Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Trial to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine GSK2186877A in Adults 65 Year of Age and Older

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00753272
First received: September 12, 2008
Last updated: September 11, 2014
Last verified: July 2013
Results First Received: April 26, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Influenza
Interventions: Biological: GSK Bio's influenza vaccine GSK2186877A
Biological: Fluarix TM

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were vaccinated during the pre-influenza season at Day 0, were contacted by phone during the surveillance period from mid November to the end of the influenza season (April-May) and were contacted by phone at Days 270 and 365 for the Year 1 influenza season 2008/2009 and the Year 2 influenza season 2009/2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
For lot-to-lot consistency analyses after Dose 1 at Day 0 of the Year 1, FluNG Group was divided in 3 sub-groups: FluNG Lot 1 Group, FluNG Lot 2 Group and FluNG Lot 3 Group: subjects received 1 dose of FluNG vaccine Lot 1, 2 or 3 at Day 0 of the Year 1. They all received Dose 2 at Day 0 of the Year 2, again from 3 different lots.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Participant Flow:   Overall Study
    FluNG Group     Fluarix Group  
STARTED     21893     21802  
COMPLETED     16911     16895  
NOT COMPLETED     4982     4907  
Adverse Event                 878                 869  
Protocol Violation                 28                 46  
Withdrawal by Subject                 2481                 2407  
Lost to Follow-up                 491                 497  
Unspecified                 1104                 1088  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Total Total of all reporting groups

Baseline Measures
    FluNG Group     Fluarix Group     Total  
Number of Participants  
[units: participants]
  21893     21802     43695  
Age  
[units: Years]
Mean ± Standard Deviation
     
Years     73.5  ± 6.09     73.5  ± 6.16     73.5  ± 6.13  
Gender  
[units: Subjects]
     
Female     12549     12422     24971  
Male     9344     9380     18724  



  Outcome Measures
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1.  Primary:   Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.   [ Time Frame: After the first dose during the corresponding surveillance period (from mid November 2008 to the end of April 2009 (end of influenza season)) ]

Measure Type Primary
Measure Title Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.
Measure Description Occurrence of PCR-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). PCR-confirmed influenza (PCI) was defined as an episode of influenza-like illness (ILI) occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by reverse transcription polymerase chain reaction (RT-PCR) analysis.
Time Frame After the first dose during the corresponding surveillance period (from mid November 2008 to the end of April 2009 (end of influenza season))  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for efficacy included eligible subjects from the One-Dose Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21573     21482  
Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.  
[units: Subjects]
  274     310  

No statistical analysis provided for Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.



2.  Primary:   Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups.   [ Time Frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study ]

Measure Type Primary
Measure Title Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups.
Measure Description Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the lot-to-lot subset of subjects.
Time Frame At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol immunogenicity cohort for the lot-to-lot consistency subset included all subjects from the One-Dose ATP cohort for immunogenicity included in the lot-to-lot subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
FluNG Lot 1 Group subjects received 1 dose of FluNG vaccine Lot 1 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 1. The vaccine was administered intramuscularly in the non-dominant deltoid.
FluNG Lot 2 Group subjects received 1 dose of FluNG vaccine Lot 2 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 2. The vaccine was administered intramuscularly in the non-dominant deltoid.
FluNG Lot 3 Group subjects received 1 dose of FluNG vaccine Lot 3 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 3. The vaccine was administered intramuscularly in the non-dominant deltoid.

Measured Values
    FluNG Group     Fluarix Group     FluNG Lot 1 Group     FluNG Lot 2 Group     FluNG Lot 3 Group  
Number of Participants Analyzed  
[units: participants]
  0     0     540     538     534  
Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
         
A/Brisbane [Day 0] (N=539,536,532)      
   
   
   
  15.9  
  ( 14.6 to 17.3 )  
  15.8  
  ( 14.5 to 17.2 )  
  15.8  
  ( 14.5 to 17.2 )  
A/Brisbane [Day 21] (N=540,538,534)      
   
   
   
  82.3  
  ( 75.0 to 90.2 )  
  83.6  
  ( 76.0 to 92.0 )  
  93.4  
  ( 84.6 to 103.1 )  
A/Uruguay [Day 0] (N=539,536,532)      
   
   
   
  18.2  
  ( 16.5 to 20.2 )  
  17.8  
  ( 16.0 to 19.9 )  
  17.3  
  ( 15.6 to 19.2 )  
A/Uruguay [Day 21] (N=540,538,534)      
   
   
   
  272.5  
  ( 243.0 to 305.6 )  
  287.5  
  ( 256.2 to 322.7 )  
  269.9  
  ( 239.9 to 303.6 )  
B/Brisbane[Day 0] (N=539,536,532)      
   
   
   
  94.2  
  ( 84.8 to 104.7 )  
  89.9  
  ( 80.6 to 100.3 )  
  87.1  
  ( 78.3 to 96.7 )  
B/Brisbane[Day 21] (N=540,538,534)      
   
   
   
  652.4  
  ( 602.0 to 707.1 )  
  596.9  
  ( 552.2 to 645.3 )  
  601.7  
  ( 555.0 to 652.4 )  

No statistical analysis provided for Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups.



3.  Secondary:   Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.   [ Time Frame: During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.
Measure Description Occurrence of PCR-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). PCR-confirmed influenza (PCI) was defined as an episode of influenza-like illness (ILI) occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by reverse transcription polymerase chain reaction (RT-PCR) analysis.
Time Frame During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol cohort for efficacy included all eligible subjects from the Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  20579     20458  
Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.  
[units: Subjects]
  262     296  

No statistical analysis provided for Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection.



4.  Secondary:   Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection.   [ Time Frame: During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection.
Measure Description Occurrence of culture-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). Culture-confirmed influenza (CCI) was defined as an episode of ILI occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by viral culture analysis.
Time Frame During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol cohort for efficacy included all eligible subjects from the Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  20579     20458  
Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection.  
[units: Subjects]
  144     145  

No statistical analysis provided for Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection.



5.  Secondary:   Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine.   [ Time Frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine.
Measure Description

Clinical influenza= An ILI episode (with an ILI onset from the 15th of November until the end of the surveillance period) with at least simultaneously fever (oral temperature of ≥37.8 degrees Celsius) and cough.

The influenza peak season = period during the study with the highest incidence of any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v).

Time Frame During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21394     21337  
Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine.  
[units: Subjects]
  202     225  

No statistical analysis provided for Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine.



6.  Secondary:   Number of Subjects Reporting All-cause Death After the First Dose of Vaccine.   [ Time Frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting All-cause Death After the First Dose of Vaccine.
Measure Description The influenza peak season = period during the study with the highest incidence of any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v).
Time Frame During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21394     21337  
Number of Subjects Reporting All-cause Death After the First Dose of Vaccine.  
[units: Subjects]
  63     88  

No statistical analysis provided for Number of Subjects Reporting All-cause Death After the First Dose of Vaccine.



7.  Secondary:   Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine   [ Time Frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine
Measure Description Respiratory disease: A diagnosis of respiratory disease included: acute respiratory infections, other diseases of upper respiratory tract, pneumonia and influenza, chronic obstructive pulmonary disease and allied conditions, pneumoconioses and other lung diseases due to external agents, other diseases of respiratory system. In case the event has a fatal outcome, the diagnosis can also be confirmed by autopsy.
Time Frame During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21394     21337  
Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine  
[units: Subjects]
  84     89  

No statistical analysis provided for Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine



8.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).   [ Time Frame: Within 365 days after the first dose (from Dose 1 at Day 0 up to Day 365 for the Year 2008/2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).
Measure Description

Adverse events of specific interest for safety monitoring are a subset of AEs that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time Frame Within 365 days after the first dose (from Dose 1 at Day 0 up to Day 365 for the Year 2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort included all subjects with one vaccine administration documented during the first year of the study.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21893     21802  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).  
[units: Subjects]
   
Any AEs     70     60  
Grade 3 AEs     13     8  
Related AEs     11     7  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).



9.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).   [ Time Frame: Within 365 days after the second dose (from Dose 1 at Day 0 up to Day 365 for the Year 2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).
Measure Description

Adverse events of specific interest for safety monitoring are a subset of AEs that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time Frame Within 365 days after the second dose (from Dose 1 at Day 0 up to Day 365 for the Year 2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort included all subjects with one vaccine administration documented in each year of the study

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  17070     17071  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).  
[units: Subjects]
   
Any AEs     35     40  
Grade 3 AEs     9     6  
Related AEs     2     0  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).



10.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).   [ Time Frame: During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).
Measure Description

Adverse events of specific interest for safety monitoring are a subset of AEs that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time Frame During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21893     21802  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).  
[units: Subjects]
   
Any AEs     103     99  
Grade 3 AEs     22     14  
Related AEs     13     7  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID).



11.  Secondary:   Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs).   [ Time Frame: During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs).
Measure Description

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Related = event assessed by the investigator as causally related to the study vaccination

Time Frame During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  21893     21802  
Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs).  
[units: Subjects]
   
Any SAEs     4071     4066  
Related SAEs     9     6  

No statistical analysis provided for Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs).



12.  Secondary:   Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms.   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms.
Measure Description Solicited local symptoms assessed were ecchymosis, pain, redness and swelling. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = considerable pain at rest that prevented normal everyday activities. Grade 3 ecchymosis/redness/swelling = ecchymosis/redness/swelling above 100 millimeter
Time Frame During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2988     2968  
Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms.  
[units: Subjects]
   
Any ecchymosis     40     18  
Ecchymosis > 100 mm     0     0  
Any pain     1225     477  
Grade 3 pain     4     3  
Any redness     240     66  
Redness > 100 mm     6     3  
Any swelling     189     40  
Swelling > 100 mm     4     0  

No statistical analysis provided for Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms.



13.  Secondary:   Number of Days With Any Grade of Solicited Local Symptoms   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ]

Measure Type Secondary
Measure Title Number of Days With Any Grade of Solicited Local Symptoms
Measure Description Solicited local symptoms assessed were ecchymosis, pain, redness and swelling
Time Frame During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  1221     476  
Number of Days With Any Grade of Solicited Local Symptoms  
[units: Days]
Mean ( Full Range )
   
Ecchymosis (N=39,18)     3.6  
  ( 1.0 to 7.0 )  
  4.0  
  ( 1.0 to 7.0 )  
Pain (N=1221,476)     2.5  
  ( 1.0 to 7.0 )  
  2.1  
  ( 1.0 to 7.0 )  
Redness (N=237,63)     2.9  
  ( 1.0 to 7.0 )  
  2.5  
  ( 1.0 to 7.0 )  
Swelling (N=186,40)     2.9  
  ( 1.0 to 7.0 )  
  2.0  
  ( 1.0 to 7.0 )  

No statistical analysis provided for Number of Days With Any Grade of Solicited Local Symptoms



14.  Secondary:   Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms
Measure Description Solicited local symptoms assessed were ecchymosis, pain, redness and swelling. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = considerable pain at rest that prevented normal everyday activities. Grade 3 ecchymosis/redness/swelling = ecchymosis/redness/swelling above 100 millimeter
Time Frame During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2441     2488  
Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms  
[units: Subjects]
   
Any ecchymosis     39     31  
Ecchymosis > 100 mm     1     0  
Any pain     998     440  
Grade 3 pain     13     7  
Any redness     212     54  
Redness > 100 mm     4     2  
Any swelling     173     38  
Swelling > 100 mm     3     0  

No statistical analysis provided for Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms



15.  Secondary:   Number of Days With Any Grade of Solicited Local Symptoms.   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ]

Measure Type Secondary
Measure Title Number of Days With Any Grade of Solicited Local Symptoms.
Measure Description Solicited local symptoms assessed were ecchymosis, pain, redness and swelling.
Time Frame During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  995     431  
Number of Days With Any Grade of Solicited Local Symptoms.  
[units: Days]
Mean ( Full Range )
   
Ecchymosis (N=28,22)     2.8  
  ( 1.0 to 7.0 )  
  3.6  
  ( 1.0 to 7.0 )  
Pain (N=995,431)     2.5  
  ( 1.0 to 7.0 )  
  2.0  
  ( 1.0 to 7.0 )  
Redness (N=202,46)     2.8  
  ( 1.0 to 7.0 )  
  2.6  
  ( 1.0 to 7.0 )  
Swelling (N=162,25)     2.5  
  ( 1.0 to 7.0 )  
  2.7  
  ( 1.0 to 7.0 )  

No statistical analysis provided for Number of Days With Any Grade of Solicited Local Symptoms.



16.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature (defined as oral temperature equal to or above (≥) 38.0 degrees Celsius). Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Grade 3 = general symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = oral temperature ≥39.0°C - ≤ 40.0°C.
Time Frame During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2986     2968  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms  
[units: Subjects]
   
Any arthralgia     391     239  
Grade 3 arthralgia     11     5  
Related arthralgia     285     163  
Any fatigue     646     417  
Grade 3 fatigue     20     15  
Related fatigue     494     295  
Any gastrointestinal     197     165  
Grade 3 gastrointestinal     6     4  
Related gastrointestinal     132     82  
Any headache     474     333  
Grade 3 headache     8     4  
Related headache     341     213  
Any myalgia     547     302  
Grade 3 myalgia     14     11  
Related myalgia     412     203  
Any shivering     245     80  
Grade 3 shivering     12     2  
Related shivering     185     49  
Temperature >= 38.0°C     72     20  
Temperature >= 39.0°C - <=40.0°C     5     2  
Related temperature     51     14  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms



17.  Secondary:   Number of Days With Any Grade of Solicited General Symptoms   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ]

Measure Type Secondary
Measure Title Number of Days With Any Grade of Solicited General Symptoms
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.
Time Frame During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  642     417  
Number of Days With Any Grade of Solicited General Symptoms  
[units: Days]
Mean ( Full Range )
   
Arthralgia (N=388,239)     2.8  
  ( 1.0 to 7.0 )  
  2.9  
  ( 1.0 to 7.0 )  
Fatigue (N=642,417)     2.5  
  ( 1.0 to 7.0 )  
  2.7  
  ( 1.0 to 7.0 )  
Gastrointestinal (N=195,164)     2.2  
  ( 1.0 to 7.0 )  
  2.2  
  ( 1.0 to 7.0 )  
Headache (N=472,332)     2.2  
  ( 1.0 to 7.0 )  
  2.3  
  ( 1.0 to 7.0 )  
Myalgia (N=544,301)     2.3  
  ( 1.0 to 7.0 )  
  2.3  
  ( 1.0 to 7.0 )  
Shivering (N=244,80)     1.6  
  ( 1.0 to 7.0 )  
  2.1  
  ( 1.0 to 7.0 )  
Temperature (N=59,16)     1.4  
  ( 1.0 to 7.0 )  
  1.3  
  ( 1.0 to 4.0 )  

No statistical analysis provided for Number of Days With Any Grade of Solicited General Symptoms



18.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms.   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms.
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature (defined as oral temperature equal to or above (≥) 38.0 degrees Celsius). Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Grade 3 = general symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = oral temperature ≥39.0°C - ≤ 40.0°C.
Time Frame During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2436     2489  
Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms.  
[units: Subjects]
   
Any arthralgia     258     176  
Grade 3 arthralgia     10     4  
Related arthralgia     169     90  
Any fatigue     457     318  
Grade 3 fatigue     8     6  
Related fatigue     307     169  
Any gastrointestinal     137     124  
Grade 3 gastrointestinal     5     8  
Related gastrointestinal     71     46  
Any headache     342     237  
Grade 3 headache     10     4  
Related headache     219     119  
Any myalgia     380     209  
Grade 3 myalgia     11     6  
Related myalgia     261     117  
Any shivering     189     88  
Grade 3 shivering     11     6  
Related shivering     127     44  
Temperature >= 38.0°C     52     25  
Temperature >= 39.0°C - <= 40.0°C     5     2  
Related temperature     33     7  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms.



19.  Secondary:   Number of Days With Any Grade of Solicited General Symptoms.   [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ]

Measure Type Secondary
Measure Title Number of Days With Any Grade of Solicited General Symptoms.
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.
Time Frame During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  446     313  
Number of Days With Any Grade of Solicited General Symptoms.  
[units: Days]
Mean ( Full Range )
   
Arthralgia (N=247,169)     2.7  
  ( 1.0 to 7.0 )  
  3.0  
  ( 1.0 to 7.0 )  
Fatigue (N=446,313)     2.6  
  ( 1.0 to 7.0 )  
  2.7  
  ( 1.0 to 7.0 )  
Gastrointestinal (N=125,115)     2.3  
  ( 1.0 to 7.0 )  
  2.6  
  ( 1.0 to 7.0 )  
Headache (N=331,229)     2.2  
  ( 1.0 to 7.0 )  
  2.4  
  ( 1.0 to 7.0 )  
Myalgia (N=370,200)     2.4  
  ( 1.0 to 7.0 )  
  2.6  
  ( 1.0 to 7.0 )  
Shivering (N=177,80)     1.6  
  ( 1.0 to 7.0 )  
  2.3  
  ( 1.0 to 7.0 )  
Temperature (N=38,13)     1.2  
  ( 1.0 to 4.0 )  
  1.5  
  ( 1.0 to 4.0 )  

No statistical analysis provided for Number of Days With Any Grade of Solicited General Symptoms.



20.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).   [ Time Frame: Within 21 days (Days 0-20) after the first dose (Year 2008/2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).
Measure Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.
Time Frame Within 21 days (Days 0-20) after the first dose (Year 2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  3015     3002  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).  
[units: Subjects]
   
Any AEs     428     427  
Grade 3 AEs     48     52  
Related AEs     83     58  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).



21.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).   [ Time Frame: Within 21 days (Days 0-20) after the second dose (Year 2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).
Measure Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.
Time Frame Within 21 days (Days 0-20) after the second dose (Year 2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2462     2520  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).  
[units: Subjects]
   
Any AEs     320     306  
Grade 3 AEs     36     26  
Related AEs     42     20  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs).



22.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit   [ Time Frame: Within 180 days (Days 0-179) after the first dose (Year 2008/2009) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit
Measure Description For each solicited and unsolicited symptom the subject experienced, the subjects were asked if they received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Grade 3 = event that prevented normal everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.
Time Frame Within 180 days (Days 0-179) after the first dose (Year 2008/2009)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  3015     3002  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit  
[units: Subjects]
   
Any AEs     1018     996  
Grade 3 AEs     223     211  
Related AEs     16     7  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit



23.  Secondary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit.   [ Time Frame: Within 180 days (Days 0-179) after the second dose (Year 2009/2010) ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit.
Measure Description For each solicited and unsolicited symptom the subject experienced, the subjects were asked if they received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Grade 3 = event that prevented normal everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.
Time Frame Within 180 days (Days 0-179) after the second dose (Year 2009/2010)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2462     2520  
Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit.  
[units: Subjects]
   
Any AEs     849     864  
Grade 3 AEs     158     154  
Related AEs     7     5  

No statistical analysis provided for Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit.



24.  Secondary:   Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.   [ Time Frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study ]

Measure Type Secondary
Measure Title Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.
Measure Description Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the immunogenicity subset of subjects.
Time Frame At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 21 of the first year of the study.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  2422     2408  
Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
A/Brisbane [Day 0] (N=2417,2397)     15.5  
  ( 14.9 to 16.1 )  
  15.3  
  ( 14.7 to 16.0 )  
A/Brisbane [Day 21] (N=2422,2408)     89.1  
  ( 85.2 to 93.2 )  
  69.9  
  ( 66.5 to 73.4 )  
A/Uruguay [Day 0] (N=2417,2397)     17.4  
  ( 16.6 to 18.3 )  
  17.4  
  ( 16.5 to 18.2 )  
A/Uruguay [Day 21] (N=2422,2408)     285.6  
  ( 270.6 to 301.4 )  
  172.3  
  ( 162.7 to 182.5 )  
B/Brisbane [Day 0] (N=2416,2397)     85.3  
  ( 81.2 to 89.7 )  
  82.4  
  ( 78.3 to 86.7 )  
B/Brisbane [Day 21] (N=2422,2408)     633.5  
  ( 609.9 to 658.0 )  
  484.8  
  ( 465.1 to 505.4 )  

No statistical analysis provided for Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.



25.  Secondary:   Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains   [ Time Frame: At Days 0 (pre-vaccination Dose 2) and 21 (post-vaccination Dose 2) of the second year (2009/2010) of the study ]

Measure Type Secondary
Measure Title Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains
Measure Description Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the immunogenicity subset of subjects.
Time Frame At Days 0 (pre-vaccination Dose 2) and 21 (post-vaccination Dose 2) of the second year (2009/2010) of the study  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 21 of the second year of the study.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  1938     1953  
Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
A/Brisbane [Day 0] (N=1932,1942)     23.9  
  ( 22.9 to 25.0 )  
  24.3  
  ( 23.2 to 25.5 )  
A/Brisbane [Day 21] (N=1936,1952)     76.9  
  ( 73.6 to 80.4 )  
  70.5  
  ( 67.1 to 74.0 )  
A/Uruguay [Day 0] (N=1932,1942)     57.8  
  ( 54.5 to 61.3 )  
  46.5  
  ( 43.9 to 49.4 )  
A/Uruguay [Day 21] (N=1937,1953)     256.8  
  ( 245.3 to 268.9 )  
  162.0  
  ( 153.9 to 170.4 )  
B/Brisbane [Day 0] (N=1933,1942)     58.6  
  ( 55.6 to 61.8 )  
  56.6  
  ( 53.6 to 59.7 )  
B/Brisbane [Day 21] (N=1938,1953)     199.2  
  ( 190.8 to 207.9 )  
  171.3  
  ( 163.6 to 179.4 )  

No statistical analysis provided for Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains



26.  Secondary:   Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.   [ Time Frame: At Days 0 (pre-vaccination Dose 1), 21 (post-vaccination Dose 1) and 180 (post-vaccination Dose 1) of the first year (2008/2009) of the study ]

Measure Type Secondary
Measure Title Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.
Measure Description Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects for 600 subjects in the persistence subset only.
Time Frame At Days 0 (pre-vaccination Dose 1), 21 (post-vaccination Dose 1) and 180 (post-vaccination Dose 1) of the first year (2008/2009) of the study  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol cohort for persistence included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 180 of the first year of the study.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  268     267  
Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
A/Brisbane [Day 0] (N=268,265)     15.4  
  ( 13.7 to 17.4 )  
  13.9  
  ( 12.4 to 15.6 )  
A/Brisbane [Day 21] (N=268,267)     75.4  
  ( 66.3 to 85.9 )  
  64.5  
  ( 55.7 to 74.7 )  
A/Brisbane [Day 180] (N=268,267)     30.4  
  ( 26.8 to 34.4 )  
  28.1  
  ( 24.8 to 31.8 )  
A/Uruguay [Day 0] (N=268,265)     19.3  
  ( 16.5 to 22.6 )  
  17.8  
  ( 15.3 to 20.7 )  
A/Uruguay [Day 21] (N=268,267)     275.0  
  ( 233.1 to 324.5 )  
  165.0  
  ( 139.0 to 195.9 )  
A/Uruguay [Day 180] (N=268,267)     97.7  
  ( 82.3 to 116.0 )  
  64.0  
  ( 53.7 to 76.3 )  
B/Brisbane [Day 0] (N=268,265)     89.3  
  ( 76.6 to 104.2 )  
  83.8  
  ( 72.3 to 97.1 )  
B/Brisbane [Day 21] (N=268,267)     573.4  
  ( 517.5 to 635.3 )  
  478.5  
  ( 422.4 to 541.9 )  
A/Brisbane [Day 180] (N=268,267)     274.6  
  ( 246.5 to 305.9 )  
  262.3  
  ( 234.7 to 293.1 )  

No statistical analysis provided for Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.



27.  Secondary:   Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.   [ Time Frame: At Days 0 (pre-vaccination Dose 2), 21 (post-vaccination Dose 2) and 180 (post-vaccination Dose 2) of the second year (2009/2010) of the study ]

Measure Type Secondary
Measure Title Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.
Measure Description Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects for 600 subjects in the persistence subset only.
Time Frame At Days 0 (pre-vaccination Dose 2), 21 (post-vaccination Dose 2) and 180 (post-vaccination Dose 2) of the second year (2009/2010) of the study  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Two-Dose According-To-Protocol cohort for persistence included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 180 of the second year of the study.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Measured Values
    FluNG Group     Fluarix Group  
Number of Participants Analyzed  
[units: participants]
  189     177  
Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
A/Brisbane [Day 0] (N=188,177)     23.4  
  ( 20.3 to 27.1 )  
  25.0  
  ( 21.3 to 29.3 )  
A/Brisbane [Day 21] (N=188,176)     80.0  
  ( 69.4 to 92.2 )  
  75.0  
  ( 63.4 to 88.6 )  
A/Brisbane [Day 180] (N=189,177)     28.5  
  ( 24.7 to 32.8 )  
  27.3  
  ( 23.5 to 31.7 )  
A/Uruguay [Day 0] (N=188,177)     68.9  
  ( 56.2 to 84.5 )  
  54.2  
  ( 44.1 to 66.5 )  
A/Uruguay [Day 21] (N=188,176)     300.6  
  ( 254.0 to 355.7 )  
  195.6  
  ( 165.5 to 231.2 )  
A/Uruguay [Day 180] (N=189,177)     105.7  
  ( 87.9 to 127.2 )  
  63.6  
  ( 53.0 to 76.3 )  
B/Brisbane [Day 0] (N=189,177)     58.5  
  ( 48.8 to 70.1 )  
  56.1  
  ( 47.0 to 67.0 )  
B/Brisbane [Day 21] (N=189,176)     225.1  
  ( 195.5 to 259.1 )  
  191.0  
  ( 161.3 to 226.3 )  
B/Brisbane [Day 180] (N=189,177)     122.9  
  ( 106.5 to 141.7 )  
  111.6  
  ( 95.8 to 130.0 )  

No statistical analysis provided for Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains.



28.  Secondary:   Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains   [ Time Frame: At Day 21 of the first year (2008/2009) of the study. ]

Measure Type Secondary
Measure Title Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains
Measure Description In the lot-to-lot subset of subject in the FluGN Group. Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Seroconversion is defined as the number of subjects with pre-vaccination HI titer (Day 0) < 1:10 and post-vaccination titer (Day 21) ≥ 1:40 or a pre-vaccination HI titer (Day 0) ≥ 1:10 and fold-increase (post/pre) ≥ 4.
Time Frame At Day 21 of the first year (2008/2009) of the study.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The One-Dose According-To-Protocol immunogenicity cohort for the lot-to-lot consistency subset included all subjects from the One-Dose ATP cohort for immunogenicity included in the lot-to-lot subset.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
FluNG Lot 1 Group subjects received 1 dose of FluNG vaccine Lot 1 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 1. The vaccine was administered intramuscularly in the non-dominant deltoid.
FluNG Lot 2 Group subjects received 1 dose of FluNG vaccine Lot 2 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 2. The vaccine was administered intramuscularly in the non-dominant deltoid.
FluNG Lot 3 Group subjects received 1 dose of FluNG vaccine Lot 3 at Day 0 of the Year 1. They received Dose 2 at Day 0 of the Year 2, again from lot 3. The vaccine was administered intramuscularly in the non-dominant deltoid.

Measured Values
    FluNG Group     Fluarix Group     FluNG Lot 1 Group     FluNG Lot 2 Group     FluNG Lot 3 Group  
Number of Participants Analyzed  
[units: participants]
  0     0     539     536     532  
Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains  
[units: Subjects]
         
A/Brisbane (N=539,536,532)             307     298     310  
A/Uruguay (N=539,536,532)             471     461     455  
B/Brisbane (N=539,536,532)             389     350     363  

No statistical analysis provided for Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains




  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Solicited symptoms: During the 7-day post-vaccination period the first year (2008/2009) and the second year (2009/2010). SAEs: During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010)
Additional Description No text entered.

Reporting Groups
  Description
FluNG Group subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).
Fluarix Group subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1).

Serious Adverse Events
    FluNG Group     Fluarix Group  
Total, serious adverse events      
# participants affected / at risk     4071/21893 (18.59%)     4066/21802 (18.65%)  
Blood and lymphatic system disorders      
Anaemia *    
# participants affected / at risk     48/21893 (0.22%)     64/21802 (0.29%)  
Iron deficiency anaemia *    
# participants affected / at risk     7/21893 (0.03%)     14/21802 (0.06%)  
Haemorrhagic anaemia *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Thrombocytopenia *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Cardiac disorders      
Atrial fibrillation *    
# participants affected / at risk     211/21893 (0.96%)     178/21802 (0.82%)  
Myocardial infarction *    
# participants affected / at risk     169/21893 (0.77%)     167/21802 (0.77%)  
Cardiac failure congestive *    
# participants affected / at risk     147/21893 (0.67%)     153/21802 (0.70%)  
Cardiac failure *    
# participants affected / at risk     98/21893 (0.45%)     102/21802 (0.47%)  
Coronary artery disease *    
# participants affected / at risk     90/21893 (0.41%)     75/21802 (0.34%)  
Angina pectoris *    
# participants affected / at risk     77/21893 (0.35%)     75/21802 (0.34%)  
Myocardial ischaemia *    
# participants affected / at risk     64/21893 (0.29%)     62/21802 (0.28%)  
Acute myocardial infarction *    
# participants affected / at risk     38/21893 (0.17%)     59/21802 (0.27%)  
Arrhythmia *    
# participants affected / at risk     35/21893 (0.16%)     26/21802 (0.12%)  
Cardiac arrest *    
# participants affected / at risk     33/21893 (0.15%)     28/21802 (0.13%)  
Bradycardia *    
# participants affected / at risk     18/21893 (0.08%)     20/21802 (0.09%)  
Angina unstable *    
# participants affected / at risk     17/21893 (0.08%)     18/21802 (0.08%)  
Atrial flutter *    
# participants affected / at risk     14/21893 (0.06%)     16/21802 (0.07%)  
Atrioventricular block *    
# participants affected / at risk     11/21893 (0.05%)     16/21802 (0.07%)  
Acute coronary syndrome *    
# participants affected / at risk     6/21893 (0.03%)     18/21802 (0.08%)  
Mitral valve incompetence *    
# participants affected / at risk     14/21893 (0.06%)     10/21802 (0.05%)  
Aortic valve stenosis *    
# participants affected / at risk     13/21893 (0.06%)     8/21802 (0.04%)  
Sick sinus syndrome *    
# participants affected / at risk     10/21893 (0.05%)     11/21802 (0.05%)  
Atrioventricular block complete *    
# participants affected / at risk     9/21893 (0.04%)     11/21802 (0.05%)  
Supraventricular tachycardia *    
# participants affected / at risk     7/21893 (0.03%)     13/21802 (0.06%)  
Left ventricular failure *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Tachyarrhythmia *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Coronary artery stenosis *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Arrhythmia supraventricular *    
# participants affected / at risk     11/21893 (0.05%)     4/21802 (0.02%)  
Ventricular fibrillation *    
# participants affected / at risk     8/21893 (0.04%)     7/21802 (0.03%)  
Cardiopulmonary failure *    
# participants affected / at risk     7/21893 (0.03%)     6/21802 (0.03%)  
Arteriosclerosis coronary artery *    
# participants affected / at risk     6/21893 (0.03%)     6/21802 (0.03%)  
Cardiac failure chronic *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Cardio-respiratory arrest *    
# participants affected / at risk     5/21893 (0.02%)     7/21802 (0.03%)  
Cardiovascular insufficiency *    
# participants affected / at risk     6/21893 (0.03%)     6/21802 (0.03%)  
Coronary artery occlusion *    
# participants affected / at risk     6/21893 (0.03%)     6/21802 (0.03%)  
Cardiac failure acute *    
# participants affected / at risk     6/21893 (0.03%)     5/21802 (0.02%)  
Atrioventricular block second degree *    
# participants affected / at risk     8/21893 (0.04%)     2/21802 (0.01%)  
Ventricular tachycardia *    
# participants affected / at risk     4/21893 (0.02%)     6/21802 (0.03%)  
Aortic valve incompetence *    
# participants affected / at risk     3/21893 (0.01%)     6/21802 (0.03%)  
Cardiogenic shock *    
# participants affected / at risk     6/21893 (0.03%)     2/21802 (0.01%)  
Tachycardia *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Ventricular extrasystoles *    
# participants affected / at risk     4/21893 (0.02%)     4/21802 (0.02%)  
Coronary artery insufficiency *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Hypertensive heart disease *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Pericarditis *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Congenital, familial and genetic disorders      
Gastrointestinal angiodysplasia *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Ear and labyrinth disorders      
Vertigo *    
# participants affected / at risk     14/21893 (0.06%)     19/21802 (0.09%)  
Vestibular disorder *    
# participants affected / at risk     5/21893 (0.02%)     8/21802 (0.04%)  
Vertigo positional *    
# participants affected / at risk     2/21893 (0.01%)     8/21802 (0.04%)  
Endocrine disorders      
Hypothyroidism *    
# participants affected / at risk     4/21893 (0.02%)     7/21802 (0.03%)  
Hyperthyroidism *    
# participants affected / at risk     1/21893 (0.00%)     9/21802 (0.04%)  
Goitre *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Eye disorders      
Cataract *    
# participants affected / at risk     16/21893 (0.07%)     20/21802 (0.09%)  
Glaucoma *    
# participants affected / at risk     3/21893 (0.01%)     8/21802 (0.04%)  
Retinal detachment *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Gastrointestinal disorders      
Inguinal hernia *    
# participants affected / at risk     37/21893 (0.17%)     26/21802 (0.12%)  
Gastrointestinal haemorrhage *    
# participants affected / at risk     19/21893 (0.09%)     29/21802 (0.13%)  
Gastritis *    
# participants affected / at risk     20/21893 (0.09%)     22/21802 (0.10%)  
Pancreatitis acute *    
# participants affected / at risk     18/21893 (0.08%)     18/21802 (0.08%)  
Gastric ulcer *    
# participants affected / at risk     16/21893 (0.07%)     18/21802 (0.08%)  
Intestinal obstruction *    
# participants affected / at risk     15/21893 (0.07%)     19/21802 (0.09%)  
Pancreatitis *    
# participants affected / at risk     18/21893 (0.08%)     11/21802 (0.05%)  
Ileus *    
# participants affected / at risk     14/21893 (0.06%)     11/21802 (0.05%)  
Small intestinal obstruction *    
# participants affected / at risk     13/21893 (0.06%)     12/21802 (0.06%)  
Constipation *    
# participants affected / at risk     11/21893 (0.05%)     13/21802 (0.06%)  
Duodenal ulcer *    
# participants affected / at risk     15/21893 (0.07%)     8/21802 (0.04%)  
Peritonitis *    
# participants affected / at risk     12/21893 (0.05%)     11/21802 (0.05%)  
Colitis *    
# participants affected / at risk     8/21893 (0.04%)     14/21802 (0.06%)  
Abdominal pain *    
# participants affected / at risk     13/21893 (0.06%)     7/21802 (0.03%)  
Colonic polyp *    
# participants affected / at risk     11/21893 (0.05%)     9/21802 (0.04%)  
Upper gastrointestinal haemorrhage *    
# participants affected / at risk     11/21893 (0.05%)     9/21802 (0.04%)  
Diarrhoea *    
# participants affected / at risk     8/21893 (0.04%)     9/21802 (0.04%)  
Gastritis erosive *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Gastrooesophageal reflux disease *    
# participants affected / at risk     7/21893 (0.03%)     10/21802 (0.05%)  
Diverticulum *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Gastric ulcer haemorrhage *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Hiatus hernia *    
# participants affected / at risk     5/21893 (0.02%)     11/21802 (0.05%)  
Colitis ischaemic *    
# participants affected / at risk     3/21893 (0.01%)     11/21802 (0.05%)  
Large intestine perforation *    
# participants affected / at risk     8/21893 (0.04%)     5/21802 (0.02%)  
Dyspepsia *    
# participants affected / at risk     4/21893 (0.02%)     8/21802 (0.04%)  
Haemorrhoids *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Rectal haemorrhage *    
# participants affected / at risk     5/21893 (0.02%)     7/21802 (0.03%)  
Reflux oesophagitis *    
# participants affected / at risk     3/21893 (0.01%)     9/21802 (0.04%)  
Dysphagia *    
# participants affected / at risk     3/21893 (0.01%)     7/21802 (0.03%)  
Faecaloma *    
# participants affected / at risk     4/21893 (0.02%)     6/21802 (0.03%)  
Lower gastrointestinal haemorrhage *    
# participants affected / at risk     2/21893 (0.01%)     8/21802 (0.04%)  
Abdominal hernia *    
# participants affected / at risk     6/21893 (0.03%)     3/21802 (0.01%)  
Oesophagitis *    
# participants affected / at risk     5/21893 (0.02%)     4/21802 (0.02%)  
Pancreatitis chronic *    
# participants affected / at risk     6/21893 (0.03%)     3/21802 (0.01%)  
Umbilical hernia *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Diverticular perforation *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Diverticulum intestinal *    
# participants affected / at risk     6/21893 (0.03%)     2/21802 (0.01%)  
Peptic ulcer *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Vomiting *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Duodenitis *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Gastric haemorrhage *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Nausea *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Oesophageal stenosis *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Gastroduodenal ulcer *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Haematochezia *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Ileus paralytic *    
# participants affected / at risk     5/21893 (0.02%)     1/21802 (0.00%)  
Intestinal polyp *    
# participants affected / at risk     5/21893 (0.02%)     1/21802 (0.00%)  
Oesophageal varices haemorrhage *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
General disorders      
Chest pain *    
# participants affected / at risk     42/21893 (0.19%)     45/21802 (0.21%)  
Death *    
# participants affected / at risk     28/21893 (0.13%)     27/21802 (0.12%)  
Sudden death *    
# participants affected / at risk     34/21893 (0.16%)     18/21802 (0.08%)  
Multi-organ failure *    
# participants affected / at risk     9/21893 (0.04%)     15/21802 (0.07%)  
Cardiac death *    
# participants affected / at risk     11/21893 (0.05%)     8/21802 (0.04%)  
Sudden cardiac death *    
# participants affected / at risk     12/21893 (0.05%)     7/21802 (0.03%)  
Non-cardiac chest pain *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Asthenia *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Pyrexia *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Device dislocation *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Oedema peripheral *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Pain *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Hepatobiliary disorders      
Cholelithiasis *    
# participants affected / at risk     44/21893 (0.20%)     45/21802 (0.21%)  
Cholecystitis *    
# participants affected / at risk     40/21893 (0.18%)     43/21802 (0.20%)  
Cholecystitis acute *    
# participants affected / at risk     23/21893 (0.11%)     17/21802 (0.08%)  
Bile duct stone *    
# participants affected / at risk     15/21893 (0.07%)     9/21802 (0.04%)  
Hepatic cirrhosis *    
# participants affected / at risk     11/21893 (0.05%)     9/21802 (0.04%)  
Cholangitis *    
# participants affected / at risk     5/21893 (0.02%)     5/21802 (0.02%)  
Biliary colic *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Immune system disorders      
Hypersensitivity *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Anaphylactic reaction *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Infections and infestations      
Pneumonia *    
# participants affected / at risk     228/21893 (1.04%)     226/21802 (1.04%)  
Urinary tract infection *    
# participants affected / at risk     129/21893 (0.59%)     111/21802 (0.51%)  
Sepsis *    
# participants affected / at risk     41/21893 (0.19%)     45/21802 (0.21%)  
Gastroenteritis *    
# participants affected / at risk     35/21893 (0.16%)     47/21802 (0.22%)  
Diverticulitis *    
# participants affected / at risk     31/21893 (0.14%)     34/21802 (0.16%)  
Cellulitis *    
# participants affected / at risk     29/21893 (0.13%)     27/21802 (0.12%)  
Bronchopneumonia *    
# participants affected / at risk     26/21893 (0.12%)     29/21802 (0.13%)  
Erysipelas *    
# participants affected / at risk     28/21893 (0.13%)     21/21802 (0.10%)  
Lobar pneumonia *    
# participants affected / at risk     16/21893 (0.07%)     19/21802 (0.09%)  
Pyelonephritis *    
# participants affected / at risk     21/21893 (0.10%)     13/21802 (0.06%)  
Appendicitis *    
# participants affected / at risk     15/21893 (0.07%)     17/21802 (0.08%)  
Upper respiratory tract infection *    
# participants affected / at risk     13/21893 (0.06%)     17/21802 (0.08%)  
Septic shock *    
# participants affected / at risk     6/21893 (0.03%)     18/21802 (0.08%)  
Gangrene *    
# participants affected / at risk     10/21893 (0.05%)     11/21802 (0.05%)  
Cystitis *    
# participants affected / at risk     5/21893 (0.02%)     12/21802 (0.06%)  
Herpes zoster *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Respiratory tract infection *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Wound infection *    
# participants affected / at risk     8/21893 (0.04%)     7/21802 (0.03%)  
Staphylococcal infection *    
# participants affected / at risk     8/21893 (0.04%)     5/21802 (0.02%)  
Urosepsis *    
# participants affected / at risk     8/21893 (0.04%)     4/21802 (0.02%)  
Sinusitis *    
# participants affected / at risk     3/21893 (0.01%)     7/21802 (0.03%)  
Osteomyelitis *    
# participants affected / at risk     2/21893 (0.01%)     7/21802 (0.03%)  
Clostridial infection *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Clostridium difficile colitis *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Infection *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Candidiasis *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Cholecystitis infective *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Gastroenteritis norovirus *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Gastroenteritis viral *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Escherichia urinary tract infection *    
# participants affected / at risk     6/21893 (0.03%)     0/21802 (0.00%)  
Infected skin ulcer *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Infective exacerbation of chronic obstructive airways diseas *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Localised infection *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Lower respiratory tract infection *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Lung infection *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Pharyngitis *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Postoperative wound infection *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Pyelonephritis acute *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Injury, poisoning and procedural complications      
Femoral neck fracture *    
# participants affected / at risk     35/21893 (0.16%)     53/21802 (0.24%)  
Femur fracture *    
# participants affected / at risk     34/21893 (0.16%)     45/21802 (0.21%)  
Hip fracture *    
# participants affected / at risk     23/21893 (0.11%)     34/21802 (0.16%)  
Humerus fracture *    
# participants affected / at risk     19/21893 (0.09%)     35/21802 (0.16%)  
Rib fracture *    
# participants affected / at risk     21/21893 (0.10%)     14/21802 (0.06%)  
Toxicity to various agents *    
# participants affected / at risk     17/21893 (0.08%)     18/21802 (0.08%)  
Radius fracture *    
# participants affected / at risk     13/21893 (0.06%)     20/21802 (0.09%)  
Contusion *    
# participants affected / at risk     20/21893 (0.09%)     12/21802 (0.06%)  
Ankle fracture *    
# participants affected / at risk     14/21893 (0.06%)     15/21802 (0.07%)  
Concussion *    
# participants affected / at risk     10/21893 (0.05%)     16/21802 (0.07%)  
Upper limb fracture *    
# participants affected / at risk     9/21893 (0.04%)     17/21802 (0.08%)  
Spinal compression fracture *    
# participants affected / at risk     14/21893 (0.06%)     11/21802 (0.05%)  
Wrist fracture *    
# participants affected / at risk     15/21893 (0.07%)     10/21802 (0.05%)  
Pelvic fracture *    
# participants affected / at risk     9/21893 (0.04%)     11/21802 (0.05%)  
Subdural haematoma *    
# participants affected / at risk     5/21893 (0.02%)     15/21802 (0.07%)  
Lumbar vertebral fracture *    
# participants affected / at risk     9/21893 (0.04%)     10/21802 (0.05%)  
Road traffic accident *    
# participants affected / at risk     9/21893 (0.04%)     9/21802 (0.04%)  
Facial bones fracture *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Head injury *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Joint dislocation *    
# participants affected / at risk     5/21893 (0.02%)     11/21802 (0.05%)  
Spinal fracture *    
# participants affected / at risk     6/21893 (0.03%)     9/21802 (0.04%)  
Laceration *    
# participants affected / at risk     8/21893 (0.04%)     6/21802 (0.03%)  
Lower limb fracture *    
# participants affected / at risk     8/21893 (0.04%)     6/21802 (0.03%)  
Fall *    
# participants affected / at risk     4/21893 (0.02%)     9/21802 (0.04%)  
Tendon rupture *    
# participants affected / at risk     10/21893 (0.05%)     3/21802 (0.01%)  
Fibula fracture *    
# participants affected / at risk     7/21893 (0.03%)     4/21802 (0.02%)  
Tibia fracture *    
# participants affected / at risk     3/21893 (0.01%)     8/21802 (0.04%)  
Traumatic brain injury *    
# participants affected / at risk     5/21893 (0.02%)     5/21802 (0.02%)  
Cervical vertebral fracture *    
# participants affected / at risk     5/21893 (0.02%)     4/21802 (0.02%)  
Hand fracture *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Meniscus lesion *    
# participants affected / at risk     1/21893 (0.00%)     8/21802 (0.04%)  
Foot fracture *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Forearm fracture *    
# participants affected / at risk     7/21893 (0.03%)     1/21802 (0.00%)  
Brain contusion *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Multiple injuries *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Overdose *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Pubis fracture *    
# participants affected / at risk     1/21893 (0.00%)     6/21802 (0.03%)  
Thoracic vertebral fracture *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Ulna fracture *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Injury *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Multiple fractures *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Post procedural haemorrhage *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Metabolism and nutrition disorders      
Dehydration *    
# participants affected / at risk     24/21893 (0.11%)     25/21802 (0.11%)  
Diabetes mellitus inadequate control *    
# participants affected / at risk     22/21893 (0.10%)     20/21802 (0.09%)  
Hypoglycaemia *    
# participants affected / at risk     23/21893 (0.11%)     18/21802 (0.08%)  
Diabetes mellitus *    
# participants affected / at risk     18/21893 (0.08%)     18/21802 (0.08%)  
Type 2 diabetes mellitus *    
# participants affected / at risk     16/21893 (0.07%)     12/21802 (0.06%)  
Hyponatraemia *    
# participants affected / at risk     9/21893 (0.04%)     11/21802 (0.05%)  
Hypokalaemia *    
# participants affected / at risk     8/21893 (0.04%)     9/21802 (0.04%)  
Diabetic foot *    
# participants affected / at risk     5/21893 (0.02%)     7/21802 (0.03%)  
Hyperkalaemia *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Hypercholesterolaemia *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Hyperglycaemia *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Cachexia *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Electrolyte imbalance *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Gout *    
# participants affected / at risk     6/21893 (0.03%)     0/21802 (0.00%)  
Hypomagnesaemia *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Musculoskeletal and connective tissue disorders      
Osteoarthritis *    
# participants affected / at risk     87/21893 (0.40%)     108/21802 (0.50%)  
Intervertebral disc protrusion *    
# participants affected / at risk     18/21893 (0.08%)     26/21802 (0.12%)  
Back pain *    
# participants affected / at risk     15/21893 (0.07%)     20/21802 (0.09%)  
Spinal column stenosis *    
# participants affected / at risk     19/21893 (0.09%)     14/21802 (0.06%)  
Rotator cuff syndrome *    
# participants affected / at risk     8/21893 (0.04%)     12/21802 (0.06%)  
Arthralgia *    
# participants affected / at risk     6/21893 (0.03%)     12/21802 (0.06%)  
Polymyalgia rheumatica *    
# participants affected / at risk     12/21893 (0.05%)     5/21802 (0.02%)  
Intervertebral disc degeneration *    
# participants affected / at risk     6/21893 (0.03%)     10/21802 (0.05%)  
Lumbar spinal stenosis *    
# participants affected / at risk     7/21893 (0.03%)     9/21802 (0.04%)  
Rheumatoid arthritis *    
# participants affected / at risk     8/21893 (0.04%)     8/21802 (0.04%)  
Spinal osteoarthritis *    
# participants affected / at risk     8/21893 (0.04%)     8/21802 (0.04%)  
Arthritis *    
# participants affected / at risk     5/21893 (0.02%)     4/21802 (0.02%)  
Bone pain *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Osteonecrosis *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Foot deformity *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Intervertebral disc disorder *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Musculoskeletal pain *    
# participants affected / at risk     6/21893 (0.03%)     0/21802 (0.00%)  
Pain in extremity *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Spondylolisthesis *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Prostate cancer *    
# participants affected / at risk     57/21893 (0.26%)     60/21802 (0.28%)  
Breast cancer *    
# participants affected / at risk     48/21893 (0.22%)     46/21802 (0.21%)  
Colon cancer *    
# participants affected / at risk     44/21893 (0.20%)     35/21802 (0.16%)  
Lung neoplasm malignant *    
# participants affected / at risk     24/21893 (0.11%)     38/21802 (0.17%)  
Bladder cancer *    
# participants affected / at risk     20/21893 (0.09%)     19/21802 (0.09%)  
Basal cell carcinoma *    
# participants affected / at risk     12/21893 (0.05%)     21/21802 (0.10%)  
Gastric cancer *    
# participants affected / at risk     15/21893 (0.07%)     13/21802 (0.06%)  
Pancreatic carcinoma *    
# participants affected / at risk     15/21893 (0.07%)     12/21802 (0.06%)  
Rectal cancer *    
# participants affected / at risk     10/21893 (0.05%)     13/21802 (0.06%)  
Bladder neoplasm *    
# participants affected / at risk     13/21893 (0.06%)     9/21802 (0.04%)  
Squamous cell carcinoma *    
# participants affected / at risk     8/21893 (0.04%)     9/21802 (0.04%)  
Malignant melanoma *    
# participants affected / at risk     9/21893 (0.04%)     7/21802 (0.03%)  
Renal cancer *    
# participants affected / at risk     10/21893 (0.05%)     6/21802 (0.03%)  
Hepatic neoplasm malignant *    
# participants affected / at risk     8/21893 (0.04%)     7/21802 (0.03%)  
Pancreatic carcinoma metastatic *    
# participants affected / at risk     7/21893 (0.03%)     8/21802 (0.04%)  
Lung adenocarcinoma *    
# participants affected / at risk     7/21893 (0.03%)     7/21802 (0.03%)  
Neoplasm malignant *    
# participants affected / at risk     9/21893 (0.04%)     5/21802 (0.02%)  
Lymphoma *    
# participants affected / at risk     9/21893 (0.04%)     4/21802 (0.02%)  
Thyroid cancer *    
# participants affected / at risk     8/21893 (0.04%)     5/21802 (0.02%)  
Metastases to liver *    
# participants affected / at risk     6/21893 (0.03%)     6/21802 (0.03%)  
Prostatic adenoma *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Colon cancer metastatic *    
# participants affected / at risk     6/21893 (0.03%)     5/21802 (0.02%)  
Brain neoplasm *    
# participants affected / at risk     5/21893 (0.02%)     5/21802 (0.02%)  
Lung neoplasm *    
# participants affected / at risk     4/21893 (0.02%)     6/21802 (0.03%)  
Transitional cell carcinoma *    
# participants affected / at risk     6/21893 (0.03%)     4/21802 (0.02%)  
Uterine cancer *    
# participants affected / at risk     6/21893 (0.03%)     4/21802 (0.02%)  
Bronchial carcinoma *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Non-hodgkin’s lymphoma *    
# participants affected / at risk     6/21893 (0.03%)     3/21802 (0.01%)  
Breast cancer metastatic *    
# participants affected / at risk     4/21893 (0.02%)     4/21802 (0.02%)  
Chronic lymphocytic leukaemia *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Colon neoplasm *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Lung cancer metastatic *    
# participants affected / at risk     4/21893 (0.02%)     4/21802 (0.02%)  
Oesophageal carcinoma *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Renal neoplasm *    
# participants affected / at risk     6/21893 (0.03%)     2/21802 (0.01%)  
Acute myeloid leukaemia *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Adenocarcinoma *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Colon adenoma *    
# participants affected / at risk     2/21893 (0.01%)     5/21802 (0.02%)  
Endometrial cancer *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Hepatic neoplasm *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Metastatic malignant melanoma *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Metastatic neoplasm *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Multiple myeloma *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Prostate cancer metastatic *    
# participants affected / at risk     1/21893 (0.00%)     6/21802 (0.03%)  
Renal cancer metastatic *    
# participants affected / at risk     1/21893 (0.00%)     6/21802 (0.03%)  
Breast cancer recurrent *    
# participants affected / at risk     4/21893 (0.02%)     2/21802 (0.01%)  
Meningioma *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Metastases to lung *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Ovarian neoplasm *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Renal cell carcinoma *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Nervous system disorders      
Cerebrovascular accident *    
# participants affected / at risk     196/21893 (0.90%)     180/21802 (0.83%)  
Transient ischaemic attack *    
# participants affected / at risk     69/21893 (0.32%)     57/21802 (0.26%)  
Syncope *    
# participants affected / at risk     54/21893 (0.25%)     43/21802 (0.20%)  
Cerebrovascular disorder *    
# participants affected / at risk     24/21893 (0.11%)     21/21802 (0.10%)  
Ischaemic stroke *    
# participants affected / at risk     17/21893 (0.08%)     28/21802 (0.13%)  
Cerebral infarction *    
# participants affected / at risk     23/21893 (0.11%)     11/21802 (0.05%)  
Epilepsy *    
# participants affected / at risk     14/21893 (0.06%)     11/21802 (0.05%)  
Carotid artery stenosis *    
# participants affected / at risk     13/21893 (0.06%)     10/21802 (0.05%)  
Vascular dementia *    
# participants affected / at risk     12/21893 (0.05%)     7/21802 (0.03%)  
Cerebral ischaemia *    
# participants affected / at risk     9/21893 (0.04%)     9/21802 (0.04%)  
Cerebral haemorrhage *    
# participants affected / at risk     9/21893 (0.04%)     4/21802 (0.02%)  
Dementia *    
# participants affected / at risk     4/21893 (0.02%)     9/21802 (0.04%)  
Dementia alzheimer’s type *    
# participants affected / at risk     9/21893 (0.04%)     4/21802 (0.02%)  
Dizziness *    
# participants affected / at risk     5/21893 (0.02%)     8/21802 (0.04%)  
Parkinson’s disease *    
# participants affected / at risk     8/21893 (0.04%)     5/21802 (0.02%)  
Presyncope *    
# participants affected / at risk     9/21893 (0.04%)     4/21802 (0.02%)  
Grand mal convulsion *    
# participants affected / at risk     4/21893 (0.02%)     8/21802 (0.04%)  
Sciatica *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Cerebral arteriosclerosis *    
# participants affected / at risk     7/21893 (0.03%)     4/21802 (0.02%)  
Subarachnoid haemorrhage *    
# participants affected / at risk     7/21893 (0.03%)     4/21802 (0.02%)  
Brain oedema *    
# participants affected / at risk     3/21893 (0.01%)     7/21802 (0.03%)  
Haemorrhagic stroke *    
# participants affected / at risk     5/21893 (0.02%)     4/21802 (0.02%)  
Vertebrobasilar insufficiency *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Convulsion *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Encephalopathy *    
# participants affected / at risk     6/21893 (0.03%)     2/21802 (0.01%)  
Parkinsonism *    
# participants affected / at risk     6/21893 (0.03%)     1/21802 (0.00%)  
Brain stem infarction *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Embolic stroke *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Vascular encephalopathy *    
# participants affected / at risk     2/21893 (0.01%)     4/21802 (0.02%)  
Psychiatric disorders      
Depression *    
# participants affected / at risk     24/21893 (0.11%)     20/21802 (0.09%)  
Completed suicide *    
# participants affected / at risk     5/21893 (0.02%)     7/21802 (0.03%)  
Delirium *    
# participants affected / at risk     6/21893 (0.03%)     4/21802 (0.02%)  
Confusional state *    
# participants affected / at risk     4/21893 (0.02%)     4/21802 (0.02%)  
Renal and urinary disorders      
Renal failure acute *    
# participants affected / at risk     60/21893 (0.27%)     45/21802 (0.21%)  
Renal failure chronic *    
# participants affected / at risk     27/21893 (0.12%)     30/21802 (0.14%)  
Renal failure *    
# participants affected / at risk     26/21893 (0.12%)     27/21802 (0.12%)  
Nephrolithiasis *    
# participants affected / at risk     14/21893 (0.06%)     20/21802 (0.09%)  
Urinary retention *    
# participants affected / at risk     13/21893 (0.06%)     15/21802 (0.07%)  
Haematuria *    
# participants affected / at risk     8/21893 (0.04%)     8/21802 (0.04%)  
Calculus ureteric *    
# participants affected / at risk     10/21893 (0.05%)     4/21802 (0.02%)  
Urethral stenosis *    
# participants affected / at risk     3/21893 (0.01%)     10/21802 (0.05%)  
Calculus bladder *    
# participants affected / at risk     6/21893 (0.03%)     5/21802 (0.02%)  
Hydronephrosis *    
# participants affected / at risk     8/21893 (0.04%)     3/21802 (0.01%)  
Urinary bladder polyp *    
# participants affected / at risk     3/21893 (0.01%)     6/21802 (0.03%)  
Calculus urinary *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Cystitis haemorrhagic *    
# participants affected / at risk     5/21893 (0.02%)     3/21802 (0.01%)  
Bladder neck obstruction *    
# participants affected / at risk     1/21893 (0.00%)     5/21802 (0.02%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia *    
# participants affected / at risk     27/21893 (0.12%)     31/21802 (0.14%)  
Uterine prolapse *    
# participants affected / at risk     7/21893 (0.03%)     3/21802 (0.01%)  
Ovarian cyst *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Prostatitis *    
# participants affected / at risk     3/21893 (0.01%)     4/21802 (0.02%)  
Uterine polyp *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease *    
# participants affected / at risk     141/21893 (0.64%)     128/21802 (0.59%)  
Pulmonary embolism *    
# participants affected / at risk     47/21893 (0.21%)     61/21802 (0.28%)  
Bronchitis *    
# participants affected / at risk     61/21893 (0.28%)     43/21802 (0.20%)  
Respiratory failure *    
# participants affected / at risk     32/21893 (0.15%)     37/21802 (0.17%)  
Asthma *    
# participants affected / at risk     33/21893 (0.15%)     17/21802 (0.08%)  
Pulmonary oedema *    
# participants affected / at risk     19/21893 (0.09%)     24/21802 (0.11%)  
Acute respiratory failure *    
# participants affected / at risk     22/21893 (0.10%)     15/21802 (0.07%)  
Pleural effusion *    
# participants affected / at risk     15/21893 (0.07%)     19/21802 (0.09%)  
Bronchitis chronic *    
# participants affected / at risk     14/21893 (0.06%)     14/21802 (0.06%)  
Pneumonia aspiration *    
# participants affected / at risk     10/21893 (0.05%)     14/21802 (0.06%)  
Dyspnoea *    
# participants affected / at risk     13/21893 (0.06%)     10/21802 (0.05%)  
Epistaxis *    
# participants affected / at risk     13/21893 (0.06%)     9/21802 (0.04%)  
Pneumothorax *    
# participants affected / at risk     7/21893 (0.03%)     4/21802 (0.02%)  
Acute pulmonary oedema *    
# participants affected / at risk     2/21893 (0.01%)     8/21802 (0.04%)  
Emphysema *    
# participants affected / at risk     2/21893 (0.01%)     7/21802 (0.03%)  
Pleurisy *    
# participants affected / at risk     6/21893 (0.03%)     3/21802 (0.01%)  
Pulmonary fibrosis *    
# participants affected / at risk     2/21893 (0.01%)     6/21802 (0.03%)  
Sleep apnoea syndrome *    
# participants affected / at risk     3/21893 (0.01%)     5/21802 (0.02%)  
Pulmonary hypertension *    
# participants affected / at risk     4/21893 (0.02%)     3/21802 (0.01%)  
Bronchiectasis *    
# participants affected / at risk     5/21893 (0.02%)     1/21802 (0.00%)  
Interstitial lung disease *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Respiratory arrest *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
Skin and subcutaneous tissue disorders      
Decubitus ulcer *    
# participants affected / at risk     6/21893 (0.03%)     7/21802 (0.03%)  
Skin ulcer *    
# participants affected / at risk     5/21893 (0.02%)     6/21802 (0.03%)  
Angioedema *    
# participants affected / at risk     4/21893 (0.02%)     5/21802 (0.02%)  
Vascular disorders      
Hypertension *    
# participants affected / at risk     82/21893 (0.37%)     83/21802 (0.38%)  
Arteriosclerosis *    
# participants affected / at risk     22/21893 (0.10%)     30/21802 (0.14%)  
Hypertensive crisis *    
# participants affected / at risk     26/21893 (0.12%)     21/21802 (0.10%)  
Circulatory collapse *    
# participants affected / at risk     23/21893 (0.11%)     18/21802 (0.08%)  
Deep vein thrombosis *    
# participants affected / at risk     13/21893 (0.06%)     24/21802 (0.11%)  
Peripheral arterial occlusive disease *    
# participants affected / at risk     19/21893 (0.09%)     13/21802 (0.06%)  
Aortic aneurysm *    
# participants affected / at risk     13/21893 (0.06%)     15/21802 (0.07%)  
Hypotension *    
# participants affected / at risk     14/21893 (0.06%)     13/21802 (0.06%)  
Haematoma *    
# participants affected / at risk     15/21893 (0.07%)     8/21802 (0.04%)  
Peripheral vascular disorder *    
# participants affected / at risk     11/21893 (0.05%)     11/21802 (0.05%)  
Aortic stenosis *    
# participants affected / at risk     11/21893 (0.05%)     7/21802 (0.03%)  
Venous thrombosis *    
# participants affected / at risk     9/21893 (0.04%)     8/21802 (0.04%)  
Thrombophlebitis *    
# participants affected / at risk     7/21893 (0.03%)     5/21802 (0.02%)  
Thrombosis *    
# participants affected / at risk     4/21893 (0.02%)     8/21802 (0.04%)  
Orthostatic hypotension *    
# participants affected / at risk     5/21893 (0.02%)     6/21802 (0.03%)  
Arterial occlusive disease *    
# participants affected / at risk     4/21893 (0.02%)     6/21802 (0.03%)  
Intermittent claudication *    
# participants affected / at risk     4/21893 (0.02%)     6/21802 (0.03%)  
Peripheral ischaemia *    
# participants affected / at risk     5/21893 (0.02%)     4/21802 (0.02%)  
Arterial thrombosis limb *    
# participants affected / at risk     4/21893 (0.02%)     4/21802 (0.02%)  
Hypovolaemic shock *    
# participants affected / at risk     5/21893 (0.02%)     2/21802 (0.01%)  
Varicose vein *    
# participants affected / at risk     6/21893 (0.03%)     1/21802 (0.00%)  
Venous thrombosis limb *    
# participants affected / at risk     3/21893 (0.01%)     3/21802 (0.01%)  
* Events were collected by non-systematic assessment




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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