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    Clinical Trial Results:
    A phase III, double-blind, randomized, placebo-controlled, multi-country and multi-center study to assess the efficacy and safety of two doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine in healthy infants.

    Summary
    EudraCT number
    2015-001541-92
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    07 Jul 2008

    Results information
    Results version number
    v2(current)
    This version publication date
    10 Aug 2016
    First version publication date
    02 Aug 2015
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Full disclosure of data set

    Trial information

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    Trial identification
    Sponsor protocol code
    444563/028/029/030,107070,72,76
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00329745
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trails Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trails Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    19 Jan 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Jul 2008
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    •In all subjects, to determine if two doses of GSK Biologicals’ HRV vaccine given concomitantly with routine vaccinations* can prevent severe rotavirus gastroenteritis (RV GE) caused by the circulating wild-type RV strains during the period starting from 2 weeks after Dose 2 until 2 years of age. (*Whenever Oral Polio Vaccination (OPV) is used a minimum 2-week interval should be observed between HRV vaccine and OPV doses.) •In all subjects, to assess the safety of HRV vaccine with respect to definite intussusception (IS) within 31 days (Day 0-Day 30) after each HRV vaccine dose.
    Protection of trial subjects
    All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 Dec 2003
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Hong Kong: 3025
    Country: Number of subjects enrolled
    Taiwan: 1141
    Country: Number of subjects enrolled
    Singapore: 6542
    Worldwide total number of subjects
    10708
    EEA total number of subjects
    0
    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)
    10708
    Children (2-11 years)
    0
    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
    -

    Pre-assignment
    Screening details
    During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    Period 1
    Period 1 title
    Primary study (up to Visit 5)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Rotarix Group
    Arm description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.
    Arm type
    Experimental

    Investigational medicinal product name
    Rotarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration, 2 doses

    Arm title
    Placebo Group
    Arm description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.
    Arm type
    Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration, 2 doses

    Number of subjects in period 1
    Rotarix Group Placebo Group
    Started
    5359
    5349
    Completed
    5215
    5170
    Not completed
    144
    179
         Protocol deviation
    2
    5
         Due to undescended testis
    1
    -
         Conflict of interest
    1
    -
         Adverse event, serious fatal
    3
    8
         Adverse event, non-fatal
    4
    2
         Consent withdrawn by subject
    40
    53
         Lost to follow-up
    93
    111
    Period 2
    Period 2 title
    Follow-up (up to Visit 6)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Rotarix Group
    Arm description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.
    Arm type
    Experimental

    Investigational medicinal product name
    Rotarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration, 2 doses

    Arm title
    Placebo Group
    Arm description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.
    Arm type
    Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration, 2 doses

    Number of subjects in period 2 [1]
    Rotarix Group Placebo Group
    Started
    4359
    4328
    Completed
    4272
    4226
    Not completed
    87
    102
         Protocol deviation
    1
    -
         Consent withdrawn by subject
    -
    1
         Lost to follow-up
    86
    101
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Some subjects who completed the study up to Visit 5, did not come back for the Visit 6 of the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rotarix Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.

    Reporting group title
    Placebo Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.

    Reporting group values
    Rotarix Group Placebo Group Total
    Number of subjects
    5359 5349 10708
    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)
    23.2 ± 2.31 23.2 ± 2.51 -
    Gender categorical
    Units: Subjects
        Female
    2631 2625 5256
        Male
    2728 2724 5452

    End points

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    End points reporting groups
    Reporting group title
    Rotarix Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.

    Reporting group title
    Placebo Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.
    Reporting group title
    Rotarix Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.

    Reporting group title
    Placebo Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.

    Primary: Number of subjects with severe rotavirus gastroenteritis (RV GE) caused by the wild RV strains.

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    End point title
    Number of subjects with severe rotavirus gastroenteritis (RV GE) caused by the wild RV strains.
    End point description
    Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Primary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    2
    51
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the wild RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    96.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    85.1
         upper limit
    99.5

    Secondary: Number of subjects reporting serious adverse events (SAEs)

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    End point title
    Number of subjects reporting serious adverse events (SAEs)
    End point description
    An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
    End point type
    Secondary
    End point timeframe
    From Visit 5 (Month 21-22) until study end (Month 33-34)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    4359
    4328
    Units: Subjects
        Any SAE(s)
    10
    11
    No statistical analyses for this end point

    Secondary: Number of subjects with severe RV GE caused by the wild RV strain of type G1

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    End point title
    Number of subjects with severe RV GE caused by the wild RV strain of type G1
    End point description
    Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    0
    21
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the wild RV strain of type G1. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo
    Comparison groups
    Placebo Group v Rotarix Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    80.8
         upper limit
    100

    Secondary: Number of subjects with severe RV GE due to non-G1 types

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    End point title
    Number of subjects with severe RV GE due to non-G1 types
    End point description
    Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
        Pooled non-G1 type
    2
    31
        G2+P4 wild-type
    0
    2
        G3+P8 wild-type
    1
    18
        G9+P8 wild-type
    1
    12
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to pooled non-G1 type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    93.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    74.7
         upper limit
    99.3
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to G2+P4 wild-type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.25
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -431.7
         upper limit
    100
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to G3+P8 wild-type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    64.9
         upper limit
    99.9
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to G9+P8 wild-type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.002
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    91.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    43.8
         upper limit
    99.8

    Secondary: Number of subjects with severe RV GE by the circulating wild-type RV strains

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    End point title
    Number of subjects with severe RV GE by the circulating wild-type RV strains
    End point description
    Subjects with severe RV GE caused by the wild RV strain of G1 type, due to non-G1 types and due to each non-G1 type. Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From Dose 1 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5359
    5349
    Units: Subjects
        G1 wild-type + P8 wild-type
    0
    22
        G2 + P4 wild-type
    0
    2
        G3 + P8 wild-type
    1
    18
        G9 + P8 wild-type
    1
    14
        Pooled non-G1
    2
    33
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by wild RV strain of G1 type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    81.8
         upper limit
    100
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by non-G1 types (pooled non-G1). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    76.3
         upper limit
    99.3
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by each non-G1 type (G2 + P4 wild-type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.25
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -431.5
         upper limit
    100
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by non-G1 type (G3 + P8 wild-type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    64.9
         upper limit
    99.9
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by non-G1 type (G9 + P8 wild-type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    92.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    53.1
         upper limit
    99.8

    Secondary: Number of subjects with RV GE episodes caused by the circulating wild-type RV strains and requiring hospitalization and/or re-hydration therapy

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    End point title
    Number of subjects with RV GE episodes caused by the circulating wild-type RV strains and requiring hospitalization and/or re-hydration therapy
    End point description
    Gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    3
    52
    Statistical analysis title
    Vaccine efficacy with respect to RV GE
    Statistical analysis description
    Vaccine efficacy with respect to RV GE caused by circulating wild-type RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    82.2
         upper limit
    98.8

    Secondary: Number of subjects with severe RV GE caused by the circulating wild-type RV strains

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    End point title
    Number of subjects with severe RV GE caused by the circulating wild-type RV strains
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    After Visit 4 (one year of age) up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5221
    5194
    Units: Subjects
    2
    36
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by circulating wild-type RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10415
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    78.5
         upper limit
    99.4

    Secondary: Number of subjects with severe RV GE caused by the circulating wild-type RV strains

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    End point title
    Number of subjects with severe RV GE caused by the circulating wild-type RV strains
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 4 (one year of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    0
    15
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the circulating wild-type RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    72.2
         upper limit
    100

    Secondary: Number of subjects with severe GE of any etiology

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    End point title
    Number of subjects with severe GE of any etiology
    End point description
    Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 5 (two years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    141
    202
    Statistical analysis title
    Vaccine efficacy with respect to severe GE
    Statistical analysis description
    Vaccine efficacy with respect to severe GE of any etiology. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    30.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.1
         upper limit
    44.2

    Secondary: Number of subjects with severe RV GE caused by the wild RV strains

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    End point title
    Number of subjects with severe RV GE caused by the wild RV strains
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    2
    64
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by wild RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    96.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    88.3
         upper limit
    99.6

    Secondary: Number of subjects with severe RV GE caused by the wild RV strain of G1 type

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    End point title
    Number of subjects with severe RV GE caused by the wild RV strain of G1 type
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    0
    26
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the wild RV strain of G1 type. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    84.8
         upper limit
    100

    Secondary: Number of subjects with severe RV GE due to non-G1 types

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    End point title
    Number of subjects with severe RV GE due to non-G1 types
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    2
    39
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to non-G1 types. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    94.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    80.2
         upper limit
    99.4

    Secondary: Number of subjects with severe RV GE due to each non-G1 type

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    End point title
    Number of subjects with severe RV GE due to each non-G1 type
    End point description
    Severe RV GE caused by each non-G1 type such as G2, G3 and G9. Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
        G2 type
    0
    4
        G3 type
    1
    22
        G9 type
    1
    14
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by non-G1 type (G2 type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.062
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -51.3
         upper limit
    100
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to non-G1 type (G3 type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    95.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    71.9
         upper limit
    99.9
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE due to non-G1 type (G9 type). Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    92.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    53.1
         upper limit
    99.8

    Secondary: Number of subjects with RV GE caused by the circulating wild-type RV strains and requiring hospitalization and/or re-hydration therapy

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    End point title
    Number of subjects with RV GE caused by the circulating wild-type RV strains and requiring hospitalization and/or re-hydration therapy
    End point description
    RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    3
    67
    Statistical analysis title
    Vaccine efficacy with respect to RV GE
    Statistical analysis description
    Vaccine efficacy with respect to RV GE caused by circulating wild-type RV strains and requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    95.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    86.4
         upper limit
    99.1

    Secondary: Number of subjects with severe RV GE caused by the circulating wild-type RV strains

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    End point title
    Number of subjects with severe RV GE caused by the circulating wild-type RV strains
    End point description
    Severe RV GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From Visit 5 (two years of age) to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    4222
    4185
    Units: Subjects
    0
    13
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the circulating wild-type RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    8407
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    67.5
         upper limit
    100

    Secondary: Number of subjects with severe GE of any etiology

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    End point title
    Number of subjects with severe GE of any etiology
    End point description
    Severe GE was defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From 2 weeks after Dose 2 up to Visit 6 (three years of age)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5263
    5256
    Units: Subjects
    192
    262
    Statistical analysis title
    Vaccine efficacy with respect to severe GE
    Statistical analysis description
    Vaccine efficacy with respect to severe GE of any etiology. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10519
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    26.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.5
         upper limit
    39.6

    Secondary: Number of subjects with Anti-rotavirus IgA seroconversion rates above the cut-off value

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    End point title
    Number of subjects with Anti-rotavirus IgA seroconversion rates above the cut-off value
    End point description
    Seroconversion was defined as the appearance of antibodies (i.e. titre ≥ cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject was defined as a subject whose titer was below the cut-off value (20 U/mL)
    End point type
    Secondary
    End point timeframe
    At Visit 1 (Day 0, pre-vaccination [Pre]) and Visit 3 (Month 2-4 [M2-4])
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    115
    124
    Units: Subjects
        Pre
    0
    0
        PII(M2-4)
    108
    1
    No statistical analyses for this end point

    Secondary: Anti-rotavirus IgA antibody Geometric Mean Concentrations (GMCs)

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    End point title
    Anti-rotavirus IgA antibody Geometric Mean Concentrations (GMCs)
    End point description
    Antibody concentrations below the cut-off (20 U/mL) of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
    End point type
    Secondary
    End point timeframe
    At Visit 1 (Day 0, pre-vaccination [Pre]) and Visit 3 (Month 2-4 [M2-4])
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    115
    124
    Units: U/mL
    geometric mean (confidence interval 95%)
        Pre
    0 (0 to 0)
    0 (0 to 0)
        PII(M2-4)
    238.6 (183.4 to 310.3)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Number of subjects with Anti-rotavirus IgA seroconversion rates above the cut-off value by country

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    End point title
    Number of subjects with Anti-rotavirus IgA seroconversion rates above the cut-off value by country
    End point description
    Seroconversion is defined as the appearance of antibodies (i.e. titre ≥ cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject was defined as a subject whose titer was below the cut-off value (20 U/mL). The results are listed for a subset of 100 subjects per country- Singapore, Hong Kong and Taiwan.
    End point type
    Secondary
    End point timeframe
    At Visit 1 (Day 0, pre-vaccination [Pre]) and Visit 3 (Month 2-4 [M2-4])
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    40
    46
    Units: Subjects
        Singapore; Pre [N= 40, 46]
    0
    0
        Singapore; PII(M2-4) [N= 40, 46]
    39
    1
        Hong Kong; Pre [N= 40, 43]
    0
    0
        Hong Kong; PII(M2-4) [N= 40, 43]
    39
    0
        Taiwan; Pre [N= 35, 35]
    0
    0
        Taiwan; PII(M2-4) [N= 35, 35]
    30
    0
    No statistical analyses for this end point

    Secondary: Anti-rotavirus IgA antibody Geometric Mean Concentrations (GMCs)

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    End point title
    Anti-rotavirus IgA antibody Geometric Mean Concentrations (GMCs)
    End point description
    Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC calculation. The
    End point type
    Secondary
    End point timeframe
    At Visit 1 (Day 0, pre-vaccination [Pre]) and Visit 3 (Month 2-4 [M2-4])
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    40
    46
    Units: U/mL
    geometric mean (confidence interval 95%)
        Singapore; Pre [N= 40, 46]
    0 (0 to 0)
    0 (0 to 0)
        Singapore; PII(M2-4) [N= 40, 46]
    368.5 (231 to 588)
    0 (0 to 0)
        Hong Kong; Pre [N= 40, 43]
    0 (0 to 0)
    0 (0 to 0)
        Hong Kong; PII(M2-4) [N= 40, 43]
    314.6 (215.1 to 460.1)
    0 (0 to 0)
        Taiwan; Pre [N= 35, 35]
    0 (0 to 0)
    0 (0 to 0)
        Taiwan; PII(M2-4) [N= 35, 35]
    105.8 (67.4 to 166.2)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Number of subjects with definite Intussusception (IS)

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    End point title
    Number of subjects with definite Intussusception (IS)
    End point description
    The diagnosis of IS was confirmed on the demonstration of invagination of the intestine at surgery or autopsy, or by using radiologic techniques: gas/liquid contrast enema or abdominal ultrasound.
    End point type
    Secondary
    End point timeframe
    From Dose 1 (Day 0) up to Visit 3 (Month 2-4), Visit 4 (Month 9-10) and Visit 5 (Month 21-22).
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5359
    5349
    Units: Subjects
        Dose 1 to Visit 3
    0
    0
        Dose 1 to Visit 4
    3
    2
        Dose 1 to Visit 5
    8
    4
    No statistical analyses for this end point

    Secondary: Number of subjects reporting serious adverse events (SAEs)

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    End point title
    Number of subjects reporting serious adverse events (SAEs)
    End point description
    An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
    End point type
    Secondary
    End point timeframe
    From Dose 1 (Day 0) until Visit 5 (Month 21-22)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5359
    5349
    Units: Subjects
        Any SAE(s)
    1001
    1098
        Fatal SAE(s)
    1
    3
    No statistical analyses for this end point

    Secondary: Number of subjects with severe RV GE caused by the circulating wild-type RV strain

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    End point title
    Number of subjects with severe RV GE caused by the circulating wild-type RV strain
    End point description
    Severe GE is defined as a gastroenteritis episode requiring hospitalization and/or re-hydration therapy (equivalent to WHO plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
    End point type
    Secondary
    End point timeframe
    From Dose 1 (Day 0) up to Visit 5 (Month 21-22)
    End point values
    Rotarix Group Placebo Group
    Number of subjects analysed
    5359
    5349
    Units: Subjects
    2
    54
    Statistical analysis title
    Vaccine efficacy with respect to severe RV GE
    Statistical analysis description
    Vaccine efficacy with respect to severe RV GE caused by the circulating wild-type RV strains. Vaccine efficacy was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo
    Comparison groups
    Rotarix Group v Placebo Group
    Number of subjects included in analysis
    10708
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Fisher exact
    Parameter type
    percent reduction
    Point estimate
    96.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    86
         upper limit
    99.6

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    Serious adverse events (SAEs): from Dose 1 until Visit 5 and from Visit 5 until study end.
    Adverse event reporting additional description
    Adverse events were not systematically followed up in this study. Only the adverse events (and serious adverse events) leading to subject withdrawal or drop-out were collected. The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    11.1
    Reporting groups
    Reporting group title
    Rotarix Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine.

    Reporting group title
    Placebo Group
    Reporting group description
    During the primary study (NCT00197210) subjects received two oral doses of placebo.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: No non-serious adverse events were planned to be assessed in this study as per the protocol.
    Serious adverse events
    Rotarix Group Placebo Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    171 / 5359 (3.19%)
    186 / 5349 (3.48%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Thrombophlebitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Circumcision
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    9 / 5359 (0.17%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia repair
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain neoplasm
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukemia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephroblastoma
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Milk allergy
         subjects affected / exposed
    3 / 5359 (0.06%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Child abuse
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Physical abuse
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Developmental delay
         subjects affected / exposed
    1 / 5359 (0.02%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperpyrexia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Irritability
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ disorder
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    11 / 5359 (0.21%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden infant death syndrome (non-fatal SAE)
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden infant death syndrome (fatal SAE)
    Additional description: This reported SAE is a fatal SAE.
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Breath holding
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crying
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased activity
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Balanitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balanoposthitis
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal swelling
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Burns third degree
         subjects affected / exposed [2]
    1 / 4359 (0.02%)
    0 / 4328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Croup infectious (Visit 5 to Visit 6)
         subjects affected / exposed [3]
    0 / 4359 (0.00%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose (Visit 5 to Visit 6)
         subjects affected / exposed [4]
    0 / 4359 (0.00%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental drug intake by child
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental exposure
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental poisoning
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropod bite
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns first degree
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns second degree
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbon monoxide poisoning
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Caustic injury
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug toxicity
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body trauma
         subjects affected / exposed
    3 / 5359 (0.06%)
    8 / 5349 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    36 / 5359 (0.67%)
    32 / 5349 (0.60%)
         occurrences causally related to treatment / all
    0 / 36
    0 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    3 / 5359 (0.06%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth injury
         subjects affected / exposed
    3 / 5359 (0.06%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open wound
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose (Visit 1 to Visit 5)
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    4 / 5359 (0.07%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    6 / 5359 (0.11%)
    6 / 5349 (0.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth fracture
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaccination complication
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Body height abnormal
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac murmur functional
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical observation
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial tachycardia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac aneurysm
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomegaly
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wolff-Parkinson-white syndrome
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Ankyloglossia congenital
         subjects affected / exposed
    2 / 5359 (0.04%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial septal defect
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cleft palate
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital epiblepharon
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cryptorchism
         subjects affected / exposed
    2 / 5359 (0.04%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal atresia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysmorphism
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngomalacia
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangioma
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcephaly
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patent ductus arteriosus
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phimosis
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Preauricular cyst
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyloric stenosis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinoblastoma
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalassaemia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Idiopathic thrombocytopenic purpura (Visit 5 to Visit 6)
         subjects affected / exposed [5]
    0 / 4359 (0.00%)
    2 / 4328 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis (Visit 5 to Visit 6)
         subjects affected / exposed [6]
    1 / 4359 (0.02%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anemia
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypochromic anemia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Idiopathic thrombocytopenic purpura (Visit 1 to Visit 5)
         subjects affected / exposed
    2 / 5359 (0.04%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anemia
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anemia
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 5359 (0.00%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration (non-fatal SAE)
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    23 / 5359 (0.43%)
    27 / 5349 (0.50%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 27
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnea
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemoptysis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infantile asthma
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease (non-fatal SAE)
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinitis allergic
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration (fatal SAE)
    Additional description: This reported SAE is a fatal SAE.
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease (fatal SAE)
    Additional description: This reported SAE is a fatal SAE.
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Febrile convulsion (Visit 5 to Visit 6)
         subjects affected / exposed [7]
    1 / 4359 (0.02%)
    0 / 4328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arachnoid cyst
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign intracranial hypertension
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain damage
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain edema
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral hemorrhage
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    17 / 5359 (0.32%)
    10 / 5349 (0.19%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 5359 (0.02%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial palsy
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile convulsion (Visit 1 to Visit 5)
         subjects affected / exposed
    73 / 5359 (1.36%)
    66 / 5349 (1.23%)
         occurrences causally related to treatment / all
    0 / 73
    0 / 66
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-barre syndrome
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head titubation
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraventricular hemorrhage
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasticity
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Chalazion
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctivitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye discharge
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye swelling
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Strabismus
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intussusception (Visit 5 to Visit 6)
         subjects affected / exposed [8]
    2 / 4359 (0.05%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis (Visit 5 to Visit 6)
         subjects affected / exposed [9]
    1 / 4359 (0.02%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal discomfort
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    3 / 5359 (0.06%)
    6 / 5349 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    6 / 5359 (0.11%)
    8 / 5349 (0.15%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 5359 (0.06%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea hemorrhagic
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    6 / 5359 (0.11%)
    6 / 5349 (0.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequent bowel movements
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis (Visit 1 to Visit 5)
         subjects affected / exposed
    12 / 5359 (0.22%)
    15 / 5349 (0.28%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastro esophageal reflux disease
         subjects affected / exposed
    0 / 5359 (0.00%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingivitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hematemesis
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hematochezia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia, obstructive
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intussusception (Visit 1 to Visit 5)
         subjects affected / exposed
    8 / 5359 (0.15%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 5359 (0.06%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatosplenomegaly
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinemia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hematuria
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyuria
         subjects affected / exposed
    6 / 5359 (0.11%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stag horn calculus
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vesicoureteric reflux
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic (Visit 5 to Visit 6)
         subjects affected / exposed [10]
    1 / 4359 (0.02%)
    0 / 4328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angioedema
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermal cyst
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis atopic (Visit 1 to Visit 5)
         subjects affected / exposed
    4 / 5359 (0.07%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis contact
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis diaper
         subjects affected / exposed
    3 / 5359 (0.06%)
    7 / 5349 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    4 / 5359 (0.07%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petechiae
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    3 / 5359 (0.06%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    5 / 5359 (0.09%)
    6 / 5349 (0.11%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria chronic
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria papular
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle twitching
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    3 / 5359 (0.06%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration (Visit 5 to Visit 6)
         subjects affected / exposed [11]
    0 / 4359 (0.00%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia (Visit 5 to Visit 6)
         subjects affected / exposed [12]
    0 / 4359 (0.00%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorexia
         subjects affected / exposed
    4 / 5359 (0.07%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    6 / 5359 (0.11%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration (Visit 1 to Visit 5)
         subjects affected / exposed
    1 / 5359 (0.02%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    2 / 5359 (0.04%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Feeding disorder of infancy or early childhood
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycemia (Visit 1 to Visit 5)
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycemic seizure
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatremia
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolemia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic disorder (non-fatal SAE)
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight gain poor
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic disorder (fatal SAE)
    Additional description: This reported SAE is a fatal SAE.
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis (Visit 5 to Visit 6)
         subjects affected / exposed [13]
    3 / 4359 (0.07%)
    2 / 4328 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract (Visit 5 to Visit 6)
         subjects affected / exposed [14]
    0 / 4359 (0.00%)
    3 / 4328 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed [15]
    0 / 4359 (0.00%)
    1 / 4328 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kawasaki's disease (Visit 5 to Visit 6)
         subjects affected / exposed [16]
    1 / 4359 (0.02%)
    0 / 4328 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    3 / 5359 (0.06%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    3 / 5359 (0.06%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acarodermatitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    5 / 5359 (0.09%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    10 / 5359 (0.19%)
    7 / 5349 (0.13%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenoviral conjunctivitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenoviral upper respiratory infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal cellulitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteremia
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteriuria
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    171 / 5359 (3.19%)
    186 / 5349 (3.48%)
         occurrences causally related to treatment / all
    0 / 171
    0 / 186
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    36 / 5359 (0.67%)
    41 / 5349 (0.77%)
         occurrences causally related to treatment / all
    0 / 36
    0 / 41
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis viral
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    23 / 5359 (0.43%)
    15 / 5349 (0.28%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter intestinal infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbuncle
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 5359 (0.06%)
    10 / 5349 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis of male external genital organ
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis orbital
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest wall abscess
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chlamydial infection
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctivitis bacterial
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctivitis infective
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctivitis viral
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Croup infectious (Visit 1 to Visit 5)
         subjects affected / exposed
    30 / 5359 (0.56%)
    29 / 5349 (0.54%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 29
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    6 / 5359 (0.11%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema infected
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis brain stem
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    5 / 5359 (0.09%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-barr virus infection
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    35 / 5359 (0.65%)
    40 / 5349 (0.75%)
         occurrences causally related to treatment / all
    0 / 35
    0 / 40
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exanthema subitum
         subjects affected / exposed
    37 / 5359 (0.69%)
    53 / 5349 (0.99%)
         occurrences causally related to treatment / all
    0 / 37
    0 / 53
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    External ear cellulitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye abscess
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Folliculitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis viral
         subjects affected / exposed
    14 / 5359 (0.26%)
    20 / 5349 (0.37%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis (Visit 1 to Visit 5)
         subjects affected / exposed
    136 / 5359 (2.54%)
    178 / 5349 (3.33%)
         occurrences causally related to treatment / all
    0 / 136
    0 / 178
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    3 / 5359 (0.06%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis caliciviral
         subjects affected / exposed
    6 / 5359 (0.11%)
    7 / 5349 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis escherichia coli
         subjects affected / exposed
    0 / 5359 (0.00%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norwalk virus
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    9 / 5359 (0.17%)
    44 / 5349 (0.82%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 44
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    27 / 5359 (0.50%)
    36 / 5349 (0.67%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 36
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis shigella
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    18 / 5359 (0.34%)
    20 / 5349 (0.37%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hematoma
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hematoma infection
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemophilus infection
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemophilus sepsis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    17 / 5359 (0.32%)
    16 / 5349 (0.30%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpangina
         subjects affected / exposed
    28 / 5359 (0.52%)
    16 / 5349 (0.30%)
         occurrences causally related to treatment / all
    0 / 28
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impetigo
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected sebaceous cyst
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious mononucleosis
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    10 / 5359 (0.19%)
    21 / 5349 (0.39%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kawasaki’s disease (Visit 1 to Visit 5)
         subjects affected / exposed
    13 / 5359 (0.24%)
    9 / 5349 (0.17%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteremia
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    2 / 5359 (0.04%)
    6 / 5349 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localized infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    8 / 5359 (0.15%)
    9 / 5349 (0.17%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis (Visit 1 to Visit 5)
         subjects affected / exposed
    2 / 5359 (0.04%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis bacterial
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Measles
         subjects affected / exposed
    3 / 5359 (0.06%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinal abscess
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myringitis bullous
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal vestibulitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    6 / 5359 (0.11%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    11 / 5359 (0.21%)
    17 / 5349 (0.32%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    19 / 5359 (0.35%)
    14 / 5349 (0.26%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae viral laryngotracheobronchitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    3 / 5359 (0.06%)
    11 / 5349 (0.21%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perianal abscess
         subjects affected / exposed
    2 / 5359 (0.04%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    32 / 5359 (0.60%)
    30 / 5349 (0.56%)
         occurrences causally related to treatment / all
    0 / 32
    0 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    27 / 5359 (0.50%)
    42 / 5349 (0.79%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 42
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia adenoviral (non-fatal SAE)
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    9 / 5359 (0.17%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 5359 (0.04%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 5359 (0.02%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyomyositis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    42 / 5359 (0.78%)
    53 / 5349 (0.99%)
         occurrences causally related to treatment / all
    0 / 42
    0 / 53
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    5 / 5359 (0.09%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    3 / 5359 (0.06%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Roseola
         subjects affected / exposed
    8 / 5359 (0.15%)
    5 / 5349 (0.09%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scarlet fever
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 5359 (0.02%)
    2 / 5349 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    4 / 5359 (0.07%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal scalded skin syndrome
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    4 / 5359 (0.07%)
    4 / 5349 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    6 / 5359 (0.11%)
    3 / 5349 (0.06%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis bacterial
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    126 / 5359 (2.35%)
    171 / 5349 (3.20%)
         occurrences causally related to treatment / all
    0 / 126
    0 / 171
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection (Visit 1 to Visit 5)
         subjects affected / exposed
    28 / 5359 (0.52%)
    38 / 5349 (0.71%)
         occurrences causally related to treatment / all
    0 / 28
    0 / 38
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 5359 (0.02%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    3 / 5359 (0.06%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    34 / 5359 (0.63%)
    31 / 5349 (0.58%)
         occurrences causally related to treatment / all
    0 / 34
    0 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral myocarditis
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pharyngitis
         subjects affected / exposed
    2 / 5359 (0.04%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral rash
         subjects affected / exposed
    13 / 5359 (0.24%)
    16 / 5349 (0.30%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral tonsillitis
         subjects affected / exposed
    1 / 5359 (0.02%)
    0 / 5349 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    25 / 5359 (0.47%)
    31 / 5349 (0.58%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia adenoviral (fatal SAE)
    Additional description: This reported SAE is a fatal SAE.
         subjects affected / exposed
    0 / 5359 (0.00%)
    1 / 5349 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This serious adverse event was reported for the time period from Visit 5 to Visit 6. The number of subjects who entered the study at Visit 5 was less than those who started and completed the study up to Visit 5.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Rotarix Group Placebo Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 5359 (0.00%)
    0 / 5349 (0.00%)

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jun 2003
    Rationale: Evaluated the safety of GSK Biologicals’ HRV vaccine, administration of OPV will be deferred from the study vaccine administration by minimum 2 weeks. (1, 2) Interim analysis of an ongoing study (rota-021) in Latin America did not establish the non-inferiority of the all-in-one formulation planned to be used in study 023 as compared to the initial formulation. The initial formulation was therefore used instead of all-in-one formulation.
    24 Feb 2004
    Unlike planned, Malaysia and Thailand did not participate in this study, for logistical and internal organizational reasons. This led to reduction of the sample size. The power was recalculated for the reduced sample size. Because of the overall reduction in sample size, it was decided that all subjects will be followed for efficacy and safety until they reach 2 years of age, instead of only a subset. The method for power computation for the primary safety objective and the statistical analysis section on safety was adapted to reflect a recommendation from the statistician from the IDMC. An exclusion criterion was added to exclude infants who could have rare underlying congenital abnormalities caused by consanguinity.
    26 Apr 2005
    An interim analysis on the safety and immunogenicity data was performed in June 2005. Unblinding at the level of individual data was restricted to the Statistician and database administration until the study end. An interim study report was written for this time point.

    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
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