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    Clinical Trial Results:
    Phase 2b multi center, randomised, partial blind parallel cohort study to assess the efficacy and safety of treatment with bepirovirsen in participants with chronic hepatitis B virus (B Clear)

    Summary
    EudraCT number
    2020-001083-29
    Trial protocol
    PL   GB   BG   IT   RO  
    Global end of trial date
    18 Mar 2022

    Results information
    Results version number
    v2(current)
    This version publication date
    07 May 2023
    First version publication date
    17 Mar 2023
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    209668
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
    Public contact
    GlaxoSmithKline, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, 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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 May 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Mar 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of the three dosing regimens of bepirovirsen in participants with chronic Hepatitis B Virus (HBV).
    Protection of trial subjects
    None.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Jul 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Bulgaria: 24
    Country: Number of subjects enrolled
    Canada: 30
    Country: Number of subjects enrolled
    France: 18
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Hong Kong: 3
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Japan: 74
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 46
    Country: Number of subjects enrolled
    Malaysia: 5
    Country: Number of subjects enrolled
    Poland: 29
    Country: Number of subjects enrolled
    Romania: 38
    Country: Number of subjects enrolled
    Russian Federation: 41
    Country: Number of subjects enrolled
    Singapore: 37
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    Thailand: 18
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    United States: 11
    Country: Number of subjects enrolled
    China: 16
    Country: Number of subjects enrolled
    Philippines: 3
    Country: Number of subjects enrolled
    South Africa: 6
    Country: Number of subjects enrolled
    Taiwan: 3
    Worldwide total number of subjects
    457
    EEA total number of subjects
    146
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    432
    From 65 to 84 years
    25
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 457 participants were randomized in the study. These 457 participants were from 2 different set of populations (referred here after as on nucleos(t)ide [NA] and not on NA therapy). Participants from these subpopulations were randomized in a ratio of 3:3:3:1 into 4 treatment arms for each population (total of 8 arms).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    GSK3228836 for 24 weeks (WK) (on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).
    Arm type
    Experimental

    Investigational medicinal product name
    GSK3228836 and NA therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK3228836 300mg once a week for 24 weeks, plus a loading dose of GSK3228836 300mg on Day 4 and 11).

    Arm title
    GSK3228836 for 12+12 WK (on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK3228836 and NA therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK3228836 300mg once a week for 12 weeks, plus a loading dose of GSK3228836 300mg on Day 4 and 11). Followed by a step down in dose of 150mg (plus placebo to match to maintain blinding) GSK3228836 once a week for 12 weeks.

    Arm title
    GSK3228836 for 12WK + Placebo for 12WK (on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by a placebo once/week for 12 weeks.
    Arm type
    Experimental and Placebo

    Investigational medicinal product name
    GSK3228836 followed by placebo and NA therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks.

    Arm title
    Placebo for 12WK + GSK3228836 for 12WK (on NA therapy)
    Arm description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo followed by GSK3228836 and NA therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks

    Arm title
    GSK3228836 for 24 WK (not on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).
    Arm type
    Experimental

    Investigational medicinal product name
    GSK3228836
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK3228836 300mg once a week for 24 weeks, plus a loading dose of GSK3228836 300mg on Day 4 and 11).

    Arm title
    GSK3228836 for 12+12 WK (not on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK3228836
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK3228836 300mg once a week for 12 weeks, plus a loading dose of GSK3228836 300mg on Day 4 and 11). Followed by a step down in dose of 150mg (plus placebo to match to maintain blinding) GSK3228836 once a week for 12 weeks.

    Arm title
    GSK3228836 12WK + Placebo for 12WK (not on NA therapy)
    Arm description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks.
    Arm type
    Experimental and Placebo

    Investigational medicinal product name
    GSK3228836 followed by placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks.

    Arm title
    Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Arm description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks
    Arm type
    Placebo and Experimental

    Investigational medicinal product name
    Placebo followed by GSK3228836
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks.

    Number of subjects in period 1
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Started
    68
    68
    68
    23
    70
    68
    68
    24
    Completed
    65
    65
    66
    22
    64
    66
    63
    24
    Not completed
    3
    3
    2
    1
    6
    2
    5
    0
         Consent withdrawn by subject
    3
    -
    1
    1
    5
    1
    4
    -
         Physician decision
    -
    -
    -
    -
    -
    1
    -
    -
         Adverse event, non-fatal
    -
    1
    1
    -
    1
    -
    1
    -
         Lost to follow-up
    -
    1
    -
    -
    -
    -
    -
    -
         Protocol deviation
    -
    1
    -
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK3228836 for 24 weeks (WK) (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12+12 WK (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836 for 12WK + Placebo for 12WK (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by a placebo once/week for 12 weeks.

    Reporting group title
    Placebo for 12WK + GSK3228836 for 12WK (on NA therapy)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks

    Reporting group title
    GSK3228836 for 24 WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12+12 WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836 12WK + Placebo for 12WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks.

    Reporting group title
    Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks

    Reporting group values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy) Total
    Number of subjects
    68 68 68 23 70 68 68 24 457
    Age categorical
    Units: Subjects
        From less than 50 years
    37 42 40 11 46 49 54 17 296
        50 years and over
    31 26 28 12 24 19 14 7 161
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    49.0 ( 11.54 ) 46.1 ( 12.60 ) 47.4 ( 11.18 ) 49.8 ( 11.21 ) 44.5 ( 11.10 ) 43.8 ( 9.92 ) 40.7 ( 11.10 ) 42.4 ( 12.02 ) -
    Sex: Female, Male
    Units: Participants
        Female
    20 19 17 6 37 27 29 13 168
        Male
    48 49 51 17 33 41 39 11 289
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    0 0 1 0 0 0 0 0 1
        Asian
    36 35 36 12 37 44 38 12 250
        Black or African American
    2 1 4 0 9 4 6 1 27
        Mixed Race
    0 0 1 0 0 0 0 0 1
        White
    30 32 26 11 24 20 24 11 178
    Subject analysis sets

    Subject analysis set title
    GSK3228836 dose level 300mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Represents Pharmacokinetic (PK) set of participants who received GSK3228836 at a dose level of 300 mg once a week. Baseline analysis was not performed for sub group population.

    Subject analysis set title
    GSK3228836 dose level 150mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Represents PK set of participants who received GSK3228836 at a dose level of 150 mg once a week. Baseline analysis was not performed for sub group population.

    Subject analysis set title
    Tenofovir disoproxil fumarate
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Tenofovir disoproxil fumarate 245 or 300mg once daily. Baseline analysis was not performed for subgroup population.

    Subject analysis set title
    Tenofovir alafenamide
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Tenofovir alafenamide 25 mg once daily or every 2 days. Baseline analysis was not performed for subgroup population.

    Subject analysis set title
    Entecavir
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Entecavir 0.5 mg once daily. Baseline analysis was not performed for subgroup population.

    Subject analysis sets values
    GSK3228836 dose level 300mg GSK3228836 dose level 150mg Tenofovir disoproxil fumarate Tenofovir alafenamide Entecavir
    Number of subjects
    12
    12
    7
    5
    16
    Age categorical
    Units: Subjects
        From less than 50 years
    0
    0
    0
    0
    0
        50 years and over
    0
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    0
    0
    0
    0
    0
        Asian
    0
    0
    0
    0
    0
        Black or African American
    0
    0
    0
    0
    0
        Mixed Race
    0
    0
    0
    0
    0
        White
    0
    0
    0
    0
    0

    End points

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    End points reporting groups
    Reporting group title
    GSK3228836 for 24 weeks (WK) (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12+12 WK (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836 for 12WK + Placebo for 12WK (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by a placebo once/week for 12 weeks.

    Reporting group title
    Placebo for 12WK + GSK3228836 for 12WK (on NA therapy)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks

    Reporting group title
    GSK3228836 for 24 WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12+12 WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836 12WK + Placebo for 12WK (not on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks.

    Reporting group title
    Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11) followed by 300 mg GSK3228836 once/week for 12 weeks

    Subject analysis set title
    GSK3228836 dose level 300mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Represents Pharmacokinetic (PK) set of participants who received GSK3228836 at a dose level of 300 mg once a week. Baseline analysis was not performed for sub group population.

    Subject analysis set title
    GSK3228836 dose level 150mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Represents PK set of participants who received GSK3228836 at a dose level of 150 mg once a week. Baseline analysis was not performed for sub group population.

    Subject analysis set title
    Tenofovir disoproxil fumarate
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Tenofovir disoproxil fumarate 245 or 300mg once daily. Baseline analysis was not performed for subgroup population.

    Subject analysis set title
    Tenofovir alafenamide
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Tenofovir alafenamide 25 mg once daily or every 2 days. Baseline analysis was not performed for subgroup population.

    Subject analysis set title
    Entecavir
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received Entecavir 0.5 mg once daily. Baseline analysis was not performed for subgroup population.

    Primary: Number of participants achieving sustained virologic response (SVR)

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    End point title
    Number of participants achieving sustained virologic response (SVR) [1]
    End point description
    The SVR was a composite endpoint defined as Hepatitis B surface antigen (HBsAg) and Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels were less than (<) Lower limit of quantitation (LLOQ) at the planned end of GSK3228836 treatment which is sustained for 24 weeks post-GSK3228836 treatment in the absence of rescue medication.
    End point type
    Primary
    End point timeframe
    Up to Week 48
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No hypothesis was tested using statistical analysis
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    68
    67
    68
    23
    70
    68
    68
    24
    Units: Participants
        Number of participants.
    6
    6
    2
    0
    7
    4
    1
    0
    No statistical analyses for this end point

    Secondary: Number of participants with categorical changes from baseline in HBsAg values

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    End point title
    Number of participants with categorical changes from baseline in HBsAg values
    End point description
    Participants who achieved a decline in HBsAg values from baseline were reported. Participants were categorized in the following categorical HBsAg decline of <0.5, greater than or equal to (>=) 0.5, >=1, >=1.5, and >=3 log10 international units per milliliter (IU/mL).
    End point type
    Secondary
    End point timeframe
    At Baseline and Week 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    68
    67
    68
    23
    70
    68
    68
    24
    Units: Participants
        HBsAg decline <0.5 log10 IU/mL
    12
    21
    37
    4
    8
    14
    29
    8
        HBsAg decline >=0.5 log10 IU/mL
    52
    42
    20
    17
    55
    48
    22
    15
        HBsAg decline >=1 log10 IU/mL
    48
    38
    14
    17
    51
    36
    18
    15
        HBsAg decline >=1.5 log10 IU/mL
    42
    32
    12
    15
    48
    30
    9
    12
        HBsAg decline >=3 log10 IU/mL
    34
    16
    5
    10
    35
    13
    4
    9
    No statistical analyses for this end point

    Secondary: Number of participants achieving HBsAg and HBV DNA<LLOQ

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    End point title
    Number of participants achieving HBsAg and HBV DNA<LLOQ
    End point description
    Participants achieving HBsAg and HBV DNA levels <LLOQ at the end of treatment (EOT) were reported.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    66
    66
    66
    22
    67
    66
    66
    24
    Units: Participants
    16
    9
    8
    4
    17
    10
    6
    1
    No statistical analyses for this end point

    Secondary: Number of participants with categorical changes from baseline in HBV DNA values

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    End point title
    Number of participants with categorical changes from baseline in HBV DNA values
    End point description
    Participants who achieved a decline in HBV DNA values from baseline were reported. Participants were categorized in the following categorical HBV DNA decline of <1, >=1, >=2, and >=3 log IU/mL.
    End point type
    Secondary
    End point timeframe
    At Baseline and Week 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    68
    67
    68
    23
    70
    67
    68
    24
    Units: Participants
        HBV DNA decline <1 log10 IU/mL
    2
    0
    0
    0
    3
    12
    21
    3
        HBV DNA decline >=1 log10 IU/mL
    11
    4
    13
    3
    51
    44
    30
    18
        HBV DNA decline >=2 log10 IU/mL
    0
    0
    0
    0
    40
    23
    19
    14
        HBV DNA decline >=3 log10 IU/mL
    0
    0
    0
    0
    27
    19
    11
    9
    No statistical analyses for this end point

    Secondary: Median time to ALT normalization

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    End point title
    Median time to ALT normalization
    End point description
    Time to ALT normalization (ALT≤ULN) in the absence of rescue medication in participants with baseline ALT>ULN. The numbers of participants analyzed at Week 24 are as follows for NA therapy population: n=6 in GSK3228836 for 24 WK, n= 7 in GSK3228836 for 12WK+12WK, n=6 in GSK3228836 for 12WK + Placebo for 12WK, n=2 in Placebo for 12WK + GSK3228836 for 12WK, respectively. The numbers of participants analyzed are as follows for the not on NA therapy population: n=20 GSK3228836 for 24WK, n=20 in GSK3228836 for 12WK +12WK, n=21 in GSK3228836 for 12WK + Placebo for 12WK, n=9 in Placebo for 12 WK + GSK3228836 12 WK arm, respectively. Note that the upper confidence limit for the GSK3228836 300mg for 24WK (on NA), Placebo for 12WK + GSK3228836 300mg for 12WK (on NA), and GSK3228836 300 mg for 24WK (not on NA) were not estimable but set to 48 weeks (maximum follow up) here.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 48
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    6
    7
    6
    2
    20
    21
    9
    24
    Units: Weeks
        median (confidence interval 95%)
    16.6 (1.1 to 48)
    4.1 (1.0 to 11.9)
    1 (1.0 to 8.1)
    7 (1.1 to 48)
    13.4 (2.1 to 48)
    15.1 (4.3 to 18.1)
    10.7 (5.1 to 21.1)
    18.1 (1 to 32.1)
    No statistical analyses for this end point

    Secondary: Number of participants with alanine aminotransferase (ALT) normalization

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    End point title
    Number of participants with alanine aminotransferase (ALT) normalization
    End point description
    The ALT normalization (ALT≤ upper limit of normal [ULN]) over time in absence of rescue medication in participants with baseline ALT>ULN. Participants who achieved ALT normalization were reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Up to Week 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    6
    7
    6
    2
    20
    20
    21
    9
    Units: Participants
        Participants with ALT > ULN, At Baseline
    6
    7
    6
    2
    20
    20
    21
    9
        Participants with ALT normalization, At Week 24
    3
    6
    5
    0
    10
    11
    8
    5
    No statistical analyses for this end point

    Secondary: Number of participants with positive Hepatitis B virus e-antibody (HBeAb)

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    End point title
    Number of participants with positive Hepatitis B virus e-antibody (HBeAb)
    End point description
    Blood samples were collected to assess HBeAb level and participants with positive HBeAb were reported.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    17
    19
    24
    7
    15
    15
    11
    7
    Units: Participants
    3
    4
    5
    2
    6
    4
    6
    3
    No statistical analyses for this end point

    Secondary: Mean HBsAg and HBV DNA levels

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    End point title
    Mean HBsAg and HBV DNA levels
    End point description
    Blood samples were collected from participants to assess HBsAg and HBV DNA levels at indicated time points.
    End point type
    Secondary
    End point timeframe
    At Baseline, Week 12, and 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    65
    65
    65
    22
    64
    63
    61
    24
    Units: Log10 (IU/mL)
    arithmetic mean (standard deviation)
        HBsAg, At Week 12
    1.20 ( 1.878 )
    1.04 ( 1.858 )
    1.76 ( 1.706 )
    3.36 ( 0.431 )
    1.39 ( 1.965 )
    1.27 ( 2.000 )
    1.57 ( 1.808 )
    3.68 ( 0.798 )
        HBsAg, At Week 24
    0.65 ( 1.939 )
    1.45 ( 1.809 )
    2.51 ( 1.536 )
    0.83 ( 1.801 )
    0.77 ( 2.016 )
    1.88 ( 1.915 )
    2.88 ( 1.511 )
    1.64 ( 2.171 )
        HBV DNA, At Week 12
    0.74 ( 0.654 )
    0.86 ( 0.700 )
    0.67 ( 0.785 )
    0.61 ( 0.682 )
    3.00 ( 2.242 )
    2.92 ( 2.142 )
    2.68 ( 1.996 )
    4.96 ( 2.074 )
        HBV DNA, At Week 24
    0.55 ( 0.654 )
    0.56 ( 0.649 )
    0.56 ( 0.714 )
    0.79 ( 0.667 )
    2.37 ( 2.137 )
    2.93 ( 2.317 )
    3.07 ( 1.938 )
    3.04 ( 2.224 )
    No statistical analyses for this end point

    Secondary: Mean values of Hepatitis B virus e antigen (HBeAg) level

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    End point title
    Mean values of Hepatitis B virus e antigen (HBeAg) level
    End point description
    Blood samples were collected from participants to assess HBeAg levels at indicated time points. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).
    End point type
    Secondary
    End point timeframe
    At Baseline, Week 12, and 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    18
    20
    24
    7
    21
    16
    16
    7
    Units: Log10 unit per milliliter (U/mL)
    arithmetic mean (standard deviation)
        HBeAg, at Baseline
    0.49 ( 1.014 )
    0.12 ( 0.756 )
    0.36 ( 1.053 )
    0.63 ( 1.323 )
    2.13 ( 1.564 )
    2.52 ( 0.919 )
    1.77 ( 1.612 )
    2.84 ( 0.743 )
        HBeAg, at Week 12
    0.06 ( 1.027 )
    -0.21 ( 0.732 )
    0.19 ( 1.089 )
    0.60 ( 1.310 )
    1.84 ( 1.805 )
    1.52 ( 1.831 )
    1.07 ( 1.551 )
    2.79 ( 0.725 )
        HBeAg, at Week 24
    -0.41 ( 0.635 )
    -0.48 ( 0.752 )
    -0.19 ( 1.071 )
    0.08 ( 1.497 )
    1.18 ( 2.064 )
    1.34 ( 1.936 )
    0.89 ( 1.667 )
    1.06 ( 2.165 )
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in HBsAg and HBV DNA levels

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    End point title
    Mean change from Baseline in HBsAg and HBV DNA levels
    End point description
    Blood samples were collected from participants to assess HBsAg and HBV DNA levels at indicated time points. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 IU/mL = -0.03 log10 IU/mL).
    End point type
    Secondary
    End point timeframe
    At Baseline, Week 12, and 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    65
    65
    65
    22
    64
    63
    61
    24
    Units: log IU/mL
    arithmetic mean (standard deviation)
        HBsAg, Week 12
    -2.09 ( 1.649 )
    -2.23 ( 1.597 )
    -1.59 ( 1.474 )
    -0.03 ( 0.089 )
    -2.37 ( 1.585 )
    -2.41 ( 1.562 )
    -2.06 ( 1.638 )
    -0.08 ( 0.292 )
        HBsAg, Week 24
    -2.62 ( 1.653 )
    -1.81 ( 1.488 )
    -0.83 ( 1.248 )
    -2.57 ( 1.671 )
    -2.96 ( 1.656 )
    -1.77 ( 1.489 )
    -0.77 ( 1.108 )
    -2.09 ( 1.764 )
        HBV DNA, Week 12
    0.24 ( 0.793 )
    0.47 ( 0.773 )
    0.16 ( 0.942 )
    0.19 ( 0.727 )
    -1.96 ( 1.365 )
    -2.22 ( 1.592 )
    -1.92 ( 1.349 )
    -0.54 ( 1.421 )
        HBV DNA, Week 24
    0.06 ( 0.831 )
    0.17 ( 0.661 )
    0.09 ( 0.928 )
    0.33 ( 0.928 )
    -2.66 ( 1.646 )
    -2.2 ( 1.68 )
    -1.52 ( 1.637 )
    -2.6 ( 2.001 )
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in HBeAg level

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    End point title
    Mean change from Baseline in HBeAg level
    End point description
    Blood samples were collected from participants to assess HBAg levels at indicated time points. Note: The units are on the log10 scale so negative values are expected (e.g. 0.933 U/mL = -0.03 log10 U/mL).
    End point type
    Secondary
    End point timeframe
    At Baseline, Week 12, and 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    18
    20
    24
    7
    21
    16
    16
    7
    Units: Log u/mL
    arithmetic mean (standard deviation)
        HBeAg, at Baseline
    0.49 ( 1.014 )
    0.12 ( 0.756 )
    0.36 ( 1.053 )
    0.63 ( 1.323 )
    2.13 ( 1.564 )
    2.52 ( 0.919 )
    1.77 ( 1.612 )
    2.84 ( 0.743 )
        HBeAg, at Week 12
    -0.52 ( 0.874 )
    -0.42 ( 0.480 )
    -0.33 ( 0.343 )
    -0.17 ( 0.453 )
    -0.65 ( 0.919 )
    -1.25 ( 1.522 )
    -0.94 ( 1.618 )
    -0.14 ( 0.313 )
        HBeAg, at WeeK 24
    -0.85 ( 1.071 )
    -0.56 ( 0.811 )
    -0.46 ( 0.595 )
    -0.56 ( 0.598 )
    -1.01 ( 1.426 )
    -1.18 ( 1.532 )
    -0.70 ( 1.673 )
    -1.78 ( 2.057 )
    No statistical analyses for this end point

    Secondary: Mean Hepatitis B virus surface antigen antibody (anti-HBsAg) level

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    End point title
    Mean Hepatitis B virus surface antigen antibody (anti-HBsAg) level
    End point description
    Blood samples were collected to assess anti-HBsAg level at indicated timepoints.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    65
    65
    66
    22
    63
    66
    63
    24
    Units: Log10 IU/mL
    arithmetic mean (standard deviation)
        At Week 36
    0.94 ( 0.534 )
    0.83 ( 0.401 )
    0.74 ( 0.333 )
    0.79 ( 0.368 )
    1.01 ( 0.660 )
    0.82 ( 0.385 )
    0.74 ( 0.347 )
    0.90 ( 0.437 )
        At Week 48
    0.88 ( 0.471 )
    0.77 ( 0.368 )
    0.70 ( 0.277 )
    0.75 ( 0.326 )
    0.91 ( 0.567 )
    0.79 ( 0.369 )
    0.71 ( 0.296 )
    0.83 ( 0.356 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in anti-HBsAg level

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    End point title
    Change from Baseline in anti-HBsAg level
    End point description
    Blood samples were collected to assess anti-HBsAg levels at indicated timepoints.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 12WK + Placebo for 12WK (on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy) GSK3228836 12WK + Placebo for 12WK (not on NA therapy) Placebo for 12WK + GSK3228836 for 12WK (not on NA therapy)
    Number of subjects analysed
    65
    65
    65
    22
    63
    66
    62
    24
    Units: Log10 IU/mL
    arithmetic mean (standard deviation)
        At Week 12
    0.28 ( 0.481 )
    0.18 ( 0.343 )
    0.11 ( 0.319 )
    0.13 ( 0.250 )
    0.37 ( 0.615 )
    0.13 ( 0.353 )
    0.12 ( 0.221 )
    0.16 ( 0.355 )
        At Week 24
    0.22 ( 0.429 )
    0.12 ( 0.335 )
    0.07 ( 0.267 )
    0.09 ( 0.239 )
    0.26 ( 0.507 )
    0.10 ( 0.319 )
    0.09 ( 0.203 )
    0.09 ( 0.203 )
    No statistical analyses for this end point

    Secondary: Mean area under the concentration-time curve from time 0 up to 24 hours (AUC0-24h) of GSK3228836

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    End point title
    Mean area under the concentration-time curve from time 0 up to 24 hours (AUC0-24h) of GSK3228836
    End point description
    Intensive pharmacokinetic (PK) sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h for GSK3228836. Participants received GSK3228836 weekly.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    GSK3228836 dose level 300mg GSK3228836 dose level 150mg
    Number of subjects analysed
    12
    12
    Units: h*ug/mL (hour*micrograms per milliliter)
        arithmetic mean (standard deviation)
    140.312 ( 37.3548 )
    55.214 ( 22.9901 )
    No statistical analyses for this end point

    Secondary: Mean maximum observed concentration (Cmax) of GSK3228836

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    End point title
    Mean maximum observed concentration (Cmax) of GSK3228836
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h for GSK3228836. Participants received GSK3228836 weekly
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    GSK3228836 dose level 300mg GSK3228836 dose level 150mg
    Number of subjects analysed
    12
    12
    Units: ug/mL
        arithmetic mean (standard deviation)
    14.956 ( 5.6592 )
    6.112 ( 2.8112 )
    No statistical analyses for this end point

    Secondary: Median time of maximum observed concentration (tmax) of GSK3228836

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    End point title
    Median time of maximum observed concentration (tmax) of GSK3228836
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h for GSK3228836. Participants received GSK3228836 weekly.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    GSK3228836 dose level 300mg GSK3228836 dose level 150mg
    Number of subjects analysed
    12
    12
    Units: h (hour)
        median (full range (min-max))
    3.017 (2.00 to 5.00)
    3.008 (2.00 to 4.02)
    No statistical analyses for this end point

    Secondary: Mean Cmax of NA therapies

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    End point title
    Mean Cmax of NA therapies
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Cmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Tenofovir disoproxil fumarate Tenofovir alafenamide Entecavir
    Number of subjects analysed
    7
    5
    16
    Units: ng/mL
        arithmetic mean (standard deviation)
    318.857 ( 95.94 )
    19.36 ( 5.85 )
    6.526 ( 2.27 )
    No statistical analyses for this end point

    Secondary: Mean Ctau of NA therapies

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    End point title
    Mean Ctau of NA therapies
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze Ctau. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once daily or every 2 days, and Entecavir 0.5 mg once daily.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Tenofovir disoproxil fumarate Tenofovir alafenamide Entecavir
    Number of subjects analysed
    5
    4
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    57.04 ( 17.0787 )
    10.31 ( 3.4802 )
    0.478 ( 0.1055 )
    No statistical analyses for this end point

    Secondary: Mean AUC0-24h of NA therapies

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    End point title
    Mean AUC0-24h of NA therapies
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze AUC0-24h. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once daily or every 2 days, and Entecavir 0.5 mg once daily.
    End point type
    Secondary
    End point timeframe
    Up to week 24
    End point values
    Tenofovir disoproxil fumarate Tenofovir alafenamide Entecavir
    Number of subjects analysed
    5
    4
    12
    Units: h*nanograms per milliliter (h*ng/mL)
        arithmetic mean (standard deviation)
    2753.908 ( 661.3392 )
    308.167 ( 104.8297 )
    24.43 ( 6.761 )
    No statistical analyses for this end point

    Secondary: Median terminal half-life (t1/2) of GSK3228836

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    End point title
    Median terminal half-life (t1/2) of GSK3228836 [2]
    End point description
    Blood samples were collected from all participants for t1/2 analysis of GSK3228836. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12 WK from both on NA and not on NA therapy were presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: For Median terminal half-life endpoint, only GSK3228836 300mg 24 weeks and 12 +12 weeks were compared. Since both arms are more comparable.
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy)
    Number of subjects analysed
    65
    63
    62
    64
    Units: Day
        median (full range (min-max))
    28.897 (7.52 to 191.98)
    24.918 (8.84 to 161.83)
    27.846 (10.19 to 149.74)
    38.205 (6.87 to 161.83)
    No statistical analyses for this end point

    Secondary: Mean Ctau of GSK3228836

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    End point title
    Mean Ctau of GSK3228836 [3]
    End point description
    Blood samples were collected from all participants for Ctau analysis of GSK3228836. Note: for this endpoint data for more comparable arms GSK3228836 for 24WK and 12 WK from both on NA and not on NA therapy were presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: For Mean Ctau endpoint, only GSK3228836 300mg 24 weeks and 12 +12 weeks were compared. Since both arms are more comparable.
    End point values
    GSK3228836 for 24 weeks (WK) (on NA therapy) GSK3228836 for 12+12 WK (on NA therapy) GSK3228836 for 24 WK (not on NA therapy) GSK3228836 for 12+12 WK (not on NA therapy)
    Number of subjects analysed
    68
    68
    70
    68
    Units: ng/mL
    arithmetic mean (standard deviation)
        Week 8 n=62, 62, 67, and 65, respectively
    21.009 ( 9.6214 )
    47.039 ( 198.1345 )
    21.663 ( 14.4479 )
    23.46 ( 16.6498 )
        Week 12 n= 66, 64, 63, and, 65, respectively
    23.162 ( 11.8963 )
    23.234 ( 11.6993 )
    21.777 ( 9.9248 )
    22.789 ( 11.7361 )
        Week 24 n=64, 61, 63 and 64, respectively
    31.102 ( 28.7535 )
    18.95 ( 14.6513 )
    28.158 ( 17.0606 )
    20.138 ( 19.023 )
    No statistical analyses for this end point

    Secondary: Median tmax of NA therapies

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    End point title
    Median tmax of NA therapies
    End point description
    Intensive PK sampling was done in a subset of participants on stable NA therapy to analyze tmax. Participants on NA therapy were stratified as per the following NA therapy Tenofovir disoproxil fumarate 245 or 300 mg once daily, Tenofovir alafenamide 25 mg once a daily or every 2 days, and Entecavir 0.5 mg once daily.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Tenofovir disoproxil fumarate Tenofovir alafenamide Entecavir
    Number of subjects analysed
    7
    5
    16
    Units: hour
        median (full range (min-max))
    1.000 (0.52 to 1.47)
    1.417 (0.93 to 1.55)
    0.983 (0.48 to 2.02)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events (AEs) and serious adverse events (SAEs) were collected from the signing of the informed consent until the final follow-up visit, up to 48 weeks.
    Adverse event reporting additional description
    The safety population (N=455) included participants who received at least one dose of study treatment. 2 participants from arms GSK3228836 300mg for 12 weeks in both on NA and not on NA therapy population, did not receive study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    GSK3228836 for 24WK (on NA)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12 WK (on NA)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836+Placebo for 12 WK (on NA therapy)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks.

    Reporting group title
    Placebo+GSK3228836 for 12WK each (not on NA)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks followed by 300 mg GSK3228836 once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11).

    Reporting group title
    GSK3228836 for 24Wk (not on NA)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 24 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11).

    Reporting group title
    GSK3228836 for 12WK (not on NA)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by step-down in dose of 150 mg (plus placebo to match to maintain participant blinding) GSK3228836 once/week for 12 weeks.

    Reporting group title
    GSK3228836+Placebo for 12WK (not on NA)
    Reporting group description
    All participants of this arm received 300 mg GSK3228836 once/week for 12 weeks (plus a loading dose of 300 mg GSK3228836 on Day 4 and 11) followed by placebo once/week for 12 weeks.

    Reporting group title
    Placebo+GSK3228836 300mg for 12WK each (on NA)
    Reporting group description
    All participants of this arm received Placebo once/week for 12 weeks followed by 300 mg GSK3228836 once/week for 12 weeks (plus placebo loading doses to match on Day 4 and 11).

    Serious adverse events
    GSK3228836 for 24WK (on NA) GSK3228836 for 12 WK (on NA) GSK3228836+Placebo for 12 WK (on NA therapy) Placebo+GSK3228836 for 12WK each (not on NA) GSK3228836 for 24Wk (not on NA) GSK3228836 for 12WK (not on NA) GSK3228836+Placebo for 12WK (not on NA) Placebo+GSK3228836 300mg for 12WK each (on NA)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    4 / 68 (5.88%)
    0 / 24 (0.00%)
    6 / 70 (8.57%)
    2 / 67 (2.99%)
    3 / 68 (4.41%)
    0 / 23 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bile duct cancer
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle injury
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Cryoglobulinaemia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Haemorrhoids
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Hepatitis B
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    GSK3228836 for 24WK (on NA) GSK3228836 for 12 WK (on NA) GSK3228836+Placebo for 12 WK (on NA therapy) Placebo+GSK3228836 for 12WK each (not on NA) GSK3228836 for 24Wk (not on NA) GSK3228836 for 12WK (not on NA) GSK3228836+Placebo for 12WK (not on NA) Placebo+GSK3228836 300mg for 12WK each (on NA)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 68 (82.35%)
    59 / 67 (88.06%)
    53 / 68 (77.94%)
    19 / 24 (79.17%)
    65 / 70 (92.86%)
    60 / 67 (89.55%)
    61 / 68 (89.71%)
    16 / 23 (69.57%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Neoplasm skin
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Leiomyoma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Haemangioma of liver
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Cervix carcinoma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    2
    0
    Hypertension
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    2
    1
    0
    0
    Vasculitis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Varicose vein
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Energy increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Asthenia
         subjects affected / exposed
    5 / 68 (7.35%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    3 / 70 (4.29%)
    1 / 67 (1.49%)
    7 / 68 (10.29%)
    0 / 23 (0.00%)
         occurrences all number
    6
    3
    1
    0
    3
    2
    11
    0
    Chest discomfort
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 68 (1.47%)
    4 / 67 (5.97%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    5 / 70 (7.14%)
    2 / 67 (2.99%)
    3 / 68 (4.41%)
    1 / 23 (4.35%)
         occurrences all number
    1
    6
    2
    0
    5
    2
    4
    1
    Injection site erosion
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    Injection site erythema
         subjects affected / exposed
    36 / 68 (52.94%)
    37 / 67 (55.22%)
    34 / 68 (50.00%)
    10 / 24 (41.67%)
    34 / 70 (48.57%)
    30 / 67 (44.78%)
    37 / 68 (54.41%)
    5 / 23 (21.74%)
         occurrences all number
    216
    175
    194
    23
    264
    150
    179
    22
    Injection site haematoma
         subjects affected / exposed
    5 / 68 (7.35%)
    3 / 67 (4.48%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    8 / 70 (11.43%)
    4 / 67 (5.97%)
    2 / 68 (2.94%)
    1 / 23 (4.35%)
         occurrences all number
    9
    15
    3
    1
    17
    12
    3
    2
    Fatigue
         subjects affected / exposed
    5 / 68 (7.35%)
    4 / 67 (5.97%)
    7 / 68 (10.29%)
    0 / 24 (0.00%)
    13 / 70 (18.57%)
    7 / 67 (10.45%)
    8 / 68 (11.76%)
    1 / 23 (4.35%)
         occurrences all number
    8
    4
    13
    0
    19
    15
    11
    1
    Feeling abnormal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Injection site discomfort
         subjects affected / exposed
    2 / 68 (2.94%)
    9 / 67 (13.43%)
    9 / 68 (13.24%)
    2 / 24 (8.33%)
    4 / 70 (5.71%)
    6 / 67 (8.96%)
    4 / 68 (5.88%)
    1 / 23 (4.35%)
         occurrences all number
    13
    62
    54
    2
    13
    25
    25
    2
    Influenza like illness
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    2
    0
    1
    0
    2
    3
    1
    0
    Injection site anaesthesia
         subjects affected / exposed
    1 / 68 (1.47%)
    3 / 67 (4.48%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    2
    8
    4
    0
    2
    2
    2
    0
    Injection site bruising
         subjects affected / exposed
    7 / 68 (10.29%)
    11 / 67 (16.42%)
    7 / 68 (10.29%)
    4 / 24 (16.67%)
    13 / 70 (18.57%)
    10 / 67 (14.93%)
    14 / 68 (20.59%)
    4 / 23 (17.39%)
         occurrences all number
    36
    17
    23
    10
    42
    29
    33
    13
    Injection site discolouration
         subjects affected / exposed
    8 / 68 (11.76%)
    9 / 67 (13.43%)
    14 / 68 (20.59%)
    2 / 24 (8.33%)
    13 / 70 (18.57%)
    11 / 67 (16.42%)
    6 / 68 (8.82%)
    2 / 23 (8.70%)
         occurrences all number
    22
    65
    92
    4
    39
    46
    37
    3
    Hyperthermia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Injection site haemorrhage
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    0
    0
    Injection site hypoaesthesia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Injection site induration
         subjects affected / exposed
    3 / 68 (4.41%)
    3 / 67 (4.48%)
    4 / 68 (5.88%)
    1 / 24 (4.17%)
    6 / 70 (8.57%)
    7 / 67 (10.45%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    14
    6
    13
    1
    20
    16
    5
    0
    Injection site nodule
         subjects affected / exposed
    1 / 68 (1.47%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    3
    2
    1
    4
    0
    3
    0
    0
    Injection site pain
         subjects affected / exposed
    11 / 68 (16.18%)
    15 / 67 (22.39%)
    21 / 68 (30.88%)
    6 / 24 (25.00%)
    20 / 70 (28.57%)
    13 / 67 (19.40%)
    14 / 68 (20.59%)
    6 / 23 (26.09%)
         occurrences all number
    45
    59
    118
    41
    198
    61
    66
    16
    Injection site pruritus
         subjects affected / exposed
    14 / 68 (20.59%)
    17 / 67 (25.37%)
    15 / 68 (22.06%)
    2 / 24 (8.33%)
    23 / 70 (32.86%)
    16 / 67 (23.88%)
    19 / 68 (27.94%)
    2 / 23 (8.70%)
         occurrences all number
    88
    78
    100
    4
    198
    85
    98
    3
    Injection site swelling
         subjects affected / exposed
    4 / 68 (5.88%)
    4 / 67 (5.97%)
    13 / 68 (19.12%)
    0 / 24 (0.00%)
    10 / 70 (14.29%)
    7 / 67 (10.45%)
    5 / 68 (7.35%)
    1 / 23 (4.35%)
         occurrences all number
    45
    12
    70
    0
    69
    44
    13
    2
    Injection site warmth
         subjects affected / exposed
    1 / 68 (1.47%)
    5 / 67 (7.46%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    4 / 68 (5.88%)
    0 / 23 (0.00%)
         occurrences all number
    2
    13
    2
    0
    39
    34
    19
    0
    Malaise
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    3 / 70 (4.29%)
    3 / 67 (4.48%)
    0 / 68 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    1
    1
    1
    1
    3
    4
    0
    3
    Nodule
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    2
    0
    1
    2
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    0
    Pain
         subjects affected / exposed
    1 / 68 (1.47%)
    3 / 67 (4.48%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    4
    2
    0
    1
    2
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    10 / 68 (14.71%)
    6 / 67 (8.96%)
    10 / 68 (14.71%)
    4 / 24 (16.67%)
    15 / 70 (21.43%)
    17 / 67 (25.37%)
    17 / 68 (25.00%)
    6 / 23 (26.09%)
         occurrences all number
    14
    8
    19
    5
    23
    38
    23
    7
    Scar inflammation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Swelling
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vaccination site pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Sensation of foreign body
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Immunodeficiency
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Type III immune complex mediated reaction
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    2 / 24 (8.33%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    1
    2
    0
    Reproductive system and breast disorders
    Cervix haemorrhage uterine
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Cervical polyp
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Pelvic pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Menstruation irregular
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Menstrual disorder
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Genital haemorrhage
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    0
    0
    Adenomyosis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Amenorrhoea
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Breast pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    1
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Vulvovaginal swelling
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Vulvovaginal inflammation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Hyperventilation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Nasal dryness
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    0 / 68 (0.00%)
    3 / 67 (4.48%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    2
    0
    1
    2
    1
    0
    Catarrh
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Dry throat
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 68 (2.94%)
    3 / 67 (4.48%)
    2 / 68 (2.94%)
    1 / 24 (4.17%)
    3 / 70 (4.29%)
    3 / 67 (4.48%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    2
    4
    3
    1
    3
    3
    0
    0
    Oropharyngeal discomfort
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Nasal pruritus
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Nasal polyps
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Reflux laryngitis
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    1
    0
    0
    1
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Stress
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Sleep disorder
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    2
    0
    1
    2
    3
    0
    Depression
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Irritability
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 68 (4.41%)
    1 / 67 (1.49%)
    3 / 68 (4.41%)
    2 / 24 (8.33%)
    8 / 70 (11.43%)
    9 / 67 (13.43%)
    7 / 68 (10.29%)
    3 / 23 (13.04%)
         occurrences all number
    3
    1
    3
    4
    11
    12
    9
    3
    Antinuclear antibody positive
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood calcium decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    3
    0
    Bilirubin conjugated increased
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    Autoantibody positive
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 68 (10.29%)
    8 / 67 (11.94%)
    4 / 68 (5.88%)
    4 / 24 (16.67%)
    17 / 70 (24.29%)
    15 / 67 (22.39%)
    12 / 68 (17.65%)
    5 / 23 (21.74%)
         occurrences all number
    13
    10
    6
    9
    25
    18
    21
    5
    Albumin urine present
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Antineutrophil cytoplasmic antibody positive
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    2 / 24 (8.33%)
    1 / 70 (1.43%)
    3 / 67 (4.48%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    0
    2
    1
    3
    1
    1
    Complement factor abnormal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Complement factor C4 decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    3 / 24 (12.50%)
    5 / 70 (7.14%)
    4 / 67 (5.97%)
    4 / 68 (5.88%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    0
    3
    5
    5
    4
    1
    Complement factor C3 decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    4 / 24 (16.67%)
    7 / 70 (10.00%)
    4 / 67 (5.97%)
    6 / 68 (8.82%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    4
    8
    5
    6
    1
    C-reactive protein increased
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    3 / 70 (4.29%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    2
    0
    1
    0
    3
    2
    0
    1
    Complement factor increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    6 / 70 (8.57%)
    1 / 67 (1.49%)
    4 / 68 (5.88%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    6
    1
    4
    1
    Blood pressure increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    0
    0
    Blood creatine increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Body temperature increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    2 / 70 (2.86%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    7
    1
    2
    0
    2
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Eosinophil count increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Crystal urine present
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Creatinine urine increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    1
    0
    Creatinine renal clearance decreased
         subjects affected / exposed
    2 / 68 (2.94%)
    6 / 67 (8.96%)
    1 / 68 (1.47%)
    2 / 24 (8.33%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    4
    21
    2
    3
    1
    10
    3
    1
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Immature granulocyte count increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Hepatitis B DNA assay positive
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Mean cell volume decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Urine analysis abnormal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    0
    Urine albumin/creatinine ratio
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Urinary sediment present
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Transaminases increased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Total complement activity decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Red blood cells urine positive
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Protein urine present
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    3 / 68 (4.41%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    0
    Platelet count decreased
         subjects affected / exposed
    4 / 68 (5.88%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    8 / 70 (11.43%)
    3 / 67 (4.48%)
    3 / 68 (4.41%)
    1 / 23 (4.35%)
         occurrences all number
    6
    0
    2
    0
    11
    6
    3
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    1
    Urine leukocyte esterase positive
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Arthropod sting
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Animal bite
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    Arthropod bite
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    Back injury
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 24 (4.17%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    1
    2
    0
    Epicondylitis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    Eye injury
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Muscle strain
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Hand fracture
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Injury
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Nail injury
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Post vaccination syndrome
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    Procedural pain
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    0
    Skin injury
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Skin laceration
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Sunburn
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Tooth avulsion
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Tooth dislocation
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    Tooth injury
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    Vaccination complication
         subjects affected / exposed
    2 / 68 (2.94%)
    2 / 67 (2.99%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    2
    3
    2
    0
    0
    1
    2
    0
    Congenital, familial and genetic disorders
    Dyschromatosis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 67 (2.99%)
    3 / 68 (4.41%)
    1 / 24 (4.17%)
    3 / 70 (4.29%)
    4 / 67 (5.97%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    4
    1
    3
    6
    2
    0
    Somnolence
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    2
    0
    Sciatica
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    2 / 68 (2.94%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    2
    6
    0
    0
    1
    2
    1
    0
    Headache
         subjects affected / exposed
    5 / 68 (7.35%)
    6 / 67 (8.96%)
    8 / 68 (11.76%)
    4 / 24 (16.67%)
    14 / 70 (20.00%)
    14 / 67 (20.90%)
    14 / 68 (20.59%)
    3 / 23 (13.04%)
         occurrences all number
    10
    8
    15
    4
    25
    50
    26
    3
    Dysgeusia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    Syncope
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Anaemia
         subjects affected / exposed
    0 / 68 (0.00%)
    3 / 67 (4.48%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    2 / 70 (2.86%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    0
    4
    1
    1
    2
    0
    1
    1
    Abnormal clotting factor
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Leukocytosis
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    3 / 70 (4.29%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    1
    0
    Lymph node pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 68 (1.47%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    3
    0
    0
    1
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Monocytosis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    2
    0
    0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Eosinophilia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    4 / 70 (5.71%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    0
    5
    2
    1
    0
    Polycythaemia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Splenomegaly
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    4 / 68 (5.88%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    5 / 70 (7.14%)
    2 / 67 (2.99%)
    3 / 68 (4.41%)
    0 / 23 (0.00%)
         occurrences all number
    6
    2
    3
    0
    9
    2
    5
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    Deafness
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Ear pain
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    1
    0
    0
    Meniere's disease
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    2
    0
    Vertigo positional
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Eye disorders
    Keratitis
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    Asthenopia
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blepharitis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Dry eye
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Noninfective conjunctivitis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Periorbital swelling
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 68 (1.47%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    1 / 70 (1.43%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    2
    1
    1
    2
    1
    1
    0
    Abdominal distension
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    3
    0
    2
    0
    1
    3
    0
    0
    Change of bowel habit
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Abdominal pain lower
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    1 / 68 (1.47%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    2
    0
    2
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    2 / 68 (2.94%)
    0 / 24 (0.00%)
    3 / 70 (4.29%)
    3 / 67 (4.48%)
    3 / 68 (4.41%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    4
    0
    4
    3
    4
    0
    Abdominal tenderness
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Angular cheilitis
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    0 / 70 (0.00%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    0 / 24 (0.00%)
    4 / 70 (5.71%)
    2 / 67 (2.99%)
    1 / 68 (1.47%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    2
    0
    5
    5
    1
    1
    Constipation
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    4 / 68 (5.88%)
    0 / 24 (0.00%)
    2 / 70 (2.86%)
    1 / 67 (1.49%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    4
    0
    2
    1
    0
    0
    Dental caries
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 67 (0.00%)
    1 / 68 (1.47%)
    1 / 24 (4.17%)
    0 / 70 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    2
    0
    1
    2
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    6 / 68 (8.82%)
    2 / 67 (2.99%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    3 / 70 (4.29%)
    3 / 67 (4.48%)
    2 / 68 (2.94%)
    1 / 23 (4.35%)
         occurrences all number
    6
    2
    0
    0
    3
    3
    2
    1
    Diverticulum intestinal
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 24 (0.00%)
    1 / 70 (1.43%)
    0 / 67 (0.00%)
    0 / 68 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 67 (0.00%)
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