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    Clinical Trial Results:
    A Phase III, randomized, observer-blind, controlled, multi-center clinical study to evaluate the efficacy, safety and immunogenicity of one and two intramuscular doses of FLUAD® versus control vaccines in unprimed healthy subjects aged 6 to <72 months.

    Summary
    EudraCT number
    		 2007-003786-41
    Trial protocol
    		 DE   FI   IT   HU   BE  
    Global end of trial date
    05 Aug 2010

    Results information
    Results version number
    		 v2(current)
    This version publication date
    28 Jul 2016
    First version publication date
    21 Dec 2014
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    re-QC study because of EudraCT system glitch and possible updates to results required.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V70P5
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00644059
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostics
    Sponsor organisation address
    Novartis Vaccines, Via Fiorentina, 1., Siena., Italy, 53100.
    Public contact
    Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000149-PIP01-07
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Nov 2010
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Aug 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the safety and tolerability of one or two 0.25mL IM doses of FLUAD in unprimed children aged 6 to <36 months, compared with Agrippal S1 and/or with Influsplit SSW (flu vaccine control), in terms of any solicited local and systemic reactions (combined) reported within 7 days after any vaccination. To demonstrate protection provided by two 0.25mL intramuscular (IM) doses of Fluad (TIV-adj) in unprimed children aged 6 to <36 months, compared with Menjugate/ Encepur Children (Non-flu vaccine control), against influenza illness caused by virus-confirmed community-acquired influenza wild type strains matching with those contained in the vaccine.
    Protection of trial subjects
    As with all injectable vaccines, appropriate medical treatment and supervision was readily available in case of rare anaphylactic reactions following administration of the study vaccine. Epinephrine 1:1000 and diphenhydramine were available in case of any anaphylactic reactions.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Nov 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Finland: 2083
    Country: Number of subjects enrolled
    Italy: 61
    Country: Number of subjects enrolled
    Germany: 2758
    Worldwide total number of subjects
    4902
    EEA total number of subjects
    4902
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    2046
    Children (2-11 years)
    2856
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 In season 2007/08: 28 active sites in Germany; In season 2008/09: 83 active sites+ 1 coordinating site in Germany, 15 sites in Finland; In season 2009/10: 15 sites in Finland, 2 sites in Italy.

    Pre-assignment
    Screening details
    		 All subjects enrolled were included in the trial. The data entered is for the overall study.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 TIV-adj
    Arm description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of adjuvanted trivalent inactivated subunit influenza vaccine
    Arm type
    		 Experimental

    Investigational medicinal product name
    Adjuvanted Trivalent influenza vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses of 0.25mL in children aged 6 to<36 months; 2 doses of 0.5mL in children aged 36 to<72 months given intramuscularly in the non-dominant arm, or in the thigh, depending on age.

    Arm title
    		 Flu-control
    Arm description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Influsplit SSW
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    A 0.25 mL pre-filled syringe pediatric dose is provided for subject aged 6 to <36 months and a 0.5 mL pre-filled syringe is provided for subject aged 36 to <72 months.

    Investigational medicinal product name
    Non adjuvanted Trivalent influenza vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses of 0.25mL (children aged 6 to<36 months) or 0.5mL children aged 36 to<72 months) given intramuscularly in the non-dominant arm, or in the thigh, depending on age.

    Arm title
    		 Non-flu Control
    Arm description
    		 Subjects aged 6 to <12 months received 2 doses of 0.5 mL of Novartis Menningocoocal C conjugate vaccine and subjects aged 12 to <72 months received 2 doses of 0.25 mL of Tick-borne encephalitis (TBE) vaccine
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Men C vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection in pre-filled syringe, Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    MenC Vaccine: 2 doses of 0.5mL in subjects aged 6 to <12 months; TBE Vacine: Children 2 doses of 0.25mL in subjects aged 12 to <72 months given intramuscularly in the non-dominant arm, or in the thigh, depending on age.

    Investigational medicinal product name
    Encepur
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses of 0.25mL was injected in subjects aged 12 to <72 months.

    Number of subjects in period 1
    		TIV-adj Flu-control Non-flu Control
    Started
    2019
    1849
    1034
    Completed
    1895
    1726
    969
    Not completed
    124
    123
    65
         Inapproopriate enrollment
    1
    -
    -
         Consent withdrawn by subject
    52
    60
    30
         Inappropriate enrollment
    -
    3
    -
         Unable to classify
    6
    2
    3
         Adverse event
    8
    5
    1
         Lost to follow-up
    37
    34
    16
         Protocol deviation
    20
    19
    15

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TIV-adj
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of adjuvanted trivalent inactivated subunit influenza vaccine

    Reporting group title
    Flu-control
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine.

    Reporting group title
    Non-flu Control
    Reporting group description
    		 Subjects aged 6 to <12 months received 2 doses of 0.5 mL of Novartis Menningocoocal C conjugate vaccine and subjects aged 12 to <72 months received 2 doses of 0.25 mL of Tick-borne encephalitis (TBE) vaccine

    Reporting group values
    		 TIV-adj Flu-control Non-flu Control Total
    Number of subjects
    		 2019 1849 1034 4902
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 31.9 ± 19.8 32.6 ± 20.1 32.2 ± 19.8 -
    Gender categorical
    Units: Subjects
        Female
    		 962 903 484 2349
        Male
    		 1057 946 550 2553

    End points

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    End points reporting groups
    Reporting group title
    TIV-adj
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of adjuvanted trivalent inactivated subunit influenza vaccine

    Reporting group title
    Flu-control
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL and those aged 36 to <72 months received 0.5 mL of each injection of Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine.

    Reporting group title
    Non-flu Control
    Reporting group description
    		 Subjects aged 6 to <12 months received 2 doses of 0.5 mL of Novartis Menningocoocal C conjugate vaccine and subjects aged 12 to <72 months received 2 doses of 0.25 mL of Tick-borne encephalitis (TBE) vaccine

    Subject analysis set title
    TIV-adj (6 to <36 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed population who provided post-baseline safety data

    Subject analysis set title
    Flu-control (6 to <36 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the exposed population who provided post-baseline safety data.

    Subject analysis set title
    Flu-control (36 to <72 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    TIV-adj (36 to <72 Months)-safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    Non-flu control (TBE/Men C Vaccine)-Safety
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the exposed population who provided post-baseline safety data.

    Subject analysis set title
    Non-Flu-control (36 to <72 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    Non-Flu control (6 to < 72 Months)-safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    Flu-control (6 to <72 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    TIV-adj (6 to <72 Months)-Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the enrolled population who provided post-baseline safety data.

    Subject analysis set title
    Flu Control (6 to <36 Months)-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Subject analysis set title
    Non-flu Control (6 to <36 Months)-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Subject analysis set title
    TIV-adj (36 to <72 Months)-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled populatio who received study vaccination.

    Subject analysis set title
    TIV-adj (6 to < 36 Months)-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Subject analysis set title
    Non-flu control (36 to <72 Months)- FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled populatio who received study vaccination.

    Subject analysis set title
    Flu control (36 to <72 Months)- FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled populatio who received study vaccination.

    Subject analysis set title
    TIV-adj-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Subject analysis set title
    Flu- control-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Subject analysis set title
    Non-flu control-FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the enrolled set who received study vaccination.

    Primary: 1. Number of Subjects (Unprimed) 6 to <36 Months Age With Local and Systemic Reactions After Any Vaccination for All Seasons, Comparison of Adjuvanted Trivalent Influenza Vaccine (aTIV) and Flu Vaccine Control.

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    End point title
    		 1. Number of Subjects (Unprimed) 6 to <36 Months Age With Local and Systemic Reactions After Any Vaccination for All Seasons, Comparison of Adjuvanted Trivalent Influenza Vaccine (aTIV) and Flu Vaccine Control. [1]
    End point description
    Safety was assessed as the number of subjects who reported solicited local or systemic adverse events after any vaccination with TIV-adj for all seasons.
    End point type
    Primary
    End point timeframe
    7 days post-vaccination
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses for this end point
    End point values
    		 TIV-adj (6 to <36 Months)-Safety Flu-control (6 to <36 Months)-Safety
    Number of subjects analysed
    1178
    1068
    Units: Number of subjects
    number (not applicable)
        Any Local
    625
    481
        Injection Site Ecchymosis
    147
    103
        Injection Site Erythema
    423
    322
        Injection Site Induration
    214
    131
        Swelling
    123
    89
        Tender. at inj.site
    330
    246
        Any Systemic
    785
    694
        Change in eat. hab.
    325
    261
        Sleepiness
    380
    312
        Unusual crying
    386
    345
        Irritability
    387
    353
        Vomiting
    131
    118
        Diarrhea
    258
    211
        Shivering
    77
    69
        Any Other
    358
    317
        Fever (38-38.9°C) (N=1177,1068)
    169
    143
        Fever (39-39.9°C) (N=1177,1068)
    61
    43
        Fever (>40.0°C) (N=1177,1068)
    3
    3
        Analg.Antipyr.Used (N=1176,1068)
    358
    317
    No statistical analyses for this end point

    Primary: 2. Percentage of Subjects (Unprimed) Aged 6 to <36 Months With Virus-Confirmed Influenza, Comparison of Adjuvanted Trivalent Influenza Vaccine and Non-Flu Control (Men C/TBE vaccine)

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    End point title
    		 2. Percentage of Subjects (Unprimed) Aged 6 to <36 Months With Virus-Confirmed Influenza, Comparison of Adjuvanted Trivalent Influenza Vaccine and Non-Flu Control (Men C/TBE vaccine)
    End point description
    Virus-confirmed influenza illnesses were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in 6 to <36 month unprimed subjects for Absolute Efficacy. This primary endpoint is only for homologous strains.
    End point type
    Primary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 Non-flu Control (6 to <36 Months)-FAS TIV-adj (6 to < 36 Months)-FAS
    Number of subjects analysed
    469
    916
    Units: Percentage of subjects
    number (not applicable)
        Season 2007/2008; N=187, 97
    0
    0
        Season 2008/2009
    4.05
    0.76
    Statistical analysis title
    		 Comparison of aTIV and Non-flu vaccine control
    Statistical analysis description
    Absolute vaccine efficacy (VE) was calculated as (1- the relative risk)100%. Relative Risk for virus-confirmed symptomatic influenza illness in the TIV-adj group vs. the non-flu control group. VE denotes the vaccine efficacy, i.e. 1-Itest/Inon-flu ctrl, where I stands for the population average incidence of influenza. Absolute efficacy of TIV-adj is at most 40% (i.e. the probability of an influenza in the test group relative to that in the non-flu vaccine group is at least 0.6)
    Comparison groups
    TIV-adj (6 to < 36 Months)-FAS v Non-flu Control (6 to <36 Months)-FAS
    Number of subjects included in analysis
    1385
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    81.36
    Confidence interval
         level
    		 97.66%
         sides
    2-sided
         lower limit
    		 49.24
         upper limit
    		 93.16

    Secondary: 3. Number of Subjects (Unprimed) of 6 to <72 Months Age With Local and Systemic Reactions After Any Vaccination

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    End point title
    		 3. Number of Subjects (Unprimed) of 6 to <72 Months Age With Local and Systemic Reactions After Any Vaccination
    End point description
    Safety was assessed as the number of subjects aged 6 to <72 months who reported solicited local or systemic adverse events after any vaccination with TIV-adj for all seasons.
    End point type
    Secondary
    End point timeframe
    7 days post-vaccination
    End point values
    		 TIV-adj (6 to <36 Months)-Safety Flu-control (6 to <36 Months)-Safety Flu-control (36 to <72 Months)-Safety TIV-adj (36 to <72 Months)-safety Non-flu control (TBE/Men C Vaccine)-Safety Non-Flu-control (36 to <72 Months)-Safety
    Number of subjects analysed
    1178
    1068
    778
    833
    607
    422
    Units: Number of Subjects
    number (not applicable)
        Any Local
    625
    481
    466
    569
    315
    232
        Inj. site ecchymosis(N=1178,833,1068,777,607,422)
    147
    103
    93
    130
    69
    49
        Inj. site erythema(N=1178,833,1068,777,607,422)
    423
    322
    269
    320
    239
    129
        Inj. site induration(N=1178,833,1068,777,607,422)
    214
    131
    152
    168
    153
    80
        Inj. site swelling(N=1178,833,1068,777,607,422)
    123
    89
    128
    155
    82
    55
        Inj. site tenderness(N=1178,0,1068,0,607,0)
    330
    246
    0
    0
    171
    0
        Inj. site pain(N=0,833,0,777,0,422)
    0
    0
    360
    477
    0
    180
        Any Systemic
    785
    694
    341
    523
    370
    211
        Change in eating habits(N=1178,0,1068,0,607,0)
    325
    261
    0
    0
    162
    0
        Sleepiness(N=1178,0,1068,0,607,0)
    380
    312
    0
    0
    186
    0
        Unusual crying(N=1178,0,1068,0,607,0)
    386
    345
    0
    0
    175
    0
        Irritability(N=1178,0,1068,0,607,0)
    387
    353
    0
    0
    187
    0
        Vomiting(N=1178,0,1068,0,607,0)
    131
    118
    0
    0
    66
    0
        Diarrhea(N=1178,0,1068,0,607,0)
    258
    211
    0
    0
    114
    0
        Shivering(N=1178,0,1068,0,607,0)
    77
    69
    0
    0
    50
    0
        Chills shivering(N=0,833,0,777,0,422)
    0
    0
    51
    130
    0
    37
        Malaise(N=0,833,0,777,0,422)
    0
    0
    118
    196
    0
    63
        Myalgia(N=0,833,0,777,0,422)
    0
    0
    100
    183
    0
    66
        Arthralgia(N=0,833,0,777,0,422)
    0
    0
    37
    82
    0
    27
        Headache(N=0,833,0,777,0,422)
    0
    0
    100
    197
    0
    54
        Sweating(N=0,833,0,777,0,422)
    0
    0
    42
    69
    0
    31
        Fatigue(N=0,833,0,777,0,422)
    0
    0
    222
    337
    0
    123
        Any Other
    358
    317
    94
    196
    159
    69
        Fever(38-38.9C)(N=1177,833,1068,775,607,421)
    169
    143
    55
    133
    62
    37
        Fever(39-39.9C)(N=1177,833,1068,775,607,421)
    61
    43
    17
    50
    34
    19
        Fever(≥40.0C)(N=1177,833,1068,775,607,421)
    3
    3
    2
    1
    2
    1
        Analg.Antipyr.Used(N=1176,833,1068,777,607,422)
    358
    317
    94
    196
    159
    69
    No statistical analyses for this end point

    Secondary: 4. Number of Subjects (Unprimed) With Unsolicited Adverse Events Reported After Any Vaccination

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    End point title
    		 4. Number of Subjects (Unprimed) With Unsolicited Adverse Events Reported After Any Vaccination
    End point description
    Number of subjects aged 6 to <36 months and in the overall age cohort (unprimed children aged 6 to <72 months) experiencing each of the unsolicited adverse events throughout the study.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 181
    End point values
    		 TIV-adj (6 to <36 Months)-Safety Flu-control (6 to <36 Months)-Safety Non-flu control (TBE/Men C Vaccine)-Safety Non-Flu control (6 to < 72 Months)-safety Flu-control (6 to <72 Months)-Safety TIV-adj (6 to <72 Months)-Safety
    Number of subjects analysed
    1177
    1069
    607
    1029
    1846
    2012
    Units: Number of subjects
    number (not applicable)
        Any AEs
    1045
    938
    530
    867
    1566
    1714
        At least possibly related AEs
    152
    124
    90
    137
    203
    262
        Serious AEs
    91
    104
    65
    110
    169
    122
        At least possibly related SAEs
    1
    1
    3
    3
    2
    2
        AEs leading to discontinuation
    6
    9
    1
    1
    10
    9
    No statistical analyses for this end point

    Secondary: 5. Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu-vaccine Control (Matched Strains)

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    End point title
    		 5. Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu-vaccine Control (Matched Strains)
    End point description
    Virus-confirmed influenza illnesses were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in subjects aged 6 to <72 months (unprimed) for Absolute Efficacy. For Relative efficacy, the comparison was made between adjuvanted influenza vaccine (TIV-adj) and flu vaccine control.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 Flu Control (6 to <36 Months)-FAS Non-flu Control (6 to <36 Months)-FAS TIV-adj (36 to <72 Months)-FAS TIV-adj (6 to < 36 Months)-FAS Non-flu control (36 to <72 Months)- FAS Flu control (36 to <72 Months)- FAS
    Number of subjects analysed
    902
    469
    698
    916
    360
    706
    Units: Percentage of subjects
    number (not applicable)
        Matched strain(Season2007/08)N=187,97,93,136,67,71
    0
    0
    0
    0
    0
    0
        Matched strain (Season2008/09)
    2.44
    4.05
    0.29
    0.76
    6.11
    3.12
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and flu controls
    Statistical analysis description
    Absolute vaccine efficacy (VE) was calculated as (1- the relative risk)100%. Relative Risk for virus-confirmed symptomatic influenza illness in the TIV-adj group vs. the non-flu control group. VE denotes the vaccine efficacy, i.e. 1-Itest/Inon-flu ctrl, where I stands for the incidence of influenza. Absolute efficacy of TIV-adj is at most 40% (i.e. the probability of an influenza in the test group relative to that in the non-flu vaccine group is at least 0.6)
    Comparison groups
    TIV-adj (36 to <72 Months)-FAS v Non-flu control (36 to <72 Months)- FAS
    Number of subjects included in analysis
    1058
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 [Poisson Regression Model]
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    95.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 80.92
         upper limit
    		 98.94
    Statistical analysis title
    		 Comparison of aTIV to Non-Flu and Flu controls
    Statistical analysis description
    Absolute vaccine efficacy (VE) was calculated as (1- the relative risk)100%. Relative Risk for virus-confirmed symptomatic influenza illness in the TIV-adj group vs. the non-flu control group. VE denotes the vaccine efficacy, i.e. 1-Itest/Inon-flu ctrl, where I stands for the incidence of influenza. Absolute efficacy of TIV-adj is at most 40% (i.e. the probability of an influenza in the test group relative to that in the non-flu vaccine group is at least 0.6)
    Comparison groups
    TIV-adj (6 to < 36 Months)-FAS v Non-flu Control (6 to <36 Months)-FAS
    Number of subjects included in analysis
    1385
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    81.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 49.24
         upper limit
    		 93.16
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and flu controls
    Statistical analysis description
    Relative efficacy for TIV-adj was to be calculated as VE = (1-Itest/Ictrl)100%, where I is the incidence of influenza, i.e. percentage of subjects with virus-confirmed symptomatic influenza A or B illness, in the investigational agent (TIV-adj) group or in the flu vaccine control group.
    Comparison groups
    TIV-adj (6 to < 36 Months)-FAS v Flu Control (6 to <36 Months)-FAS
    Number of subjects included in analysis
    1818
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 0.73
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and Flu controls
    Statistical analysis description
    Relative efficacy for TIV-adj was to be calculated as VE = (1-Itest/Ictrl)100%, where I is the incidence of influenza, i.e. percentage of subjects with virus-confirmed symptomatic influenza A or B illness, in the investigational agent (TIV-adj) group or in the flu vaccine control group.
    Comparison groups
    TIV-adj (36 to <72 Months)-FAS v Flu control (36 to <72 Months)- FAS
    Number of subjects included in analysis
    1404
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Vaccine Efficacy]
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 0.38

    Secondary: 6. Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu Vaccine Control (Any Strains)

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    End point title
    		 6. Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu Vaccine Control (Any Strains)
    End point description
    Virus-confirmed influenza illnesses (regardless of antigenic match to those contained in the vaccine) were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in subjects aged 6 to <72 months (unprimed) for Absolute Efficacy. For Relative efficacy, the comparison was made between adjuvanted influenza vaccine (TIV-adj) and flu vaccine control.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 Flu Control (6 to <36 Months)-FAS Non-flu Control (6 to <36 Months)-FAS TIV-adj (36 to <72 Months)-FAS TIV-adj (6 to < 36 Months)-FAS Non-flu control (36 to <72 Months)- FAS Flu control (36 to <72 Months)- FAS
    Number of subjects analysed
    902
    469
    698
    916
    360
    706
    Units: Percentage of subjects
    number (not applicable)
        Any Strain (Season 2007/08)N=187,97,93,136,67,71
    0
    2.06
    0.74
    0
    2.99
    0
        Any Strain (Season 2008/09)
    2.77
    4.26
    0.43
    0.98
    6.39
    3.54
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and Flu controls
    Statistical analysis description
    Absolute vaccine efficacy (VE) was calculated as (1- the relative risk)100%. Relative Risk for virus-confirmed symptomatic influenza illness in the TIV-adj group vs. the non-flu control group. VE denotes the vaccine efficacy, i.e. 1-Itest/Inon-flu ctrl, where I stands for the incidence of influenza. Absolute efficacy of TIV-adj is at most 40% (i.e. the probability of an influenza in the test group relative to that in the non-flu vaccine group is at least 0.6).
    Comparison groups
    TIV-adj (36 to <72 Months)-FAS v Non-flu control (36 to <72 Months)- FAS
    Number of subjects included in analysis
    1058
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    92.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 77.35
         upper limit
    		 97.24
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and Flu controls
    Statistical analysis description
    Relative efficacy for TIV-adj was to be calculated as VE = (1-Itest/Ictrl)100%, where I is the incidence of influenza, i.e. percentage of subjects with virus-confirmed symptomatic influenza A or B illness, in the investigational agent (TIV-adj) group or in the flu vaccine control group.
    Comparison groups
    TIV-adj (6 to < 36 Months)-FAS v Flu Control (6 to <36 Months)-FAS
    Number of subjects included in analysis
    1818
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    64.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.21
         upper limit
    		 83.28
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and Flu controls
    Statistical analysis description
    Absolute vaccine efficacy (VE) was calculated as (1- the relative risk)100%. Relative Risk for virus-confirmed symptomatic influenza illness in the TIV-adj group vs. the non-flu control group. VE denotes the vaccine efficacy, i.e. 1-Itest/Inon-flu ctrl, where I stands for the population average incidence of influenza. Absolute efficacy of TIV-adj is at most 40% (i.e. the probability of an influenza in the test group relative to that in the non-flu vaccine group is at least 0.6)
    Comparison groups
    TIV-adj (6 to < 36 Months)-FAS v Non-flu Control (6 to <36 Months)-FAS
    Number of subjects included in analysis
    1385
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    79.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 54.78
         upper limit
    		 90.42
    Statistical analysis title
    		 Comparison of aTIV to Non-flu and Flu controls
    Statistical analysis description
    Relative efficacy for TIV-adj was to be calculated as VE = (1-Itest/Ictrl)100%, where I is the incidence of influenza, i.e. percentage of subjects with virus-confirmed symptomatic influenza A or B illness, in the investigational agent (TIV-adj) group or in the flu vaccine control group.
    Comparison groups
    TIV-adj (36 to <72 Months)-FAS v Flu control (36 to <72 Months)- FAS
    Number of subjects included in analysis
    1404
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Poisson Regression Model
    Parameter type
    		 Vaccine Efficacy
    Point estimate
    85.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 58.95
         upper limit
    		 94.99

    Secondary: 7. Number of Subjects (Unprimed) With Influenza Like Illnesses (ILIs) in the 6 to <72 Months Age Cohort for Combined Seasons 2007/08 and 2008/09

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    End point title
    		 7. Number of Subjects (Unprimed) With Influenza Like Illnesses (ILIs) in the 6 to <72 Months Age Cohort for Combined Seasons 2007/08 and 2008/09
    End point description
    Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine in 6 to <72 month old subjects for Influenza like illnesses for seasons 2007/08 and 2008/09.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 TIV-adj-FAS Flu- control-FAS Non-flu control-FAS
    Number of subjects analysed
    1937
    1772
    993
    Units: Number of subjects
    number (not applicable)
        Subjects with ILI
    425
    436
    253
        Outpatient visits
    290
    293
    174
        Inpatient visits
    20
    26
    19
        Outcome (Recovered)
    414
    431
    248
        Outcome (Alive with sequelae)
    5
    2
    2
        Outcome (Lost to follow-up)
    3
    1
    0
        Outcome (ILI persisting)
    3
    1
    3
        Outcome (Not available)
    0
    1
    0
    No statistical analyses for this end point

    Secondary: 8. Number of Subjects With Influenza Like Illnesses (ILIs) in the 6 to <36 Months and in Overall Age Cohort (Unprimed Subjects Aged 6 to <72 Months) for Combined Seasons 2007/08 and 2008/09.

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    End point title
    		 8. Number of Subjects With Influenza Like Illnesses (ILIs) in the 6 to <36 Months and in Overall Age Cohort (Unprimed Subjects Aged 6 to <72 Months) for Combined Seasons 2007/08 and 2008/09.
    End point description
    Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine for Influenza like illnesses for seasons 2007/08 and 2008/09.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 Flu Control (6 to <36 Months)-FAS Non-flu Control (6 to <36 Months)-FAS TIV-adj (6 to < 36 Months)-FAS TIV-adj-FAS Flu- control-FAS Non-flu control-FAS
    Number of subjects analysed
    995
    566
    1103
    1937
    1772
    993
    Units: Number of subjects
    number (not applicable)
        Subjects with ILI
    272
    163
    280
    425
    436
    253
        Outpatient visits
    183
    113
    192
    290
    293
    174
        Inpatient visits
    19
    14
    13
    20
    26
    19
        Outcome (Recovered)
    267
    159
    269
    414
    431
    248
        Outcome (Alive with sequelae)
    2
    2
    5
    5
    2
    2
        Outcome (Lost to follow-up)
    1
    0
    3
    3
    1
    0
        Outcome (ILI persisting)
    1
    2
    3
    3
    1
    3
        Outcome (Not available)
    1
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: 9. Loss of Days of Usual Activity (Job, School, Day Care, Household/Family/Community Activities) Due to Influenza Like Illness (ILI) in Subjects in Aged 6 to <72 and 6 to <36 Months and in Direct Caregivers Living in the Household.

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    End point title
    		 9. Loss of Days of Usual Activity (Job, School, Day Care, Household/Family/Community Activities) Due to Influenza Like Illness (ILI) in Subjects in Aged 6 to <72 and 6 to <36 Months and in Direct Caregivers Living in the Household.
    End point description
    Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine for Influenza like illnesses for seasons 2007/08 and 2008/09.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    425
    436
    253
    Units: Days
    arithmetic mean (standard deviation)
        Mean bed days (6 to <72 mths)(N=419,426,250)
    1.9 ± 2.3
    1.9 ± 2.4
    2.3 ± 2.7
        Mean bed days (6 to <36 mths)(N=274,263,160)
    2 ± 2.5
    1.8 ± 2.4
    2.1 ± 2.4
        Mean inactive days(6 to <72 mths)(N=417,427,249)
    3.1 ± 3.3
    2.9 ± 3.7
    3.3 ± 3.5
        Mean inactive days(6 to <36 mths)(N=273,264,160)
    2.9 ± 3.3
    2.6 ± 3.3
    3 ± 3.6
    No statistical analyses for this end point

    Secondary: 10. Number of Events of Influenza Like Illness for Combined Seasons 2007/08 and 2008/09.

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    End point title
    		 10. Number of Events of Influenza Like Illness for Combined Seasons 2007/08 and 2008/09.
    End point description
    The number of events of Influenza like Illness reported by subjects aged 6 to <72 months was assessed for combined seasons 2007/08 and 2008/09.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    425
    436
    253
    Units: Events
    arithmetic mean (standard deviation)
        Mean ILI events (6 to <72 mths)(N=425,436,253)
    1.2 ± 0.5
    1.2 ± 0.5
    1.3 ± 0.6
        Mean ILI events (6 to <36 mths)(N=280,272,163)
    1.3 ± 0.5
    1.3 ± 0.5
    1.3 ± 0.6
    No statistical analyses for this end point

    Secondary: 11. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <36 Months or Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 11. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <36 Months or Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    The immunogenicity was assessed in terms of Geometric mean titer ratios (GMRs) of study day 29/study day 1, study day 50/study day 1, study day 181/study day 1 were evaluated. The criteria for evaluation is GMR >2.5
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    166
    165
    83
    Units: Ratios
    geometric mean (confidence interval 95%)
        Day 29:1 A/Brisbane/2007 (A/H1N1) (N=165,163,82)
    17 (15 to 20)
    1.83 (1.57 to 2.13)
    1.03 (0.83 to 1.27)
        Day 50:1 A/Brisbane/2007 (A/H1N1) (N=160,162,78)
    83 (70 to 98)
    4.55 (3.84 to 5.39)
    1.11 (0.87 to 1.4)
        Day 181:1 A/Brisbane/2007 (A/H1N1) (N=161,163,80)
    19 (17 to 21)
    2.4 (2.11 to 2.73)
    1.02 (0.85 to 1.22)
        Day 29:1 A/Brisbane/2007 (A/H3N2) (N=165,163,82)
    15 (13 to 18)
    1.58 (1.38 to 1.81)
    1.07 (0.88 to 1.29)
        Day 50:1 A/Brisbane/2007 (A/H3N2) (N=160,162,78)
    86 (73 to 102)
    5.57 (4.73 to 6.55)
    1.04 (0.83 to 1.32)
        Day 181:1 A/Brisbane/2007 (A/H3N2) (N=161,163,80)
    30 (24 to 37)
    6.16 (4.97 to 7.63)
    2.1 (1.55 to 2.83)
        Day 29:1 B/Florida/2006 (N=165,163,82)
    2.11 (1.86 to 2.39)
    1.41 (1.24 to 1.6)
    1.06 (0.89 to 1.26)
        Day 50:1 B/Florida/2006 (N=160,162,78)
    14 (13 to 16)
    2.05 (1.81 to 2.31)
    1.02 (0.86 to 1.22)
        Day 181:1 B/Florida/2006 (N=161,163,80)
    4.22 (3.79 to 4.68)
    1.45 (1.31 to 1.61)
    1.05 (0.91 to 1.22)
        Day 29:1A/SolomonIsland/2006(A/H1N1)(N=165,163,82)
    2.1 (1.81 to 2.42)
    1.41 (1.22 to 1.62)
    0.97 (0.79 to 1.18)
        Day 50:1A/SolomonIsland/2006(A/H1N1)(N=160,162,78)
    18 (16 to 21)
    1.96 (1.7 to 2.25)
    0.98 (0.8 to 1.19)
        Day181:1A/SolomonIsland/2006(A/H1N1)(N=161,163,80)
    6.52 (5.79 to 7.34)
    1.6 (1.42 to 1.8)
    0.99 (0.84 to 1.16)
        Day 29:1 A/Wisconsin/2009 (A/H3N2)(N=165,163,82)
    4.56 (4.07 to 5.11)
    1.17 (1.05 to 1.31)
    0.95 (0.81 to 1.11)
        Day 50:1 A/Wisconsin/2009 (A/H3N2)(N=160,162,78)
    43 (37 to 50)
    3.01 (2.59 to 3.51)
    1.04 (0.84 to 1.29)
        Day181:1 A/Wisconsin/2009 (A/H3N2)(N=161,163,80)
    20 (16 to 25)
    5.06 (4.03 to 6.37)
    2.22 (1.61 to 3.06)
        Day 29:1 B/Brisbane/2008 (N=164,163,82)
    1.08 (1.04 to 1.11)
    1.02 (0.098 to 1.05)
    1 (0.96 to 1.05)
        Day 50:1 B/Brisbane/2008 (N=159,162,78)
    1.94 (1.8 to 2.08)
    1.11 (1.03 to 1.19)
    1.02 (0.93 to 1.14)
        Day181:1 B/Brisbane/2008 (N=160,163,80)
    1.04 (0.98 to 1.11)
    1.05 (0.98 to 1.11)
    1.26 (1.15 to 1.37)
    No statistical analyses for this end point

    Secondary: 12. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of Geometric Mean Titers (GMTs), in Unprimed Subjects Aged 6 to <36 Months for Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 12. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of Geometric Mean Titers (GMTs), in Unprimed Subjects Aged 6 to <36 Months for Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    Immunogenicity was analyzed in terms of Geometric Mean Titers (GMTs) as measured by hemagglutination inhibition (HI) assay. For each strain and each vaccine group, least squares GMTs, associated 2-sided 95% confidence interval were determined for all time points. Superiority analysis: GMT-TIV-adj/GMT-Flu-control >1 should be elicited to show that GMT-TIV-adj is superior to GMT-Flu-control
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    166
    165
    83
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 1 A/Brisbane/2007 (A/H1N1)
    6.21 (5.33 to 7.24)
    7.52 (6.45 to 8.76)
    5.93 (4.8 to 7.33)
        Day 29 A/Brisbane/2007 (A/H1N1) (N=165,163,82)
    105 (82 to 136)
    14 (11 to 18)
    6.13 (4.33 to 8.69)
        Day 50 A/Brisbane/2007 (A/H1N1) (N=160,162,78)
    513 (405 to 652)
    35 (27 to 44)
    6.57 (4.71 to 9.16)
        Day 181 A/Brisbane/2007 (A/H1N1) (N=161,163,80)
    118 (95 to 146)
    18 (15 to 22)
    6.1 (4.51 to 8.25)
        Day 1 A/Brisbane/2007 (A/H3N2)
    5.85 (5.13 to 6.67)
    5.8 (5.09 to 6.6)
    5.66 (4.73 to 6.77)
        Day 29 A/Brisbane/2007 (A/H3N2) (N=165,163,82)
    90 (76 to 107)
    9.17 (7.71 to 11)
    6.04 (4.75 to 7.69)
        Day 50 A/Brisbane/2007 (A/H3N2) (N=160,162,78)
    510 (426 to 609)
    32 (27 to 39)
    6 (4.68 to 7.68)
        Day 181 A/Brisbane/2007 (A/H3N2) (N=161,163,80)
    176 (141 to 220)
    36 (29 to 45)
    12 (8.74 to 16)
        Day 1 B/Florida/2006
    6.01 (5.59 to 6.45)
    6 (5.59 to 6.44)
    5.87 (5.32 to 6.47)
        Day 29 B/Florida/2006 (N=165,163,82)
    13 (11 to 15)
    8.45 (7.11 to 10)
    6.19 (4.87 to 7.87)
        Day 50 B/Florida/2006 (N=160,162,78)
    86 (74 to 100)
    12 (11 to 14)
    6.09 (4.95 to 7.49)
        Day 181 B/Florida/2006 (N=161,163,80)
    25 (22 to 29)
    8.72 (7.65 to 9.95)
    6.21 (5.16 to 7.48)
        Day 1 A/SolomonIslands/2006(A/H1N1)
    6.66 (5.56 to 7.98)
    8.19 (6.85 to 9.8)
    6.24 (4.87 to 8)
        Day 29 A/SolomonIslands/2006(A/H1N1)(N=165,163,82)
    14 (11 to 19)
    12 (8.69 to 15)
    6.08 (4.12 to 8.98)
        Day 50 A/SolomonIslands/2006(A/H1N1)(N=160,162,78)
    122 (94 to 157)
    16 (13 to 21)
    6.1 (4.27 to 8.73)
        Day181 A/SolomonIslands/2006(A/H1N1)(N=161,163,80)
    44 (34 to 55)
    13 (10 to 17)
    6.2 (4.46 to 8.61)
        Day 1 A/Wisconsin/2009 (A/H3N2)
    6.09 (5.26 to 7.06)
    6.74 (5.83 to 7.8)
    6.16 (5.03 to 7.53)
        Day 29 A/Wisconsin/2009 (A/H3N2)(N=165,163,82)
    28 (23 to 33)
    7.86 (6.57 to 9.39)
    5.87 (4.59 to 7.52)
        Day 50 A/Wisconsin/2009 (A/H3N2)(N=160,162,78)
    261 (218 to 313)
    20 (17 to 24)
    6.47 (5.03 to 8.32)
        Day181 A/Wisconsin/2009(A/H3N2)(N=161,163,80)
    123 (97 to 156)
    34 (27 to 43)
    14 (9.81 to 19)
        Day 1 B/Brisbane/2008 (N=165,165,83)
    5 (5 to 5)
    5 (5 to 5)
    5 (5 to 5)
        Day 29 B/Brisbane/2008 (N=165,163,82)
    5.38 (5.21 to 5.56)
    5.08 (4.91 to 5.24)
    5 (4.78 to 5.23)
        Day 50 B/Brisbane/2008 (N=160,162,78)
    9.64 (8.96 to 10)
    5.55 (5.16 to 5.97)
    5.12 (4.63 to 5.68)
        Day181 B/Brisbane/2008 (N=161,163,80)
    5.21 (4.89 to 5.54)
    5.23 (4.92 to 5.56)
    6.28 (5.75 to 6.84)
    Statistical analysis title
    		 GMT A/H1N1; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.02
    Statistical analysis title
    		 GMT A/H1N1; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    7.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.42
         upper limit
    		 11
    Statistical analysis title
    		 GMT A/H1N1; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11
         upper limit
    		 21
    Statistical analysis title
    		 GMT A/H1N1; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    6.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.83
         upper limit
    		 8.68
    Statistical analysis title
    		 GMT A/H3N2; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.21
    Statistical analysis title
    		 GMT A/H3N2; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    9.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.76
         upper limit
    		 12
    Statistical analysis title
    		 GMT A/H3N2; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12
         upper limit
    		 20
    Statistical analysis title
    		 GMT A/H3N2; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    4.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.64
         upper limit
    		 6.65
    Statistical analysis title
    		 GMT B; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[B/Florida/2006]
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.1
    Statistical analysis title
    		 GMT B; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Florida/2006]
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 1.9
    Statistical analysis title
    		 GMT B; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Florida/2006]
    Point estimate
    6.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.72
         upper limit
    		 8.53
    Statistical analysis title
    		 GMT B; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Florida/2006]
    Point estimate
    2.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.44
         upper limit
    		 3.5
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.04
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.78
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    7.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.33
         upper limit
    		 11
    Statistical analysis title
    		 GMT A/H1N1(Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <36 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    3.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.4
         upper limit
    		 4.55
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.1
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    3.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.78
         upper limit
    		 4.51
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10
         upper limit
    		 16
    Statistical analysis title
    		 GMT A/H3N2(Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    Flu-control v TIV-adj
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.61
         upper limit
    		 4.95
    Statistical analysis title
    		 GMT B (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1
    Statistical analysis title
    		 GMT B (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.11
    Statistical analysis title
    		 GMT B (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.57
         upper limit
    		 1.92
    Statistical analysis title
    		 GMT B (Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <36 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.08

    Secondary: 13. Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With HI Titer ≥1:40 in Season 2008/09 HI Assay (Homologous and Heterologous Strains)

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    End point title
    		 13. Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With HI Titer ≥1:40 in Season 2008/09 HI Assay (Homologous and Heterologous Strains)
    End point description
    Percentage of subjects achieving seroprotection (i.e., with HI titer ≥1:40) at study day 1, study day 29, study day 50 and a study day 181 and associated 95% CI. The lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%.
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj (6 to <36 Months)-Safety Flu-control (6 to <36 Months)-Safety Non-flu control (TBE/Men C Vaccine)-Safety
    Number of subjects analysed
    166
    165
    83
    Units: Percentages of subjects
    number (confidence interval 95%)
        Day 1 A/Brisbane/2007 (A/H1N1)
    5 (3 to 10)
    11 (7 to 17)
    5 (1 to 12)
        Day 29 A/Brisbane/2007 (A/H1N1) (N=165,163,82)
    92 (86 to 95)
    20 (14 to 27)
    6 (2 to 14)
        Day 50 A/Brisbane/2007 (A/H1N1) (N=160,162,78)
    100 (98 to 100)
    38 (31 to 46)
    6 (2 to 14)
        Day 181 A/Brisbane/2007 (A/H1N1) (N=161,163,80)
    98 (94 to 99)
    25 (19 to 33)
    6 (2 to 14)
        Day 1 A/Brisbane/2007 (A/H3N2)
    4 (1 to 8)
    4 (1 to 8)
    2 (0 to 8)
        Day 29 A/Brisbane/2007 (A/H3N2) (N=165,163,82)
    95 (90 to 97)
    12 (7 to 18)
    4 (1 to 10)
        Day 50 A/Brisbane/2007 (A/H3N2) (N=160,162,78)
    99 (97 to 100)
    45 (37 to 53)
    4 (1 to 11)
        Day 181 A/Brisbane/2007 (A/H3N2) (N=161,163,80)
    100 (98 to 100)
    45 (37 to 53)
    21 (13 to 32)
        Day 1 B/Florida/2006
    2 (1 to 6)
    2 (0 to 5)
    1 (0.03 to 7)
        Day 29 B/Florida/2006 (N=165,163,82)
    12 (8 to 18)
    12 (8 to 18)
    4 (1 to 10)
        Day 50 B/Florida/2006 (N=160,162,78)
    88 (81 to 92)
    19 (13 to 25)
    3 (0 to 9)
        Day 181 B/Florida/2006 (N=161,163,80)
    40 (33 to 48)
    13 (9 to 20)
    3 (0 to 9)
        Day 1 A/SolomonIslands/2006(A/H1N1)
    5 (3 to 10)
    11 (7 to 17)
    5 (1 to 12)
        Day 29 A/SolomonIslands/2006(A/H1N1)(N=165,163,82)
    15 (10 to 21)
    13 (9 to 20)
    5 (1 to 12)
        Day 50 A/SolomonIslands/2006(A/H1N1)(N=160,162,78)
    95 (90 to 98)
    24 (18 to 31)
    5 (1 to 13)
        Day181 A/SolomonIslands/2006(A/H1N1)(N=161,163,80)
    61 (53 to 68)
    19 (13 to 26)
    5 (1 to 12)
        Day 1 A/Wisconsin/2009 (A/H3N2)
    4 (1 to 8)
    5 (2 to 9)
    2 (0 to 8)
        Day 29 A/Wisconsin/2009 (A/H3N2)(N=165,163,82)
    37 (30 to 45)
    6 (3 to 10)
    2 (0 to 9)
        Day 50 A/Wisconsin/2009 (A/H3N2)(N=160,162,78)
    100 (98 to 100)
    30 (23 to 37)
    4 (1 to 11)
        Day181 A/Wisconsin/2009 (A/H3N2)(N=161,163,80)
    99 (97 to 100)
    42 (34 to 50)
    23 (14 to 33)
        Day 1 B/Brisbane/2008 (N=166,165,83)
    0 (0 to 2)
    0 (0 to 2)
    0 (0 to 4)
        Day 29 B/Brisbane/2008 (N=165,163,82)
    1 (0.015 to 3)
    0 (0 to 2)
    0 (0 to 4)
        Day 50 B/Brisbane/2008 (N=160,162,78
    5 (2 to 10)
    0 (0 to 2)
    0 (0 to 5)
        Day181 B/Brisbane/2008 (N=161,163,80)
    0 (0 to 2)
    1 (0.016 to 3)
    6 (2 to 14)
    No statistical analyses for this end point

    Secondary: 14. Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With Seroconversion From Baseline, for Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 14. Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With Seroconversion From Baseline, for Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    HI assay was used for the analysis. Seroconversion is defined as negative pre-vaccination serum (<10)/ post-vaccination HI titer ≥1:40. Seroconversion is defined as either pre-vaccination HI titer <10 and a post-vaccination HI titer ≥1:40 or a prevaccination HI titer ≥10 and a minimum four-fold rise in post-vaccination HI antibody titer. The lower bound of the two-sided 95% confidence interval (CI) for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40%.
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    165
    163
    82
    Units: Percentages of subjects
    number (confidence interval 95%)
        Day29 A/Brisbane/2007(A/H1N1)
    92 (86 to 95)
    19 (13 to 26)
    1 (0.031 to 7)
        Day50 A/Brisbane/2007(A/H1N1)(N=160,162,78)
    100 (98 to 100)
    38 (30 to 46)
    1 (0.032 to 7)
        Day181A/Brisbane/2007(A/H1N1)(N=161,163,80)
    97 (93 to 99)
    24 (18 to 31)
    1 (0.032 to 7)
        Day29 A/Brisbane/2007(A/H3N2)
    93 (88 to 97)
    10 (6 to 16)
    1 (0.031 to 7)
        Day50 A/Brisbane/2007(A/H3N2)(N=160,162,78)
    98 (95 to 100)
    44 (36 to 52)
    1 (0.032 to 7)
        Day181A/Brisbane/2007(A/H3N2)(N=161,163,80)
    98 (94 to 99)
    42 (35 to 50)
    19 (11 to 29)
        Day29 B/Florida/2006
    12 (8 to 18)
    12 (8 to 18)
    0 (0 to 4)
        Day50 B/Florida/2006 (N=160,162,78)
    88 (81 to 92)
    19 (13 to 25)
    0 (0 to 5)
        Day181B/Florida/2006 (N=161,163,80)
    39 (31 to 46)
    12 (7 to 18)
    1 (0.032 to 7)
        Day29A/Sol.Islands/2006(A/H1N1)
    14 (9 to 20)
    13 (8 to 19)
    0 (0 to 4)
        Day50A/Sol.Islands/2006(A/H1N1)(N=160,162,78)
    94 (89 to 97)
    23 (17 to 30)
    0 (0 to 5)
        Day181A/Sol.Islands/2006(A/H1N1)(N=161,163,80)
    60 (52 to 68)
    18 (12 to 25)
    0 (0 to 5)
        Day29 A/Wisconsin/2009(A/H3N2)
    36 (28 to 44)
    4 (1 to 8)
    0 (0 to 4)
        Day50 A/Wisconsin/2009(A/H3N2)(N=160,162,78)
    100 (98 to 100)
    27 (20 to 35)
    1 (0.032 to 7)
        Day181A/Wisconsin/2009(A/H3N2)(N=161,163,80)
    97 (93 to 99)
    39 (31 to 47)
    20 (12 to 30)
        Day29 B/Brisbane/2008
    1 (0.015 to 3)
    0 (0 to 2)
    0 (0 to 45)
        Day 50:1 B/Brisbane/2008 (N=160,162,78)
    5 (2 to 12)
    0 (0 to 2)
    0 (0 to 5)
        Day181 B/Brisbane/2008 (N=161,163,80)
    0 (0 to 2)
    1 (0.016 to 3)
    6 (2 to 14)
    No statistical analyses for this end point

    Secondary: 15. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of Geometric Mean Titers (GMTs), in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 15. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of Geometric Mean Titers (GMTs), in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    Immunogenicity was analyzed in terms of Geometric Mean Titers (GMTs) as measured by hemagglutination inhibition (HI) assay. For each strain and each vaccine group, least squares GMTs, associated 2-sided 95% confidence interval were determined for all time points Superiority analysis: GMT-TIV-adj/GMT-Flu-control >1 and GMT-TIV-adj/GMT-Non Flu control >1 should be elicited to show that GMT-TIV-adj is superior to GMT-Flu-control/Non Flu-control
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    319
    316
    158
    Units: Titers
    geometric mean (confidence interval 95%)
        Day 1 A/Brisbane/2007 (A/H1N1)
    9.63 (8.28 to 11)
    10 (8.59 to 12)
    9.48 (7.67 to 12)
        Day29A/Brisbane/2007(A/H1N1) (N=316,313,156)
    232 (185 to 291)
    36 (29 to 45)
    9.42 (6.85 to 13)
        Day50A/Brisbane/2007(A/H1N1) (N=310,309,150)
    735 (608 to 888)
    89 (74 to 108)
    9.91 (7.58 to 13)
        Day181A/Brisbane/2007(A/H1N1) (N=309,310,151)
    186 (155 to 225)
    43 (35 to 51)
    9.65 (7.41 to 13)
        Day1A/Brisbane/2007(A/H3N2)
    12 (10 to 15)
    12 (9.83 to 14)
    12 (8.98 to 15)
        Day 29 A/Brisbane/2007 (A/H3N2) (N=316,313,156)
    209 (167 to 261)
    33 (26 to 41)
    12 (8.83 to 17)
        Day 50 A/Brisbane/2007 (A/H3N2) (N=310,309,150)
    762 (634 to 915)
    95 (79 to 115)
    12 (9.18 to 15)
        Day 181 A/Brisbane/2007 (A/H3N2) (N=309,310,151)
    295 (245 to 356)
    94 (78 to 114)
    26 (20 to 34)
        Day 1 B/Florida/2006
    6.37 (6.01 to 6.75)
    6.57 (6.2 to 6.96)
    6.41 (5.92 to 6.95)
        Day 29 B/Florida/2006 (N=316,313,156)
    21 (18 to 25)
    14 (12 to 16)
    6.54 (5.26 to 8.13)
        Day 50 B/Florida/2006 (N=310,309,150)
    109 (97 to 123)
    22 (19 to 25)
    6.67 (5.64 to 7.88)
        Day 181 B/Florida/2006 (N=309,310,151)
    32 (29 to 36)
    13 (11 to 14)
    6.92 (6.01 to 7.98)
        Day 1 A/SolomonIslands/2006(A/H1N1)
    11 (9.47 to 14)
    12 (9.89 to 14)
    10 (8.16 to 13)
        Day29 A/SolomonIslands/2006(A/H1N1)(N=316,313,150)
    40 (30 to 53)
    23 (18 to 31)
    10 (7.12 to 15)
        Day50 A/SolomonIslands/2006(A/H1N1)(N=310,309,150)
    228 (182 to 287)
    41 (33 to 51)
    11 (7.63 to 15)
        Day181A/SolomonIslands/2006(A/H1N1)(N=309,310,151)
    88 (70 to 109)
    28 (23 to 35)
    11 (7.76 to 14)
        Day 1 A/Wisconsin/2009 (A/H3N2)
    15 (12 to 18)
    15 (12 to 19)
    13 (9.97 to 18)
        Day 29 A/Wisconsin/2009 (A/H3N2) (N=316,313,156)
    98 (75 to 127)
    31 (24 to 40)
    13 (8.74 to 18)
        Day 50 A/Wisconsin/2009 (A/H3N2) (N=310,309,150)
    518 (420 to 639)
    70 (57 to 87)
    14 (10 to 19)
        Day181 A/Wisconsin/2009 (A/H3N2) (N=309,310,151)
    261 (212 to 322)
    98 (79 to 121)
    34 (26 to 46)
        Day 1 B/Brisbane/2008)
    5.05 (4.99 to 5.11)
    5.05 (5 to 5.11)
    5.08 (5 to 5.16)
        Day 29 B/Brisbane/2008 (N=316,313,156)
    6.31 (5.97 to 6.66)
    5.57 (5.28 to 5.89)
    5.11 (4.74 to 5.52)
        Day 50 B/Brisbane/2008 (N=310,309,150)
    12 (11 to 13)
    6.69 (6.23 to 7.17)
    5.2 (4.71 to 5.75)
        Day181 B/Brisbane/2008 (N=309,310,151)
    6.12 (5.77 to 6.49)
    5.67 (5.35 to 6.01)
    6.12 (5.64 to 6.65)
    Statistical analysis title
    		 GMT A/H1N1; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.19
    Statistical analysis title
    		 GMT A/H1N1; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    6.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.69
         upper limit
    		 8.76
    Statistical analysis title
    		 GMT A/H1N1; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay
    Comparison groups
    Flu-control v TIV-adj
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    8.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.36
         upper limit
    		 11
    Statistical analysis title
    		 GMT A/H1N1; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Brisbane/2007 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H1N1)]
    Point estimate
    4.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.38
         upper limit
    		 5.65
    Statistical analysis title
    		 GMT A/H3N2; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.35
    Statistical analysis title
    		 GMT A/H3N2; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    6.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.72
         upper limit
    		 8.73
    Statistical analysis title
    		 GMT A/H3N2; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    7.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.2
         upper limit
    		 10
    Statistical analysis title
    		 GMT A/H3N2; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Brisbane/2007 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[A/Brisbane/2007 (A/H3N2)]
    Point estimate
    3.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.42
         upper limit
    		 4.05
    Statistical analysis title
    		 GMT B; Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[B/Florida/2006]
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.05
    Statistical analysis title
    		 GMT B; Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[B/Florida/2006]
    Point estimate
    1.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 1.93
    Statistical analysis title
    		 GMT B; Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[B/Florida/2006]
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.25
         upper limit
    		 5.88
    Statistical analysis title
    		 GMT B; Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain B/Florida/2006 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT[B/Florida/2006]
    Point estimate
    2.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.22
         upper limit
    		 2.93
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.22
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    1.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 2.51
    Statistical analysis title
    		 GMT A/H1N1 (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    5.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.08
         upper limit
    		 7.63
    Statistical analysis title
    		 GMT A/H1N1(Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Solomon Islands/2006 (A/H1N1) in terms of GMTs in subjects aged 6 to <72 months by HI assay
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Solomon Islands/2006 (A/H1N1)]
    Point estimate
    3.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.3
         upper limit
    		 4.2
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.3
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    3.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.19
         upper limit
    		 4.49
    Statistical analysis title
    		 GMT A/H3N2 (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    7.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.51
         upper limit
    		 9.82
    Statistical analysis title
    		 GMT A/H3N2(Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain A/Wisconsin/2009 (A/H3N2) in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [A/Wisconsin/2009 (A/H3N2)]
    Point estimate
    2.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2
         upper limit
    		 3.55
    Statistical analysis title
    		 GMT B (Hetero); Day 1-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 1 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.01
    Statistical analysis title
    		 GMT B (Hetero); Day 29-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 29 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 1.22
    Statistical analysis title
    		 GMT B (Hetero); Day 50-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 50 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.63
         upper limit
    		 1.97
    Statistical analysis title
    		 GMT B (Hetero); Day 181-TIV-adj vs Flu-control
    Statistical analysis description
    To demonstrate superiority of immunogenicity of TIV-adj compared to Flu-control on Day 181 for strain B/Brisbane/2008 in terms of GMTs in subjects aged 6 to <72 months by HI assay.
    Comparison groups
    TIV-adj v Flu-control
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 ANOVA
    Parameter type
    		 GMT [B/Brisbane/2008]
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1.17

    Secondary: 16. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 16. Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    Hemagglutination Inhibition (HI) assay was used for the analysis. Geometric mean titer ratios (GMRs) of study day 29/study day 1, study day 50/study day 1, study day 181/study day 1 were evaluated. The criteria for evaluation is GMR >2.5
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    319
    316
    158
    Units: Ratio
    geometric mean (confidence interval 95%)
        Day 29:1A/Brisbane/2007(A/H1N1;N=316,313,156)
    24 (21 to 27)
    3.6 (3.17 to 4.08)
    0.99 (0.83 to 1.18)
        Day 50:1A/Brisbane/2007(A/H1N1;N=310,309,150)
    76 (67 to 86)
    9 (7.89 to 10)
    1.02 (0.84 to 1.22)
        Day 181:1A/Brisbane/2007(A/H1N1;N=309,310,151)
    19 (17 to 21)
    4.31 (3.89 to 4.77)
    1.02 (0.88 to 1.17)
        Day 29:1A/Brisbane/2007(A/H3N2;N=316,313,156)
    17 (15 to 19)
    2.73 (2.4 to 3.09)
    1.03 (0.86 to 1.23)
        Day50:1A/Brisbane/2007(A/H3N2;N=310,309,150)
    60 (52 to 69)
    8.03 (6.93 to 9.3)
    0.98 (0.8 to 1.21)
        Day 181:1A/Brisbane/2007(A/H3N2;N=309,310,151)
    24 (20 to 28)
    7.96 (6.71 to 9.44)
    2.21 (1.73 to 2.81)
        Day 29:1B/Florida/2006(N=316,313,156)
    3.32 (2.94 to 3.75)
    2.06 (1.83 to 2.33)
    1.03 (0.87 to 1.22)
        Day 50:1B/Florida/2006(N=310,309,150)
    17 (15 to 19)
    3.29 (2.98 to 3.63)
    1.03 (0.9 to 1.18)
        Day 181:1B/Florida/2006(N=309,310,151)
    5.05 (4.67 to 5.46)
    1.92 (1.78 to 2.08)
    1.06 (0.95 to 1.19)
        Day 29:1A/Sol.Island/2006(A/H1N1;N=316,313,156)
    3.51 (3.09 to 3.98)
    1.96 (1.72 to 2.22)
    0.99 (0.83 to 1.14)
        Day 50:1A/Sol.Island/2006A/H1N1;N=310,309,150)
    20 (18 to 22)
    3.49 (3.12 to 3.89)
    0.97 (0.83 to 1.14)
        Day 181:1A/Sol.Island/2006A/H1N1;N=309,310,151)
    7.63 (6.98 to 8.34)
    2.41 (2.2 to 2.63)
    1.01 (0.89 to 1.14)
        Day 29:1A/Wisconsin/2009(A/H3N2;N=316,313,156)
    6.59 (5.92 to 7.34)
    2.04 (1.83 to 2.27)
    0.93 (0.8 to 1.09)
        Day 50:1A/Wisconsin/2009(A/H3N2;N=310,309,150)
    34 (30 to 38)
    4.6 (4.07 to 5.2)
    0.98 (0.83 to 1.17)
        Day 181:1A/Wisconsin/2009(A/H3N2;N=309,310,151)
    18 (15 to 21)
    6.69 (5.36 to 7.6)
    2.59 (2 to 3.29)
        Day 29:1B/Brisbane/2008(N=315,313,156)
    1.25 (1.19 to 1.31)
    1.1 (1.05 to 1.16)
    1.01 (0.94 to 1.08)
        Day 50:1B/Brisbane/2008(N=309,309,150)
    2.38 (2.23 to 2.55)
    1.32 (1.24 to 1.42)
    1.02 (0.93 to 1.13)
        Day 181:1B/Brisbane/2008(N=308,310,151)
    1.21 (1.15 to 1.28)
    1.12 (1.06 to 1.19)
    1.21 (1.11 to 1.31)
    No statistical analyses for this end point

    Secondary: 17. Percentages of Subjects With HI Titers ≥ 1:40 in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 Homologous and Heterologous Strains

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    End point title
    		 17. Percentages of Subjects With HI Titers ≥ 1:40 in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 Homologous and Heterologous Strains
    End point description
    Hemagglutination Inhibition (HI) assay was used for the analysis. Percentage of subjects achieving seroprotection (i.e., with HI titer ≥1:40) at study day 1, study day 29, study day 50 and a study day 181 and associated 95% Confidence Intervals. The lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%.
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    319
    316
    158
    Units: Percentages of subjects
    number (confidence interval 95%)
        Day 1 A/Brisbane/2007 (A/H1N1)
    20 (16 to 25)
    21 (17 to 26)
    16 (11 to 23)
        Day29A/Brisbane/2007(A/H1N1) (N=316,313,156)
    96 (93 to 98)
    40 (35 to 46)
    17 (11 to 23)
        Day50A/Brisbane/2007(A/H1N1) (N=310,309,150)
    100 (99 to 100)
    59 (54 to 65)
    17 (12 to 24)
        Day181A/Brisbane/2007(A/H1N1) (N=309,310,151)
    98 (96 to 99)
    49 (43 to 54)
    18 (12 to 25)
        Day1A/Brisbane/2007(A/H3N2)
    23 (18 to 28)
    22 (17 to 27)
    20 (14 to 27)
        Day 29 A/Brisbane/2007 (A/H3N2) (N=316,313,156)
    96 (93 to 98)
    35 (30 to 40)
    21 (15 to 28)
        Day 50 A/Brisbane/2007 (A/H3N2) (N=310,309,150)
    99 (97 to 100)
    65 (60 to 71)
    21 (14 to 28)
        Day 181 A/Brisbane/2007 (A/H3N2) (N=309,310,151)
    100 (98 to 100)
    65 (60 to 70)
    41 (33 to 49)
        Day 1 B/Florida/2006
    2 (1 to 4)
    2 (1 to 5)
    4 (1 to 8)
        Day 29 B/Florida/2006 (N=316,313,156)
    28 (23 to 33)
    26 (21 to 31)
    4 (1 to 8)
        Day 50 B/Florida/2006 (N=310,309,150)
    93 (89 to 95)
    38 (33 to 44)
    3 (1 to 8)
        Day 181 B/Florida/2006 (N=309,310,151)
    52 (46 to 57)
    23 (18 to 28)
    4 (1 to 8)
        Day 1 A/SolomonIslands/2006(A/H1N1)
    21 (16 to 26)
    22 (17 to 27)
    18 (12 to 25)
        Day29 A/SolomonIslands/2006(A/H1N1)(N=316,313,150)
    32 (27 to 38)
    24 (20 to 29)
    18 (12 to 25)
        Day50 A/SolomonIslands/2006(A/H1N1)(N=310,309,150)
    96 (94 to 98)
    45 (39 to 51)
    18 (12 to 25)
        Day181A/SolomonIslands/2006(A/H1N1)(N=309,310,151)
    72 (67 to 77)
    34 (29 to 40)
    18 (12 to 25)
        Day 1 A/Wisconsin/2009 (A/H3N2)
    25 (21 to 31)
    25 (20 to 30)
    21 (15 to 28)
        Day 29 A/Wisconsin/2009 (A/H3N2) (N=316,313,156)
    60 (54 to 66)
    29 (24 to 34)
    21 (14 to 28)
        Day 50 A/Wisconsin/2009 (A/H3N2) (N=310,309,150)
    100 (98 to 100)
    54 (48 to 59)
    21 (15 to 29)
        Day181 A/Wisconsin/2009 (A/H3N2) (N=309,310,151)
    100 (98 to 100)
    63 (57 to 68)
    43 (35 to 51)
        Day 1 B/Brisbane/2008)
    0 (0 to 1)
    0 (0 to 1)
    1 (0.016 to 3)
        Day 29 B/Brisbane/2008 (N=316,313,156)
    3 (2 to 6)
    1 (0 to 3)
    1 (0.016 to 4)
        Day 50 B/Brisbane/2008 (N=310,309,150)
    10 (7 to 14)
    3 (1 to 5)
    0 (0 to 2)
        Day181 B/Brisbane/2008 (N=309,310,151)
    3 (1 to 5)
    3 (1 to 5)
    5 (2 to 10)
    No statistical analyses for this end point

    Secondary: 18. Percentages of Subjects With Seroconversion and Vaccine Group Differences in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 (Homologous and Heterologous Strains)

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    End point title
    		 18. Percentages of Subjects With Seroconversion and Vaccine Group Differences in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 (Homologous and Heterologous Strains)
    End point description
    HI assay was used for the analysis. Seroconversion is defined as negative pre-vaccination serum (<10)/ post-vaccination HI titer ≥1:40. Seroconversion is defined as either pre-vaccination HI titer <10 and a post-vaccination HI titer ≥1:40 or a prevaccination HI titer ≥10 and a minimum 4-fold rise in post-vaccination HI antibody titer. The lower bound of the two-sided 95% confidence interval (CI) for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40%.
    End point type
    Secondary
    End point timeframe
    On study days 1, 29, 50 and 181
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    319
    316
    158
    Units: Ratios
    geometric mean (confidence interval 95%)
        Day 29:1A/Brisbane/2007(A/H1N1;N=316,313,156)
    96 (93 to 98)
    40 (34 to 45)
    1 (0.016 to 4)
        Day 50:1A/Brisbane/2007(A/H1N1;N=10,309,150)
    100 (99 to 100)
    59 (53 to 64)
    1 (0 to 5)
        Day 181:1A/Brisbane/2007(A/H1N1;N=309,310,151)
    98 (96 to 99)
    48 (42 to 53)
    1 (0 to 5)
        Day 29:1A/Brisbane/2007(A/H3N2;N=316,313,156)
    94 (91 to 97)
    31 (26 to 37)
    1 (0.016 to 4)
        Day 50:1A/Brisbane/2007(A/H3N2;N=310,309,150)
    97 (95 to 99)
    63 (57 to 68)
    2 (0 to 6)
        Day 181:1A/Brisbane/2007(A/H3N2;N=309,310,151)
    93 (90 to 96)
    56 (51 to 62)
    23 (17 to 31)
        Day 29:1B/Florida/2006(N=316,313,156)
    28 (23 to 33)
    26 (21 to 31)
    0 (0 to 2)
        Day 50:1B/Florida/2006(N=310,309,150)
    93 (89 to 95)
    38 (32 to 43)
    1 (0.017 to 4)
        Day 181:1B/Florida/2006(N=309,310,151)
    50 (44 to 56)
    19 (15 to 24)
    1 (0 to 5)
        Day 29:1A/Sol.Island/2006(A/H1N1;N=316,313,156)
    32 (27 to 37)
    24 (19 to 29)
    0 (0 to 2)
        Day 50:1A/Sol.Island/2006A/H1N1;N=310,309,150)
    96 (93 to 98)
    44 (39 to 50)
    0 (0 to 2)
        Day 181:1A/Sol.Island/2006A/H1N1;N=309,310,151)
    72 (66 to 76)
    33 (27 to 38)
    0 (0 to 2)
        Day 29:1A/Wisconsin/2009(A/H3N2;N=316,313,156)
    58 (53 to 64)
    23 (19 to 28)
    1 (0.016 to 4)
        Day 50:1A/Wisconsin/2009(A/H3N2;N=310,309,150)
    98 (96 to 99)
    49 (43 to 54)
    2 (0 to 6)
        Day 181:1A/Wisconsin/2009(A/H3N2;N=309,310,151)
    92 (89 to 95)
    52 (46 to 58)
    25 (18 to 33)
        Day 29:1B/Brisbane/2008(N=315,313,156)
    3 (2 to 6)
    1 (0 to 3)
    0 (0 to 2)
        Day 50:1B/Brisbane/2008(N=309,309,150)
    10 (7 to 14)
    3 (1 to 5)
    0 (0 to 2)
        Day 181:1B/Brisbane/2008(N=308,310,151)
    2 (1 to 5)
    3 (1 to 5)
    5 (2 to 10)
    No statistical analyses for this end point

    Secondary: 19. Number of Subjects With Local and Systemic Reactions for Egg and Cell Derived Inactivated Novel Swine Origin A/H1N1 Subunit Influenza Vaccines After Each Vaccination for All Seasons

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    End point title
    		 19. Number of Subjects With Local and Systemic Reactions for Egg and Cell Derived Inactivated Novel Swine Origin A/H1N1 Subunit Influenza Vaccines After Each Vaccination for All Seasons
    End point description
    Adequate data was not available to conduct this analysis.
    End point type
    Secondary
    End point timeframe
    7 days post-vaccination
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: Subjects
    Notes
    [2] - Adequate data was not available to conduct this analysis.
    [3] - Adequate data was not available to conduct this analysis.
    [4] - Adequate data was not available to conduct this analysis.
    No statistical analyses for this end point

    Secondary: 20. Indirect Protective Effect of Fluad (NH Composition 2007/2008), Compared to Non-flu and Flu Control, in Connection to Household-contact Persons Via Questioning of the Parents About ILI of Persons Living in the Same Household as the Study Child

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    End point title
    		 20. Indirect Protective Effect of Fluad (NH Composition 2007/2008), Compared to Non-flu and Flu Control, in Connection to Household-contact Persons Via Questioning of the Parents About ILI of Persons Living in the Same Household as the Study Child
    End point description
    As per an amendment to the protocol, the Secondary efficacy endpoints were evaluated in enrolled subjects only and the household members were not included in the trial for the evaluation of indirect vaccine efficacy.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    Units: Subjects
    Notes
    [5] - Adequate data was not available to conduct this analysis.
    [6] - Adequate data was not available to conduct this analysis.
    [7] - Adequate data was not available to conduct this analysis.
    No statistical analyses for this end point

    Secondary: 21. Incidence Rate of the 2009-2010 H1N1 Swine Pandemic Caused by a Novel Influenza A (H1N1) Virus of Swine Origin in Unprimed Children Aged 6 to <36 and 6 to <72 Months

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    End point title
    		 21. Incidence Rate of the 2009-2010 H1N1 Swine Pandemic Caused by a Novel Influenza A (H1N1) Virus of Swine Origin in Unprimed Children Aged 6 to <36 and 6 to <72 Months
    End point description
    Adequate data was not available for assessing the incidence rates of the 2009-2010 swine pandemic caused by a novel influenza A (H1N1) virus of swine origin.
    End point type
    Secondary
    End point timeframe
    3 weeks after 2nd vaccination
    End point values
    		 TIV-adj Flu-control Non-flu Control
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    Units: Incidence
    Notes
    [8] - Adequate data was not available to conduct this analysis.
    [9] - Adequate data was not available to conduct this analysis.
    [10] - Adequate data was not available to conduct this analysis.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    3 years (3 consecutive influenza seasons: 2007/08, 2008/09 and 2009/10).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12
    Reporting groups
    Reporting group title
    TIV-adj_0.25
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL of each injection of adjuvanted trivalent inactivated subunit influenza vaccine

    Reporting group title
    TIV-adj_0.5
    Reporting group description
    		 Subjects aged 36 to < 72 months received 0.5 mL of each injection of adjuvanted trivalent inactivated subunit influenza vaccine

    Reporting group title
    Flu-control_0.25
    Reporting group description
    		 Subjects aged 6 to < 36 months received 0.25 mL of each injection of non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine

    Reporting group title
    Flu-control_0.5
    Reporting group description
    		 Subjects aged 36 to < 72 months received 0.5 mL of each injection of non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine

    Reporting group title
    Non-Flu-control (TBE/Men C Vaccine)
    Reporting group description
    		 Subjects aged 6 to <12 months received 2 doses of 0.5 mL of Novartis Menningocoocal C conjugate vaccine and subjects aged 12 to <72 months received 2 doses of 0.25 mL of Tick-borne encephalitis (TBE) vaccine

    Reporting group title
    Non-Flu-control (TBE vaccine)
    Reporting group description
    		 subjects aged 12 to <72 months received 2 doses of 0.25 mL of TBE vaccine.

    Serious adverse events
    		 TIV-adj_0.25 TIV-adj_0.5 Flu-control_0.25 Flu-control_0.5 Non-Flu-control (TBE/Men C Vaccine) Non-Flu-control (TBE vaccine)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    91 / 1177 (7.73%)
    31 / 835 (3.71%)
    104 / 1069 (9.73%)
    65 / 777 (8.37%)
    65 / 607 (10.71%)
    45 / 422 (10.66%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain neoplasm
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Adenoidectomy
         subjects affected / exposed
    1 / 1177 (0.08%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain tumour operation
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patent ductus arteriosus repair
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toe amputation
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillectomy
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Developmental delay
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbances
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 1177 (0.17%)
    1 / 835 (0.12%)
    1 / 1069 (0.09%)
    2 / 777 (0.26%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Child abuse
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Scrotal oedema
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Apnoea
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    2 / 1069 (0.19%)
    0 / 777 (0.00%)
    2 / 607 (0.33%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillar disorder
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillar haemorrhage
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Attention deficit/hyperactivity disorder
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphemia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abnormal behaviour
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Paracentesis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colonoscopy
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental exposure
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    6 / 1177 (0.51%)
    2 / 835 (0.24%)
    1 / 1069 (0.09%)
    1 / 777 (0.13%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    2 / 777 (0.26%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug toxicity
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electric shock
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal injury
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    1 / 1069 (0.09%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture base
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic brain injury
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaccination failure
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropod bite
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental poisoning
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cyanosis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Acquired epileptic aphasia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    1 / 1177 (0.08%)
    1 / 835 (0.12%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    2 / 607 (0.33%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile convulsion
         subjects affected / exposed
    2 / 1177 (0.17%)
    1 / 835 (0.12%)
    4 / 1069 (0.37%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Petit mal epilepsy
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphthous stomatitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    3 / 1069 (0.28%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malabsorption
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Henoch-Schonlein purpura
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Photosensitivity reaction
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropod infestation
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    2 / 607 (0.33%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    8 / 1177 (0.68%)
    3 / 835 (0.36%)
    7 / 1069 (0.65%)
    0 / 777 (0.00%)
    3 / 607 (0.49%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 3
    0 / 7
    0 / 0
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 1177 (0.00%)
    1 / 835 (0.12%)
    2 / 1069 (0.19%)
    1 / 777 (0.13%)
    1 / 607 (0.16%)
    3 / 422 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exanthema subitum
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    14 / 1177 (1.19%)
    1 / 835 (0.12%)
    13 / 1069 (1.22%)
    3 / 777 (0.39%)
    8 / 607 (1.32%)
    2 / 422 (0.47%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 1
    0 / 14
    0 / 3
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 1177 (0.08%)
    1 / 835 (0.12%)
    5 / 1069 (0.47%)
    0 / 777 (0.00%)
    3 / 607 (0.49%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 5
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    2 / 607 (0.33%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    12 / 1177 (1.02%)
    8 / 835 (0.96%)
    39 / 1069 (3.65%)
    40 / 777 (5.15%)
    33 / 607 (5.44%)
    31 / 422 (7.35%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 8
    0 / 39
    0 / 41
    1 / 34
    0 / 34
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    1 / 835 (0.12%)
    2 / 1069 (0.19%)
    1 / 777 (0.13%)
    3 / 607 (0.49%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 1177 (0.42%)
    2 / 835 (0.24%)
    5 / 1069 (0.47%)
    3 / 777 (0.39%)
    2 / 607 (0.33%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 5
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudocroup
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    2 / 1069 (0.19%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    4 / 1177 (0.34%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 1177 (0.17%)
    1 / 835 (0.12%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    2 / 1177 (0.17%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsilitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    2 / 1069 (0.19%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    2 / 1069 (0.19%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotavirus infection
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    1 / 607 (0.16%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lice infestation
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acetonaemia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 1177 (0.08%)
    2 / 835 (0.24%)
    1 / 1069 (0.09%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    1 / 777 (0.13%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Feeding disorder of infancy or early childhood
         subjects affected / exposed
    1 / 1177 (0.08%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    0 / 422 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 1177 (0.00%)
    0 / 835 (0.00%)
    0 / 1069 (0.00%)
    0 / 777 (0.00%)
    0 / 607 (0.00%)
    1 / 422 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 TIV-adj_0.25 TIV-adj_0.5 Flu-control_0.25 Flu-control_0.5 Non-Flu-control (TBE/Men C Vaccine) Non-Flu-control (TBE vaccine)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1101 / 1177 (93.54%)
    769 / 835 (92.10%)
    989 / 1069 (92.52%)
    686 / 777 (88.29%)
    567 / 607 (93.41%)
    375 / 422 (88.86%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 1177 (0.51%)
    201 / 835 (24.07%)
    6 / 1069 (0.56%)
    120 / 777 (15.44%)
    5 / 607 (0.82%)
    66 / 422 (15.64%)
         occurrences all number
    6
    303
    9
    150
    5
    88
    Somnolence
         subjects affected / exposed
    381 / 1177 (32.37%)
    1 / 835 (0.12%)
    315 / 1069 (29.47%)
    1 / 777 (0.13%)
    186 / 607 (30.64%)
    0 / 422 (0.00%)
         occurrences all number
    550
    1
    424
    1
    274
    0
    General disorders and administration site conditions
    Chills
    alternative assessment type: Systematic
         subjects affected / exposed
    77 / 1177 (6.54%)
    131 / 835 (15.69%)
    69 / 1069 (6.45%)
    51 / 777 (6.56%)
    50 / 607 (8.24%)
    37 / 422 (8.77%)
         occurrences all number
    94
    158
    82
    55
    59
    41
    Crying
    alternative assessment type: Systematic
         subjects affected / exposed
    390 / 1177 (33.14%)
    5 / 835 (0.60%)
    349 / 1069 (32.65%)
    3 / 777 (0.39%)
    178 / 607 (29.32%)
    0 / 422 (0.00%)
         occurrences all number
    609
    5
    552
    3
    277
    0
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 1177 (0.08%)
    338 / 835 (40.48%)
    2 / 1069 (0.19%)
    224 / 777 (28.83%)
    2 / 607 (0.33%)
    122 / 422 (28.91%)
         occurrences all number
    1
    494
    2
    325
    2
    168
    Injection site erythema
    alternative assessment type: Systematic
         subjects affected / exposed
    423 / 1177 (35.94%)
    321 / 835 (38.44%)
    325 / 1069 (30.40%)
    268 / 777 (34.49%)
    240 / 607 (39.54%)
    128 / 422 (30.33%)
         occurrences all number
    612
    463
    450
    375
    377
    197
    Injection site haemorrhage
    alternative assessment type: Systematic
         subjects affected / exposed
    146 / 1177 (12.40%)
    131 / 835 (15.69%)
    107 / 1069 (10.01%)
    93 / 777 (11.97%)
    69 / 607 (11.37%)
    49 / 422 (11.61%)
         occurrences all number
    174
    149
    120
    105
    86
    61
    Injection site induration
    alternative assessment type: Systematic
         subjects affected / exposed
    214 / 1177 (18.18%)
    169 / 835 (20.24%)
    131 / 1069 (12.25%)
    152 / 777 (19.56%)
    154 / 607 (25.37%)
    79 / 422 (18.72%)
         occurrences all number
    273
    211
    155
    199
    239
    115
    Injection site pain
    alternative assessment type: Systematic
         subjects affected / exposed
    334 / 1177 (28.38%)
    478 / 835 (57.25%)
    250 / 1069 (23.39%)
    360 / 777 (46.33%)
    173 / 607 (28.50%)
    179 / 422 (42.42%)
         occurrences all number
    454
    747
    354
    536
    250
    280
    Injection site swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    123 / 1177 (10.45%)
    156 / 835 (18.68%)
    90 / 1069 (8.42%)
    128 / 777 (16.47%)
    83 / 607 (13.67%)
    54 / 422 (12.80%)
         occurrences all number
    144
    190
    112
    169
    113
    72
    Malaise
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 1177 (0.00%)
    196 / 835 (23.47%)
    1 / 1069 (0.09%)
    120 / 777 (15.44%)
    0 / 607 (0.00%)
    64 / 422 (15.17%)
         occurrences all number
    0
    244
    1
    154
    0
    75
    Pyrexia
    alternative assessment type: Systematic
         subjects affected / exposed
    482 / 1177 (40.95%)
    299 / 835 (35.81%)
    412 / 1069 (38.54%)
    183 / 777 (23.55%)
    221 / 607 (36.41%)
    125 / 422 (29.62%)
         occurrences all number
    750
    437
    606
    246
    334
    165
    Gastrointestinal disorders
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    309 / 1177 (26.25%)
    45 / 835 (5.39%)
    260 / 1069 (24.32%)
    35 / 777 (4.50%)
    147 / 607 (24.22%)
    10 / 422 (2.37%)
         occurrences all number
    434
    50
    378
    41
    219
    11
    Enteritis
         subjects affected / exposed
    54 / 1177 (4.59%)
    23 / 835 (2.75%)
    60 / 1069 (5.61%)
    18 / 777 (2.32%)
    33 / 607 (5.44%)
    11 / 422 (2.61%)
         occurrences all number
    61
    27
    78
    20
    42
    12
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    188 / 1177 (15.97%)
    64 / 835 (7.66%)
    166 / 1069 (15.53%)
    70 / 777 (9.01%)
    102 / 607 (16.80%)
    23 / 422 (5.45%)
         occurrences all number
    240
    73
    211
    77
    122
    26
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    246 / 1177 (20.90%)
    176 / 835 (21.08%)
    210 / 1069 (19.64%)
    166 / 777 (21.36%)
    119 / 607 (19.60%)
    97 / 422 (22.99%)
         occurrences all number
    331
    242
    273
    233
    147
    125
    Skin and subcutaneous tissue disorders
    Dermatitis diaper
         subjects affected / exposed
    76 / 1177 (6.46%)
    4 / 835 (0.48%)
    62 / 1069 (5.80%)
    5 / 777 (0.64%)
    40 / 607 (6.59%)
    2 / 422 (0.47%)
         occurrences all number
    88
    4
    95
    5
    46
    2
    Hyperhidrosis
         subjects affected / exposed
    1 / 1177 (0.08%)
    69 / 835 (8.26%)
    1 / 1069 (0.09%)
    42 / 777 (5.41%)
    1 / 607 (0.16%)
    31 / 422 (7.35%)
         occurrences all number
    1
    85
    1
    45
    1
    35
    Psychiatric disorders
    Eating disorder
         subjects affected / exposed
    327 / 1177 (27.78%)
    3 / 835 (0.36%)
    263 / 1069 (24.60%)
    1 / 777 (0.13%)
    161 / 607 (26.52%)
    2 / 422 (0.47%)
         occurrences all number
    457
    4
    363
    1
    227
    2
    Irritability
         subjects affected / exposed
    394 / 1177 (33.47%)
    8 / 835 (0.96%)
    358 / 1069 (33.49%)
    6 / 777 (0.77%)
    192 / 607 (31.63%)
    4 / 422 (0.95%)
         occurrences all number
    645
    8
    590
    6
    309
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 1177 (0.08%)
    85 / 835 (10.18%)
    1 / 1069 (0.09%)
    39 / 777 (5.02%)
    1 / 607 (0.16%)
    26 / 422 (6.16%)
         occurrences all number
    1
    99
    1
    50
    1
    31
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 1177 (0.00%)
    183 / 835 (21.92%)
    0 / 1069 (0.00%)
    102 / 777 (13.13%)
    1 / 607 (0.16%)
    66 / 422 (15.64%)
         occurrences all number
    0
    243
    0
    126
    1
    82
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    164 / 1177 (13.93%)
    83 / 835 (9.94%)
    156 / 1069 (14.59%)
    65 / 777 (8.37%)
    91 / 607 (14.99%)
    45 / 422 (10.66%)
         occurrences all number
    207
    93
    186
    72
    106
    50
    Bronchitis
         subjects affected / exposed
    169 / 1177 (14.36%)
    68 / 835 (8.14%)
    153 / 1069 (14.31%)
    66 / 777 (8.49%)
    95 / 607 (15.65%)
    50 / 422 (11.85%)
         occurrences all number
    229
    86
    203
    91
    122
    63
    Ear infection
         subjects affected / exposed
    131 / 1177 (11.13%)
    57 / 835 (6.83%)
    132 / 1069 (12.35%)
    49 / 777 (6.31%)
    72 / 607 (11.86%)
    22 / 422 (5.21%)
         occurrences all number
    207
    71
    202
    65
    113
    27
    Gastroenteritis
         subjects affected / exposed
    178 / 1177 (15.12%)
    75 / 835 (8.98%)
    152 / 1069 (14.22%)
    85 / 777 (10.94%)
    94 / 607 (15.49%)
    36 / 422 (8.53%)
         occurrences all number
    211
    87
    190
    96
    110
    37
    Nasopharyngitis
         subjects affected / exposed
    153 / 1177 (13.00%)
    78 / 835 (9.34%)
    161 / 1069 (15.06%)
    74 / 777 (9.52%)
    89 / 607 (14.66%)
    36 / 422 (8.53%)
         occurrences all number
    226
    102
    202
    95
    105
    47
    Otitis media
         subjects affected / exposed
    250 / 1177 (21.24%)
    109 / 835 (13.05%)
    226 / 1069 (21.14%)
    110 / 777 (14.16%)
    130 / 607 (21.42%)
    62 / 422 (14.69%)
         occurrences all number
    372
    132
    328
    146
    211
    90
    Respiratory tract infection
         subjects affected / exposed
    76 / 1177 (6.46%)
    29 / 835 (3.47%)
    62 / 1069 (5.80%)
    37 / 777 (4.76%)
    44 / 607 (7.25%)
    17 / 422 (4.03%)
         occurrences all number
    136
    44
    122
    66
    75
    20
    Rhinitis
         subjects affected / exposed
    260 / 1177 (22.09%)
    122 / 835 (14.61%)
    219 / 1069 (20.49%)
    97 / 777 (12.48%)
    123 / 607 (20.26%)
    57 / 422 (13.51%)
         occurrences all number
    315
    146
    276
    109
    157
    63
    Tonsillitis
         subjects affected / exposed
    64 / 1177 (5.44%)
    38 / 835 (4.55%)
    42 / 1069 (3.93%)
    38 / 777 (4.89%)
    25 / 607 (4.12%)
    25 / 422 (5.92%)
         occurrences all number
    77
    48
    45
    49
    27
    32
    Upper respiratory tract infection
         subjects affected / exposed
    362 / 1177 (30.76%)
    170 / 835 (20.36%)
    306 / 1069 (28.62%)
    156 / 777 (20.08%)
    174 / 607 (28.67%)
    85 / 422 (20.14%)
         occurrences all number
    550
    237
    525
    212
    272
    105
    Viral infection
         subjects affected / exposed
    63 / 1177 (5.35%)
    35 / 835 (4.19%)
    60 / 1069 (5.61%)
    28 / 777 (3.60%)
    20 / 607 (3.29%)
    19 / 422 (4.50%)
         occurrences all number
    87
    42
    80
    33
    26
    26

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Sep 2007
    Change in the co-coordinating investigator
    12 Mar 2008
    The trial V70P5 was started late (in November 2007) during which there was a very high risk of influenza circulation; therefore the enrollment of subjects was stopped prematurely in January 2008 resulting in a low sample size (about 650 subjects). In order to reach the target sample size of 4400 subjects, the protocol was amended to start the enrollment before the start of influenza season 2008/09 in new study sites using a Spring/Fall vaccination schedule. The safety follow-up for the subjects enrolled in this season was extended to 12 months after the vaccination for recording serious adverse events, new onset chronic diseases, and concomitant medications to treat these events
    15 Jul 2008
    The study was now considered to be carried out in two parts: Part I (influenza season 2007/08) and Part II (influenza season 2008/09). The trial was planned to be restarted during early fall 2008 in Germany and Finland (influenza season 2008/09) to evaluate efficacy, safety and immunogenicity (in a subgroup) of two vaccines doses, administered following the conventional vaccination schedule, 4 weeks apart. Secondary efficacy endpoints were to be evaluated in enrolled subjects only and the household members were not to be included in the trial for the evaluation of indirect vaccine efficacy. Cell mediated immune responses were not to be explored. Influsplit SSW (also marketed with the brand name of Fluarix, GlaxoSmithKline) (NH composition 2008/09) split influenza vaccine was to be administered during the second year of the trial (influenza season 2008/09) as flu vaccine comparator. The planned overall sample size was increased (5500 subjects) and children were to be enrolled and randomized in a 2:2:1 ratio to one of the three vaccine groups [FLUAD (2200 subjects): Influsplit SSW (2200 subjects):Menjugate/Encepur children (overall 1100 subjects)]; As secondary efficacy endpoints to be evaluated during the second year of the study (influenza season 2008/09) Fluad vaccine efficacy relative to the split flu vaccine control has been added.
    17 Oct 2008
    Administrative changes
    19 May 2009
    The study was extended to include third consecutive influenza season 2009/10 and approximately 3500 unprimed healthy children aged 6 to < 36 months were planned to be enrolled. The 6 to <36 month-old subjects were to be randomly allocated in a 2:2:1 ratio, to one of the three vaccine groups (TIV-adj (Fluad), or Influsplit SSW, or menjugate/Encepur Children). Each subject was to receive intramuscularly, depending on the assigned vaccine, two 0.25mL doses of either Fluad or Influsplit SSW, or two 0.5mL doses of Menjugate (if 6 to <12 months of age), or two 0.25mL doses of Encepur Children (if ≥12 months of age). During Part III of the study a subset of approximately 550 children were to be enrolled, in selected study centers, for the immunogenicity evaluation. The primary end points were to demonstrate the safety and tolerability of TIV-adj compared with Flu-control, and the clinical protection provided by TIV-adj, compared with Non-flu control, in unprimed children aged 6 to <36 months. The safety and tolerability, as well as the clinical protection provided by TIV-adj in the whole age population (6 to <72 months) was to be evaluated as secondary study end points. An interim analysis was planned on data for all local and systemic reactions and all adverse events recorded during Part I of the study (influenza season 2007/2008) and for all local and systemic reactions and all adverse events recorded up to three weeks after second vaccination in all subjects enrolled during Part II of the study (influenza season 2008/2009). This interim analysis was to be performed, before start of the Part III of the study, by an independent safety Data Monitoring Committee (DMC). Details on the statistical methods to analyze the primary efficacy endpoints and primary safety endpoint have been added
    10 Jun 2009
    In order to provide the subjects who were randomized to Menjugate/Encepur Children vaccines during Part III of the study (2009/10 Influenza season) with a third dose, an additional follow up clinic visit was added to the study design, to comply with the current SPC of the vaccines. This additional follow up clinic visit was to occur after the unblinding of Part III of the study (i.e. after the study visit/telephone call scheduled at day 181 or at the end of the influenza surveillance period, whichever was longer).
    27 Jul 2009
    In order to provide the subjects who were randomized to Menjugate/Encepur Children vaccines during Part III of the study (2009/10 Influenza season) with a third dose, an additional follow up clinic visit was added to the study design, to comply with the current SPC of the vaccines. This additional follow up clinic visit was to occur after the unblinding of Part III of the study (i.e. after the study visit/telephone call scheduled at day 181 or at the end of the influenza surveillance period, whichever was longer). Subjects were to be offered the H1N1sw vaccine (Focetria (H1N1sw) or FCC (H1N1sw) that has been assigned to their country, only in the dose and formulation that was regulatory approved for their age. These vaccinations were completely voluntary, however, if the vaccines were not approved and available within the timelines of the trial (before Day 181), the trial was to end without these additional vaccines administered. If subjects had access to a competitor H1N1sw vaccine that was approved and available before the Novartis H1N1sw vaccines, they were to follow the H1N1 visit schedule to assess the safety of the competitor vaccine. ILI symptoms and swabs would be collected from Visit 1 till the End of Study Secondary absolute efficacy objectives were amended to include the evaluation of the number of a) all-cause hospitalizations, b) hospitalizations due to confirmed influenza, c) all-cause outpatient medical visits and d) outpatient medical visits due to influenza illness or influenza symptoms in view of the 2009-2010 H1N1 swine pandemic caused by a novel influenza A (H1N1) virus of swine origin. As well as the potential for vaccination against this pandemic strain in unprimed children aged 6 to <36 months, if adequate data is available. Data regarding the booster doses of Non-flu control vaccine (Menjugate® /Encephur®Children) in the season 2009/10 will not be presented as an addendum to this CSR.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/21995388
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