.00%) 
Lower respiratory tract infection  1  1/201 (0.50%)  1/209 (0.48%)  0/205 (0.00%) 
Abscess limb  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Bronchopulmonary aspergillosis  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Cellulitis  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Endocarditis  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Influenza  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Lung infection  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Oral herpes  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Pneumonia bacterial  1  0/201 (0.00%)  1/209 (0.48%)  1/205 (0.49%) 
Pneumonia necrotising  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Pneumonia pseudomonal  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Staphylococcal infection  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Tracheobronchitis  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Urinary tract infection  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Vestibular neuronitis  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Viral infection  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  1/201 (0.50%)  1/209 (0.48%)  0/205 (0.00%) 
Endotracheal intubation complication  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Post procedural complication  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Tracheostomy malfunction  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Blood bilirubin increased  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
ECG signs of ventricular hypertrophy  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Electrocardiogram QT prolonged  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Hypoalbuminaemia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Hypocalcaemia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Gouty arthritis  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lymphoma  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Myelodysplastic syndrome  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Nervous system disorders       
Encephalopathy  1  1/201 (0.50%)  0/209 (0.00%)  1/205 (0.49%) 
Cerebral haemorrhage  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Intraventricular haemorrhage  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Ischaemic stroke  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Neuromyopathy  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Seizure  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Psychiatric disorders       
Agitation  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Confusional state  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Delirium febrile  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Mental status changes  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  4/201 (1.99%)  0/209 (0.00%)  0/205 (0.00%) 
Chronic kidney disease  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
IgA nephropathy  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Renal impairment  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory failure  1  5/201 (2.49%)  4/209 (1.91%)  5/205 (2.44%) 
Acute respiratory distress syndrome  1  4/201 (1.99%)  3/209 (1.44%)  0/205 (0.00%) 
Chronic obstructive pulmonary  1  1/201 (0.50%)  2/209 (0.96%)  2/205 (0.98%) 
Bronchospasm  1  0/201 (0.00%)  0/209 (0.00%)  2/205 (0.98%) 
Dyspnoea  1  1/201 (0.50%)  0/209 (0.00%)  1/205 (0.49%) 
Respiratory distress  1  0/201 (0.00%)  2/209 (0.96%)  0/205 (0.00%) 
Hypoxia  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Pneumonia aspiration  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Pneumothorax  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Pulmonary embolism  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Pulmonary fibrosis  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
Pulmonary haemorrhage  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Respiratory disorderv  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Acute respiratory failure  1  1/201 (0.50%)  1/209 (0.48%)  1/205 (0.49%) 
Skin and subcutaneous tissue disorders       
Subcutaneous emphysema  1  1/201 (0.50%)  1/209 (0.48%)  0/205 (0.00%) 
Decubitus ulcer  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Dermatitis allergic  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Surgical and medical procedures       
Mechanical ventilation  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/201 (0.50%)  0/209 (0.00%)  0/205 (0.00%) 
Distributive shock  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Hypotension  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Hypovolaemic shock  1  0/201 (0.00%)  0/209 (0.00%)  1/205 (0.49%) 
Shock haemorrhagic  1  0/201 (0.00%)  1/209 (0.48%)  0/205 (0.00%) 
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intravenous (IV) Zanamivir 300mg Twice Daily Intravenous (IV) Zanamivir 600mg Twice Daily Oral Oseltamivir 75mg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/201 (8.46%)   26/209 (12.44%)   24/205 (11.71%) 
Gastrointestinal disorders       
Diarrhoea  1  10/201 (4.98%)  15/209 (7.18%)  14/205 (6.83%) 
Constipation  1  7/201 (3.48%)  13/209 (6.22%)  10/205 (4.88%) 
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment