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    Clinical Trial Results:
    Open label extension study to evaluate the long-term safety and tolerability of dupilumab in patients with asthma who participated in a previous dupilumab asthma clinical study

    Summary
    EudraCT number
    		 2013-003856-19
    Trial protocol
    		 ES   IT   PL   DE   GB   NL   HU   BE   DK   SE   Outside EU/EEA  
    Global end of trial date
    11 Oct 2019

    Results information
    Results version number
    		 v1
    This version publication date
    25 Apr 2020
    First version publication date
    25 Apr 2020
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LTS12551
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02134028
    WHO universal trial number (UTN)
    		 U1111-1117-6745
    Other trial identifiers
    		 Study Name: Liberty Asthma Traverse
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 Avenue Pierre Brossolette, Chilly Mazarin, France, 91380
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001501-PIP02-13
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Nov 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long-term safety and tolerability of dupilumab in subjects with asthma who participated in a previous dupilumab asthma clinical study (DRI12544, PDY14192, EFC13579, or EFC13691).
    Protection of trial subjects
    The study was conducted by investigators experienced in the treatment of adults and paediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort. Adult subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    		 Subjects continued the background therapy dose regimen as maintained in the parent study or as modified based on Investigator's judgment throughout the study i.e. medium or high dose of inhaled corticosteroid (ICS) and a second controller medication (eg, long-acting beta-agonist [LABA], leukotriene receptor antagonist [LTRA]) was continued throughout the study. Third controller was allowed (including daily oral corticosteroids (OCS [(prednisone or prednisolone]) for subjects from study EFC13691). Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Aug 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Poland: 146
    Country: Number of subjects enrolled
    Romania: 11
    Country: Number of subjects enrolled
    Spain: 62
    Country: Number of subjects enrolled
    United Kingdom: 16
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    France: 47
    Country: Number of subjects enrolled
    Germany: 44
    Country: Number of subjects enrolled
    Hungary: 10
    Country: Number of subjects enrolled
    Italy: 36
    Country: Number of subjects enrolled
    Japan: 160
    Country: Number of subjects enrolled
    Turkey: 105
    Country: Number of subjects enrolled
    United States: 366
    Country: Number of subjects enrolled
    Mexico: 138
    Country: Number of subjects enrolled
    Argentina: 208
    Country: Number of subjects enrolled
    Australia: 36
    Country: Number of subjects enrolled
    South Africa: 50
    Country: Number of subjects enrolled
    Ukraine: 228
    Country: Number of subjects enrolled
    Korea, Republic of: 74
    Country: Number of subjects enrolled
    Chile: 213
    Country: Number of subjects enrolled
    Canada: 43
    Country: Number of subjects enrolled
    Russian Federation: 172
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Brazil: 73
    Country: Number of subjects enrolled
    Taiwan: 7
    Country: Number of subjects enrolled
    Colombia: 17
    Worldwide total number of subjects
    2282
    EEA total number of subjects
    383
    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)
    89
    Adults (18-64 years)
    1917
    From 65 to 84 years
    276
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was initiated at 365 sites in 27 countries. Subjects who successfully completed treatment in studies DRI12544 (NCT01854047), EFC13579 (NCT02414854), EFC13691 (NCT02528214) and PDY14192 (NCT02573233) were eligible to continue their treatment in this extension study LTS12551.

    Pre-assignment
    Screening details
    		 A total of 2282 subjects were enrolled and treated in this extension study.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Subjects from DRI12544: Placebo/Dupilumab
    Arm description
    		 Subjects who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 milligram (mg) on Day 1 followed by a subcutaneous (SC) dose of dupilumab 300 mg every 2 weeks (q2w) for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from DRI12544: Dupilumab/Dupilumab
    Arm description
    		 Subjects who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from EFC13579: Placebo/Dupilumab
    Arm description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from EFC13579: Dupilumab/Dupilumab
    Arm description
    		 Subjects who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from EFC13691: Placebo/Dupilumab
    Arm description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from EFC13691: Dupilumab/Dupilumab
    Arm description
    		 Subjects who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from PDY14192: Placebo/Dupilumab
    Arm description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Arm title
    		 Subjects from PDY14192: Dupilumab/Dupilumab
    Arm description
    		 Subjects who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dupilumab
    Investigational medicinal product code
    SAR231893
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dupilumab 300 mg, SC injection q2w in abdomen (avoiding navel and waist areas), the upper thighs, or upper arms (lateral side).

    Number of subjects in period 1
    		Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Started
    111
    421
    517
    1013
    97
    90
    19
    14
    Completed
    102
    379
    465
    908
    83
    76
    15
    11
    Not completed
    9
    42
    52
    105
    14
    14
    4
    3
         Adverse Event
    3
    19
    13
    32
    4
    5
    1
    2
         Poor compliance to protocol
    1
    1
    3
    7
    1
    1
    -
    -
         Unspecified
    4
    22
    33
    64
    8
    6
    2
    1
         Lack of efficacy
    1
    -
    3
    2
    1
    2
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Subjects from DRI12544: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 milligram (mg) on Day 1 followed by a subcutaneous (SC) dose of dupilumab 300 mg every 2 weeks (q2w) for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from DRI12544: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab Total
    Number of subjects
    		 111 421 517 1013 97 90 19 14 2282
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.1 ± 12.3 49.8 ± 12.5 48.2 ± 15.1 47.9 ± 15.2 51.3 ± 12.4 51.7 ± 12.9 41.8 ± 10.6 44.9 ± 10.8 -
    Gender categorical
    Units: Subjects
        Female
    		 69 259 335 618 57 53 7 10 1408
        Male
    		 42 162 182 395 40 37 12 4 874
    Race
    Units: Subjects
        Caucasian/White
    		 88 339 445 844 91 86 17 12 1922
        Black/of African descent
    		 1 8 17 43 1 2 2 1 75
        Asian/Oriental
    		 18 70 51 116 1 0 0 1 257
        American Indian or Alaska Native
    		 0 0 0 0 2 0 0 0 2
        Native Hawaiian or Other Pacific Islander
    		 0 1 0 1 0 1 0 0 3
        Other
    		 4 3 4 9 2 1 0 0 23

    End points

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    End points reporting groups
    Reporting group title
    Subjects from DRI12544: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 milligram (mg) on Day 1 followed by a subcutaneous (SC) dose of dupilumab 300 mg every 2 weeks (q2w) for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from DRI12544: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Primary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) [1]
    End point description
    An Adverse Event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have causal relationship with treatment. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment emergent AE period (time from first dose of investigational medicinal product [IMP] in LTS12551 up to the last dose of dupilumab plus 12 weeks). A Serious AE (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Analysis was performed on exposed population which included subjects who actually received at least 1 dose or part of a dose of the IMP.
    End point type
    Primary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 12 weeks (up to 108 weeks)
    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: As the endpoint was descriptive in nature, hence no statistical analysis was provided.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: subjects
    number (not applicable)
        Any TEAE
    88
    369
    414
    789
    74
    70
    18
    13
        Any treatment emergent SAE
    14
    42
    48
    106
    12
    10
    0
    4
        Any TEAE leading to death
    0
    3
    0
    1
    0
    0
    0
    0
        AnyTEAE led to permanent treatment discontinuation
    3
    19
    12
    31
    4
    5
    1
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities During the TEAE Period

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    End point title
    		 Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities During the TEAE Period
    End point description
    Criteria for potentially clinically significant vital sign abnormalities: •Systolic blood pressure (SBP): Less than or equal to (≤) 95 millimetres of mercury (mmHg) and decrease from baseline (DFB) greater than or equal to (≥) 20 mmHg; ≥ 160 mmHg and increase from baseline (IFB) ≥ 20 mmHg •Diastolic blood pressure (DBP): ≤ 45 mmHg and DFB ≥ 10 mmHg; ≥ 110 mmHg and IFB ≥ 10 mmHg •Heart rate (HR): ≤ 50 beats per minute (bpm) and DFB ≥20 bpm; ≥120 bpm and IFB ≥20 bpm •Respiratory rate (RR): less than (<) 12 breaths/min(b/m); greater than (>) 20 b/m •Weight (Wt.) (kg): ≥5 percent (%) DFB; ≥ 5% IFB •Temperature (T): ≥ 38.0 degree Celsius (°C) rectal/ear/temporal; ≥37.5°C oral; ≥ 37.2°C axillary. Analysis was performed on exposed population. Here, ‘n’=subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 12 weeks (up to 108 weeks)
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: subjects
    number (not applicable)
        SBP:≤95&DFB≥20mmHg(n=111,421,516,1013,97,90,19,14)
    4
    12
    19
    40
    0
    1
    2
    0
        SBP≥160&IFB≥20mmHg(n=111,421,516,1013,97,90,19,14)
    2
    17
    21
    45
    6
    1
    1
    3
        DBP:≤45&DFB≥10mmHg(n=111,421,516,1013,97,90,19,14)
    1
    1
    11
    15
    0
    0
    0
    0
        DBP≥110&IFB≥10mmHg(n=111,421,516,1013,97,90,19,14)
    0
    4
    15
    20
    2
    0
    0
    0
        HR:≤50&DFB ≥20bpm(n=111,421,516,1013,97,90,19,14)
    0
    3
    2
    12
    0
    0
    0
    0
        HR:≥120&IFB ≥20bpm(n=111,421,516,1013,97,90,19,14)
    0
    0
    2
    5
    1
    0
    0
    0
        RR:<12 b/m(n=111,421,516,1013,97,90,19,14)
    5
    17
    18
    24
    4
    0
    2
    3
        RR:>20 b/m(n=111,421,516,1013,97,90,19,14)
    23
    104
    88
    195
    18
    12
    4
    0
        Wt.:≥5% DFB (n=111,421,516,1013,97,90,19,14)
    32
    106
    146
    261
    22
    29
    3
    3
        Wt.≥5% IFB(n=111,421,485,958;96,89,19,14)
    45
    181
    189
    378
    29
    37
    8
    5
        T:≥38.0°C(n=111,421,516,1013,97,90,19,14)
    0
    0
    1
    1
    0
    0
    0
    0
        T:≥37.5°C(n=111,421,516,1013,97,90,19,14)
    1
    0
    9
    6
    0
    0
    0
    0
        T:≥37.2°C(n=111,421,516,1013,97,90,19,14)
    3
    21
    4
    16
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Haematological Parameters (Red blood cells [RBCs], Platelets and Coagulation) During the TEAE Period

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    End point title
    		 Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Haematological Parameters (Red blood cells [RBCs], Platelets and Coagulation) During the TEAE Period
    End point description
    Criteria for potentially clinically significant abnormalities: •Haemoglobin (Hb): ≤ 115 grams per litre (g/L)(Male [M]), 95 g/L (Female[ F]); ≥ 185 g/L, 165 g/L (Female); DFB ≥ 20 g/L •Haematocrit (Hc): ≤ 0.37 volume/volume (v/v) (M); ≤ 0.32 v/v (F); ≥ 0.55 v/v (M); 0.5 v/v (F) •RBCs: ≥ 6 Tera/L •Platelets: < 100 Giga(G)/L; ≥ 700 G/L Analysis was performed on exposed population. Here, ‘n’=subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 12 weeks (up to 108 weeks)
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: subjects
    number (not applicable)
        Hb:≤115g/L,≤95g/L(n=111,421,514,1009,97,90,19,14)
    2
    7
    12
    29
    0
    3
    0
    0
        Hb:≥185g/L,≥165g/L(n=111,421,514,1009,97,90,19,14)
    1
    3
    8
    4
    2
    1
    0
    0
        Hb: DFB ≥20 g/L(n=111,421,513,1008,97,90,19,14)
    13
    41
    40
    118
    11
    7
    0
    0
        Hc:≤0.37;≤0.32v/v(n=111,421,514,1007,97,90,19,14)
    6
    19
    23
    47
    3
    5
    0
    0
        Hc:≥0.55;≥0.5v/v(n=111,421,514,1007, 97,90,19,14)
    3
    6
    26
    36
    3
    3
    0
    1
        RBCs: ≥6 Tera/L(n=111,421,514,1009, 97,90,19,14)
    1
    5
    28
    15
    0
    2
    0
    1
        Platelets:<100G/L(n=111,421,514,1007,97,90,19,14)
    0
    2
    2
    1
    1
    0
    0
    1
        Platelets:≥700G/L(n=111,421,514,1007, 97,90,19,14)
    0
    1
    1
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Severe Exacerbation Events During the Treatment Period

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    End point title
    		 Number of Severe Exacerbation Events During the Treatment Period
    End point description
    Severe asthma exacerbation events were defined as a deterioration of asthma which required: use of systemic corticosteroids for ≥ 3 days, (subjects from study EFC13691, and who were taking systemic corticosteroids: the use of systemic corticosteroids at least double the current dose and for ≥3 days.) or, hospitalisation or emergency room visit because of asthma, required systemic corticosteroids. Analysis was performed on exposed population.
    End point type
    Secondary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: number of events
        number (not applicable)
    62
    242
    234
    437
    35
    41
    3
    1
    No statistical analyses for this end point

    Secondary: Annualised Event Rate Per Subject-Years for Severe Exacerbation During The Treatment Period

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    End point title
    		 Annualised Event Rate Per Subject-Years for Severe Exacerbation During The Treatment Period
    End point description
    The annualised event rate per subject-years was defined as the total number of events that occurred during the treatment period divided by the total number of subject-years during the treatment period. Analysis was performed on exposed population.
    End point type
    Secondary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: exacerbation events per subject-years
        number (not applicable)
    0.314
    0.330
    0.351
    0.331
    0.302
    0.391
    0.149
    0.077
    No statistical analyses for this end point

    Secondary: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 48 and 96

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    End point title
    		 Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 48 and 96
    End point description
    FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as parent study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: litres
    arithmetic mean (standard deviation)
        Week 48 (n=105,396,486, 951,88,82,16,11)
    0.24 ± 0.42
    0.28 ± 0.45
    0.34 ± 0.44
    0.36 ± 0.53
    0.31 ± 0.50
    0.33 ± 0.53
    0.23 ± 0.40
    0.01 ± 0.21
        Week 96 (n=102,380,219,447,32,28,5,2)
    0.22 ± 0.44
    0.27 ± 0.46
    0.33 ± 0.44
    0.31 ± 0.47
    0.36 ± 0.66
    0.25 ± 0.46
    0.14 ± 0.41
    0.01 ± 0.12
    No statistical analyses for this end point

    Secondary: Change From Baseline in Percent Predicted FEV1 at Weeks 48 and 96

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    End point title
    		 Change From Baseline in Percent Predicted FEV1 at Weeks 48 and 96
    End point description
    FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For this analysis, baseline was defined as parent study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: percent predicted FEV1
    arithmetic mean (standard deviation)
        Week 48 (n=105,396,486, 951,88,82,16,11)
    9.21 ± 13.61
    10.42 ± 14.61
    11.74 ± 14.27
    12.16 ± 16.58
    10.45 ± 15.03
    12.41 ± 18.27
    5.88 ± 10.06
    1.36 ± 8.35
        Week 96 (n=102,380,219,447,32,28,5,2)
    8.86 ± 14.47
    10.68 ± 15.10
    12.53 ± 14.50
    11.25 ± 14.55
    13.06 ± 19.57
    10.00 ± 15.79
    4.20 ± 9.60
    2.00 ± 2.83
    No statistical analyses for this end point

    Secondary: Change From Baseline in Forced Vital Capacity (FVC) at Weeks 48 and 96

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    End point title
    		 Change From Baseline in Forced Vital Capacity (FVC) at Weeks 48 and 96
    End point description
    FVC was a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as parent study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48, and Week 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: litres
    arithmetic mean (standard deviation)
        Week 48 (n=105,396,486, 951,88,82,16,11)
    0.22 ± 0.45
    0.25 ± 0.50
    0.30 ± 0.48
    0.35 ± 0.60
    0.29 ± 0.56
    0.38 ± 0.56
    0.21 ± 0.42
    0.05 ± 0.30
        Week 96 (n=102,380,219,447,32,28,5,2)
    0.16 ± 0.47
    0.22 ± 0.52
    0.27 ± 0.48
    0.25 ± 0.50
    0.38 ± 0.82
    0.22 ± 0.42
    0.08 ± 0.29
    0.05 ± 0.40
    No statistical analyses for this end point

    Secondary: Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 48 and 96

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    End point title
    		 Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 48 and 96
    End point description
    FEF was the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. For this analysis, baseline was defined as parent study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48, and Week 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: litres/second
    arithmetic mean (standard deviation)
        Week 48 (n=105,396,486, 951,88,82,16,11)
    0.27 ± 0.55
    0.31 ± 0.55
    0.39 ± 0.57
    0.39 ± 0.66
    0.34 ± 0.56
    0.29 ± 0.66
    0.23 ± 0.44
    0.04 ± 0.26
        Week 96 (n=102,380,219,447,32,28,5,2)
    0.28 ± 0.57
    0.32 ± 0.55
    0.38 ± 0.53
    0.36 ± 0.61
    0.42 ± 0.64
    0.27 ± 0.53
    0.19 ± 0.41
    0.04 ± 0.14
    No statistical analyses for this end point

    Secondary: Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Mean Scores at Weeks 24 and 48

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    End point title
    		 Change From Baseline in Asthma Control Questionnaire 5-Question Version (ACQ-5) Mean Scores at Weeks 24 and 48
    End point description
    The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Subjects were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total mean score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. For this analysis, baseline was defined as the parent study baseline. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Weeks 24, and 48 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 24 (n=110, 421, 513, 1005, 96, 87, 19, 13)
    -1.37 ± 0.91
    -1.48 ± 1.10
    1.61 ± 1.08
    -1.68 ± 1.05
    -1.09 ± 1.10
    -1.15 ± 1.17
    -0.96 ± 1.03
    -0.80 ± 0.46
        Week 48 (n= 105, 400, 488, 957, 90, 78, 15, 11)
    -1.33 ± 1.07
    -1.57 ± 1.11
    -1.64 ± 1.08
    -1.69 ± 1.08
    -1.21 ± 1.00
    -1.06 ± 1.25
    -0.89 ± 1.02
    -0.87 ± 0.58
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving ACQ-5 Score Response (ACQ-5 Responders) at Weeks 24 and 48

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    End point title
    		 Percentage of Subjects Achieving ACQ-5 Score Response (ACQ-5 Responders) at Weeks 24 and 48
    End point description
    ACQ-5 response was defined as change from baseline in ACQ-5 scores ≥ 0.5. The ACQ-5 has 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Subjects were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 mean total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    At Weeks 24, and 48 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: percentage of subjects
    number (not applicable)
        Week 24 (n=110, 421,513, 1005,96, 87,19, 13)
    82.7
    80.8
    84.0
    86.5
    67.7
    70.1
    57.9
    69.2
        Week 48 (n=105,400,488, 957, 90, 78,15, 11)
    79.0
    82.3
    85.7
    86.7
    75.6
    70.5
    60.0
    72.7
    No statistical analyses for this end point

    Secondary: Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Scores at Weeks 24 and 48

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    End point title
    		 Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Scores at Weeks 24 and 48 [2]
    End point description
    The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), and environmental stimuli (4 items). Each item was scored on a 7-point likert scale ranged from 1=severely impaired to 7=not impaired. The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired); higher scores indicated better quality of life. For this analysis, baseline was defined as the parent study baseline. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Weeks 24, and 48 of this extension study
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed for the subjects from Studies DRI12544, EFC13579, and EFC13691 only.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 24 (n= 108,413,495, 948, 95, 98)
    1.07 ± 0.99
    1.28 ± 1.24
    1.38 ± 1.15
    1.38 ± 1.16
    0.99 ± 1.10
    0.97 ± 1.26
        Week 48 (n= 103, 397, 473, 908, 90, 79)
    1.07 ± 1.13
    1.40 ± 1.19
    1.39 ± 1.17
    1.40 ± 1.18
    1.06 ± 0.98
    1.00 ± 1.23
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving AQLQ Global Score Response (AQLQ Responders) at Weeks 24 and 48

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    End point title
    		 Percentage of Subjects Achieving AQLQ Global Score Response (AQLQ Responders) at Weeks 24 and 48 [3]
    End point description
    AQLQ global response was defined as subjects with change from baseline in AQLQ global score ≥ 0.5. The AQLQ was designed to measure the functional impairments that are most troublesome to adults as a result of their asthma. The AQLQ comprises of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item is scored on a 7-point likert scale (1=severely impaired, 7=not impaired). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired). Higher scores indicated better quality of life. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    At Weeks 24, and 48 of this extension study
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed for the subjects from Studies DRI12544, EFC13579, and EFC13691 only.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    Units: percentage of subjects
    number (not applicable)
        Week 24 (n=108,413,495,948,95,88)
    67.6
    73.6
    77.6
    77.2
    64.2
    61.4
        Week 48 (n=103,397,473,908,90,79)
    65.0
    76.3
    77.4
    78.4
    73.3
    68.4
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Dupilumab Over Time Till Week 96

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    End point title
    		 Serum Concentrations of Dupilumab Over Time Till Week 96
    End point description
    For this analysis, baseline was defined as the parent study baseline. Analysis was performed on Pharmacokinetics (PK) population which consisted of all the subjects who had actually received at least one dose or part of a dose of dupilumab in the LTS12551 study, with at least one non-missing and evaluable pre-dose serum concentration value after the first dose of dupilumab in the LTS12551 study. Here, ‘n’=subjects with available data for each specified category and '99999' represented that data was not calculated for specified category due to none of the evaluable subjects.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Weeks 0, 4, 12, 24, 48, 72, and 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1008
    96
    90
    19
    14
    Units: nanogram per millilitre
    geometric mean (geometric coefficient of variation)
        Baseline (n=110,413,0,993,0,88,0,14)
    0.00 ± 0.000
    0.00 ± 1990.640
    99999 ± 99999
    0.00 ± 2286.888
    99999 ± 99999
    0.00 ± 0.000
    99999 ± 99999
    0.00 ± 0.000
        Week 0 (n=110,417,0,968,0,88,0,14)
    0.00 ± 0.000
    0.00 ± 0.000
    37230.97 ± 73.261
    37230.97 ± 73.261
    99999 ± 99999
    40754.49 ± 54.858
    99999 ± 99999
    52545.41 ± 44.678
        Week 4 (n=109,414,500,971,93,88,18,13)
    46848.70 ± 43.149
    40704.77 ± 47.293
    25847.86 ± 49.371
    50566.66 ± 55.104
    25868.25 ± 53.450
    48295.93 ± 52.655
    23336.89 ± 50.542
    56486.58 ± 45.755
        Week 12 (n=111,417,501,973,94,87, 16,12)
    54467.13 ± 50.267
    48155.26 ± 52.353
    45406.55 ± 51.399
    55140.49 ± 53.114
    44064.95 ± 57.100
    50904.34 ± 51.233
    49026.51 ± 41.619
    55365.35 ± 53.317
        Week 24 (n=108,405,500,973,90,83,16,11)
    47023.84 ± 51.645
    49730.56 ± 53.625
    50984.57 ± 53.744
    54897.58 ± 54.044
    57363.72 ± 57.889
    44219.42 ± 55.383
    63080.82 ± 51.224
    60643.16 ± 41.617
        Week 48 (n=106,397,484,951, 89,82,16,11)
    46355.26 ± 52.612
    45919.75 ± 55.932
    41867.50 ± 60.345
    41849.96 ± 62.049
    36219.47 ± 67.530
    36564.41 ± 60.959
    24864.79 ± 58.016
    53320.11 ± 46.714
        Week 72 (n=105,385,227,453,35,29,5,2)
    44771.52 ± 56.256
    46842.64 ± 53.335
    45628.10 ± 56.232
    46372.55 ± 57.719
    60117.76 ± 62.390
    32029.19 ± 66.785
    40362.88 ± 55.567
    26383.90 ± 120.013
        Week 96 (n=101,381,222,446,33,29,5,2)
    42431.08 ± 59.222
    42661.18 ± 59.658
    38908.58 ± 64.633
    39088.60 ± 62.897
    49810.65 ± 65.546
    19030.70 ± 67.237
    42360.37 ± 49.409
    56378.01 ± 7.140
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Antidrug Antibodies (ADA) Response

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    End point title
    		 Percentage of Subjects With Antidrug Antibodies (ADA) Response
    End point description
    ADA response were categorised as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as an ADA positive response in the assay post first dose, when baseline results were negative or missing. 2) Treatment boosted was defined as: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. The criteria for positive was defined as "30 to > 10,000”, where low titer (< 1,000); moderate (1,000 ≤ titer ≤ 10,000) and high titer (> 10,000). Analysis was performed on ADA population which consisted of all subjects who had actually received at least one dose or part of a dose of dupilumab in the LTS12551 study, with at least one pre-dose sample that was assayed successfully using the ADA assay after the first dose of dupilumab in the LTS12551 study.
    End point type
    Secondary
    End point timeframe
    From the first IMP injection in LTS12551 to the last IMP injection plus 2 weeks (up to 96 weeks)
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    515
    1008
    95
    90
    19
    14
    Units: percentage of subjects
    number (not applicable)
        Treatment-emergent ADA
    10.8
    12.1
    9.5
    4.5
    7.4
    8.9
    0
    7.1
        Treatment-boosted ADA
    0
    0
    0
    0
    1.1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Blood Eosinophils Cells Count at Weeks 48 and 96

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    End point title
    		 Change From Baseline in Blood Eosinophils Cells Count at Weeks 48 and 96
    End point description
    For this analysis, baseline was defined as parent study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    517
    1013
    97
    90
    19
    14
    Units: giga per litre
    arithmetic mean (standard deviation)
        Week 48 (n=103,386,474, 935,87,82,14,10)
    0.007 ± 0.475
    -0.041 ± 0.588
    -0.096 ± 0.428
    -0.099 ± 0.360
    0.098 ± 0.450
    0.016 ± 0.382
    -0.066 ± 0.181
    -0.026 ± 0.187
        Week 96 (n=102,381,218,435,30,29,4,2)
    -0.074 ± 0.251
    -0.081 ± 0.562
    -0.161 ± 0.391
    -0.114 ± 0.354
    -0.051 ± 0.399
    0.083 ± 0.642
    -0.103 ± 0.039
    0.025 ± 0.134
    No statistical analyses for this end point

    Secondary: Change From Baseline in Morning Peak Expiratory Flow (PEF) at Weeks 48 and 96- Subject From Study DRI12544

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    End point title
    		 Change From Baseline in Morning Peak Expiratory Flow (PEF) at Weeks 48 and 96- Subject From Study DRI12544 [4]
    End point description
    The PEF was a subject's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Morning PEF was performed within 15 minutes after arising (between 5:30 AM and 10 AM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent study DRI12544 baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: litres per minute
    arithmetic mean (standard deviation)
        Week 48 (n=110,407)
    13.26 ± 76.71
    22.95 ± 70.06
        Week 96 (n=92,340)
    13.63 ± 83.88
    21.69 ± 77.70
    No statistical analyses for this end point

    Secondary: Change From Baseline in Evening Peak Expiratory Flow (PEF) at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in Evening Peak Expiratory Flow (PEF) at Weeks 48 and 96- Subjects From Study DRI12544 [5]
    End point description
    The PEF was a subject's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at morning and evening. Evening PEF was performed in the evening (between 5:30 PM and 10 PM) prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-point.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: litres per minute
    arithmetic mean (standard deviation)
        Week 48 (n=109,406)
    4.65 ± 75.00
    11.97 ± 72.19
        Week 96 (n=89,327)
    1.16 ± 79.47
    10.05 ± 79.47
    No statistical analyses for this end point

    Secondary: Change From Baseline in Morning Asthma Symptom Scores at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in Morning Asthma Symptom Scores at Weeks 48 and 96- Subjects From Study DRI12544 [6]
    End point description
    Morning asthma symptom score was determined using AM (ante meridiem) symptom scoring system which evaluated subject's overall asthma symptoms experienced during the night. It ranges from 0 to 4 as: 0=no asthma symptoms, slept through the night, 1=slept well, but some complaints in the morning. No nighttime awakenings, 2=woke up once because of asthma (including early awakening), 3=woke up several times because of asthma (including early awakening), 4=bad night, awake most of the night because of asthma; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 48 (n=110,410)
    -0.49 ± 0.78
    -0.68 ± 0.79
        Week 96 (n=92,324)
    -0.52 ± 0.90
    -0.76 ± 0.81
    No statistical analyses for this end point

    Secondary: Change From Baseline in Evening Asthma Symptom Scores at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in Evening Asthma Symptom Scores at Weeks 48 and 96- Subjects From Study DRI12544 [7]
    End point description
    Evening asthma symptom score was determined using PM (post meridiem) symptom scoring system which evaluated subject's overall asthma symptoms experienced during the day. It ranged from 0 to 4 as: 0=very well, no asthma symptoms, 1=one episode of wheezing, cough, or breathlessness, 2=more than one episode of wheezing, cough, or breathlessness without interference of normal activities, 3=wheezing, cough, or breathlessness most of the day, which interfered to some extent with normal activities, 4=asthma very bad, unable to carry out daily activities as usual; higher scores indicated more severe symptoms. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48, and Week 96 of this extension study
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 48 (n=109,407)
    -0.47 ± 0.81
    -0.72 ± 0.85
        Week 96 (n=88,330)
    -0.49 ± 0.94
    -0.79 ± 0.88
    No statistical analyses for this end point

    Secondary: Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol for Symptom Relief at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol for Symptom Relief at Weeks 48 and 96- Subjects From Study DRI12544 [8]
    End point description
    The number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations was recorded daily by the subjects in an electronic diary/PEF meter. Mean number of inhalations in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48, and Week 96 of this extension study
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: number of inhalations per day
    arithmetic mean (standard deviation)
        Week 48 (n=108,406)
    -0.00 ± 3.65
    -0.68 ± 4.80
        Week 96 (n=88,325)
    -0.14 ± 4.17
    -0.82 ± 5.18
    No statistical analyses for this end point

    Secondary: Change From Baseline in Number of Nocturnal Awakenings at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in Number of Nocturnal Awakenings at Weeks 48 and 96- Subjects From Study DRI12544 [9]
    End point description
    The number of nocturnal awakening because of asthma symptoms were recorded every morning by the subjects in an electronic diary. Mean number of awakenings in last 7 days prior to each visit was calculated and was used in computation of data reported. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, 'n'=subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: nocturnal awakenings
    arithmetic mean (standard deviation)
        Week 48 (n=110,410)
    -0.27 ± 0.54
    -0.43 ± 0.89
        Week 96 (n=92,344)
    -0.29 ± 0.58
    -0.49 ± 0.96
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline in Oral Corticosteroid (OCS) Dose at Weeks 48, and 96- Subjects From Study EFC13691

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    End point title
    		 Percent Change from Baseline in Oral Corticosteroid (OCS) Dose at Weeks 48, and 96- Subjects From Study EFC13691 [10]
    End point description
    OCS was allowed as background controller medication for the subjects from study EFC13691 only. For this analysis, baseline was defined as parent study EFC13691 baseline. Analysis was performed on exposed population. Here, ‘n’ = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Weeks 48 and 96 of this extension study
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study EFC13691 and not for the subjects from other studies.
    End point values
    		 Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab
    Number of subjects analysed
    97
    90
    Units: percent change
    arithmetic mean (standard deviation)
        Week 48 (n=77,57)
    55.32 ± 42.98
    80.23 ± 30.44
        Week 96 (n=28,19)
    71.37 ± 29.37
    88.16 ± 26.83
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving a Reduction of 50% or Greater (≥ 50% ) in OCS Dose Over Time at Weeks 48 and 96- Subjects From Study EFC13691

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    End point title
    		 Percentage of Subjects Achieving a Reduction of 50% or Greater (≥ 50% ) in OCS Dose Over Time at Weeks 48 and 96- Subjects From Study EFC13691 [11]
    End point description
    OCS was allowed as background controller medication for the subjects from study EFC13691 only. Percentage of subjects who achieved a reduction of ≥ 50% in OCS dose were reported. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Weeks 48 and 96 of this extension study
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study EFC13691 and not for the subjects from other studies.
    End point values
    		 Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab
    Number of subjects analysed
    97
    90
    Units: percentage of subjects
    number (not applicable)
        Week 48 (n=77,57)
    64.9
    86.0
        Week 96 (n=28,19)
    82.1
    94.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Background OCS Completely Tapered off Over Time at Weeks 48 and 96-Subjects From Study EFC13691

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    End point title
    		 Percentage of Subjects With Background OCS Completely Tapered off Over Time at Weeks 48 and 96-Subjects From Study EFC13691 [12]
    End point description
    OCS was allowed as background controller medication for the subjects from study EFC13691 only. Number of subjects who gradually discontinued or reduced therapeutic dose were reported in this end-point. Analysis was performed on exposed population. Here, ‘n’=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Weeks 48, and 96 of this extension study
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study EFC13691 and not for the subjects from other studies.
    End point values
    		 Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab
    Number of subjects analysed
    97
    90
    Units: percentage of subjects
    number (not applicable)
        Week 48 (n=77,57)
    31.2
    59.6
        Week 96 (n=28,19)
    42.9
    78.9
    No statistical analyses for this end point

    Secondary: Change From Baseline in European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Scores at Weeks 48 and 96- Subject From Study DRI12544

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    End point title
    		 Change From Baseline in European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Scores at Weeks 48 and 96- Subject From Study DRI12544 [13]
    End point description
    EQ-5D-3L: validated and reliable self-report health status questionnaire consisted of EQ-5D descriptive system and visual analogue scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: no problem, some problems, and severe problems. The 5 dimensional 3-level systems was converted into single index utility score, and the score was 0 – 100, where 100=best health state; and 0=worst health state; where higher scores indicated better outcome. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis performed on exposed population. Here, ‘n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 48 (n=100,370)
    0.13 ± 0.20
    0.14 ± 0.21
        Week 96 (n=69,294)
    0.12 ± 0.18
    0.13 ± 0.21
    No statistical analyses for this end point

    Secondary: Change From Baseline in EQ-5D-3L VAS Scores at Weeks 48 and 96- Subjects From Study DRI12544

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    End point title
    		 Change From Baseline in EQ-5D-3L VAS Scores at Weeks 48 and 96- Subjects From Study DRI12544 [14]
    End point description
    EQ-5D VAS was used to record a subject's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0=worst imaginable health state and 100=best imaginable health state, where higher states indicated better outcomes. For this analysis, baseline was defined as parent DRI12544 study baseline. Analysis was performed on exposed population. Here, ‘n'=subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline of parent study, Week 48 and Week 96 of this extension study
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be collected and analysed only for the subjects from Study DRI12544 and not for the subjects from other studies.
    End point values
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab
    Number of subjects analysed
    111
    421
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 48 (n=100,370)
    10.10 ± 15.40
    12.88 ± 18.76
        Week 96 (n=69,294)
    9.90 ± 18.92
    13.95 ± 18.81
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All AEs were collected from first dose of IMP up to 12 weeks after last dose of IMP (i.e. from Baseline up to Week 108)
    Adverse event reporting additional description
    Reported AE and deaths were TEAEs that developed, worsened, or became serious during the TEAE period (time from the first dose of dupilumab in LTS12551 up to the last dose of dupilumab plus 12 weeks) (i.e. up to 108 weeks). Analysis was performed on safety population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Subjects from DRI12544: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed treatment of placebo (for dupilumab) and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from DRI12544: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab and post-treatment period in study DRI12544, received a loading dose of dupilumab 600 mg on Day 1 followed by a SC dose of dupilumab 300 mg q2w for 96 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13579: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment for dupilumab in study EFC13579 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with ICS therapy/LABA therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from EFC13691: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study EFC13691 and, who were enrolled before amendment 4 received a SC dose of dupilumab 300 mg q2w for 96 weeks and those who were enrolled after amendment 4 received a SC dose of dupilumab 300 mg q2w for 48 weeks in combination with OCS and ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Placebo/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of placebo (for dupilumab) in study PDY14192 received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with CS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Reporting group title
    Subjects from PDY14192: Dupilumab/Dupilumab
    Reporting group description
    		 Subjects who completed the treatment of dupilumab in study PDY14192, received a SC dose of dupilumab 300 mg q2w for up to 96 weeks in combination with ICS therapy in this extension study. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.

    Serious adverse events
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 111 (12.61%)
    42 / 421 (9.98%)
    48 / 517 (9.28%)
    106 / 1013 (10.46%)
    12 / 97 (12.37%)
    10 / 90 (11.11%)
    0 / 19 (0.00%)
    4 / 14 (28.57%)
         number of deaths (all causes)
    0
    1
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma Gastric
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma Of Colon
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal Cell Carcinoma
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    3 / 1013 (0.30%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    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
    Benign Ovarian Tumour
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Bowen's Disease
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    2 / 517 (0.39%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon Adenoma
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Endometrial Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma Of Breast
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Follicular Thyroid Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric Adenoma
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hodgkin's Disease
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal Proliferative Breast Lesion
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Juvenile Melanoma Benign
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Large Intestine Benign Neoplasm
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung Cancer Metastatic
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases To Central Nervous System
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Small Cell Lung Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Osteochondroma
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary Thyroid Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    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
    Prostate Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Prostate Cancer Stage I
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Rectal Cancer
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Squamous Cell Carcinoma Of Skin
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    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
    Uterine Leiomyoma
         subjects affected / exposed
    0 / 111 (0.00%)
    3 / 421 (0.71%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    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
    Vascular disorders
    Aortic Dilatation
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    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
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypertensive Crisis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Spontaneous
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    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
    Pregnancy
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    General disorders and administration site conditions
    Adverse Drug Reaction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Injection Site Erythema
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    Anaphylactic Reaction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Eosinophilic Granulomatosis With Polyangiitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    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
    Hypersensitivity
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    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
    Social circumstances
    Miscarriage Of Partner
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Reproductive system and breast disorders
    Adenomyosis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign Prostatic Hyperplasia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Endometrial Hyperplasia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Haemorrhagic Ovarian Cyst
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Ovarian Cyst
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Vaginal Prolapse
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    4 / 111 (3.60%)
    2 / 421 (0.48%)
    13 / 517 (2.51%)
    18 / 1013 (1.78%)
    0 / 97 (0.00%)
    5 / 90 (5.56%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 13
    0 / 19
    0 / 0
    0 / 5
    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
    Atelectasis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal Septum Deviation
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal Septum Perforation
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Pleural Effusion
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    Pneumothorax
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    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
    Pulmonary Oedema
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis Noninfective
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status Asthmaticus
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Vocal Cord Polyp
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed Mood
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Depression
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Suicide Attempt
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Injury, poisoning and procedural complications
    Ankle Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Chemical Peritonitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Craniocerebral Injury
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial Bones Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Forearm Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Hand Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Head Injury
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision Site Pain
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Lower Limb Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Lumbar Vertebral Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Meniscus Injury
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Post Procedural Complication
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Post Procedural Constipation
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Pulmonary Contusion
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin Laceration
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper Limb Fracture
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Congenital, familial and genetic disorders
    Odontogenic Cyst
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Coronary Syndrome
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute Left Ventricular Failure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina Unstable
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic Valve Incompetence
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Atrial Fibrillation
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    2 / 517 (0.39%)
    5 / 1013 (0.49%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 2
    0 / 10
    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
    Atrioventricular Block Complete
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac Failure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    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
    Myocarditis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Carotid Artery Disease
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Cerebral Infarction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Dizziness
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Headache
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive Cerebrovascular Disease
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Idiopathic Intracranial Hypertension
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuritis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic Neuritis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Paraesthesia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Parkinson's Disease
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Seizure
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Syncope
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thalamic Infarction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Angle Closure Glaucoma
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Serous Retinal Detachment
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal Incarcerated Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Abdominal Pain
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diaphragmatic Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    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
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis Erosive
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Eosinophilic
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Inguinal Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Intestinal Obstruction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intra-Abdominal Haemorrhage
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large Intestine Polyp
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    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
    Oesophageal Food Impaction
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Retroperitoneum Cyst
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Tooth Impacted
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Umbilical Hernia
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Vomiting
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis Acute
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    4 / 1013 (0.39%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 4
    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
    Hepatomegaly
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Skin and subcutaneous tissue disorders
    Erythema Nodosum
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash Erythematous
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Rash Vesicular
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Iga Nephropathy
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Urinary Incontinence
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    Osteoarthritis
         subjects affected / exposed
    0 / 111 (0.00%)
    3 / 421 (0.71%)
    1 / 517 (0.19%)
    4 / 1013 (0.39%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 4
    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
    Osteonecrosis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Pain In Extremity
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Rotator Cuff Syndrome
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Abscess Limb
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    Bronchopulmonary Aspergillosis Allergic
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    Cellulitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Cervicitis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic Sinusitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Diverticulitis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes Simplex Encephalitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Influenza
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Large Intestine Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection Bacterial
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Mycobacterium Avium Complex Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    Pneumonia
         subjects affected / exposed
    3 / 111 (2.70%)
    4 / 421 (0.95%)
    4 / 517 (0.77%)
    7 / 1013 (0.69%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 4
    1 / 7
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Pyelonephritis Acute
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Salmonellosis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Sialoadenitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Sinusitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Diabetes Mellitus
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Diabetic Metabolic Decompensation
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Subjects from DRI12544: Placebo/Dupilumab Subjects from DRI12544: Dupilumab/Dupilumab Subjects from EFC13579: Placebo/Dupilumab Subjects from EFC13579: Dupilumab/Dupilumab Subjects from EFC13691: Placebo/Dupilumab Subjects from EFC13691: Dupilumab/Dupilumab Subjects from PDY14192: Placebo/Dupilumab Subjects from PDY14192: Dupilumab/Dupilumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    80 / 111 (72.07%)
    323 / 421 (76.72%)
    357 / 517 (69.05%)
    666 / 1013 (65.75%)
    56 / 97 (57.73%)
    55 / 90 (61.11%)
    18 / 19 (94.74%)
    13 / 14 (92.86%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pituitary Tumour Benign
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 111 (4.50%)
    16 / 421 (3.80%)
    19 / 517 (3.68%)
    29 / 1013 (2.86%)
    5 / 97 (5.15%)
    2 / 90 (2.22%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    5
    19
    20
    37
    7
    2
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 111 (0.90%)
    10 / 421 (2.38%)
    5 / 517 (0.97%)
    8 / 1013 (0.79%)
    5 / 97 (5.15%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    12
    5
    15
    5
    1
    0
    1
    Injection Site Bruising
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    1
    2
    0
    0
    0
    1
    Injection Site Erythema
         subjects affected / exposed
    26 / 111 (23.42%)
    55 / 421 (13.06%)
    35 / 517 (6.77%)
    50 / 1013 (4.94%)
    5 / 97 (5.15%)
    2 / 90 (2.22%)
    8 / 19 (42.11%)
    6 / 14 (42.86%)
         occurrences all number
    102
    412
    148
    295
    12
    29
    21
    29
    Injection Site Haematoma
         subjects affected / exposed
    4 / 111 (3.60%)
    2 / 421 (0.48%)
    4 / 517 (0.77%)
    4 / 1013 (0.39%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    4
    2
    4
    7
    3
    0
    0
    2
    Injection Site Haemorrhage
         subjects affected / exposed
    5 / 111 (4.50%)
    5 / 421 (1.19%)
    5 / 517 (0.97%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    7
    5
    5
    4
    0
    0
    2
    0
    Injection Site Oedema
         subjects affected / exposed
    4 / 111 (3.60%)
    14 / 421 (3.33%)
    14 / 517 (2.71%)
    15 / 1013 (1.48%)
    0 / 97 (0.00%)
    2 / 90 (2.22%)
    3 / 19 (15.79%)
    2 / 14 (14.29%)
         occurrences all number
    9
    84
    32
    58
    0
    8
    6
    4
    Injection Site Pain
         subjects affected / exposed
    9 / 111 (8.11%)
    18 / 421 (4.28%)
    15 / 517 (2.90%)
    14 / 1013 (1.38%)
    0 / 97 (0.00%)
    2 / 90 (2.22%)
    1 / 19 (5.26%)
    2 / 14 (14.29%)
         occurrences all number
    18
    28
    40
    51
    0
    9
    3
    2
    Injection Site Pruritus
         subjects affected / exposed
    12 / 111 (10.81%)
    16 / 421 (3.80%)
    15 / 517 (2.90%)
    7 / 1013 (0.69%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    23
    54
    36
    20
    2
    0
    3
    0
    Injection Site Reaction
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    3 / 517 (0.58%)
    5 / 1013 (0.49%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    3
    10
    0
    0
    1
    0
    Injection Site Warmth
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    20
    1
    0
    1
    0
    Malaise
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    Peripheral Swelling
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    3 / 517 (0.58%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    3
    2
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 111 (0.90%)
    8 / 421 (1.90%)
    0 / 517 (0.00%)
    16 / 1013 (1.58%)
    1 / 97 (1.03%)
    3 / 90 (3.33%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    12
    0
    20
    1
    4
    0
    1
    Immune system disorders
    Drug Hypersensitivity
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    4 / 1013 (0.39%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    4
    2
    0
    0
    1
    Multiple Allergies
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Endometriosis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Metrorrhagia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 111 (3.60%)
    16 / 421 (3.80%)
    10 / 517 (1.93%)
    22 / 1013 (2.17%)
    3 / 97 (3.09%)
    3 / 90 (3.33%)
    3 / 19 (15.79%)
    0 / 14 (0.00%)
         occurrences all number
    4
    24
    12
    29
    3
    4
    3
    0
    Dyspnoea
         subjects affected / exposed
    2 / 111 (1.80%)
    10 / 421 (2.38%)
    8 / 517 (1.55%)
    12 / 1013 (1.18%)
    2 / 97 (2.06%)
    2 / 90 (2.22%)
    2 / 19 (10.53%)
    1 / 14 (7.14%)
         occurrences all number
    2
    11
    8
    23
    7
    3
    2
    1
    Nasal Congestion
         subjects affected / exposed
    1 / 111 (0.90%)
    5 / 421 (1.19%)
    3 / 517 (0.58%)
    5 / 1013 (0.49%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    5
    3
    5
    0
    1
    1
    0
    Oropharyngeal Pain
         subjects affected / exposed
    3 / 111 (2.70%)
    13 / 421 (3.09%)
    11 / 517 (2.13%)
    20 / 1013 (1.97%)
    2 / 97 (2.06%)
    5 / 90 (5.56%)
    1 / 19 (5.26%)
    1 / 14 (7.14%)
         occurrences all number
    5
    13
    11
    22
    2
    5
    1
    1
    Paranasal Sinus Discomfort
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Sinus Congestion
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    2 / 517 (0.39%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    3
    0
    0
    1
    0
    1
    Sputum Increased
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    1
    0
    Upper Respiratory Tract Congestion
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Wheezing
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    3 / 517 (0.58%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    5
    4
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    7 / 517 (1.35%)
    10 / 1013 (0.99%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    7
    11
    1
    0
    0
    1
    Insomnia
         subjects affected / exposed
    2 / 111 (1.80%)
    6 / 421 (1.43%)
    6 / 517 (1.16%)
    8 / 1013 (0.79%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    3
    7
    6
    8
    1
    0
    1
    0
    Sleep Disorder
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    Investigations
    Blood Glucose Increased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    1
    0
    C-Reactive Protein Increased
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Epstein-Barr Virus Test Positive
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    White Blood Cells Urine Positive
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    6 / 111 (5.41%)
    40 / 421 (9.50%)
    28 / 517 (5.42%)
    45 / 1013 (4.44%)
    5 / 97 (5.15%)
    5 / 90 (5.56%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    9
    44
    31
    48
    5
    6
    2
    0
    Arthropod Bite
         subjects affected / exposed
    2 / 111 (1.80%)
    4 / 421 (0.95%)
    3 / 517 (0.58%)
    9 / 1013 (0.89%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    2
    5
    3
    9
    0
    1
    1
    0
    Concussion
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    Contusion
         subjects affected / exposed
    3 / 111 (2.70%)
    14 / 421 (3.33%)
    12 / 517 (2.32%)
    14 / 1013 (1.38%)
    0 / 97 (0.00%)
    2 / 90 (2.22%)
    0 / 19 (0.00%)
    3 / 14 (21.43%)
         occurrences all number
    3
    27
    13
    18
    0
    3
    0
    3
    Fall
         subjects affected / exposed
    2 / 111 (1.80%)
    7 / 421 (1.66%)
    12 / 517 (2.32%)
    33 / 1013 (3.26%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    2
    8
    12
    38
    1
    0
    2
    0
    Intentional Overdose
         subjects affected / exposed
    1 / 111 (0.90%)
    3 / 421 (0.71%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    0
    2
    2
    0
    1
    0
    Limb Injury
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    3 / 517 (0.58%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    1
    2
    3
    4
    0
    1
    0
    2
    Lip Injury
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Muscle Strain
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    7 / 1013 (0.69%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    7
    0
    0
    0
    1
    Skin Laceration
         subjects affected / exposed
    1 / 111 (0.90%)
    5 / 421 (1.19%)
    10 / 517 (1.93%)
    7 / 1013 (0.69%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    5
    10
    7
    0
    1
    1
    0
    Stab Wound
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Tooth Fracture
         subjects affected / exposed
    3 / 111 (2.70%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    3
    1
    1
    2
    0
    0
    0
    1
    Wrist Fracture
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    2 / 517 (0.39%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    Nervous system disorders
    Carpal Tunnel Syndrome
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    3 / 111 (2.70%)
    12 / 421 (2.85%)
    8 / 517 (1.55%)
    6 / 1013 (0.59%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    3
    13
    8
    7
    2
    0
    3
    0
    Dysaesthesia
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    13 / 111 (11.71%)
    47 / 421 (11.16%)
    47 / 517 (9.09%)
    74 / 1013 (7.31%)
    4 / 97 (4.12%)
    5 / 90 (5.56%)
    4 / 19 (21.05%)
    1 / 14 (7.14%)
         occurrences all number
    14
    141
    69
    145
    4
    5
    9
    1
    Migraine
         subjects affected / exposed
    2 / 111 (1.80%)
    3 / 421 (0.71%)
    7 / 517 (1.35%)
    9 / 1013 (0.89%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    2
    3
    14
    9
    0
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    1 / 111 (0.90%)
    3 / 421 (0.71%)
    1 / 517 (0.19%)
    4 / 1013 (0.39%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    1
    4
    1
    0
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    1
    Somnolence
         subjects affected / exposed
    1 / 111 (0.90%)
    4 / 421 (0.95%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    6
    1
    1
    2
    0
    0
    1
    Syncope
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    3
    1
    0
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    1 / 517 (0.19%)
    6 / 1013 (0.59%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    1
    6
    0
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    3 / 517 (0.58%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    3
    2
    0
    0
    0
    1
    Eye disorders
    Dry Eye
         subjects affected / exposed
    0 / 111 (0.00%)
    4 / 421 (0.95%)
    2 / 517 (0.39%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    5
    2
    1
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    1 / 517 (0.19%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    1
    0
    Abdominal Pain
         subjects affected / exposed
    3 / 111 (2.70%)
    12 / 421 (2.85%)
    9 / 517 (1.74%)
    13 / 1013 (1.28%)
    4 / 97 (4.12%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    3
    13
    11
    16
    4
    1
    0
    1
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 111 (0.00%)
    5 / 421 (1.19%)
    6 / 517 (1.16%)
    10 / 1013 (0.99%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    5
    6
    11
    1
    1
    0
    1
    Dental Caries
         subjects affected / exposed
    1 / 111 (0.90%)
    6 / 421 (1.43%)
    4 / 517 (0.77%)
    9 / 1013 (0.89%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    2
    6
    4
    9
    1
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 111 (2.70%)
    16 / 421 (3.80%)
    7 / 517 (1.35%)
    25 / 1013 (2.47%)
    4 / 97 (4.12%)
    3 / 90 (3.33%)
    2 / 19 (10.53%)
    2 / 14 (14.29%)
         occurrences all number
    3
    20
    9
    27
    4
    3
    2
    2
    Dyspepsia
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    7 / 1013 (0.69%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    2
    1
    8
    1
    0
    0
    1
    Gastrointestinal Disorder
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    1 / 111 (0.90%)
    13 / 421 (3.09%)
    13 / 517 (2.51%)
    21 / 1013 (2.07%)
    2 / 97 (2.06%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    14
    15
    23
    2
    0
    0
    1
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    2 / 111 (1.80%)
    6 / 421 (1.43%)
    8 / 517 (1.55%)
    14 / 1013 (1.38%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    3 / 19 (15.79%)
    1 / 14 (7.14%)
         occurrences all number
    2
    36
    8
    52
    0
    0
    4
    1
    Oesophagitis
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    1 / 517 (0.19%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 111 (1.80%)
    4 / 421 (0.95%)
    5 / 517 (0.97%)
    13 / 1013 (1.28%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    4 / 19 (21.05%)
    0 / 14 (0.00%)
         occurrences all number
    2
    4
    5
    15
    0
    0
    5
    0
    Skin and subcutaneous tissue disorders
    Dermatitis Atopic
         subjects affected / exposed
    0 / 111 (0.00%)
    2 / 421 (0.48%)
    5 / 517 (0.97%)
    9 / 1013 (0.89%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    5
    5
    11
    1
    0
    0
    1
    Dyshidrotic Eczema
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Papulopustular Rosacea
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Pityriasis Alba
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Rash Generalised
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    1
    0
    Rosacea
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    3 / 1013 (0.30%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    3
    0
    0
    0
    1
    Solar Dermatitis
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    1
    Renal and urinary disorders
    Leukocyturia
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    Urinary Retention
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    9 / 111 (8.11%)
    23 / 421 (5.46%)
    23 / 517 (4.45%)
    22 / 1013 (2.17%)
    7 / 97 (7.22%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    10
    29
    29
    22
    7
    1
    0
    2
    Back Pain
         subjects affected / exposed
    4 / 111 (3.60%)
    30 / 421 (7.13%)
    23 / 517 (4.45%)
    52 / 1013 (5.13%)
    5 / 97 (5.15%)
    0 / 90 (0.00%)
    2 / 19 (10.53%)
    3 / 14 (21.43%)
         occurrences all number
    4
    33
    28
    67
    5
    0
    2
    4
    Bursitis
         subjects affected / exposed
    1 / 111 (0.90%)
    2 / 421 (0.48%)
    2 / 517 (0.39%)
    1 / 1013 (0.10%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    2
    2
    1
    1
    0
    0
    1
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 111 (0.00%)
    6 / 421 (1.43%)
    3 / 517 (0.58%)
    3 / 1013 (0.30%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    6
    3
    3
    2
    0
    0
    1
    Muscle Spasms
         subjects affected / exposed
    1 / 111 (0.90%)
    4 / 421 (0.95%)
    7 / 517 (1.35%)
    9 / 1013 (0.89%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    1 / 14 (7.14%)
         occurrences all number
    2
    6
    9
    10
    0
    0
    1
    1
    Myalgia
         subjects affected / exposed
    5 / 111 (4.50%)
    14 / 421 (3.33%)
    7 / 517 (1.35%)
    12 / 1013 (1.18%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    5
    14
    7
    14
    0
    1
    2
    0
    Myositis
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    2 / 517 (0.39%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    2
    2
    0
    0
    1
    0
    Pain In Extremity
         subjects affected / exposed
    2 / 111 (1.80%)
    6 / 421 (1.43%)
    7 / 517 (1.35%)
    16 / 1013 (1.58%)
    1 / 97 (1.03%)
    3 / 90 (3.33%)
    1 / 19 (5.26%)
    1 / 14 (7.14%)
         occurrences all number
    2
    6
    8
    16
    1
    3
    1
    1
    Rotator Cuff Syndrome
         subjects affected / exposed
    1 / 111 (0.90%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    2 / 1013 (0.20%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    1
    2
    0
    0
    0
    1
    Tendonitis
         subjects affected / exposed
    2 / 111 (1.80%)
    4 / 421 (0.95%)
    0 / 517 (0.00%)
    5 / 1013 (0.49%)
    1 / 97 (1.03%)
    2 / 90 (2.22%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    3
    4
    0
    5
    1
    2
    0
    1
    Trismus
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    15 / 111 (13.51%)
    80 / 421 (19.00%)
    63 / 517 (12.19%)
    117 / 1013 (11.55%)
    9 / 97 (9.28%)
    14 / 90 (15.56%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    30
    135
    100
    181
    10
    15
    0
    0
    Bronchitis Viral
         subjects affected / exposed
    1 / 111 (0.90%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    4 / 1013 (0.39%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    4
    0
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 111 (0.00%)
    5 / 421 (1.19%)
    5 / 517 (0.97%)
    18 / 1013 (1.78%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    5
    5
    21
    1
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    6 / 111 (5.41%)
    7 / 421 (1.66%)
    10 / 517 (1.93%)
    26 / 1013 (2.57%)
    0 / 97 (0.00%)
    2 / 90 (2.22%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    6
    8
    14
    31
    0
    2
    1
    0
    Genital Herpes
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    Gingivitis
         subjects affected / exposed
    1 / 111 (0.90%)
    3 / 421 (0.71%)
    0 / 517 (0.00%)
    1 / 1013 (0.10%)
    0 / 97 (0.00%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    3
    0
    1
    0
    1
    0
    1
    Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    5 / 111 (4.50%)
    44 / 421 (10.45%)
    30 / 517 (5.80%)
    67 / 1013 (6.61%)
    9 / 97 (9.28%)
    7 / 90 (7.78%)
    2 / 19 (10.53%)
    2 / 14 (14.29%)
         occurrences all number
    5
    52
    39
    79
    11
    10
    2
    2
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 111 (0.90%)
    6 / 421 (1.43%)
    6 / 517 (1.16%)
    17 / 1013 (1.68%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    6
    7
    18
    1
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    27 / 111 (24.32%)
    109 / 421 (25.89%)
    99 / 517 (19.15%)
    191 / 1013 (18.85%)
    17 / 97 (17.53%)
    16 / 90 (17.78%)
    3 / 19 (15.79%)
    6 / 14 (42.86%)
         occurrences all number
    47
    208
    149
    293
    30
    22
    8
    8
    Oral Candidiasis
         subjects affected / exposed
    1 / 111 (0.90%)
    9 / 421 (2.14%)
    6 / 517 (1.16%)
    14 / 1013 (1.38%)
    1 / 97 (1.03%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    5
    19
    9
    19
    1
    0
    2
    0
    Pharyngitis
         subjects affected / exposed
    16 / 111 (14.41%)
    37 / 421 (8.79%)
    26 / 517 (5.03%)
    59 / 1013 (5.82%)
    1 / 97 (1.03%)
    4 / 90 (4.44%)
    0 / 19 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    21
    57
    30
    75
    1
    5
    0
    0
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    6 / 517 (1.16%)
    7 / 1013 (0.69%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    6
    7
    1
    1
    0
    1
    Post Procedural Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    Postoperative Wound Infection
         subjects affected / exposed
    0 / 111 (0.00%)
    0 / 421 (0.00%)
    0 / 517 (0.00%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Pulpitis Dental
         subjects affected / exposed
    1 / 111 (0.90%)
    2 / 421 (0.48%)
    0 / 517 (0.00%)
    5 / 1013 (0.49%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    1
    2
    0
    6
    0
    0
    2
    0
    Respiratory Tract Infection
         subjects affected / exposed
    3 / 111 (2.70%)
    15 / 421 (3.56%)
    5 / 517 (0.97%)
    18 / 1013 (1.78%)
    0 / 97 (0.00%)
    2 / 90 (2.22%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    3
    17
    6
    25
    0
    2
    2
    0
    Respiratory Tract Infection Viral
         subjects affected / exposed
    0 / 111 (0.00%)
    3 / 421 (0.71%)
    6 / 517 (1.16%)
    11 / 1013 (1.09%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    6
    7
    15
    0
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    7 / 111 (6.31%)
    11 / 421 (2.61%)
    6 / 517 (1.16%)
    22 / 1013 (2.17%)
    4 / 97 (4.12%)
    1 / 90 (1.11%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    8
    11
    7
    25
    4
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    9 / 111 (8.11%)
    33 / 421 (7.84%)
    32 / 517 (6.19%)
    50 / 1013 (4.94%)
    2 / 97 (2.06%)
    4 / 90 (4.44%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    16
    56
    43
    66
    2
    4
    1
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    18 / 111 (16.22%)
    60 / 421 (14.25%)
    65 / 517 (12.57%)
    130 / 1013 (12.83%)
    8 / 97 (8.25%)
    6 / 90 (6.67%)
    2 / 19 (10.53%)
    0 / 14 (0.00%)
         occurrences all number
    30
    87
    96
    213
    12
    15
    4
    0
    Urinary Tract Infection
         subjects affected / exposed
    5 / 111 (4.50%)
    26 / 421 (6.18%)
    17 / 517 (3.29%)
    42 / 1013 (4.15%)
    4 / 97 (4.12%)
    3 / 90 (3.33%)
    0 / 19 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    7
    31
    20
    53
    4
    3
    0
    1
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 111 (1.80%)
    11 / 421 (2.61%)
    13 / 517 (2.51%)
    30 / 1013 (2.96%)
    1 / 97 (1.03%)
    1 / 90 (1.11%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    3
    15
    16
    48
    4
    3
    1
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 111 (0.00%)
    1 / 421 (0.24%)
    1 / 517 (0.19%)
    0 / 1013 (0.00%)
    0 / 97 (0.00%)
    0 / 90 (0.00%)
    1 / 19 (5.26%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Jun 2015
    Following amendment were done: opened eligibility for study entry to United States subjects in the DRI12544 study, as well as to eligible subjects from PDY14192, EFC13579, and EFC13691 studies; changes to inclusion/ exclusion criteria; changes to IMP formulation: as the prefilled syringes became available, subjects were switched to prefilled syringes instead of the vial packaging.
    31 Oct 2016
    Following amendment were done: amended the open-label treatment duration to 48 weeks (1 year); shortened the 16-week post-treatment period to 12 weeks; simplified the study procedures; harmonised protocol exclusion criteria with asthma parent study protocols.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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