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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections with Pseudomonas aeruginosa in Subjects with Non-Cystic Fibrosis Bronchiectasis, including 28 Day Open-Label Extension and Pharmacokinetic Substudy (ORBIT-3)

    Summary
    EudraCT number
    		 2013-005348-28
    Trial protocol
    		 GB   HU   IT   ES   LV   RO   IE   PL  
    Global end of trial date
    14 Oct 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Apr 2018
    First version publication date
    25 Apr 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ARD-3150-1201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01515007
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Aradigm Corporation
    Sponsor organisation address
    3929 Point Eden Way, Hayward, California, United States, 94545
    Public contact
    Clinical Operations, Aradigm Corporation, +1 510 265 8895, JacksonA@aradigm.com
    Scientific contact
    Medical and Drug Development, Aradigm Corporation, +1 510 265 8838, froehlichj@aradigm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Sep 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Aug 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the efficacy of Linhaliq compared to placebo in the management of chronic lung infections with P. aeruginosa in subjects with non-cystic fibrosis (non-CF) bronchiectasis by evaluating the time to first pulmonary exacerbation in the Double-Blind Phase.
    Protection of trial subjects
    The study was designed and monitored in accordance with Sponsor procedures, which comply with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Mar 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
    Poland: 6
    Country: Number of subjects enrolled
    Romania: 14
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 30
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Latvia: 9
    Country: Number of subjects enrolled
    United States: 52
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Israel: 23
    Country: Number of subjects enrolled
    Australia: 70
    Country: Number of subjects enrolled
    South Africa: 14
    Country: Number of subjects enrolled
    Taiwan: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Worldwide total number of subjects
    278
    EEA total number of subjects
    101
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    109
    From 65 to 84 years
    165
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    		 102 clinical sites screened at least one subject for the study. Sites were located in Australia, Canada, Germany, Hungary, Ireland, Israel, Italy, Latvia, Poland, Romania, South Africa, South Korea, Spain, Taiwan, the United Kingdom (UK), and the US. The first subject was screened on 31 March 2014, and the final subject screened on 19 August 2015.

    Pre-assignment
    Screening details
    		 514 subjects were enrolled and screened. Subjects who met all eligibility criteria were randomized in a 2:1 ratio to receive once daily inhaled treatment with Pulmaquin or placebo.

    Period 1
    Period 1 title
    Double-Blind Phase (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Active
    Arm description
    		 Liquid mixture of liposome-encapsulated and unencapsulated ciprofloxacin
    Arm type
    		 Experimental

    Investigational medicinal product name
    Linhaliq
    Investigational medicinal product code
    ARD-3150
    Other name
    Pulmaquin
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    The administered dose was 189 mg (6 mL) of ciprofloxacin comprised of one vial of 135 mg (3mL) liposome-encapsulated ciprofloxacin dispersion and one vial of 54 mg (3mL) free ciprofloxacin solution given once daily by oral inhalation using a nebuliser; the dosing regimen was 6 cycles of 28 days on treatment, followed by 28 days off treatment.

    Arm title
    		 Placebo
    Arm description
    		 Liquid mixture of empty liposomes and normal saline
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    The administered dose was 6 mL placebo, comprised of one vial of 3 mL empty liposomes and one vial of 3 mL normal saline solution once daily by oral inhalation using a nebuliser; the dosing regimen was 6 cycles of 28 days on treatment, followed by 28 days off treatment.

    Number of subjects in period 1
    		Active Placebo
    Started
    183
    95
    Completed
    142
    77
    Not completed
    41
    18
         Adverse event, serious fatal
    5
    3
         Physician decision
    3
    1
         Consent withdrawn by subject
    14
    11
         Per-Protocol Defined Pulmonory Exacerbation
    1
    -
         Adverse event, non-fatal
    11
    -
         Other
    -
    1
         Lost to follow-up
    3
    1
         Lack of efficacy
    2
    -
         Protocol deviation
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Active
    Reporting group description
    		 Liquid mixture of liposome-encapsulated and unencapsulated ciprofloxacin

    Reporting group title
    Placebo
    Reporting group description
    		 Liquid mixture of empty liposomes and normal saline

    Reporting group values
    		 Active Placebo Total
    Number of subjects
    		 183 95 278
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 68.0 (21 to 86) 69 (21 to 87) -
    Gender categorical
    Units: Subjects
        Female
    		 127 67 194
        Male
    		 56 28 84

    End points

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    End points reporting groups
    Reporting group title
    Active
    Reporting group description
    		 Liquid mixture of liposome-encapsulated and unencapsulated ciprofloxacin

    Reporting group title
    Placebo
    Reporting group description
    		 Liquid mixture of empty liposomes and normal saline

    Primary: Time to First Pulmonary Exacerbation

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    End point title
    		 Time to First Pulmonary Exacerbation
    End point description
    Median time to first pulmonary exacerbation
    End point type
    Primary
    End point timeframe
    March 2014 to August 2016
    End point values
    		 Active Placebo
    Number of subjects analysed
    183
    95
    Units: Number of days
        median (confidence interval 95%)
    214.0 (114.0 to 289.0)
    136.0 (81.0 to 339.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9743
    Method
    		 Stratified Unweighted Log-Rank Test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.38

    Secondary: Frequency of Pulmonary Exacerbations

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    End point title
    		 Frequency of Pulmonary Exacerbations
    End point description
    End point type
    Secondary
    End point timeframe
    March 2014 to August 2016
    End point values
    		 Active Placebo
    Number of subjects analysed
    183
    95
    Units: Number of Pulmonary Exacerbations
        arithmetic mean (standard error)
    1.09 ( 0.10 )
    1.31 ( 0.12 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2565
    Method
    		 Stratified Negative Binomial Regression
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.12
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.136
    Method
    		 Counting Process
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.06

    Secondary: Frequency of Moderate and Severe Pulmonary Exacerbations

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    End point title
    		 Frequency of Moderate and Severe Pulmonary Exacerbations
    End point description
    End point type
    Secondary
    End point timeframe
    March 2014 to August 2016
    End point values
    		 Active Placebo
    Number of subjects analysed
    183
    95
    Units: Number of Pulmonary Exacerbations
        arithmetic mean (standard error)
    0.86 ( 0.10 )
    1.13 ( 0.13 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Active
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0998
    Method
    		 Stratified Negative Binomial Regression
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.05
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.038
    Method
    		 Counting Process
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.99

    Secondary: Frequency of Severe Pulmonary Exacerbations

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    End point title
    		 Frequency of Severe Pulmonary Exacerbations
    End point description
    End point type
    Secondary
    End point timeframe
    March 2014 to August 2016
    End point values
    		 Active Placebo
    Number of subjects analysed
    183
    95
    Units: Number of Pulmonary Exacerbations
        arithmetic mean (standard error)
    0.22 ( 0.22 )
    0.28 ( 0.28 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4827
    Method
    		 Stratified Negative Binomial Regression
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.51
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    278
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.399
    Method
    		 Counting Process
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.32

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    March 2014 to August 2016
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Active
    Reporting group description
    		 Liquid mixture of liposome-encapsulated and unencapsulated ciprofloxacin

    Reporting group title
    Placebo
    Reporting group description
    		 Liquid mixture of empty liposomes and normal saline

    Serious adverse events
    		 Active Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 183 (30.60%)
    24 / 95 (25.26%)
         number of deaths (all causes)
    5
    3
         number of deaths resulting from adverse events
    5
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Granulomatosis with polyangiitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 183 (0.55%)
    3 / 95 (3.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vessel puncture site haematoma
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exercise tolerance decreased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asphyxia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Asthma
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial secretion retention
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    5 / 183 (2.73%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    11 / 183 (6.01%)
    8 / 95 (8.42%)
         occurrences causally related to treatment / all
    2 / 16
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    7 / 183 (3.83%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    5 / 183 (2.73%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sputum increased
         subjects affected / exposed
    1 / 183 (0.55%)
    4 / 95 (4.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Breath sounds abnormal
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest X-ray abnormal
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibrin D dimer increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forced expiratory volume decreased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (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
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Left ventricle outflow tract obstruction
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 183 (0.55%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         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
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (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
    Nephrotic syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (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
    Appendicitis perforated
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 183 (1.09%)
    5 / 95 (5.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 183 (3.83%)
    6 / 95 (6.32%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sputum purulent
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         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 / 183 (0.55%)
    0 / 95 (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
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Active Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    164 / 183 (89.62%)
    87 / 95 (91.58%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acrochordon
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Basal cell carcinoma
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Craniopharyngioma
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Vascular neoplasm
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Granulomatosis with polyangiitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Haematoma
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Hypertension
         subjects affected / exposed
    3 / 183 (1.64%)
    3 / 95 (3.16%)
         occurrences all number
    3
    5
    Hypertensive crisis
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Hypotension
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Surgical and medical procedures
    Spinal laminectomy
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    8 / 183 (4.37%)
    3 / 95 (3.16%)
         occurrences all number
    8
    3
    Chest discomfort
         subjects affected / exposed
    10 / 183 (5.46%)
    3 / 95 (3.16%)
         occurrences all number
    10
    5
    Chest pain
         subjects affected / exposed
    11 / 183 (6.01%)
    5 / 95 (5.26%)
         occurrences all number
    14
    5
    Chills
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Device dislocation
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Exercise tolerance decreased
         subjects affected / exposed
    43 / 183 (23.50%)
    22 / 95 (23.16%)
         occurrences all number
    61
    38
    fatigue
         subjects affected / exposed
    71 / 183 (38.80%)
    40 / 95 (42.11%)
         occurrences all number
    133
    79
    Feeling cold
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gravitational oedema
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hernia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Injection site discomfort
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Malaise
         subjects affected / exposed
    16 / 183 (8.74%)
    14 / 95 (14.74%)
         occurrences all number
    20
    23
    Oedema
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Oedema peripheral
         subjects affected / exposed
    7 / 183 (3.83%)
    1 / 95 (1.05%)
         occurrences all number
    8
    1
    Pain
         subjects affected / exposed
    6 / 183 (3.28%)
    1 / 95 (1.05%)
         occurrences all number
    6
    1
    Peripheral swelling
         subjects affected / exposed
    2 / 183 (1.09%)
    2 / 95 (2.11%)
         occurrences all number
    2
    2
    Product taste abnormal
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    47 / 183 (25.68%)
    31 / 95 (32.63%)
         occurrences all number
    73
    51
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Seasonal allergy
         subjects affected / exposed
    4 / 183 (2.19%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Breast mass
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Allergic sinusitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Asthma
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Bronchial secretion retention
         subjects affected / exposed
    1 / 183 (0.55%)
    2 / 95 (2.11%)
         occurrences all number
    4
    2
    Bronchospasm
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    4
    1
    Catarrh
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Choking sensation
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    113 / 183 (61.75%)
    55 / 95 (57.89%)
         occurrences all number
    279
    137
    Dysphonia
         subjects affected / exposed
    3 / 183 (1.64%)
    7 / 95 (7.37%)
         occurrences all number
    3
    7
    Dyspnoea
         subjects affected / exposed
    98 / 183 (53.55%)
    45 / 95 (47.37%)
         occurrences all number
    189
    105
    Dyspnoea exertional
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Epistaxis
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Haemoptysis
         subjects affected / exposed
    27 / 183 (14.75%)
    9 / 95 (9.47%)
         occurrences all number
    43
    9
    Hypopnoea
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hypoxia
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Increased viscosity of bronchial secretion
         subjects affected / exposed
    23 / 183 (12.57%)
    12 / 95 (12.63%)
         occurrences all number
    31
    15
    Lung infiltration
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    6 / 183 (3.28%)
    4 / 95 (4.21%)
         occurrences all number
    8
    4
    Obstructive airways disorder
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Oropharyngeal pain
         subjects affected / exposed
    9 / 183 (4.92%)
    7 / 95 (7.37%)
         occurrences all number
    11
    8
    Paranasal sinus discomfort
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Pharyngeal erythema
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Pharyngeal oedema
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Pleurisy
         subjects affected / exposed
    4 / 183 (2.19%)
    3 / 95 (3.16%)
         occurrences all number
    6
    5
    Pleuritic pain
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Productive cough
         subjects affected / exposed
    5 / 183 (2.73%)
    0 / 95 (0.00%)
         occurrences all number
    5
    0
    Prolonged expiration
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Pulmonary mass
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rales
         subjects affected / exposed
    8 / 183 (4.37%)
    2 / 95 (2.11%)
         occurrences all number
    9
    2
    Respiratory failure
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Respiratory tract congestion
         subjects affected / exposed
    7 / 183 (3.83%)
    1 / 95 (1.05%)
         occurrences all number
    8
    4
    Respiratory tract irritation
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    3 / 183 (1.64%)
    6 / 95 (6.32%)
         occurrences all number
    3
    6
    Rhonchi
         subjects affected / exposed
    6 / 183 (3.28%)
    1 / 95 (1.05%)
         occurrences all number
    9
    1
    Sinus congestion
         subjects affected / exposed
    0 / 183 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    0
    4
    Sinus polyp
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Sputum decreased
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Sputum discoloured
         subjects affected / exposed
    8 / 183 (4.37%)
    4 / 95 (4.21%)
         occurrences all number
    8
    4
    Sputum increased
         subjects affected / exposed
    82 / 183 (44.81%)
    43 / 95 (45.26%)
         occurrences all number
    156
    98
    Sputum retention
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Throat irritation
         subjects affected / exposed
    4 / 183 (2.19%)
    2 / 95 (2.11%)
         occurrences all number
    10
    2
    Upper-airway cough syndrome
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Wheezing
         subjects affected / exposed
    69 / 183 (37.70%)
    35 / 95 (36.84%)
         occurrences all number
    129
    70
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Anxiety
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Depressed mood
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    3 / 183 (1.64%)
    3 / 95 (3.16%)
         occurrences all number
    3
    3
    Disorientation
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    2 / 183 (1.09%)
    4 / 95 (4.21%)
         occurrences all number
    2
    4
    Major depression
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Mental status changes
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Nightmare
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Panic attack
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    dysthymic disorder
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Bacterial test positive
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Blood cholesterol increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Blood urine present
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Body temperature increased
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Breath sounds abnormal
         subjects affected / exposed
    42 / 183 (22.95%)
    16 / 95 (16.84%)
         occurrences all number
    54
    23
    Cardiac murmur
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Chest X-ray
         subjects affected / exposed
    4 / 183 (2.19%)
    3 / 95 (3.16%)
         occurrences all number
    4
    3
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Forced expiratory volume decreased
         subjects affected / exposed
    62 / 183 (33.88%)
    19 / 95 (20.00%)
         occurrences all number
    86
    25
    Forced vital capacity decreased
         subjects affected / exposed
    37 / 183 (20.22%)
    14 / 95 (14.74%)
         occurrences all number
    48
    22
    Heart rate increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Heart rate irregular
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Lymph node palpable
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Lymphocyte count increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Mean cell volume increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Monocyte count increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Occult blood positive
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Oxygen saturation decreased
         subjects affected / exposed
    4 / 183 (2.19%)
    0 / 95 (0.00%)
         occurrences all number
    7
    0
    Protein urine present
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Pulmonary function test decreased
         subjects affected / exposed
    19 / 183 (10.38%)
    11 / 95 (11.58%)
         occurrences all number
    33
    23
    Spirometry abnormal
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Sputum abnormal
         subjects affected / exposed
    22 / 183 (12.02%)
    12 / 95 (12.63%)
         occurrences all number
    38
    25
    Staphylococcus test positive
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Urinary sediment present
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    4 / 183 (2.19%)
    2 / 95 (2.11%)
         occurrences all number
    5
    2
    Weight increased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    White blood cells urine positive
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Arthropod bite
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Arthropod sting
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Chemical burn of skin
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Chest injury
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Contusion
         subjects affected / exposed
    2 / 183 (1.09%)
    5 / 95 (5.26%)
         occurrences all number
    4
    7
    Epicondylitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Facial bones fracture
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Fall
         subjects affected / exposed
    4 / 183 (2.19%)
    2 / 95 (2.11%)
         occurrences all number
    4
    3
    Head injury
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Incisional hernia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Laceration
         subjects affected / exposed
    3 / 183 (1.64%)
    3 / 95 (3.16%)
         occurrences all number
    5
    3
    Ligament sprain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Muscle strain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rib fracture
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Skin wound
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Soft tissue injury
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Thermal burn
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Tooth fracture
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Atrial fibrillation
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Bradycardia
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Bundle branch block left
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Cardiomyopathy
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Cor pulmonale
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Nervous system disorders
    Anosmia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Aphonia
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Autonomic nervous system imbalance
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    15 / 183 (8.20%)
    5 / 95 (5.26%)
         occurrences all number
    21
    5
    Dysarthria
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Dysgeusia
         subjects affected / exposed
    19 / 183 (10.38%)
    6 / 95 (6.32%)
         occurrences all number
    48
    7
    Encephalopathy
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    21 / 183 (11.48%)
    11 / 95 (11.58%)
         occurrences all number
    35
    12
    Hemiparesis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Hypersomnia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hypogeusia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    39 / 183 (21.31%)
    18 / 95 (18.95%)
         occurrences all number
    61
    29
    Memory impairment
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    13
    0
    Neuralgia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Poor quality sleep
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Restless legs syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Sciatica
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Sinus headache
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Tremor
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 183 (2.73%)
    0 / 95 (0.00%)
         occurrences all number
    5
    0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Leukocytosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Deafness neurosensory
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Ear congestion
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    2
    Ear discomfort
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Ear haemorrhage
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Ear pain
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Hypoacusis
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Middle ear effusion
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    2
    Motion sickness
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Otorrhoea
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Vertigo
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Dacryostenosis acquired
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Eye pain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Macular degeneration
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Ocular discomfort
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Ocular hypertension
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Uveitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Xerophthalmia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain
         subjects affected / exposed
    8 / 183 (4.37%)
    0 / 95 (0.00%)
         occurrences all number
    9
    0
    Abdominal pain upper
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Change of bowel habit
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Coating in mouth
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    5 / 183 (2.73%)
    3 / 95 (3.16%)
         occurrences all number
    5
    3
    Diarrhoea
         subjects affected / exposed
    7 / 183 (3.83%)
    9 / 95 (9.47%)
         occurrences all number
    8
    11
    Diverticulum
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    3 / 183 (1.64%)
    2 / 95 (2.11%)
         occurrences all number
    4
    2
    Dyspepsia
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Dysphagia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Faecaloma
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Frequent bowel movements
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gastric ulcer
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 183 (0.55%)
    3 / 95 (3.16%)
         occurrences all number
    1
    3
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hiatus hernia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia oral
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Lip swelling
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Mouth ulceration
         subjects affected / exposed
    1 / 183 (0.55%)
    2 / 95 (2.11%)
         occurrences all number
    2
    2
    Nausea
         subjects affected / exposed
    16 / 183 (8.74%)
    4 / 95 (4.21%)
         occurrences all number
    24
    4
    Rectal haemorrhage
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Retching
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    5
    0
    Stomatitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Swollen tongue
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Tongue discolouration
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Tongue disorder
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Tongue eruption
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Vomiting
         subjects affected / exposed
    9 / 183 (4.92%)
    3 / 95 (3.16%)
         occurrences all number
    9
    3
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Jaundice
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Actinic keratosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Blister rupture
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Decubitus ulcer
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dermal cyst
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Dry skin
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Macule
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Miliaria
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Nail bed inflammation
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    6 / 183 (3.28%)
    1 / 95 (1.05%)
         occurrences all number
    7
    1
    Rash
         subjects affected / exposed
    6 / 183 (3.28%)
    2 / 95 (2.11%)
         occurrences all number
    8
    2
    Rash erythematous
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rash papular
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Skin lesion
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Urticaria
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Vasculitic rash
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Dysuria
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Haematuria
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Nephrolithiasis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Nocturia
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Pollakiuria
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Renal cyst
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hyperparathyroidism secondary
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    10 / 183 (5.46%)
    4 / 95 (4.21%)
         occurrences all number
    12
    4
    Arthritis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Arthritis reactive
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    13 / 183 (7.10%)
    3 / 95 (3.16%)
         occurrences all number
    16
    4
    Groin pain
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Joint range of motion decreased
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Limb discomfort
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Muscle spasms
         subjects affected / exposed
    3 / 183 (1.64%)
    2 / 95 (2.11%)
         occurrences all number
    4
    2
    Muscular weakness
         subjects affected / exposed
    3 / 183 (1.64%)
    0 / 95 (0.00%)
         occurrences all number
    4
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 183 (1.64%)
    2 / 95 (2.11%)
         occurrences all number
    3
    2
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Musculoskeletal pain
         subjects affected / exposed
    3 / 183 (1.64%)
    3 / 95 (3.16%)
         occurrences all number
    4
    3
    Myalgia
         subjects affected / exposed
    5 / 183 (2.73%)
    2 / 95 (2.11%)
         occurrences all number
    7
    2
    Neck pain
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Osteoarthritis
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    2
    Osteopenia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Pain in extremity
         subjects affected / exposed
    11 / 183 (6.01%)
    1 / 95 (1.05%)
         occurrences all number
    13
    1
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Rhabdomyolysis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 183 (0.55%)
    2 / 95 (2.11%)
         occurrences all number
    2
    2
    Soft tissue mass
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Spinal column stenosis
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Tendonitis
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Tenosynovitis stenosans
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Acute sinusitis
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    1
    Bacterial disease carrier
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Bacterial vaginosis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    5
    1
    Candida infection
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    2
    Cellulitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Corneal infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Cystitis
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Ear infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Eye infection
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Fungal infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Gastrointestinal infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Gingival abscess
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Haemophilus infection
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    2
    Helicobacter infection
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    2
    Herpes simplex
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Impetigo
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Infected cyst
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    4 / 183 (2.19%)
    3 / 95 (3.16%)
         occurrences all number
    4
    3
    Laryngitis
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    2
    2
    Localised infection
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Lower respiratory tract infection
         subjects affected / exposed
    5 / 183 (2.73%)
    4 / 95 (4.21%)
         occurrences all number
    7
    7
    Lung infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    8 / 183 (4.37%)
    5 / 95 (5.26%)
         occurrences all number
    11
    5
    Onychomycosis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    6 / 183 (3.28%)
    1 / 95 (1.05%)
         occurrences all number
    7
    1
    Oral herpes
         subjects affected / exposed
    3 / 183 (1.64%)
    2 / 95 (2.11%)
         occurrences all number
    3
    2
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Otitis media
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Peritonitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 183 (0.55%)
    2 / 95 (2.11%)
         occurrences all number
    1
    2
    Pneumonia
         subjects affected / exposed
    6 / 183 (3.28%)
    3 / 95 (3.16%)
         occurrences all number
    6
    3
    Pseudomonas infection
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Respiratory tract infection
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    3
    0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    5 / 183 (2.73%)
    3 / 95 (3.16%)
         occurrences all number
    7
    3
    Sepsis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Septic shock
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Sialoadenitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Sinobronchitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    4 / 183 (2.19%)
    5 / 95 (5.26%)
         occurrences all number
    5
    8
    Sputum purulent
         subjects affected / exposed
    34 / 183 (18.58%)
    13 / 95 (13.68%)
         occurrences all number
    54
    19
    Tooth abscess
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 183 (4.92%)
    1 / 95 (1.05%)
         occurrences all number
    13
    1
    Urinary tract infection
         subjects affected / exposed
    9 / 183 (4.92%)
    2 / 95 (2.11%)
         occurrences all number
    10
    2
    Vestibular neuronitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 183 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    Viral pharyngitis
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Wound infection
         subjects affected / exposed
    0 / 183 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 183 (1.09%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Dehydration
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Gout
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 183 (0.55%)
    1 / 95 (1.05%)
         occurrences all number
    1
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 183 (1.64%)
    1 / 95 (1.05%)
         occurrences all number
    3
    1
    Hypovolaemia
         subjects affected / exposed
    2 / 183 (1.09%)
    0 / 95 (0.00%)
         occurrences all number
    2
    0
    Iron deficiency
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0
    Lactose intolerance
         subjects affected / exposed
    1 / 183 (0.55%)
    0 / 95 (0.00%)
         occurrences all number
    1
    0

    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
    For support, Contact us.
    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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