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Safety and Immunogenicity of A/H1N1-SOIV (Swine Flu) Vaccine With and Without Adjuvant in Non-Elderly and Elderly Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00973349
Recruitment Status : Completed
First Posted : September 9, 2009
Results First Posted : May 25, 2011
Last Update Posted : December 7, 2015
Sponsor:
Collaborator:
Novartis Vaccines
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Condition Influenza
Intervention Biological: MF59-eH1N1_f
Enrollment 2719
Recruitment Details Participants were enrolled at 21 sites in the US.
Pre-assignment Details  
Arm/Group Title 3.75_(50)MF59 (18-64 Years) 7.5 w/o MF59 (18-64 Years) 7.5_(50)MF59 (18-64 Years) 7.5_(100)MF59 (18-64 Years) 15 w/o MF59 (18-64 Years) 15_(50)MF59 (18-64 Years) 15_(100)MF59 (18-64 Years) 30 w/o MF59(18-64 Years) 3.75_(50)MF59 (≥ 65 Years) 7.5 w/o MF59 (≥ 65 Years) 7.5_(50)MF59 (≥ 65 Years) 7.5_(100)MF59 (≥ 65 Years) 15 w/o MF59 (≥ 65 Years) 15_(50)MF59 (≥ 65 Years) 15_(100)MF59 (≥ 65 Years) 30 w/o MF59(≥ 65 Years)
Hide Arm/Group Description 50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22 1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22 50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22 100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22 1 dose of 15 µg A/H1N1 administered on study day 1 and day 22 50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22 100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22 1 dose of 30 µg A/H1N1 administered on study day 1 and day 22 50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22 1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22 50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22 100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22 1 dose of 15 µg A/H1N1 administered on study day 1 and day 22 50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22 100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22 1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Period Title: Overall Study
Started 170 168 171 168 170 169 174 169 171 169 174 169 169 171 170 167
Completed 166 165 166 163 165 165 172 166 167 163 174 167 168 171 168 165
Not Completed 4 3 5 5 5 4 2 3 4 6 0 2 1 0 2 2
Reason Not Completed
Adverse Event             0             0             0             0             1             0             0             0             1             0             0             0             0             0             1             0
Withdrawal by Subject             1             2             2             3             2             0             2             2             0             2             0             1             0             0             0             0
Lost to Follow-up             3             1             2             2             1             3             0             1             2             1             0             1             0             0             0             1
Inappropriate enrolment             0             0             1             0             0             0             0             0             0             2             0             0             1             0             1             1
Protocol Violation             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
Unable to classify             0             0             0             0             1             1             0             0             0             1             0             0             0             0             0             0
Arm/Group Title 3.75_(50)MF59 (18 to 64) 7.5 w/o MF59 (18 to 64) 7.5_(50)MF59 (18 to 64) 7.5_(100)MF59 (18 to 64) 15 w/o MF59 (18 to 64) 15_(50)MF59 (18 to 64) 15_(100)MF59 (18 to 64) 30 w/o MF59 (18 to 64) 3.75_(50)MF59 (≥ 65 ) 7.5 w/o MF59 (≥ 65) 7.5_(50)MF59 (≥ 65) 7.5_(100)MF59 (≥ 65) 15 w/o MF59 (≥ 65) 15_(50)MF59 (≥ 65) 15_(100)MF59 (≥ 65) 30 w/o MF59 (≥ 65) Total
Hide Arm/Group Description 50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen in subjects 18 to 64 years of age 1 dose of 7.5 µg A/H1N1 in subjects 18 to 64 years of age 50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen in subjects 18 to 64 years of age 100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen in subjects 18 to 64 years of age 1 dose of 15 µg A/H1N1 in subjects 18 to 64 years of age 50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen in subjects 18 to 64 years of age 100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen 1 dose of 30 µg A/H1N1 in subjects 18 to 64 years of age 50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen in subjects ≥ 65 years of age 1 dose of 7.5 µg A/H1N1 in subjects ≥ 65 years of age 50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen in subjects ≥ 65 years of age 100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen in subjects ≥ 65 years of age 1 dose of 15 µg A/H1N1 in subjects ≥ 65 years of age 50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen in subjects ≥ 65 years of age 100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen in subjects ≥ 65 years of age 1 dose of 30 µg A/H1N1 in subjects ≥ 65 years of age Total of all reporting groups
Overall Number of Baseline Participants 155 153 157 153 155 154 159 154 170 168 172 168 168 171 169 166 2592
Hide Baseline Analysis Population Description
ITT population for immunology assessments. Participants from one center excluded for GCP issues.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 153 participants 157 participants 153 participants 155 participants 154 participants 159 participants 154 participants 170 participants 168 participants 172 participants 168 participants 168 participants 171 participants 169 participants 166 participants 2592 participants
40.3  (12.8) 39.8  (12.9) 39.1  (13.5) 40.6  (12.2) 41.8  (12.9) 39.7  (13.1) 38.8  (11.9) 40.8  (13.0) 70.8  (5.1) 71.8  (5.6) 71.4  (5.6) 70.7  (5.1) 71.0  (5.0) 70.4  (4.9) 71.3  (5.2) 70.8  (5.3) 39.6  (12.8)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 155 participants 153 participants 157 participants 153 participants 155 participants 154 participants 159 participants 154 participants 170 participants 168 participants 172 participants 168 participants 168 participants 171 participants 169 participants 166 participants 2592 participants
Male(18 to 64 or ≥65 years) 61 62 57 59 57 69 71 63 54 88 71 70 68 74 79 76 1079
Female(18 to 64 or ≥65 yrs) 94 91 100 94 98 85 88 91 116 80 101 98 100 97 90 90 1513
1.Primary Outcome
Title Immunogenicity Results After Each Vaccination by Vaccine Group, in Participants 18 to 64 Years of Age
Hide Description Seroconversion is defined by CBER (Center for Biologics Evaluation, Research and Review) as the percentage of participants with either a prevaccination HI titer <1:10 and a post vaccination HI titer > 40 or a pre-vaccination HI titer > 10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seroprotection is defined as participants having HI antibody titer ≥1:40.
Time Frame 21 days after each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on the per protocol population.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 146 142 142 141 141 138 149 144
Measure Type: Number
Unit of Measure: Participants
Seroprotection Day 22 129 126 135 134 133 135 147 141
Seroconversion Day 22 113 100 123 126 127 124 135 130
Seroprotection Day 43 138 133 136 137 135 137 145 142
Seroconversion Day 43 118 104 123 129 126 125 139 132
Seroprotection Day 202 (N=79,65,78,80,73,74,74,76) 68 51 67 70 56 59 65 69
Seroconversion Day 202 (N=79,65,78,80,73,74,74,76) 50 32 48 53 49 49 51 55
Seroprotection Day 387(N=105,95,88,84,91,91,106,84 76 78 66 67 66 74 89 69
Seroconversion Day387(N=105,95,88,84,91,91,106,84) 52 48 50 53 58 62 71 54
2.Primary Outcome
Title Immunogenicity Results After Each Vaccination by Vaccine Group, in Participants ≥65 Years of Age
Hide Description Seroconversion is defined by CBER as the percentage of participants with either a prevaccination HI titer <1:10 and a post vaccination HI titer > 40 or a pre-vaccination HI titer > 10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seroprotection is defined as participants having HI antibody titer ≥1:40.
Time Frame 21 days after each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the per protocol set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 150 147 164 148 159 155 154 150
Measure Type: Number
Unit of Measure: Participants
Seroprotection Day 22 122 119 126 122 136 141 142 135
Seroconversion Day 22 89 76 102 92 104 110 111 108
Seroprotection Day 43 131 116 132 131 126 136 143 136
Seroconversion Day 43 90 75 103 95 94 106 113 103
Seroprotection Day 202 (N=80,71,85,79,84,82,87,82) 54 41 45 52 55 45 63 57
Seroconversion Day 202 (N=80,71,85,79,84,82,87,82) 31 16 30 31 35 27 38 36
Seroprotection Day 387(N=84,87,98,86,106,93,89,99) 50 56 55 57 67 55 65 69
Seroconversion Day 387(N=84,87,98,86,106,93,89,99) 30 25 26 33 37 30 47 32
3.Secondary Outcome
Title Geometric Mean HI Titer by Vaccine Groups; in Participants 18 to 64 Years of Age and ≥65 Years of Age
Hide Description Geometric mean hemagglutinin inhibition (HI) titer = GMT
Time Frame 21 days after each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the per protocol set. For this analysis, total subjects enrolled were stratified and randomized in two age groups, according to the CBER criteria, 18 to 64 years and over 64 years of age.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 296 289 306 289 300 293 303 294
Geometric Mean (95% Confidence Interval)
Unit of Measure: Geometric Mean Titer
Day 22(18-64yrs;N=146,142,142,141,141,138,149,144)
299
(234 to 382)
238
(185 to 306)
379
(295 to 486)
551
(429 to 708)
536
(417 to 689)
538
(418 to 693)
677
(530 to 864)
637
(497 to 817)
Day 43(18-64yrs;N=146,142,142,141,141,138,149,144)
327
(262 to 409)
239
(198 to 299)
359
(286 to 449)
538
(429 to 675)
412
(328 to 517)
494
(393 to 621)
618
(496 to 771)
497
(397 to 622)
Day 22 (≥65 yrs;N=150,147,164,148,159,155,154,150)
138
(107 to 178)
133
(103 to 172)
146
(114 to 185)
184
(143 to 238)
187
(146 to 238)
203
(159 to 261)
252
(197 to 324)
237
(184 to 305)
Day 43 (≥65 yrs;N=150,147,164,148,159,155,154,150)
135
(107 to 171)
118
(93 to 149)
131
(104 to 164)
167
(132 to 212)
151
(120 to 190)
164
(130 to 207)
240
(190 to 302)
211
(167 to 267)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 7.5 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 1.265
Confidence Interval (2-Sided) 95%
0.998 to 1.603
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 7.5_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.999
Confidence Interval (2-Sided) 95%
0.791 to 1.262
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 7.5_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.708
Confidence Interval (2-Sided) 95%
0.558 to 0.897
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 15 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.861
Confidence Interval (2-Sided) 95%
0.681 to 1.089
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 15_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.754
Confidence Interval (2-Sided) 95%
0.596 to 0.956
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.548
Confidence Interval (2-Sided) 95%
0.434 to 0.693
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 3.75_(50)MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.646
Confidence Interval (2-Sided) 95%
0.510 to 0.817
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 7.5_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at 43
Estimated Value 0.790
Confidence Interval (2-Sided) 95%
0.625 to 1.000
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 7.5_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at 43
Estimated Value 0.560
Confidence Interval (2-Sided) 95%
0.441 to 0.710
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 15 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at 43
Estimated Value 0.681
Confidence Interval (2-Sided) 95%
0.538 to 0.862
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 15_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at 43
Estimated Value 0.597
Confidence Interval (2-Sided) 95%
0.470 to 0.757
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.434
Confidence Interval (2-Sided) 95%
0.342 to 0.549
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 7.5 w/o MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.511
Confidence Interval (2-Sided) 95%
0.403 to 0.647
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 7.5_(50)MF59, 7.5_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.708
Confidence Interval (2-Sided) 95%
0.560 to 0.896
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 7.5_(50)MF59, 15 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.862
Confidence Interval (2-Sided) 95%
0.683 to 1.088
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 7.5_(50)MF59, 15_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.755
Confidence Interval (2-Sided) 95%
0.597 to 0.954
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 7.5_(50)MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.549
Confidence Interval (2-Sided) 95%
0.435 to 0.692
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection 7.5_(50)MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.646
Confidence Interval (2-Sided) 95%
0.511 to 0.817
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 7.5_(100)MF59, 15 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 1.217
Confidence Interval (2-Sided) 95%
0.961 to 1.541
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection 7.5_(100)MF59, 15_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 1.066
Confidence Interval (2-Sided) 95%
0.841 to 1.352
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 7.5_(100)MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.775
Confidence Interval (2-Sided) 95%
0.612 to 0.981
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection 7.5_(100)MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67.
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.912
Confidence Interval (2-Sided) 95%
0.719 to 1.157
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 15 w/o MF59, 15_(50)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.876
Confidence Interval (2-Sided) 95%
0.692 to 1.109
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection 15 w/o MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.637
Confidence Interval (2-Sided) 95%
0.504 to 0.804
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection 15 w/o MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.750
Confidence Interval (2-Sided) 95%
0.593 to 0.949
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection 15_(50)MF59, 15_(100)MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.727
Confidence Interval (2-Sided) 95%
0.574 to 0.919
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection 15_(50)MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 0.856
Confidence Interval (2-Sided) 95%
0.675 to 1.084
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection 15_(100)MF59, 30 w/o MF59
Comments Two-sided 95% CI around the point estimates were to be presented for each endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The 2-sided CIs were examined against a non-inferiority margin of 0.67
Method of Estimation Estimation Parameter Geometric mean ratio at day 43
Estimated Value 1.178
Confidence Interval (2-Sided) 95%
0.931 to 1.489
Estimation Comments Pairwise Comparisons of GMTs (95% CI) Between Vaccination Groups at Day 43, on the pooled age groups.
4.Secondary Outcome
Title Number of Subjects With Seroconversion and With HI ≥1:40, in Participants 18 to 60 Years of Age
Hide Description Immunogenicity evaluation after each vaccination by vaccine group according to CHMP (Committee for Medicinal Products for Human Use) criteria. Seroconversion is defined as the percentage of participants with either a prevaccination HI titer <1:10 and a post vaccination HI titer > 40 or a pre-vaccination HI titer > 10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seroprotection is defined as Hemagglutinin Inhibition (HI) antibody titer ≥1:40.
Time Frame 21 days after each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the per protocol set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 135 130 132 132 122 124 141 127
Measure Type: Number
Unit of Measure: Participants
Seroprotection Day 22 121 118 126 125 116 121 140 125
Seroconversion Day 22 108 95 116 118 111 113 129 116
Seroprotection Day 43 128 124 126 128 118 123 138 126
Seroconversion Day 43 112 98 115 122 110 114 132 119
5.Secondary Outcome
Title Number of Subjects With Seroconversion and With HI ≥1:40, in Participants ≥61 Years of Age
Hide Description Immunogenicity evaluation after each vaccination by vaccine group according to CHMP criteria. Seroconversion is defined as the percentage of participants with either a prevaccination HI titer <1:10 and a post vaccination HI titer > 40 or a pre-vaccination HI titer > 10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seroprotection is defined as Hemagglutinin Inhibition (HI) antibody titer ≥1:40.
Time Frame 21 days after each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the per protocol set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 161 159 174 157 178 169 162 167
Measure Type: Number
Unit of Measure: Participants
Seroprotection Day 22 130 127 135 131 153 155 149 151
Seroconversion Day 22 94 81 109 100 120 121 117 122
Seroprotection Day 43 140 125 142 140 143 150 150 152
Seroconversion Day 43 96 81 111 102 110 117 120 116
6.Secondary Outcome
Title Geometric Mean Ratio From Baseline, in Participants 18 to 60 Years of Age and ≥61 Years of Age
Hide Description Immunogenicity evaluation after each vaccination by vaccine group according to CHMP criteria. Geometric Mean Ratio (GMR) of the hemagglutinin inhibition (HI)titers.
Time Frame 21 days after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the per protocol set. For this analysis, total subjects enrolled were stratified and randomized in two age groups, according to the CHMP criteria, 18 to 60 years and over 60 years of age.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 296 289 306 289 300 293 303 294
Geometric Mean (95% Confidence Interval)
Unit of Measure: Geometric Mean Ratio
Day 22 (18-60y; N=135,130,132,132,122,124,141,127)
19
(15 to 26)
15
(11 to 20)
23
(17 to 31)
33
(25 to 44)
40
(30 to 54)
36
(27 to 49)
44
(33 to 58)
47
(35 to 63)
Day 43 (18-60y; N=135,130,132,132,122,124,141,127)
20
(16 to 27)
15
(11 to 20)
22
(17 to 28)
33
(25 to 43)
31
(23 to 40)
33
(25 to 44)
40
(31 to 51)
37
(28 to 48)
Day 22 (≥61yrs; N=161,159,174,157,178,169,162,167)
6.11
(4.8 to 7.78)
4.65
(3.65 to 5.94)
7.46
(5.91 to 9.41)
8.63
(6.75 to 11)
8.37
(6.64 to 11)
9.6
(7.57 to 12)
11
(9.04 to 15)
10
(7.97 to 13)
Day 43 (≥61 yrs;N=161,159,174,157,178,169,162,167)
6.2
(4.97 to 7.75)
4.18
(3.34 to 5.23)
6.77
(5.47 to 8.4)
7.78
(6.21 to 9.75)
6.72
(5.43 to 8.31)
7.78
(6.25 to 9.68)
11
(8.76 to 14)
8.8
(7.07 to 11)
7.Secondary Outcome
Title Number of Participants Reporting Solicited Local and Systemic Reactions After the First Vaccination, in Participants 18 to 64 Years of Age
Hide Description Solicited local and systemic reactions that occurred within 7 days after the day of vaccination were used as indicators of reactogenicity.
Time Frame 7 days after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The population used in analysis was the safety set
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 169 168 170 165 170 168 173 168
Measure Type: Number
Unit of Measure: Participants
Pain 67 38 51 78 27 57 78 44
Erythema 2 2 2 4 3 2 4 0
Swelling 9 6 4 6 4 3 13 3
Induration 11 5 9 9 8 8 15 7
Tenderness 63 44 59 79 42 64 89 51
Chills 6 9 11 8 9 8 14 10
Myalgia 29 22 28 29 21 30 37 24
Arthralgia 14 13 17 10 11 10 6 7
Headache 37 39 42 32 43 39 36 36
Nausea 14 15 19 8 12 13 16 13
Vomiting (N=169, 168, 169, 165, 170, 168, 173,168) 3 3 2 1 3 2 1 2
Diarrhoea 11 7 19 5 11 15 6 7
Fatigue 25 28 27 17 27 27 26 27
Oral Temp. (≥40°C) 0 0 0 0 0 0 0 0
Stay Home 6 6 4 3 8 9 9 6
8.Secondary Outcome
Title Number of Participants Reporting Solicited Local and Systemic Reactions After the Second Vaccination, in Participants 18 to 64 Years of Age
Hide Description Solicited local and systemic reactions that occurred within 7 days after the day of vaccination were used as indicators of reactogenicity.
Time Frame 7 days after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the safety set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 164 163 162 160 162 160 169 163
Measure Type: Number
Unit of Measure: Participants
Pain 46 32 39 42 35 43 54 45
Erythema (N=164,163,162,160,162,160,169,163) 2 1 3 1 3 1 4 1
Swelling (N=164,163,162,160,162,160,169,162) 10 2 5 8 6 4 9 2
Induration (N=164,163,162,160,162,160,169,163) 7 5 6 7 5 11 13 11
Tenderness (N=164,163,162,160,162,160,169,163) 51 33 52 56 44 58 66 56
Chills (N=164,163,162,160,162,160,169,163) 9 3 4 5 5 7 5 2
Myalgia (N=164,163,162,160,162,160,169,163) 22 18 14 20 20 16 24 10
Arthralgia (N=164,163,162,160,162,160,169,163) 7 4 7 7 6 7 14 3
Headache(N=164,163,162,160,162,160,169,163) 28 17 26 23 25 32 26 17
Nausea(N=164,163,162,160,162,160,169,163) 5 7 9 8 4 9 13 6
Vomiting (N=164,163,162,160,162,160,169,163) 0 1 1 0 1 1 2 0
Diarrhoea(N=164,163,162,160,162,160,169,163) 5 11 8 5 6 8 7 5
Fatigue(N=164,163,162,160,162,160,169,163) 17 12 15 18 12 18 26 10
Oral Temp ≥40°C 0 0 0 0 0 0 0 0
Stay Home (N=164,163,161,160,162,159,169,163) 4 3 5 0 2 3 6 0
Analg/antipyr (N=164,163,162,160,162,160,169,163) 11 6 7 5 9 14 10 9
9.Secondary Outcome
Title Number of Participants Reporting Solicited Local and Systemic Reactions After the First Vaccination, in Participants ≥65 Years of Age
Hide Description Solicited local and systemic reactions that occurred within 7 days after the day of vaccination were used as indicators of reactogenicity.
Time Frame 7 days after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the safety set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 170 166 173 169 169 171 169 167
Measure Type: Number
Unit of Measure: Participants
Pain 18 8 22 30 15 27 16 19
Erythema 1 1 1 2 3 2 3 5
Swelling 1 6 2 14 1 1 1 10
Induration 8 8 5 10 2 6 7 14
Tenderness 27 10 23 42 24 28 39 32
Chills 6 8 5 4 6 1 5 3
Myalgia 20 14 19 21 17 15 21 14
Arthralgia 13 9 13 12 11 10 11 10
Headache 23 21 22 25 16 22 17 14
Nausea 2 4 2 3 6 5 6 7
Vomitting (N=170,166,173,169.169,170,169,167) 0 2 0 0 0 1 0 0
Diarrhoea 5 10 14 9 9 12 9 6
Fatigue 23 20 21 19 20 15 22 13
Oral Temp ≥40°C 0 0 1 0 0 0 0 0
Stay Home 8 3 8 3 2 4 5 4
Analg/antipyr (N=170,166,172,169.167,171,169,166) 9 7 7 11 7 6 5 2
10.Secondary Outcome
Title Number of Participants Reporting Solicited Local and Systemic Reactions After the Second Vaccination, in Participants ≥65 Years of Age
Hide Description Solicited local and systemic reactions that occurred within 7 days after the day of vaccination were used as indicators of reactogenicity.
Time Frame 7 days after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was on the safety set.
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59
Hide Arm/Group Description:
50% of MF59 (an adjuvant) with 3.75 µg A/H1N1 antigen administered on day 1 and day 22
1 dose of 7.5 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 7.5 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 15 µg A/H1N1 administered on study day 1 and day 22
50% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
100% of MF59 (an adjuvant) with 15 µg A/H1N1 antigen administered on study day 1 and day 22
1 dose of 30 µg A/H1N1 administered on study day 1 and day 22
Overall Number of Participants Analyzed 164 156 171 160 166 168 165 165
Measure Type: Number
Unit of Measure: Participants
Pain (N=164,156,171,160,166,168,165,165) 12 8 17 16 17 15 17 14
Erythema (N=163,156,171,160,166,168,165,164) 1 0 1 5 3 1 5 2
Swelling (N=163,156,171,160,166,168,165,164) 1 1 3 4 1 3 6 3
Induration (N=163,156,171,160,166,168,165,164) 3 3 7 4 2 6 7 6
Tenderness (N=164,156,171,160,166,168,165,164) 22 12 26 30 25 26 31 18
Chills (N=163,156,171,160,166,168,165,164) 2 7 7 4 5 3 5 3
Myalgia (N=163,156,171,160,166,168,165,164) 20 14 15 9 16 12 11 7
Arthralgia (N=163,156,171,160,166,168,165,164) 15 8 11 5 9 7 7 3
Headache (N=163,156,171,160,166,168,165,164) 14 13 17 12 15 10 11 10
Nausea (N=163,156,171,160,166,168,165,164) 4 5 5 3 7 4 4 2
Vomiting (N=164,156,171,160,166,168,165,165) 0 1 2 1 1 1 0 0
Diarrhoea (N=163,156,171,160,166,168,165,164) 4 5 10 2 6 6 6 2
Fatigue (N=163,156,171,160,166,168,165,164) 19 9 14 7 14 8 11 5
Oral Temp≥40°C (N=164,156,171,160,166,168,165,165) 0 0 1 0 0 0 0 0
Stay Home(N=163,156,171,159,166,168,165,164) 3 5 5 1 2 0 0 2
Analg/antipyr (N=164,156,171,160,166,167,165,163) 2 7 10 4 1 1 3 3
Time Frame All solicited AEs were collected for the first 3 weeks after each vaccination. SAEs, new onset of chronic diseases, AEs that led to withdrawal from study and AEs associated with medically attended visits, were collected for the whole study (days 1-387).
Adverse Event Reporting Description A systematic AE is equivalent to an event that was solicited by the diary card, while a non-systematic event is equivalent to an event not solicited by the diary card. Safety was analyzed with data from all study centers; 10 enrolled participants were excluded for not receiving study vaccine or not providing safety data after first vaccination.
 
Arm/Group Title 3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59 3.75_(50)MF59 (Above 65 Yrs) 7.5 w/o MF59 (≥65 Yrs) 7.5_(50)MF59 (≥65 Yrs) 7.5_(100)MF59 (≥65 Yrs) 15 w/o MF59 (≥ 65 Yrs) 15_(50)MF59 (≥65 Yrs) 15_(100)MF59 (≥65 Yrs) 30 w/o MF59 (≥65 Yrs)
Hide Arm/Group Description 50% of MF59 with the lowest amount of A/H1N1 antigen 1 dose of 7.5 µg A/H1N1 50% of MF59 with 7.5 µg A/H1N1 antigen 100% of MF59 with 7.5 µg A/H1N1 antigen 1 dose of 15 µg A/H1N1 50% of MF59 with 15 µg A/H1N1 antigen 100% of MF59 with 15 µg A/H1N1 antigen 1 dose of 30 µg A/H1N1 50% of MF59 with the lowest amount of A/H1N1 antigen 1 dose of 7.5 µg A/H1N1 50% of MF59 with 7.5 µg A/H1N1 antigen 100% of MF59 with 7.5 µg A/H1N1 antigen 1 dose of 15 µg A/H1N1 50% of MF59 with 15 µg A/H1N1 antigen 100% of MF59 with 15 µg A/H1N1 antigen 1 dose of 30 µg A/H1N1
All-Cause Mortality
3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59 3.75_(50)MF59 (Above 65 Yrs) 7.5 w/o MF59 (≥65 Yrs) 7.5_(50)MF59 (≥65 Yrs) 7.5_(100)MF59 (≥65 Yrs) 15 w/o MF59 (≥ 65 Yrs) 15_(50)MF59 (≥65 Yrs) 15_(100)MF59 (≥65 Yrs) 30 w/o MF59 (≥65 Yrs)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59 3.75_(50)MF59 (Above 65 Yrs) 7.5 w/o MF59 (≥65 Yrs) 7.5_(50)MF59 (≥65 Yrs) 7.5_(100)MF59 (≥65 Yrs) 15 w/o MF59 (≥ 65 Yrs) 15_(50)MF59 (≥65 Yrs) 15_(100)MF59 (≥65 Yrs) 30 w/o MF59 (≥65 Yrs)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/170 (2.94%)   5/168 (2.98%)   5/171 (2.92%)   5/165 (3.03%)   6/170 (3.53%)   6/169 (3.55%)   5/174 (2.87%)   7/168 (4.17%)   9/170 (5.29%)   16/166 (9.64%)   18/173 (10.40%)   11/169 (6.51%)   12/169 (7.10%)   20/171 (11.70%)   14/169 (8.28%)   10/167 (5.99%) 
Blood and lymphatic system disorders                                 
Anaemia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Cardiac disorders                                 
Cardiac Arrest * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cardiomyopathy * 1  0/170 (0.00%)  0/168 (0.00%)  1/171 (0.58%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Myocardial Infarction * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  2/173 (1.16%)  0/169 (0.00%)  0/169 (0.00%)  2/171 (1.17%)  0/169 (0.00%)  1/167 (0.60%) 
Angina Pectoris * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Aortic Valve imcompetence * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Atrial Fibrillation * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  1/173 (0.58%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Bradycardia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cardiac Failure Congestive * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Cardiogenic shock * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Coronary artery disease * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  2/173 (1.16%)  1/169 (0.59%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  2/167 (1.20%) 
Coronary artery occlusion * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Ear and labyrinth disorders                                 
Vertigo * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Endocrine disorders                                 
Diabetes Mellitus * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Inappropriate antidiuretic hormone secretion  1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Eye disorders                                 
Retinal Detachment * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Gastrointestinal disorders                                 
Colitis Ischaemic * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Colitis Ulcerative * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Gastric Ulcer * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  2/171 (1.17%)  0/169 (0.00%)  0/167 (0.00%) 
Gastritis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Intestinal Mass * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Intestinal Obstructuction * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Pancreatitis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Small Intestinal Obstruction * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
General disorders                                 
Dehydration * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Malaise  1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Pyrexia  1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Suicide Attempt * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Chest Pain * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  2/173 (1.16%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Hernia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Hepatobiliary disorders                                 
Gallbladder non-functioning * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Biliary Colic * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Cholecystitis * 1  0/170 (0.00%)  1/168 (0.60%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cholecystitis Acute * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cholelithiasis * 1  0/170 (0.00%)  1/168 (0.60%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  1/173 (0.58%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cholestasis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Gallbladder Disorder * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Infections and infestations                                 
Cellulitis * 1  0/170 (0.00%)  0/168 (0.00%)  1/171 (0.58%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Influenza * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  2/166 (1.20%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Pneumonia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  2/166 (1.20%)  1/173 (0.58%)  0/169 (0.00%)  2/169 (1.18%)  1/171 (0.58%)  0/169 (0.00%)  1/167 (0.60%) 
Lobar Pneumonia * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cholecystitis Infective * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cytomegalovirus Infection * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Diverticulitis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Gastroenteritis Viral * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Labyrinthitis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Sepsis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Staphylococcal Infection * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
H1N1 Influenza * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Injury, poisoning and procedural complications                                 
Ankle Fracture * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  1/169 (0.59%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Road Traffic Accident * 1  1/170 (0.59%)  0/168 (0.00%)  2/171 (1.17%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  2/171 (1.17%)  0/169 (0.00%)  0/167 (0.00%) 
Incisional Hernia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Splenic Rupture * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Traumatic Lung Injury * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Arthropod Bite * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Fall * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  1/166 (0.60%)  2/173 (1.16%)  1/169 (0.59%)  0/169 (0.00%)  2/171 (1.17%)  0/169 (0.00%)  0/167 (0.00%) 
Head Injury * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Injury * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Patella fracture * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Rib Fracture * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Scapula Fracture * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Skin Laceration * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Traumatic Brain Injury * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Urinary Retention Postoperative * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Investigations                                 
Blood Pressure Increased * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Transaminases Increased * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Metabolism and nutrition disorders                                 
Glucose Tolerance Impaired * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Hypokalaemia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Hyponatraemia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Musculoskeletal and connective tissue disorders                                 
Arthritis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Arthritis Reactive * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Intervertebral Disc Degeneration * 1  0/170 (0.00%)  1/168 (0.60%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Musculoskeletal Chest Pain * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Arthralgia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Intervertebral Disc Protrusion * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Lumbar Spinal Stenosis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Myalgia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Osteoarthritis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  4/171 (2.34%)  3/169 (1.78%)  1/167 (0.60%) 
Spinal Column Stenosis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  2/169 (1.18%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Synovial Cyst * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
Acoustic Neuroma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
B-Cell Lymphoma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Colon Cancer * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Gallbladder Cancer * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Penis Carcinoma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Prostate Cancer * 1  0/170 (0.00%)  1/168 (0.60%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  3/169 (1.78%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Breast Cancer Stage I * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Cholesteatoma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Leukaemia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  1/167 (0.60%) 
Lung Carcinoma Cell Type Unspecified Stage I * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Malignant Melanoma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Parathyroid Tumour Benign * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  1/169 (0.59%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Thyroid Neoplasm * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Uterine Cancer * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Nervous system disorders                                 
Cerebral Infarction * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Syncope * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  2/171 (1.17%)  1/169 (0.59%)  0/167 (0.00%) 
Migraine * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Viith Nerve Paralysis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Carotid Artery Occlusion * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Cerebral Haemorrhage * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Cerebrovascular Accident * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  0/169 (0.00%)  0/167 (0.00%) 
Convulsion * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Dementia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Grand Mal Convulsion * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Subarachnoid Haemorrhage * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  1/169 (0.59%)  0/167 (0.00%) 
Transient Ischaemic Attack * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  1/169 (0.59%)  1/167 (0.60%) 
Pregnancy, puerperium and perinatal conditions                                 
Abortion Spontaneous * 1  0/170 (0.00%)  1/168 (0.60%)  1/171 (0.58%)  0/165 (0.00%)  1/170 (0.59%)  1/169 (0.59%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Abortion Spontaneus Complete * 1  0/170 (0.00%)  0/168 (0.00%)  1/171 (0.58%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Eclampsia * 1  0/170 (0.00%)  0/168 (0.00%)  1/171 (0.58%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Psychiatric disorders                                 
Depression * 1  0/170 (0.00%)  1/168 (0.60%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Psychotic Disorder * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  1/170 (0.59%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Suicidal Ideation * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Anxiety * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Renal and urinary disorders                                 
Renal Failure * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Renal Failure Acute * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Urinary Retention * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Reproductive system and breast disorders                                 
Menstruation Irregular * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Benign Prostatic Hyperplasia * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Prostatic Obstruction * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Respiratory, thoracic and mediastinal disorders                                 
Pleurisy * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  1/168 (0.60%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Pulmonary Embolism * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  1/165 (0.61%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Tonsillar Hypertrophy * 1  1/170 (0.59%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Pulmonary Oedema * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Respiratory Failure * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  1/167 (0.60%) 
Surgical and medical procedures                                 
Intestinal Resection * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  1/174 (0.57%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Ankle Operation * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Knee Arthroplasty * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  1/171 (0.58%)  1/169 (0.59%)  0/167 (0.00%) 
Vascular disorders                                 
Arteriosclerosis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  1/166 (0.60%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Intra-abdominal Haemorrhage * 1  0/170 (0.00%)  0/168 (0.00%)  1/171 (0.58%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Aneurysm * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Aortic Stenosis * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  1/169 (0.59%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Arterial Occlusive Disease * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  1/170 (0.59%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Haematoma * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  0/173 (0.00%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  1/169 (0.59%)  0/167 (0.00%) 
Hypertensive Emergency * 1  0/170 (0.00%)  0/168 (0.00%)  0/171 (0.00%)  0/165 (0.00%)  0/170 (0.00%)  0/169 (0.00%)  0/174 (0.00%)  0/168 (0.00%)  0/170 (0.00%)  0/166 (0.00%)  1/173 (0.58%)  0/169 (0.00%)  0/169 (0.00%)  0/171 (0.00%)  0/169 (0.00%)  0/167 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
3.75_(50)MF59 7.5 w/o MF59 7.5_(50)MF59 7.5_(100)MF59 15 w/o MF59 15_(50)MF59 15_(100)MF59 30 w/o MF59 3.75_(50)MF59 (Above 65 Yrs) 7.5 w/o MF59 (≥65 Yrs) 7.5_(50)MF59 (≥65 Yrs) 7.5_(100)MF59 (≥65 Yrs) 15 w/o MF59 (≥ 65 Yrs) 15_(50)MF59 (≥65 Yrs) 15_(100)MF59 (≥65 Yrs) 30 w/o MF59 (≥65 Yrs)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   125/170 (73.53%)   108/168 (64.29%)   121/171 (70.76%)   128/165 (77.58%)   113/170 (66.47%)   122/169 (72.19%)   130/174 (74.71%)   110/168 (65.48%)   102/170 (60.00%)   88/166 (53.01%)   101/173 (58.38%)   118/169 (69.82%)   104/169 (61.54%)   109/171 (63.74%)   97/169 (57.40%)   99/167 (59.28%) 
Gastrointestinal disorders                                 
Nausea  1  20/170 (11.76%)  18/168 (10.71%)  25/171 (14.62%)  15/165 (9.09%)  16/170 (9.41%)  18/169 (10.65%)  27/174 (15.52%)  17/168 (10.12%)  6/170 (3.53%)  10/166 (6.02%)  9/173 (5.20%)  7/169 (4.14%)  12/169 (7.10%)  8/171 (4.68%)  11/169 (6.51%)  9/167 (5.39%) 
Diarrhoea  1  17/170 (10.00%)  18/168 (10.71%)  24/171 (14.04%)  13/165 (7.88%)  21/170 (12.35%)  18/169 (10.65%)  12/174 (6.90%)  15/168 (8.93%)  11/170 (6.47%)  17/166 (10.24%)  22/173 (12.72%)  16/169 (9.47%)  13/169 (7.69%)  17/171 (9.94%)  16/169 (9.47%)  9/167 (5.39%) 
General disorders                                 
Injection site pain  1  97/170 (57.06%)  68/168 (40.48%)  90/171 (52.63%)  109/165 (66.06%)  72/170 (42.35%)  102/169 (60.36%)  112/174 (64.37%)  80/168 (47.62%)  42/170 (24.71%)  23/166 (13.86%)  42/173 (24.28%)  60/169 (35.50%)  51/169 (30.18%)  57/171 (33.33%)  50/169 (29.59%)  47/167 (28.14%) 
Fatigue  1  33/170 (19.41%)  33/168 (19.64%)  35/171 (20.47%)  31/165 (18.79%)  31/170 (18.24%)  37/169 (21.89%)  36/174 (20.69%)  31/168 (18.45%)  36/170 (21.18%)  24/166 (14.46%)  29/173 (16.76%)  23/169 (13.61%)  26/169 (15.38%)  19/171 (11.11%)  28/169 (16.57%)  17/167 (10.18%) 
Injection site erythema  1  23/170 (13.53%)  15/168 (8.93%)  21/171 (12.28%)  14/165 (8.48%)  15/170 (8.82%)  11/169 (6.51%)  23/174 (13.22%)  13/168 (7.74%)  15/170 (8.82%)  12/166 (7.23%)  15/173 (8.67%)  22/169 (13.02%)  16/169 (9.47%)  14/171 (8.19%)  23/169 (13.61%)  21/167 (12.57%) 
Injection site induration  1  15/170 (8.82%)  9/168 (5.36%)  15/171 (8.77%)  13/165 (7.88%)  12/170 (7.06%)  14/169 (8.28%)  20/174 (11.49%)  17/168 (10.12%)  11/170 (6.47%)  11/166 (6.63%)  11/173 (6.36%)  10/169 (5.92%)  5/169 (2.96%)  10/171 (5.85%)  15/169 (8.88%)  20/167 (11.98%) 
Injection site swelling  1  16/170 (9.41%)  9/168 (5.36%)  10/171 (5.85%)  9/165 (5.45%)  10/170 (5.88%)  8/169 (4.73%)  15/174 (8.62%)  5/168 (2.98%)  2/170 (1.18%)  6/166 (3.61%)  5/173 (2.89%)  13/169 (7.69%)  3/169 (1.78%)  3/171 (1.75%)  6/169 (3.55%)  12/167 (7.19%) 
Chills  1  15/170 (8.82%)  13/168 (7.74%)  15/171 (8.77%)  12/165 (7.27%)  13/170 (7.65%)  15/169 (8.88%)  15/174 (8.62%)  11/168 (6.55%)  8/170 (4.71%)  12/166 (7.23%)  10/173 (5.78%)  8/169 (4.73%)  9/169 (5.33%)  4/171 (2.34%)  8/169 (4.73%)  6/167 (3.59%) 
Infections and infestations                                 
Nasopharyngitis * 1  9/170 (5.29%)  8/168 (4.76%)  8/171 (4.68%)  6/165 (3.64%)  5/170 (2.94%)  3/169 (1.78%)  2/174 (1.15%)  1/168 (0.60%)  7/170 (4.12%)  6/166 (3.61%)  8/173 (4.62%)  10/169 (5.92%)  4/169 (2.37%)  6/171 (3.51%)  7/169 (4.14%)  5/167 (2.99%) 
Sinusitis * 1  8/170 (4.71%)  6/168 (3.57%)  19/171 (11.11%)  11/165 (6.67%)  16/170 (9.41%)  7/169 (4.14%)  6/174 (3.45%)  13/168 (7.74%)  8/170 (4.71%)  9/166 (5.42%)  13/173 (7.51%)  9/169 (5.33%)  9/169 (5.33%)  8/171 (4.68%)  5/169 (2.96%)  7/167 (4.19%) 
Upper Respiratory Tract infection * 1  4/170 (2.35%)  14/168 (8.33%)  9/171 (5.26%)  11/165 (6.67%)  8/170 (4.71%)  9/169 (5.33%)  13/174 (7.47%)  6/168 (3.57%)  7/170 (4.12%)  9/166 (5.42%)  5/173 (2.89%)  14/169 (8.28%)  7/169 (4.14%)  6/171 (3.51%)  8/169 (4.73%)  11/167 (6.59%) 
Bronchitis * 1  3/170 (1.76%)  10/168 (5.95%)  4/171 (2.34%)  6/165 (3.64%)  7/170 (4.12%)  5/169 (2.96%)  3/174 (1.72%)  5/168 (2.98%)