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    Clinical Trial Results:
    26-Week Randomized, Double-Blinded, Active Controlled Study Comparing the Safety of Mometasone Furoate/Formoterol Fumarate MDI Fixed Dose Combination Versus Mometasone Furoate MDI Monotherapy in Adolescents and Adults With Persistent Asthma

    Summary
    EudraCT number
    		 2011-002142-13
    Trial protocol
    		 HU   EE   CZ   LV   GB   ES   DE   IE   SK   PL   IT   BG   Outside EU/EEA  
    Global end of trial date
    30 Nov 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jul 2017
    First version publication date
    09 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    P202 (also known as P06241)
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01471340
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Nov 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Nov 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare serious asthma outcomes (a composite endpoint defined as asthma-related: hospitalizations, intubations and deaths) in participants treated with mometasone furoate/formoterol fumarate (MF/F) versus participants treated with mometasone furoate (MF), each administered by a metered-dose inhaler (MDI), twice daily (BID), and assessed by a non-inferiority test.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human participants participating in biomedical research. The following additional measure(s) defined for this study were provided for protection of trial participants: albuterol/salbutamol hydrofluoroalkane (HFA) MDI administered as needed as rescue medication; systemic corticosteroids (tablets, suspension, or injection) were provided only as an emergency rescue medication at the discretion of the investigator.
    Background therapy
    		 Placebo MDIs were provided for on-site training on inhaler use.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Jan 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 360
    Country: Number of subjects enrolled
    Australia: 43
    Country: Number of subjects enrolled
    Brazil: 274
    Country: Number of subjects enrolled
    Bulgaria: 510
    Country: Number of subjects enrolled
    Canada: 201
    Country: Number of subjects enrolled
    Chile: 217
    Country: Number of subjects enrolled
    China: 169
    Country: Number of subjects enrolled
    Colombia: 215
    Country: Number of subjects enrolled
    Croatia: 83
    Country: Number of subjects enrolled
    Czech Republic: 438
    Country: Number of subjects enrolled
    Estonia: 60
    Country: Number of subjects enrolled
    France: 24
    Country: Number of subjects enrolled
    Germany: 152
    Country: Number of subjects enrolled
    Guatemala: 209
    Country: Number of subjects enrolled
    Hungary: 134
    Country: Number of subjects enrolled
    Ireland: 51
    Country: Number of subjects enrolled
    Israel: 29
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    Korea, Republic of: 90
    Country: Number of subjects enrolled
    Latvia: 520
    Country: Number of subjects enrolled
    Malaysia: 123
    Country: Number of subjects enrolled
    Mexico: 396
    Country: Number of subjects enrolled
    Peru: 528
    Country: Number of subjects enrolled
    Poland: 622
    Country: Number of subjects enrolled
    Puerto Rico: 42
    Country: Number of subjects enrolled
    Romania: 461
    Country: Number of subjects enrolled
    Russian Federation: 535
    Country: Number of subjects enrolled
    Serbia: 684
    Country: Number of subjects enrolled
    Slovakia: 202
    Country: Number of subjects enrolled
    South Africa: 369
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    Taiwan: 61
    Country: Number of subjects enrolled
    Ukraine: 1234
    Country: Number of subjects enrolled
    United Kingdom: 253
    Country: Number of subjects enrolled
    United States: 2412
    Worldwide total number of subjects
    11729
    EEA total number of subjects
    3538
    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)
    1037
    Adults (18-64 years)
    9094
    From 65 to 84 years
    1588
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants (either sex, any race, >= 12 yr of age) had a diagnosis of asthma for at least 1 yr, used daily asthma controller medication for at least 4 wk prior to randomisation and had a history of at least one asthma exacerbation requiring hospitalisation or systemic corticosteroid in the previous year (excluding the 4 wk before randomisation).

    Pre-assignment
    Screening details
    		 During a screening period that lasted up to 2 weeks, all participants remained on their incoming asthma medication.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MF/F MDI BID
    Arm description
    		 MF/F MDI, administered as 200/10 mcg BID or 400/10 mcg BID
    Arm type
    		 Experimental

    Investigational medicinal product name
    MF/F MDI
    Investigational medicinal product code
    MK-0887A
    Other name
    DULERA / ZENHALE
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    MF/F MDI administered as two puffs of 100/5 mcg or 200/5 mcg, twice daily, with oral inhalation of a pressurized inhalation aerosol

    Investigational medicinal product name
    Oral prednisone or prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone or prednisolone for acute administration as emergency rescue medication at the discretion of the investigator

    Investigational medicinal product name
    Albuterol/Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    Albuterol 90 mcg HFA MDI/Salbutamol 100 mcg HFA MDI for as needed asthma symptom relief

    Arm title
    		 MF MDI BID
    Arm description
    		 MF MDI, administered as 200 mcg BID or 400 mcg BID
    Arm type
    		 Active comparator

    Investigational medicinal product name
    MF MDI
    Investigational medicinal product code
    Other name
    ASMANEX
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    MF MDI administered as two puffs of 100 mcg or 200 mcg, twice daily, with oral inhalation of a pressurized inhalation aerosol

    Investigational medicinal product name
    Oral prednisone or prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone or prednisolone for acute administration as emergency rescue medication at the discretion of the investigator

    Investigational medicinal product name
    Albuterol/Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    Albuterol 90 mcg HFA MDI/Salbutamol 100 mcg HFA MDI for as needed asthma symptom relief

    Number of subjects in period 1
    		MF/F MDI BID MF MDI BID
    Started
    5868
    5861
    Completed
    5868
    5861
    Period 2
    Period 2 title
    Treatment, Including Safety Follow-Up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MF/F MDI BID
    Arm description
    		 MF/F MDI, administered as 200/10 mcg BID or 400/10 mcg BID
    Arm type
    		 Experimental

    Investigational medicinal product name
    MF/F MDI
    Investigational medicinal product code
    MK-0887A
    Other name
    DULERA / ZENHALE
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    MF/F MDI administered as two puffs of 100/5 mcg or 200/5 mcg, twice daily, with oral inhalation of a pressurized inhalation aerosol

    Investigational medicinal product name
    Albuterol/Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    Albuterol 90 mcg HFA MDI/Salbutamol 100 mcg HFA MDI for as needed asthma symptom relief

    Investigational medicinal product name
    Oral prednisone or prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone or prednisolone for acute administration as emergency rescue medication at the discretion of the investigator

    Arm title
    		 MF MDI BID
    Arm description
    		 MF MDI, administered as 200 mcg BID or 400 mcg BID
    Arm type
    		 Active comparator

    Investigational medicinal product name
    MF MDI
    Investigational medicinal product code
    MK-0887
    Other name
    DULERA / ZENHALE
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    MF MDI administered as two puffs of 100 mcg or 200 mcg, twice daily, with oral inhalation of a pressurized inhalation aerosol

    Investigational medicinal product name
    Albuterol/Salbutamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Pressurised inhalation
    Routes of administration
    Inhalation use
    Dosage and administration details
    Albuterol 90 mcg HFA MDI/Salbutamol 100 mcg HFA MDI for as needed asthma symptom relief

    Investigational medicinal product name
    Oral prednisone or prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone or prednisolone for acute administration as emergency rescue medication at the discretion of the investigator

    Number of subjects in period 2
    		MF/F MDI BID MF MDI BID
    Started
    5868
    5861
    Completed
    5862
    5855
    Not completed
    6
    6
         Death
    5
    4
         Study terminated by sponsor
    1
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MF/F MDI BID
    Reporting group description
    		 MF/F MDI, administered as 200/10 mcg BID or 400/10 mcg BID

    Reporting group title
    MF MDI BID
    Reporting group description
    		 MF MDI, administered as 200 mcg BID or 400 mcg BID

    Reporting group values
    		 MF/F MDI BID MF MDI BID Total
    Number of subjects
    		 5868 5861 11729
    Age Categorical
    Three participants with a calculated age of less than 12 years are included in the adolescent subgroup. One participant was less than 2 weeks under the age of 12 at the time of randomisation. Two other participants were at least 12 years of age at the time of randomisation.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 491 546 1037
        Adults (18-64 years)
    		 4578 4516 9094
        From 65-84 years
    		 797 791 1588
        85 years and over
    		 2 8 10
    Age Continuous
    Age of randomized participants at baseline
    Units: years
        arithmetic mean (standard deviation)
    		 45.3 ( 17.2 ) 44.8 ( 17.6 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 3841 3875 7716
        Male
    		 2027 1986 4013
    Subject analysis sets

    Subject analysis set title
    MF/F MDI BID
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    MF/F MDI administered as 200/10 mcg BID or 400/10 mcg BID

    Subject analysis set title
    MF MDI BID
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    MF MDI administered as 200 mcg BID or 400 mcg BID

    Subject analysis sets values
    		 MF/F MDI BID MF MDI BID
    Number of subjects
    5868
    5861
    Age Categorical
    Three participants with a calculated age of less than 12 years are included in the adolescent subgroup. One participant was less than 2 weeks under the age of 12 at the time of randomisation. Two other participants were at least 12 years of age at the time of randomisation.
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    491
    546
        Adults (18-64 years)
    4578
    4516
        From 65-84 years
    797
    791
        85 years and over
    2
    8
    Age Continuous
    Age of randomized participants at baseline
    Units: years
        arithmetic mean (standard deviation)
    45.3 ( 17.2 )
    44.8 ( 17.6 )
    Gender Categorical
    Units: Subjects
        Female
    3841
    3875
        Male
    2027
    1986

    End points

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    End points reporting groups
    Reporting group title
    MF/F MDI BID
    Reporting group description
    		 MF/F MDI, administered as 200/10 mcg BID or 400/10 mcg BID

    Reporting group title
    MF MDI BID
    Reporting group description
    		 MF MDI, administered as 200 mcg BID or 400 mcg BID
    Reporting group title
    MF/F MDI BID
    Reporting group description
    		 MF/F MDI, administered as 200/10 mcg BID or 400/10 mcg BID

    Reporting group title
    MF MDI BID
    Reporting group description
    		 MF MDI, administered as 200 mcg BID or 400 mcg BID

    Subject analysis set title
    MF/F MDI BID
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    MF/F MDI administered as 200/10 mcg BID or 400/10 mcg BID

    Subject analysis set title
    MF MDI BID
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    MF MDI administered as 200 mcg BID or 400 mcg BID

    Primary: Time-to-First Serious Asthma Outcomes (SAO: Composite of Asthma-Related Hospitalisations, Asthma-Related Intubations, and Asthma-Related Deaths) in MF/F Participants vs MF Participants

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    End point title
    		 Time-to-First Serious Asthma Outcomes (SAO: Composite of Asthma-Related Hospitalisations, Asthma-Related Intubations, and Asthma-Related Deaths) in MF/F Participants vs MF Participants
    End point description
    The primary safety endpoint was the time-to-first SAO (a composite endpoint of asthma-related hospitalisations, asthma-related intubations, and asthma-related deaths) in participants treated with MF/F MDI BID versus participants treated with MF MDI BID. The time-to-first SAO was assessed by a non-inferiority test, in which the criteria for non-inferiority were defined by the upper bound limit of 2.0 for the 95% confidence interval of the hazard ratio (HR) of MF/F MDI BID to MF MDI BID. The analysed population for assessment of time-to-first SAO was all participants who received at least one dose of randomised treatment assignment (intention-to-treat principle).
    End point type
    Primary
    End point timeframe
    Up to 26 weeks, or 7 days after the last treatment dose, whichever occurred later
    End point values
    		 MF/F MDI BID MF MDI BID
    Number of subjects analysed
    5868
    5861
    Units: Number of participants
    number (not applicable)
        Total Number of SAO
    39
    32
    Statistical analysis title
    		 Difference in Time-to-First SAO
    Statistical analysis description
    For analysis of the time-to-first SAO, MF/F MDI BID was considered non-inferior to MF MDI BID if the upper bound of the two-sided 95% confidence interval (CI) of the hazard ratio (HR) of MF/F MDI BID versus MF MDI BID was lower than 2.0 (noninferiority margin).
    Comparison groups
    MF/F MDI BID v MF MDI BID
    Number of subjects included in analysis
    11729
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    		 Cox proportional-hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.94
    Notes
    [1] - The HR and 95% CI were based on the Cox proportional-hazard model with covariates of treatment (MF/F or MF) and ICS dose level (200 or 400 mcg).

    Secondary: Time-to-First Asthma Exacerbation in MF/F Participants vs MF Participants

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    End point title
    		 Time-to-First Asthma Exacerbation in MF/F Participants vs MF Participants
    End point description
    A key secondary efficacy endpoint was the time-to-first protocol-defined asthma exacerbation (SAEX). The SAEX were deteriorations of asthma requiring: the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 consecutive days, an in-patient hospitalisation, or an ED visit less than 24 hours that required systemic corticosteroids in participants treated with MF/F MDI BID versus participants treated with MF MDI BID. Superiority of MF/F MDI BID was determined if the HR of MF/F MDI BID to MF MDI BID is less than 1 and achieved statistical significance (one sided p-value < 0.025). The analysed population for assessment of time-to-first asthma exacerbation was all treated participants who received at least one dose of randomised treatment assignment (intention-to-treat principle).
    End point type
    Secondary
    End point timeframe
    Up to 26 weeks, or 7 days after the last treatment dose, whichever occurred later
    End point values
    		 MF/F MDI BID MF MDI BID
    Number of subjects analysed
    5868
    5861
    Units: First SAEX
        Number of Participants with First SAEX
    708
    779
    Statistical analysis title
    		 Difference in Time-to-First Exacerbation
    Statistical analysis description
    Superiority of MF/F MDI BID was determined if the HR of MF/F MDI BID to MF MDI BID was less than 1 and achieved statistical significance (one-sided p-value < 0.025).
    Comparison groups
    MF/F MDI BID v MF MDI BID
    Number of subjects included in analysis
    11729
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.021
    Method
    		 Cox proportional-hazard model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 0.98
    Notes
    [2] - The HR and 95% CI were based on the Cox proportional-hazard model with covariates of treatment (MF/F or MF) and ICS dose level (200 or 400 mcg).

    Other pre-specified: Number of SAO Components in MF/F Participants vs MF Participants

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    End point title
    		 Number of SAO Components in MF/F Participants vs MF Participants
    End point description
    To further examine the primary safety endpoint, each component of the SAO composite (asthma-related hospitalisations, asthma-related intubations, and asthma-related deaths) was tabulated for descriptive purposes only to show the relative contribution of each component to the SAO composite. Hospitalisation was defined as an inpatient stay or >= 24 hour stay in an observational area in an emergency department or equivalent healthcare facility. Intubation was defined as endotracheal intubation only. The analysed population for tabulation of time-to-first SAO components was all participants who received at least one dose of randomised treatment assignment (intention-to-treat principle).
    End point type
    Other pre-specified
    End point timeframe
    Up to 26 weeks, or 7 days after the last treatment dose, whichever occurred later
    End point values
    		 MF/F MDI BID MF MDI BID
    Number of subjects analysed
    5868
    5861
    Units: Number of participants
        First SAO
    39
    32
        Asthma-related hospitalisations
    39
    32
        Asthma-related intubations
    0
    0
        Asthma-related deaths
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 26 weeks, or 7 days after the last treatment dose, whichever occurred later
    Adverse event reporting additional description
    The safety analysis set was defined as all participants who received at least one dose of randomised treatment assignment (intention-to-treat principle). Non-serious AEs were only collected for participants who discontinued treatment due to an AE.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    MF/F MDI BID
    Reporting group description
    		 -

    Reporting group title
    MF MDI BID
    Reporting group description
    		 -

    Serious adverse events
    		 MF/F MDI BID MF MDI BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    136 / 5868 (2.32%)
    137 / 5861 (2.34%)
         number of deaths (all causes)
    5
    4
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of spinal cord
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carcinoid tumour of the duodenum
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medullary thyroid cancer
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian adenoma
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 5868 (0.05%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion incomplete
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion missed
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ectopic pregnancy
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foetal death
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Fibrocystic breast disease
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicocele
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    32 / 5868 (0.55%)
    31 / 5861 (0.53%)
         occurrences causally related to treatment / all
    0 / 34
    0 / 34
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 5868 (0.05%)
    4 / 5861 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary oedema
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol abuse
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Depression
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophreniform disorder
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Chest X-ray abnormal
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 5868 (0.02%)
    4 / 5861 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional product misuse
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    2 / 5868 (0.03%)
    3 / 5861 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 5868 (0.02%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    3 / 5868 (0.05%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomegaly
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Coronary artery thrombosis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diastolic dysfunction
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiploic appendagitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric dysplasia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal sphincter insufficiency
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 5868 (0.02%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 5868 (0.03%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 5868 (0.02%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin hypertrophy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 5868 (0.02%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basedow's disease
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess intestinal
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anicteric leptospirosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    6 / 5868 (0.10%)
    4 / 5861 (0.07%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    3 / 5868 (0.05%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 5868 (0.05%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema infected
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Helicobacter gastritis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious mononucleosis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis cryptococcal
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    10 / 5868 (0.17%)
    6 / 5861 (0.10%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperosmolar state
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 5868 (0.02%)
    2 / 5861 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 MF/F MDI BID MF MDI BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 5868 (1.45%)
    101 / 5861 (1.72%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatic cancer
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Ovarian adenoma
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Hot flush
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Pregnancy, puerperium and perinatal conditions
    Ectopic pregnancy
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Asthenia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Chest discomfort
         subjects affected / exposed
    1 / 5868 (0.02%)
    3 / 5861 (0.05%)
         occurrences all number
    1
    3
    Chest pain
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Feeling jittery
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Mucosal inflammation
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Immune system disorders
    Allergic oedema
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Hypersensitivity
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    8 / 5868 (0.14%)
    10 / 5861 (0.17%)
         occurrences all number
    8
    10
    Bronchospasm
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Bronchospasm paradoxical
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    2 / 5868 (0.03%)
    6 / 5861 (0.10%)
         occurrences all number
    2
    6
    Dysphonia
         subjects affected / exposed
    4 / 5868 (0.07%)
    5 / 5861 (0.09%)
         occurrences all number
    4
    5
    Dyspnoea
         subjects affected / exposed
    4 / 5868 (0.07%)
    5 / 5861 (0.09%)
         occurrences all number
    4
    5
    Hypopnoea
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Interstitial lung disease
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Laryngeal hypertrophy
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Laryngeal oedema
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Pulmonary embolism
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Respiratory tract congestion
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Throat irritation
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences all number
    2
    1
    Vocal cord disorder
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    0 / 5868 (0.00%)
    3 / 5861 (0.05%)
         occurrences all number
    0
    3
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Completed suicide
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Insomnia
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Investigations
    Heart rate increased
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Weight increased
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Myocardial infarction acute
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Angina pectoris
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Arrhythmia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Cardiac failure
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Cardiomegaly
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Coronary artery thrombosis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Myocardial infarction
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences all number
    2
    1
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Nervous system disorders
    Aphonia
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Dizziness
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Dysgeusia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Epilepsy
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    3 / 5868 (0.05%)
    7 / 5861 (0.12%)
         occurrences all number
    3
    7
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Ischaemic stroke
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    2 / 5868 (0.03%)
    1 / 5861 (0.02%)
         occurrences all number
    2
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    3 / 5868 (0.05%)
    0 / 5861 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Glossodynia
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Oral discomfort
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Oral mucosal erythema
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Retching
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    2 / 5868 (0.03%)
    3 / 5861 (0.05%)
         occurrences all number
    2
    3
    Tongue discomfort
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences all number
    2
    0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Angioedema
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Dermatitis acneiform
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Lichen planus
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Endocrine disorders
    Basedow's disease
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Joint swelling
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 5868 (0.02%)
    1 / 5861 (0.02%)
         occurrences all number
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    2 / 5861 (0.03%)
         occurrences all number
    0
    2
    Candida infection
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    2 / 5868 (0.03%)
    0 / 5861 (0.00%)
         occurrences all number
    2
    0
    Pneumonia
         subjects affected / exposed
    2 / 5868 (0.03%)
    2 / 5861 (0.03%)
         occurrences all number
    2
    2
    Sinusitis
         subjects affected / exposed
    1 / 5868 (0.02%)
    0 / 5861 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 5868 (0.00%)
    3 / 5861 (0.05%)
         occurrences all number
    0
    3
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 5868 (0.00%)
    1 / 5861 (0.02%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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