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    Clinical Trial Results:
    A 24-week, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Phase 2 Study of Different Doses of VX-509 in Adult Subjects With Active Rheumatoid Arthritis on Stable Methotrexate Therapy with 104-Week Open-Label Extension

    Summary
    EudraCT number
    2011-004419-22
    Trial protocol
    DE   CZ   HU   EE   SK   BG  
    Global end of trial date
    31 Jul 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    28 Jun 2016
    First version publication date
    07 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    VX11-509-102
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01590459
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States, 02210-1862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.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
    18 Sep 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy. To evaluate the safety and tolerability of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    Subjects had been receiving MTX coadministered with folic or folinic acid (at least 5 mg/week) for at least 12 weeks before screening, and had been receiving MTX at a stable dose between 10 mg and 25 mg, orally or subcutaneously administered, per week for at least 8 consecutive weeks.
    Evidence for comparator
    There was no active comparator.
    Actual start date of recruitment
    01 May 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Ukraine: 18
    Country: Number of subjects enrolled
    United States: 83
    Country: Number of subjects enrolled
    Argentina: 15
    Country: Number of subjects enrolled
    Bulgaria: 40
    Country: Number of subjects enrolled
    Czech Republic: 29
    Country: Number of subjects enrolled
    Estonia: 16
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Hungary: 24
    Country: Number of subjects enrolled
    Mexico: 41
    Country: Number of subjects enrolled
    Poland: 39
    Country: Number of subjects enrolled
    Romania: 3
    Country: Number of subjects enrolled
    Russian Federation: 21
    Country: Number of subjects enrolled
    Serbia: 14
    Worldwide total number of subjects
    358
    EEA total number of subjects
    166
    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)
    295
    From 65 to 84 years
    63
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 359 subjects were enrolled, of which 358 subjects received study drug. Subjects with less than a 20% reduction from baseline in tender joints, swollen joints, and subject-assessed pain at Week 8 or later were eligible to enroll in Escape arm and received 150 mg VX-509 qd or 200 mg VX-509 qd.

    Period 1
    Period 1 title
    24 Week Treatment Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    VX-509-matched placebo up to 24 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509-matched placebo up to 24 weeks.

    Arm title
    VX-509 100 mg qd
    Arm description
    VX-509 100 milligram (mg) once daily (qd) up to 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 100 mg qd up to 24 weeks.

    Arm title
    VX- 509 150 mg qd
    Arm description
    VX-509 150 mg qd up to 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 150 mg qd up to 24 weeks.

    Arm title
    VX-509 200 mg qd
    Arm description
    VX-509 200 mg qd up to 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 200 mg qd up to 24 weeks.

    Arm title
    VX-509 100 mg bid
    Arm description
    VX-509 100 mg twice daily (bid) for up to 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 100 mg bid up to 24 weeks.

    Number of subjects in period 1
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Started
    71
    71
    72
    72
    72
    Completed
    58
    57
    60
    59
    61
    Not completed
    13
    14
    12
    13
    11
         Refused further dosing for reason other than AE
    2
    2
    5
    2
    6
         Death
    -
    -
    -
    -
    1
         Noncompliance with study drug
    -
    1
    -
    -
    -
         Physician decision
    1
    2
    -
    -
    -
         Did not meet eligibility criteria
    1
    1
    -
    2
    -
         Adverse event
    6
    6
    7
    9
    3
         Unspecified
    1
    1
    -
    -
    -
         Lost to follow-up
    2
    1
    -
    -
    1
    Period 2
    Period 2 title
    Open Label Extension (OLE)
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    VX-509 150 mg qd - OLE
    Arm description
    VX-509 150 mg qd up to 104 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 150 mg qd up to 104 weeks.

    Arm title
    VX-509 200 mg qd - OLE
    Arm description
    VX-509 200 mg qd up to 104 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-509
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-509 200 mg qd up to 104 weeks.

    Number of subjects in period 2 [1]
    VX-509 150 mg qd - OLE VX-509 200 mg qd - OLE
    Started
    47
    218
    Completed
    0
    0
    Not completed
    47
    218
         Refused further dosing for reason other than AE
    2
    6
         Death
    -
    1
         Required prohibited medication
    -
    1
         Did not meet eligibility criteria
    -
    8
         Adverse event
    2
    8
         Study terminated by sponsor
    42
    188
         Unspecified
    -
    5
         Lost to follow-up
    1
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only subjects who completed 24 weeks of treatment in the Treatment Period and who had at least an ACR20-CRP response were eligible for OLE.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    VX-509-matched placebo up to 24 weeks.

    Reporting group title
    VX-509 100 mg qd
    Reporting group description
    VX-509 100 milligram (mg) once daily (qd) up to 24 weeks.

    Reporting group title
    VX- 509 150 mg qd
    Reporting group description
    VX-509 150 mg qd up to 24 weeks.

    Reporting group title
    VX-509 200 mg qd
    Reporting group description
    VX-509 200 mg qd up to 24 weeks.

    Reporting group title
    VX-509 100 mg bid
    Reporting group description
    VX-509 100 mg twice daily (bid) for up to 24 weeks.

    Reporting group values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid Total
    Number of subjects
    71 71 72 72 72 358
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    52.7 ± 13.16 53.5 ± 11.33 50.1 ± 11.81 53.2 ± 13.21 55.7 ± 12.23 -
    Gender categorical
    Units: Subjects
        Female
    62 51 58 56 62 289
        Male
    9 20 14 16 10 69

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    VX-509-matched placebo up to 24 weeks.

    Reporting group title
    VX-509 100 mg qd
    Reporting group description
    VX-509 100 milligram (mg) once daily (qd) up to 24 weeks.

    Reporting group title
    VX- 509 150 mg qd
    Reporting group description
    VX-509 150 mg qd up to 24 weeks.

    Reporting group title
    VX-509 200 mg qd
    Reporting group description
    VX-509 200 mg qd up to 24 weeks.

    Reporting group title
    VX-509 100 mg bid
    Reporting group description
    VX-509 100 mg twice daily (bid) for up to 24 weeks.
    Reporting group title
    VX-509 150 mg qd - OLE
    Reporting group description
    VX-509 150 mg qd up to 104 weeks.

    Reporting group title
    VX-509 200 mg qd - OLE
    Reporting group description
    VX-509 200 mg qd up to 104 weeks.

    Subject analysis set title
    VX-509 150 mg qd - Treatment Period, After Escape
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subjects with less than a 20% reduction from baseline in tender joints, swollen joints, and subject-assessed pain at Week 8 or later enrolled in Escape arm and received VX-509 150 mg qd.

    Subject analysis set title
    VX-509 200 mg qd - Treatment Period, After Escape
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Subjects with less than a 20% reduction from baseline in tender joints, swollen joints, and subject-assessed pain at Week 8 or later were enrolled in Escape arm and received VX-509 200 mg qd.

    Primary: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) C-Reactive Protein (ACR20-CRP) Response at Week 12

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    End point title
    Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) C-Reactive Protein (ACR20-CRP) Response at Week 12
    End point description
    ACR20-CRP response: greater than equal to (>=) 20% improvement in tender joints count (TJC); >= 20% improvement in swollen joints count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: subject assessment of pain (assessed on 0-100 mm VAS, higher score = more pain); subject global assessment of disease activity (assessed on 0-10 point scale, higher score = more disease activity); physician global assessment of disease activity (assessed on 0-10 point scale, higher score = more disease activity); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP levels. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: percentage of subjects
        number (not applicable)
    18.3
    46.5
    66.7
    56.9
    68.1
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    VX-509 100 mg qd v Placebo
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0002
    Method
    Wald asymptotic test
    Parameter type
    Proportion difference
    Point estimate
    28.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.5
         upper limit
    42.8
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    VX- 509 150 mg qd v Placebo
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wald asymptotic test
    Parameter type
    Proportion difference
    Point estimate
    48.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    34.2
         upper limit
    62.5
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v VX-509 200 mg qd
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wald asymptotic test
    Parameter type
    Proportion difference
    Point estimate
    38.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    24.1
         upper limit
    53.2
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    VX-509 100 mg bid v Placebo
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wald asymptotic test
    Parameter type
    Proportion difference
    Point estimate
    49.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    35.7
         upper limit
    63.8

    Primary: Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 12

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    End point title
    Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 12
    End point description
    DAS28-4 (CRP) was calculated from SJC and TJC using the 28 joints count, CRP milligram per liter [mg/L] and subject general health visual analogue scale score. A score of less than (<2.6) implied remission, <=3.2 implied low disease activity. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    70
    70
    69
    71
    Units: units on scale
        least squares mean (standard error)
    -0.76 ± 0.157
    -2.05 ± 0.146
    -2.22 ± 0.14
    -2.48 ± 0.146
    -2.39 ± 0.142
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    VX-509 100 mg qd v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Mixed effect model
    Parameter type
    Treatment difference
    Point estimate
    -1.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.68
         upper limit
    -0.88
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    VX- 509 150 mg qd v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Mixed effect model
    Parameter type
    Treatment difference
    Point estimate
    -1.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.85
         upper limit
    -1.06
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    VX-509 200 mg qd v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Mixed effect model
    Parameter type
    Treatment difference
    Point estimate
    -1.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.11
         upper limit
    -1.32
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    VX-509 100 mg bid v Placebo
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Mixed effect model
    Parameter type
    Treatment difference
    Point estimate
    -1.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.01
         upper limit
    -1.23

    Primary: Safety and Tolerability as Assessed by Adverse Events (AEs) Through Week 24

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    End point title
    Safety and Tolerability as Assessed by Adverse Events (AEs) Through Week 24 [1]
    End point description
    AE: any untoward medical occurrence in a subject during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE included serious as well as non-serious AEs. Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Safety set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Through Week 24
    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: Statistical analysis was not planned for safety endpoint.
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: number of subjects
    number (not applicable)
        Subjects with AEs
    30
    37
    44
    49
    42
    11
    36
        Subjects with SAEs
    4
    3
    6
    5
    7
    1
    5
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving ACR-CRP Responses

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    End point title
    Percentage of Subjects Achieving ACR-CRP Responses
    End point description
    ACR20-CRP at Week 24 and ACR50/70-CRP at Week 12 and 24 are reported. ACR20-CRP is defined in first primary endpoint. ACR50/70-CRP response: >=50%/70% improvement in TJC; >=50%/70% improvement in SJC; and >=50%/70% improvement in at least 3 of 5 remaining ACR core measures: subject assessment of pain (assessed on 0-100 mm VAS, higher score = more pain); subject global assessment of disease activity (assessed on 0-10 point scale, higher score = more disease activity); physician global assessment of disease activity (assessed on 0-10 point scale, higher score = more disease activity); self-assessed disability (disability index of the HAQ); and CRP levels. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: percentage of subjects
    number (not applicable)
        Week 24: ACR20 CRP
    16.9
    60.6
    61.1
    61.1
    62.5
        Week 12: ACR50 CRP
    7
    22.5
    38.9
    34.7
    38.9
        Week 12: ACR70 CRP
    2.8
    9.9
    11.1
    9.7
    22.2
        Week 24: ACR50 CRP
    7
    38
    38.9
    40.3
    47.2
        Week 24: ACR70 CRP
    2.8
    16.9
    18.1
    15.3
    25
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved a Moderate or Good Response with European League Against Rheumatism (EULAR) Response at Week 12 and 24

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    End point title
    Percentage of Subjects who Achieved a Moderate or Good Response with European League Against Rheumatism (EULAR) Response at Week 12 and 24
    End point description
    DAS28-4 (CRP) EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28-4 (CRP) =< 3.2; moderate responders: change from baseline >1.2 with DAS28-4 (CRP) >3.2 or change from baseline >0.6 to =<1.2 with DAS28-4 (CRP) =<5.1; non-responders: change from baseline =< 0.6 or change from baseline >0.6 and =<1.2 with DAS28-4 CPR >5.1. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: percentage of subjects
    number (not applicable)
        Week 12
    25.4
    57.7
    69.4
    65.3
    68.1
        Week 24
    19.7
    56.3
    62.5
    61.1
    61.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with DAS28-4 (CRP) Remission at Week 12 and 24

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    End point title
    Percentage of Subjects with DAS28-4 (CRP) Remission at Week 12 and 24
    End point description
    DAS28-4 (CRP) is defined in second primary endpoint. DAS28-4 (CRP) score <2.6 was considered remission. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: percentage of subjects
    number (not applicable)
        Week 12
    2.8
    16.9
    29.2
    22.2
    30.6
        Week 24
    5.6
    21.1
    29.2
    27.8
    31.9
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-4 (CRP) at Week 24

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    End point title
    Change from Baseline in DAS28-4 (CRP) at Week 24
    End point description
    DAS28-4 (CRP) is defined in second primary endpoint. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    70
    70
    69
    71
    Units: units on scale
        least squares mean (standard error)
    -1.51 ± 0.215
    -2.35 ± 0.158
    -2.35 ± 0.148
    -2.68 ± 0.156
    -2.86 ± 0.154
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved Remission as Defined by the ACR/EULAR Criteria

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    End point title
    Percentage of Subjects who Achieved Remission as Defined by the ACR/EULAR Criteria
    End point description
    Subject was considered to be in remission when either scores on the tender joint count, swollen joint count, CRP (in mg/dL), and subject global assessment (0 to 10 scale) were all <=1; or score on the Simplified Disease Activity Index (SDAI) was <=3.3. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: percentage of subjects
    number (not applicable)
        Week 12
    0
    5.6
    5.6
    6.9
    6.9
        Week 24
    0
    9.9
    11.1
    6.9
    15.3
    No statistical analyses for this end point

    Secondary: Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12 and Week 24

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    End point title
    Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12 and Week 24
    End point description
    The HAQ-DI is a self-completed subject questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Domain score = total score of individual questions divided by total number of questions. HAQ-DI total score = total of domain scores divided by number of domains, range: 0 (best) to 3 (worst). Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid
    Number of subjects analysed
    71
    71
    72
    72
    72
    Units: units on scale
    least squares mean (standard error)
        Week 12
    -0.28 ± 0.071
    -0.49 ± 0.068
    -0.58 ± 0.065
    -0.63 ± 0.068
    -0.62 ± 0.066
        Week 24
    -0.6 ± 0.09
    -0.62 ± 0.07
    -0.65 ± 0.067
    -0.79 ± 0.069
    -0.75 ± 0.068
    No statistical analyses for this end point

    Secondary: Change from Baseline in Subject Global Assessment of Disease Activity at Week 12 and 24

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    End point title
    Change from Baseline in Subject Global Assessment of Disease Activity at Week 12 and 24
    End point description
    Subject assessed overall arthritis activity on an 11-point scale ranging from 0 (none) to 10 (extreme). Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and Week 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 19, 45)
    -1.3 ± 2.31
    -2.6 ± 2.62
    -2.8 ± 2.13
    -2.8 ± 2.37
    -3.6 ± 2.66
    -2.2 ± 1.8
    -2.3 ± 1.88
        Week 24 (n= 17, 44, 53, 47, 50, 27, 55)
    -1.9 ± 3.2
    -3.9 ± 2.19
    -2.9 ± 2.46
    -3.7 ± 2.3
    -4.5 ± 2.34
    -3.4 ± 2.55
    -3.1 ± 2.8
    No statistical analyses for this end point

    Secondary: Change from Baseline in Subject Assessment of Pain Visual Analog Scale (VAS) Score at Week 12 and 24

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    End point title
    Change from Baseline in Subject Assessment of Pain Visual Analog Scale (VAS) Score at Week 12 and 24
    End point description
    Subjects indicated the amount of pain they were experiencing using a 100 millimeter (mm) VAS. VAS range: 0 mm (no pain) to 100 mm (pain as bad as it could be). Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: millimeter (mm)
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 19, 45)
    -10.1 ± 22.68
    -22.4 ± 26.57
    -24.4 ± 22.51
    -25.5 ± 25.17
    -31.6 ± 25.02
    -22.5 ± 18.67
    -22.1 ± 18.54
        Week 24 (n= 17, 44, 53, 47, 50, 27, 55)
    -19.3 ± 32.17
    -34.8 ± 22.3
    -25.8 ± 26.78
    -34.8 ± 25.38
    -41.4 ± 23.09
    -31.8 ± 24.99
    -30 ± 22.04
    No statistical analyses for this end point

    Secondary: Change from Baseline in Subject General Health VAS Score at Week 12 and 24

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    End point title
    Change from Baseline in Subject General Health VAS Score at Week 12 and 24
    End point description
    Subjects rated their health using a 100 mm VAS. VAS range: 0 mm (very well) to 100 mm (extremely bad). Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: millimeter (mm)
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 18, 45)
    -7.3 ± 24.3
    -18.6 ± 23.69
    -19.7 ± 24.69
    -21.2 ± 23.3
    -23.8 ± 26.17
    -21.6 ± 26.95
    -22.6 ± 24.48
        Week 24 (n= 17, 44, 53, 47, 49, 26, 55)
    -18.2 ± 33.1
    -24.2 ± 24.2
    -19 ± 23.89
    -28.9 ± 23.1
    -35.4 ± 25.41
    -29.3 ± 27.33
    -31.8 ± 24.15
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Physical Component and Mental Component of the Short Form-36 (SF-36) at Week 12 and 24

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    End point title
    Change from Baseline in the Physical Component and Mental Component of the Short Form-36 (SF-36) at Week 12 and 24
    End point description
    SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (CS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline in physical (PC) and mental component (MC) norm based scores (NBS) are reported. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 – MC NBS (n= 39, 52, 59, 52, 58, 15, 42)
    2.056 ± 10.7207
    4.525 ± 11.5951
    5.022 ± 9.3893
    6.039 ± 10.8664
    5.886 ± 10.7011
    1.76 ± 10.5982
    3.558 ± 10.047
        Week 12 – PC NBS (n= 39, 51, 59, 52, 58, 15, 42)
    5.508 ± 7.7841
    6.116 ± 5.8375
    7.447 ± 7.2476
    8.642 ± 6.9517
    8.936 ± 8.4752
    5.482 ± 5.4057
    4.383 ± 5.4056
        Week 24 – MC NBS (n= 17, 44, 53, 47, 50, 27, 55)
    7.429 ± 12.3269
    4.641 ± 11.3092
    5.347 ± 10.068
    8.479 ± 9.9463
    7.705 ± 11.9373
    4.669 ± 9.4316
    4.157 ± 8.4898
        Week 24 – PC NBS (n= 17, 43, 53, 47, 50, 27, 55)
    10.411 ± 8.2095
    8.12 ± 6.9881
    9.066 ± 8.8524
    11.444 ± 7.9637
    11.168 ± 7.3012
    8.961 ± 8.5279
    6.977 ± 7.4528
    No statistical analyses for this end point

    Secondary: Change from Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) Score at Week 12 and 24

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    End point title
    Change from Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) Score at Week 12 and 24
    End point description
    The RAQoL questionnaire is a 30-item self-administered measure that was specifically designed to assess the health-related quality of life of people with RA. Each item is in the form a simple statement to which subjects respond “Yes” or “No.” “Yes” scores 1 and “No” scores 0. The overall score is the sum of the individual item scores, ranging from 0 to 30, with a lower score indicating better quality of life. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 19, 45)
    -3.05 ± 7.247
    -5.37 ± 8.049
    -5.11 ± 5.272
    -6.67 ± 6.597
    -6.59 ± 7.923
    -2.37 ± 6.066
    -2.89 ± 7.101
        Week 24 (n= 17, 44, 53, 47, 50, 27, 55)
    -5.35 ± 9.219
    -7.34 ± 9.514
    -6.16 ± 6.404
    -8.76 ± 7.053
    -7.98 ± 7.249
    -4.78 ± 7.49
    -4.65 ± 6.692
    No statistical analyses for this end point

    Secondary: Change from Baseline in Subject-Assessed Duration of Morning Stiffness at Week 12 and 24

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    End point title
    Change from Baseline in Subject-Assessed Duration of Morning Stiffness at Week 12 and 24
    End point description
    Morning stiffness was defined as stiffness in and around the joints, assessed by subject. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: minutes
    arithmetic mean (standard deviation)
        Week 12 (38, 51, 59, 52, 57, 19, 44)
    -37 ± 49.44
    -64.1 ± 63.19
    -60.4 ± 69.91
    -61.3 ± 49.71
    -73 ± 63.25
    -35.3 ± 88.65
    -39.9 ± 60.21
        Week 24 (16, 43, 52, 47, 50, 27, 54)
    -59.7 ± 68.03
    -71.5 ± 52.66
    -72.3 ± 71.22
    -67.1 ± 52.35
    -79.1 ± 74.01
    -72.4 ± 52.75
    -67.2 ± 71.91
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Chronic illness Therapy-Fatigue (FACIT-F) Scale Score at Week 12 and 24

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    End point title
    Change from Baseline in Functional Assessment of Chronic illness Therapy-Fatigue (FACIT-F) Scale Score at Week 12 and 24
    End point description
    The FACIT-F is a 13-item self-administered tool that measures an individual’s level of fatigue during usual daily activities over the past week. The level of fatigue is measured on a five-point Likert-type scale from 4 = not at all fatigued to 0 = very much fatigued; some questions are reverse-scored. The FACIT-Fatigue score is the sum of the individual item scores multiplied by 13 and divided by the number of items answered; the range is 0 to 52, with higher scores indicating better quality of life. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 19, 45)
    5.13 ± 10.603
    5.76 ± 10.845
    6.36 ± 7.998
    8.49 ± 10.299
    10.39 ± 10.994
    3.11 ± 8.333
    3.38 ± 8.778
        Week 24 (n= 17, 44, 53, 47, 50, 27, 55)
    9.24 ± 12.77
    8.45 ± 11.487
    6.83 ± 9.468
    12.23 ± 11.309
    12.69 ± 10.017
    7.3 ± 11.207
    6.04 ± 8.604
    No statistical analyses for this end point

    Secondary: Change from Baseline in Medical Outcomes Study-Sleep Module questionnaire (MOS-Sleep) Overall 9-Item Index Score at Week 12 amd 24

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    End point title
    Change from Baseline in Medical Outcomes Study-Sleep Module questionnaire (MOS-Sleep) Overall 9-Item Index Score at Week 12 amd 24
    End point description
    The MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Overall Sleep Problems Index is a 9-item sub-scale; norm based scores (NBS) range from 0 to 100, lower scores indicate fewer sleep problems. Full analysis set included all randomized subjects who received at least 1 dose of study drug
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 (39, 51, 57, 51, 55, 19, 45)
    5.541 ± 10.2069
    6.162 ± 8.1018
    6.107 ± 7.0598
    5.752 ± 8.5562
    7.834 ± 7.6625
    2.143 ± 8.44
    5.862 ± 7.4288
        Week 24 (17, 44, 50, 44, 49, 27, 55)
    9.906 ± 13.1697
    6.953 ± 8.6609
    7.102 ± 6.4437
    8.325 ± 9.4486
    7.303 ± 7.8772
    4.471 ± 7.3857
    5.281 ± 7.0525
    No statistical analyses for this end point

    Secondary: Change from Baseline in the EuroQol (EQ-5D) Total Score at Week 12 and 24

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    End point title
    Change from Baseline in the EuroQol (EQ-5D) Total Score at Week 12 and 24
    End point description
    The EQ-5D is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. Full analysis set included all randomized subjects who received at least 1 dose of study drug
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and 24
    End point values
    Placebo VX-509 100 mg qd VX- 509 150 mg qd VX-509 200 mg qd VX-509 100 mg bid VX-509 150 mg qd - Treatment Period, After Escape VX-509 200 mg qd - Treatment Period, After Escape
    Number of subjects analysed
    71
    71
    72
    72
    72
    29
    64
    Units: units on scale
    arithmetic mean (standard deviation)
        Week 12 (n= 39, 52, 59, 52, 58, 19, 45)
    0.1413 ± 0.2555
    0.1313 ± 0.19425
    0.1146 ± 0.16821
    0.1767 ± 0.19794
    0.1621 ± 0.18571
    0.0634 ± 0.15886
    0.0785 ± 0.17708
        Week 24 (n= 17, 44, 52, 47, 50, 27, 55)
    0.1875 ± 0.27244
    0.1797 ± 0.24581
    0.136 ± 0.18494
    0.2294 ± 0.20718
    0.1974 ± 0.20298
    0.1305 ± 0.19656
    0.1093 ± 0.17024
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    First dose of study drug up to 28 days after last dose of study drug
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Placebo - Before Escape
    Reporting group description
    VX-509-matched placebo qd up to 24 weeks.

    Reporting group title
    VX-509 100 mg qd - Before Escape
    Reporting group description
    VX-509 100 mg qd up to 24 weeks.

    Reporting group title
    VX- 509 150 mg qd - Before Escape
    Reporting group description
    VX-509 150 mg qd up to 24 weeks.

    Reporting group title
    VX-509 200 mg qd - Before Escape
    Reporting group description
    VX-509 200 mg qd up to 24 weeks.

    Reporting group title
    VX-509 100 mg bid - Before Escape
    Reporting group description
    VX-509 100 mg bid up to 24 weeks.

    Reporting group title
    VX-509 150 mg qd - After Escape
    Reporting group description
    VX-509 150 mg qd up to 24 weeks.

    Reporting group title
    VX-509 200 mg qd - After Escape
    Reporting group description
    VX-509 200 mg qd up to 24 weeks.

    Reporting group title
    VX-509 150 mg qd - OLE
    Reporting group description
    VX-509 150 mg qd up to 104 weeks.

    Reporting group title
    VX-509 200 mg qd - OLE
    Reporting group description
    VX-509 200 mg qd up to 104 weeks.

    Serious adverse events
    Placebo - Before Escape VX-509 100 mg qd - Before Escape VX- 509 150 mg qd - Before Escape VX-509 200 mg qd - Before Escape VX-509 100 mg bid - Before Escape VX-509 150 mg qd - After Escape VX-509 200 mg qd - After Escape VX-509 150 mg qd - OLE VX-509 200 mg qd - OLE
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 71 (5.63%)
    3 / 71 (4.23%)
    6 / 72 (8.33%)
    5 / 72 (6.94%)
    7 / 72 (9.72%)
    1 / 29 (3.45%)
    5 / 64 (7.81%)
    6 / 47 (12.77%)
    22 / 218 (10.09%)
         number of deaths (all causes)
    0
    0
    0
    1
    1
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Surgical and medical procedures
    Umbilical hernia repair
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    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
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Adenomyosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Injury, poisoning and procedural complications
    Spinal compression fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    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
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Orthostatic intolerance
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Chorioretinitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Skin and subcutaneous tissue disorders
    Panniculitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    3 / 218 (1.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    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
    Placebo - Before Escape VX-509 100 mg qd - Before Escape VX- 509 150 mg qd - Before Escape VX-509 200 mg qd - Before Escape VX-509 100 mg bid - Before Escape VX-509 150 mg qd - After Escape VX-509 200 mg qd - After Escape VX-509 150 mg qd - OLE VX-509 200 mg qd - OLE
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 71 (40.85%)
    36 / 71 (50.70%)
    43 / 72 (59.72%)
    47 / 72 (65.28%)
    41 / 72 (56.94%)
    11 / 29 (37.93%)
    36 / 64 (56.25%)
    28 / 47 (59.57%)
    118 / 218 (54.13%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    5 / 72 (6.94%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    2 / 47 (4.26%)
    8 / 218 (3.67%)
         occurrences all number
    0
    0
    2
    5
    1
    0
    0
    2
    9
    Hypotension
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Blood pressure fluctuation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Haemorrhagic vasculitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Thrombosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Flushing
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Phlebitis superficial
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign breast neoplasm
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Benign lymph node neoplasm
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Bowen's disease
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Lung neoplasm
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Thyroid neoplasm
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    3 / 72 (4.17%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    1
    0
    0
    4
    1
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    7
    2
    0
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    5 / 218 (2.29%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    1
    5
    Chest discomfort
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Hunger
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    Spinal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    2
    Early satiety
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Chest pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Inflammation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Oedema
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    0
    0
    2
    Anxiety
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Abnormal dreams
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Nervousness
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    Tension
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Initial insomnia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Major depression
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Menstruation irregular
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Prostatitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Vaginal prolapse
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Vulvovaginal burning sensation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Ovarian cyst
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Adenomyosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Amenorrhoea
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Menopausal symptoms
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vaginal inflammation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    4 / 218 (1.83%)
         occurrences all number
    1
    2
    4
    0
    0
    0
    0
    2
    4
    Contusion
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    2 / 218 (0.92%)
         occurrences all number
    0
    1
    3
    0
    1
    0
    1
    1
    3
    Ligament sprain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    2 / 47 (4.26%)
    2 / 218 (0.92%)
         occurrences all number
    1
    0
    0
    1
    2
    0
    0
    2
    2
    Animal bite
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    0
    Bone fissure
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Foot fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Laceration
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Skeletal injury
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    Pubis fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Humerus fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Rib fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Ankle fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Arthropod bite
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Meniscus lesion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Muscle strain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Road traffic accident
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Spinal compression fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Upper limb fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vaccination complication
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    5 / 72 (6.94%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    2
    0
    4
    9
    2
    0
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    5 / 72 (6.94%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    2 / 47 (4.26%)
    5 / 218 (2.29%)
         occurrences all number
    1
    0
    3
    5
    1
    0
    1
    2
    6
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    3 / 72 (4.17%)
    3 / 72 (4.17%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    3 / 218 (1.38%)
         occurrences all number
    0
    0
    2
    3
    3
    0
    0
    3
    3
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    4 / 72 (5.56%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    4 / 218 (1.83%)
         occurrences all number
    0
    0
    1
    2
    4
    0
    0
    1
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    4 / 72 (5.56%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    4 / 218 (1.83%)
         occurrences all number
    0
    0
    0
    4
    1
    0
    1
    1
    4
    Blood triglycerides increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    3 / 72 (4.17%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    3
    1
    0
    1
    1
    0
    1
    Transaminases increased
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    0
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    3 / 218 (1.38%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    1
    3
    Cardiac murmur
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Human chorionic gonadotropin increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Red blood cell sedimentation rate increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    2
    1
    Weight decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    2
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    3 / 218 (1.38%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    4
    Candida test positive
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood prolactin increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Body temperature increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Lipids increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    1
    0
    1
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    3 / 218 (1.38%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    4
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    1
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    5 / 218 (2.29%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    5
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Angina pectoris
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Bradycardia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Bundle branch block left
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Cardiac failure
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Conduction disorder
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Myocardial ischaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    2 / 47 (4.26%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    2
    2
    Hypochromic anaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Anaemia megaloblastic
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 71 (4.23%)
    0 / 71 (0.00%)
    5 / 72 (6.94%)
    4 / 72 (5.56%)
    3 / 72 (4.17%)
    0 / 29 (0.00%)
    2 / 64 (3.13%)
    0 / 47 (0.00%)
    9 / 218 (4.13%)
         occurrences all number
    3
    0
    5
    4
    3
    0
    2
    0
    10
    Oropharyngeal pain
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
    2 / 72 (2.78%)
    2 / 72 (2.78%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    1 / 47 (2.13%)
    2 / 218 (0.92%)
         occurrences all number
    1
    1
    2
    2
    2
    0
    1
    1
    2
    Epistaxis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    3 / 72 (4.17%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    1 / 218 (0.46%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    1
    1
    Nasal congestion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    2
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Sinus congestion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    2 / 218 (0.92%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Lung infiltration
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    1 / 47 (2.13%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 71 (1.41%)
    6 / 71 (8.45%)
    7 / 72 (9.72%)
    6 / 72 (8.33%)
    6 / 72 (8.33%)
    0 / 29 (0.00%)
    2 / 64 (3.13%)
    0 / 47 (0.00%)
    6 / 218 (2.75%)
         occurrences all number
    3
    7
    17
    21
    6
    0
    2
    0
    6
    Dizziness
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 72 (2.78%)
    2 / 72 (2.78%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    2
    2
    1
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    2 / 72 (2.78%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    3 / 218 (1.38%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    0
    4
    Somnolence
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    1
    Facial nerve disorder
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    1 / 64 (1.56%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    1
    Poor quality sleep
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Radicular pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Sleep paralysis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 29 (3.45%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    0 / 218 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cluster headache
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hypotonia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Mental impairment
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Syncope
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 29 (0.00%)
    0 / 64 (0.00%)
    0 / 47 (0.00%)
    1 / 218 (0.46%)
         occurrences all number