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    Clinical Trial Results:
    Effects of oral Levosimendan (ODM-109) on respiratory function in patients with ALS

    Summary
    EudraCT number
    		 2017-002754-36
    Trial protocol
    		 IE   GB   BE   FI   AT   ES   NL   FR   IT  
    Global end of trial date
    26 Jun 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 May 2021
    First version publication date
    27 May 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    3119002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03505021
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Orion Corporation
    Sponsor organisation address
    Orionintie 1, Espoo, Finland, 02200
    Public contact
    Clinical Trials Information, Orion Corporation, +358 0104261, clinicaltrials@orionpharma.com
    Scientific contact
    Clinical Trials Information, Orion Corporation, +358 0104261, clinicaltrials@orionpharma.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
    26 Jun 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Jun 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jun 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to confirm that levosimendan can significantly improve respiratory function measured by supine slow vital capacity (SVC) in amyotrophic lateral sclerosis (ALS) patients.
    Protection of trial subjects
    Adverse events were followed by sponsor and the independent data and safety monitoring board (DSMB). Futility analyses were conducted by DSMB when approximately 50% and when all the subjects had been treated for 12 weeks. The study included frequent assessment of safety measurements typical of clinical trials, including blood pressure, heart rate 12-lead ECG, safety laboratory tests and adverse events. These were performed before, during and after study drug treatment. Specific criteria were in place for the withdrawal of patients from study treatment, including increased heart rate, pregnancy and need for invasive ventilator support. The investigator could also withdraw the treatment if considered to be in the best interests of the subject. Patients were free to leave the study at any time but were also withdrawn in the event of a safety finding of clinical concern.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Jun 2018
    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
    Canada: 47
    Country: Number of subjects enrolled
    Italy: 34
    Country: Number of subjects enrolled
    United States: 150
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Spain: 59
    Country: Number of subjects enrolled
    Sweden: 26
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    Austria: 7
    Country: Number of subjects enrolled
    Belgium: 22
    Country: Number of subjects enrolled
    Finland: 13
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 80
    Country: Number of subjects enrolled
    Ireland: 5
    Country: Number of subjects enrolled
    Australia: 20
    Worldwide total number of subjects
    496
    EEA total number of subjects
    270
    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)
    328
    From 65 to 84 years
    166
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients with amyotrophic lateral sclerosis (ALS) were recruited.

    Pre-assignment
    Screening details
    		 Male or female subjects with a diagnosis of probable or definite ALS according to El Escorial revised criteria, disease duration from symptom onset of 12-48 months, written or verbal IC obtained. Able to swallow study treatment capsules. Sitting SVC between 60-90% of the predicted value at screening visit. Stable riluzole and/or edaravone allowed.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Levosimendan
    Arm description
    		 The daily dose of oral levosimendan was 1-2 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    levosimendan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg capsule in the morning and when the dose was increased to 1 mg twice daily (after two weeks), the second dose was normally taken 12 hours later.

    Arm title
    		 Placebo
    Arm description
    		 Oral placebo matching levosimendan capsules was given once or twice daily.
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo capsule in the morning and when the dose was increased to one capsule twice daily (after two weeks), the second dose was normally taken 12 hours later.

    Number of subjects in period 1
    		Levosimendan Placebo
    Started
    329
    167
    Completed
    217
    112
    Not completed
    112
    55
         Adverse event, serious fatal
    9
    8
         Consent withdrawn by subject
    6
    1
         Disease progression
    33
    17
         Adverse event, non-fatal
    26
    9
         Personal reason
    21
    12
         Other
    11
    5
         Lost to follow-up
    5
    3
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 496 496
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 328 328
        From 65-84 years
    		 166 166
        85 years and over
    		 2 2
    Gender categorical
    Units: Subjects
        Female
    		 189 189
        Male
    		 307 307

    End points

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    End points reporting groups
    Reporting group title
    Levosimendan
    Reporting group description
    		 The daily dose of oral levosimendan was 1-2 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Oral placebo matching levosimendan capsules was given once or twice daily.

    Primary: Change from baseline to 12 weeks in supine SVC

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    End point title
    		 Change from baseline to 12 weeks in supine SVC
    End point description
    End point type
    Primary
    End point timeframe
    From baseline to 12 weeks
    End point values
    		 Levosimendan Placebo
    Number of subjects analysed
    288
    147
    Units: percent of predicted
        least squares mean (confidence interval 95%)
    -6.731 (-8.290 to -5.171)
    -6.988 (-9.052 to -4.925)
    Statistical analysis title
    		 Change from baseline, SVC (supine)
    Statistical analysis description
    Least square (LS) means estimate, repeated measures ANCOVA with missing data imputation
    Comparison groups
    Placebo v Levosimendan
    Number of subjects included in analysis
    435
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8253
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.258
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.032
         upper limit
    		 2.547

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From signing an informed consent until 25 days from stopping the treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Levosimendan
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Levosimendan Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    89 / 326 (27.30%)
    45 / 166 (27.11%)
         number of deaths (all causes)
    27
    17
         number of deaths resulting from adverse events
    27
    17
    Vascular disorders
    AORTIC STENOSIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSIVE CRISIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC DEATH
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CATHETER SITE INFLAMMATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 27
    0 / 17
    EUTHANASIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         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
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    1 / 326 (0.31%)
    0 / 166 (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
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    7 / 326 (2.15%)
    3 / 166 (1.81%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMPHYSEMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERCAPNIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOVENTILATION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARYNGEAL OEDEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NASAL CONGESTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    8 / 326 (2.45%)
    2 / 166 (1.20%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PRODUCTIVE COUGH
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    9 / 326 (2.76%)
    4 / 166 (2.41%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY ACIDOSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY DEPRESSION
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    13 / 326 (3.99%)
    5 / 166 (3.01%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY MUSCLE WEAKNESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WHEEZING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INSOMNIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESTLESSNESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    BRAIN CONTUSION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CERVICAL VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CLAVICLE FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FACIAL BONES FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    13 / 326 (3.99%)
    6 / 166 (3.61%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAND FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEAD INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    JOINT INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LIP INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMORRHAGE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PROCEDURAL PAIN
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKULL FRACTURED BASE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ULNA FRACTURE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER LIMB FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIO-RESPIRATORY ARREST
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CORONARY ARTERY DISSECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIASTOLIC DYSFUNCTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SINUS TACHYCARDIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STRESS CARDIOMYOPATHY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    AMYOTROPHIC LATERAL SCLEROSIS
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRAIN INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERCAPNIC COMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTRAVENTRICULAR HAEMORRHAGE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LACUNAR STROKE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SOMNOLENCE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBARACHNOID HAEMORRHAGE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UNRESPONSIVE TO STIMULI
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    BREAST CANCER
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOPHARYNGEAL CANCER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO LIVER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    VERTIGO POSITIONAL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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 DISTENSION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC ULCER HAEMORRHAGE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ILEUS
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ILEUS PARALYTIC
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PEPTIC ULCER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLELITHIASIS
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DECUBITUS ULCER
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERHIDROSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INGROWING NAIL
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    HAEMATURIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUROGENIC BLADDER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URETHRAL OBSTRUCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    APPENDICITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CATHETER SITE CELLULITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CATHETER SITE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTEROBACTER BACTERAEMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NASOPHARYNGITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    12 / 326 (3.68%)
    7 / 166 (4.22%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY SEPSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SERRATIA BACTERAEMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STOMA SITE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    5 / 166 (3.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULAR DEVICE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (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
    DEHYDRATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    		 Levosimendan Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    312 / 326 (95.71%)
    157 / 166 (94.58%)
    Vascular disorders
    ARTERIOSCLEROSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    5 / 326 (1.53%)
    3 / 166 (1.81%)
         occurrences all number
    5
    3
    HAEMATOMA
         subjects affected / exposed
    4 / 326 (1.23%)
    4 / 166 (2.41%)
         occurrences all number
    4
    4
    HOT FLUSH
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    HYPERTENSION
         subjects affected / exposed
    8 / 326 (2.45%)
    9 / 166 (5.42%)
         occurrences all number
    8
    10
    HYPOTENSION
         subjects affected / exposed
    3 / 326 (0.92%)
    2 / 166 (1.20%)
         occurrences all number
    4
    2
    ILIAC ARTERY STENOSIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    2
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    5 / 326 (1.53%)
    0 / 166 (0.00%)
         occurrences all number
    5
    0
    PERIPHERAL COLDNESS
         subjects affected / exposed
    0 / 326 (0.00%)
    3 / 166 (1.81%)
         occurrences all number
    0
    3
    RAYNAUD'S PHENOMENON
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    THROMBOSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    CENTRAL VENOUS CATHETERISATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DENTAL IMPLANTATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    GASTROSTOMY
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences all number
    5
    1
    MECHANICAL VENTILATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Pregnancy, puerperium and perinatal conditions
    CEPHALHAEMATOMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    16 / 326 (4.91%)
    1 / 166 (0.60%)
         occurrences all number
    19
    1
    CATHETER SITE BRUISE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CATHETER SITE HAEMORRHAGE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CATHETER SITE PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CHEST DISCOMFORT
         subjects affected / exposed
    4 / 326 (1.23%)
    4 / 166 (2.41%)
         occurrences all number
    6
    4
    CHEST PAIN
         subjects affected / exposed
    9 / 326 (2.76%)
    4 / 166 (2.41%)
         occurrences all number
    12
    6
    CHILLS
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    CYST
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    DISCOMFORT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DISEASE PROGRESSION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    FATIGUE
         subjects affected / exposed
    30 / 326 (9.20%)
    10 / 166 (6.02%)
         occurrences all number
    33
    11
    FEELING COLD
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    FEELING JITTERY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    GAIT DISTURBANCE
         subjects affected / exposed
    9 / 326 (2.76%)
    2 / 166 (1.20%)
         occurrences all number
    9
    2
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    MALAISE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    MEDICAL DEVICE PAIN
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MEDICAL DEVICE SITE ERYTHEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    MEDICAL DEVICE SITE HAEMORRHAGE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    OEDEMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    OEDEMA PERIPHERAL
         subjects affected / exposed
    26 / 326 (7.98%)
    12 / 166 (7.23%)
         occurrences all number
    28
    14
    PAIN
         subjects affected / exposed
    11 / 326 (3.37%)
    2 / 166 (1.20%)
         occurrences all number
    12
    2
    PARADOXICAL DRUG REACTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PERIPHERAL SWELLING
         subjects affected / exposed
    7 / 326 (2.15%)
    3 / 166 (1.81%)
         occurrences all number
    7
    4
    PYREXIA
         subjects affected / exposed
    4 / 326 (1.23%)
    4 / 166 (2.41%)
         occurrences all number
    5
    5
    SECRETION DISCHARGE
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences all number
    4
    3
    SWELLING FACE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VESSEL PUNCTURE SITE BRUISE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    ALLERGY TO ARTHROPOD BITE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CONTRAST MEDIA ALLERGY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SEASONAL ALLERGY
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    Social circumstances
    LOSS OF PERSONAL INDEPENDENCE IN DAILY ACTIVITIES
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ERECTILE DYSFUNCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MENOPAUSAL SYMPTOMS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MENSTRUATION IRREGULAR
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PROSTATITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PROSTATOMEGALY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ATELECTASIS
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    BRONCHITIS CHRONIC
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    BRONCHOSPASM
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CHOKING
         subjects affected / exposed
    5 / 326 (1.53%)
    2 / 166 (1.20%)
         occurrences all number
    5
    2
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    COUGH
         subjects affected / exposed
    16 / 326 (4.91%)
    13 / 166 (7.83%)
         occurrences all number
    19
    15
    COUGH DECREASED
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    DIAPHRAGM MUSCLE WEAKNESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DIAPHRAGMATIC PARALYSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    DIAPHRAGMATIC SPASM
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    DYSPHONIA
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    DYSPNOEA
         subjects affected / exposed
    54 / 326 (16.56%)
    30 / 166 (18.07%)
         occurrences all number
    61
    35
    DYSPNOEA AT REST
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    EMPHYSEMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    EPISTAXIS
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    HYPERACTIVE PHARYNGEAL REFLEX
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPERVENTILATION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    HYPOVENTILATION
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    HYPOXIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    INCREASED BRONCHIAL SECRETION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    INCREASED UPPER AIRWAY SECRETION
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    INCREASED VISCOSITY OF UPPER RESPIRATORY SECRETION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LARYNGOSPASM
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NASAL CONGESTION
         subjects affected / exposed
    5 / 326 (1.53%)
    4 / 166 (2.41%)
         occurrences all number
    5
    4
    NASAL DRYNESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NASAL POLYPS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NASAL PRURITUS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    5 / 326 (1.53%)
    6 / 166 (3.61%)
         occurrences all number
    5
    6
    ORTHOPNOEA
         subjects affected / exposed
    6 / 326 (1.84%)
    3 / 166 (1.81%)
         occurrences all number
    6
    3
    PHARYNGEAL ERYTHEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    PRODUCTIVE COUGH
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences all number
    5
    3
    PULMONARY CONGESTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    PULMONARY MASS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    RESPIRATORY FAILURE
         subjects affected / exposed
    17 / 326 (5.21%)
    12 / 166 (7.23%)
         occurrences all number
    17
    12
    RESPIRATORY MUSCLE WEAKNESS
         subjects affected / exposed
    2 / 326 (0.61%)
    3 / 166 (1.81%)
         occurrences all number
    2
    3
    RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    RHINITIS ALLERGIC
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    RHINORRHOEA
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences all number
    4
    1
    SINUS CONGESTION
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    SLEEP APNOEA SYNDROME
         subjects affected / exposed
    5 / 326 (1.53%)
    3 / 166 (1.81%)
         occurrences all number
    6
    3
    SPUTUM RETENTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    UPPER RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    UPPER-AIRWAY COUGH SYNDROME
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    VOCAL CORD DYSFUNCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    WHEEZING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    ABNORMAL DREAMS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ADJUSTMENT DISORDER WITH DEPRESSED MOOD
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    AFFECT LABILITY
         subjects affected / exposed
    6 / 326 (1.84%)
    4 / 166 (2.41%)
         occurrences all number
    6
    4
    AFFECTIVE DISORDER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    AGITATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    ANXIETY
         subjects affected / exposed
    18 / 326 (5.52%)
    6 / 166 (3.61%)
         occurrences all number
    18
    6
    CONFUSIONAL STATE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    DEPRESSED MOOD
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    DEPRESSION
         subjects affected / exposed
    13 / 326 (3.99%)
    4 / 166 (2.41%)
         occurrences all number
    13
    4
    FEAR
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    HALLUCINATION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    INITIAL INSOMNIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    INSOMNIA
         subjects affected / exposed
    22 / 326 (6.75%)
    10 / 166 (6.02%)
         occurrences all number
    22
    10
    MENTAL DISORDER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MIDDLE INSOMNIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PANIC ATTACK
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    RESTLESSNESS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SLEEP DISORDER
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    STRESS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    TENSION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Product issues
    DEVICE OCCLUSION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    6 / 326 (1.84%)
    3 / 166 (1.81%)
         occurrences all number
    7
    3
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences all number
    5
    3
    BACTERIAL TEST
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BACTERIAL TEST POSITIVE
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    BLOOD CALCIUM DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    5 / 326 (1.53%)
    2 / 166 (1.20%)
         occurrences all number
    6
    2
    BLOOD FOLATE DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLOOD GLUCOSE INCREASED
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    BLOOD POTASSIUM INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLOOD PRESSURE INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    BLOOD PRESSURE ORTHOSTATIC INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    BLOOD SODIUM INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLOOD THYROID STIMULATING HORMONE DECREASED
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    BLOOD THYROID STIMULATING HORMONE INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    BLOOD URINE PRESENT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BODY TEMPERATURE INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    C-REACTIVE PROTEIN INCREASED
         subjects affected / exposed
    6 / 326 (1.84%)
    3 / 166 (1.81%)
         occurrences all number
    6
    3
    CARDIAC MURMUR
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences all number
    4
    3
    ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    EOSINOPHIL COUNT INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    FORCED VITAL CAPACITY DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    7 / 326 (2.15%)
    3 / 166 (1.81%)
         occurrences all number
    7
    3
    GASTRIC PH DECREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    GLUCOSE URINE PRESENT
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    HAEMOGLOBIN DECREASED
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    HEART RATE DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    HEART RATE INCREASED
         subjects affected / exposed
    64 / 326 (19.63%)
    5 / 166 (3.01%)
         occurrences all number
    68
    5
    HEPATIC ENZYME INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    INTRAOCULAR PRESSURE INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MONOCYTE COUNT INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NEUTROPHIL COUNT INCREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    ORTHOSTATIC HEART RATE RESPONSE INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    OXYGEN SATURATION DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    PLATELET COUNT INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PROTEIN URINE PRESENT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PULMONARY FUNCTION TEST DECREASED
         subjects affected / exposed
    7 / 326 (2.15%)
    2 / 166 (1.20%)
         occurrences all number
    7
    2
    RED BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SLOW VITAL CAPACITY DECREASED
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    TRANSAMINASES INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    TROPONIN INCREASED
         subjects affected / exposed
    8 / 326 (2.45%)
    1 / 166 (0.60%)
         occurrences all number
    9
    1
    TROPONIN T INCREASED
         subjects affected / exposed
    10 / 326 (3.07%)
    2 / 166 (1.20%)
         occurrences all number
    10
    2
    URINE ANALYSIS ABNORMAL
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    URINE LEUKOCYTE ESTERASE POSITIVE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VITAL CAPACITY DECREASED
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    WEIGHT DECREASED
         subjects affected / exposed
    26 / 326 (7.98%)
    15 / 166 (9.04%)
         occurrences all number
    27
    15
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    WHITE BLOOD CELL COUNT INCREASED
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    WHITE BLOOD CELLS URINE POSITIVE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    ANIMAL BITE
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    ANKLE FRACTURE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    BACK INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BONE CONTUSION
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    BONE FISSURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BURNS SECOND DEGREE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CLAVICLE FRACTURE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    CONCUSSION
         subjects affected / exposed
    3 / 326 (0.92%)
    4 / 166 (2.41%)
         occurrences all number
    4
    4
    CONTUSION
         subjects affected / exposed
    21 / 326 (6.44%)
    8 / 166 (4.82%)
         occurrences all number
    23
    9
    CRANIOCEREBRAL INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    EYE CONTUSION
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    EYE INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    FACIAL BONES FRACTURE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    FALL
         subjects affected / exposed
    86 / 326 (26.38%)
    45 / 166 (27.11%)
         occurrences all number
    150
    100
    FIBULA FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    FOOT FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    GASTROSTOMY TUBE SITE COMPLICATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HAND FRACTURE
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    HEAD INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    HUMERUS FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPHAEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    INCISION SITE HAEMATOMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    INCISION SITE IMPAIRED HEALING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    JOINT DISLOCATION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    JOINT INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LIGAMENT RUPTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LIGAMENT SPRAIN
         subjects affected / exposed
    8 / 326 (2.45%)
    2 / 166 (1.20%)
         occurrences all number
    9
    2
    LIMB INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    3 / 166 (1.81%)
         occurrences all number
    0
    3
    LIP INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    MUSCLE INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MUSCLE STRAIN
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MUSCULOSKELETAL FOREIGN BODY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NASAL INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    POST LUMBAR PUNCTURE SYNDROME
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    POST-TRAUMATIC PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    PROCEDURAL PAIN
         subjects affected / exposed
    5 / 326 (1.53%)
    0 / 166 (0.00%)
         occurrences all number
    5
    0
    RADIUS FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    RIB FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    3 / 326 (0.92%)
    2 / 166 (1.20%)
         occurrences all number
    3
    3
    SCRATCH
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SCROTAL HAEMATOMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SKIN ABRASION
         subjects affected / exposed
    5 / 326 (1.53%)
    1 / 166 (0.60%)
         occurrences all number
    7
    1
    SKIN INJURY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SKIN LACERATION
         subjects affected / exposed
    17 / 326 (5.21%)
    12 / 166 (7.23%)
         occurrences all number
    20
    15
    SPINAL FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    STOMA SITE DISCOMFORT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    STOMA SITE PAIN
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    STOMA SITE REACTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    THERMAL BURN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    TOOTH FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    UPPER LIMB FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    WOUND
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    WRIST FRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    AORTIC VALVE SCLEROSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    BRADYCARDIA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    CARDIAC DISCOMFORT
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CARDIAC FLUTTER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CARDIAC HYPERTROPHY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CARDIOMYOPATHY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CARDIOVASCULAR DISORDER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    DIASTOLIC DYSFUNCTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LONG QT SYNDROME
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MITRAL VALVE INCOMPETENCE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    NODAL RHYTHM
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PALPITATIONS
         subjects affected / exposed
    17 / 326 (5.21%)
    4 / 166 (2.41%)
         occurrences all number
    23
    4
    SINUS TACHYCARDIA
         subjects affected / exposed
    13 / 326 (3.99%)
    0 / 166 (0.00%)
         occurrences all number
    14
    0
    TACHYCARDIA
         subjects affected / exposed
    32 / 326 (9.82%)
    8 / 166 (4.82%)
         occurrences all number
    41
    11
    TACHYCARDIA PAROXYSMAL
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    VENTRICULAR EXTRASYSTOLES
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    VENTRICULAR HYPERTROPHY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    Nervous system disorders
    AGEUSIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    AMYOTROPHIC LATERAL SCLEROSIS
         subjects affected / exposed
    4 / 326 (1.23%)
    4 / 166 (2.41%)
         occurrences all number
    4
    4
    ATAXIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BALANCE DISORDER
         subjects affected / exposed
    2 / 326 (0.61%)
    3 / 166 (1.81%)
         occurrences all number
    2
    3
    BURNING SENSATION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    CERVICAL RADICULOPATHY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    COGNITIVE DISORDER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DEMENTIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    DEPRESSED LEVEL OF CONSCIOUSNESS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DIZZINESS
         subjects affected / exposed
    21 / 326 (6.44%)
    13 / 166 (7.83%)
         occurrences all number
    35
    14
    DROOLING
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    DYSARTHRIA
         subjects affected / exposed
    6 / 326 (1.84%)
    1 / 166 (0.60%)
         occurrences all number
    6
    1
    DYSGEUSIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    3
    FINE MOTOR SKILL DYSFUNCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HEADACHE
         subjects affected / exposed
    101 / 326 (30.98%)
    36 / 166 (21.69%)
         occurrences all number
    142
    49
    HYPERREFLEXIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPOAESTHESIA
         subjects affected / exposed
    4 / 326 (1.23%)
    2 / 166 (1.20%)
         occurrences all number
    4
    2
    INTENTION TREMOR
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LETHARGY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MENTAL IMPAIRMENT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MIGRAINE
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    MONOPARESIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MUSCLE CONTRACTIONS INVOLUNTARY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MUSCLE SPASTICITY
         subjects affected / exposed
    7 / 326 (2.15%)
    1 / 166 (0.60%)
         occurrences all number
    7
    1
    NEURALGIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    NEUROLOGICAL DECOMPENSATION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PARAESTHESIA
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    PAROSMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PERONEAL NERVE PALSY
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    POOR QUALITY SLEEP
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    PRESYNCOPE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    RADIAL NERVE PALSY
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    RESTLESS LEGS SYNDROME
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SCIATICA
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    SOMNOLENCE
         subjects affected / exposed
    6 / 326 (1.84%)
    3 / 166 (1.81%)
         occurrences all number
    6
    3
    SPEECH DISORDER
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences all number
    5
    1
    SYNCOPE
         subjects affected / exposed
    8 / 326 (2.45%)
    2 / 166 (1.20%)
         occurrences all number
    8
    3
    TASTE DISORDER
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    TENSION HEADACHE
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    TREMOR
         subjects affected / exposed
    4 / 326 (1.23%)
    2 / 166 (1.20%)
         occurrences all number
    4
    2
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    ANAEMIA MACROCYTIC
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    BASAL CELL CARCINOMA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    BENIGN NEOPLASM OF THYROID GLAND
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BOWEN'S DISEASE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    HYPOPHARYNGEAL CANCER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LEUKOCYTOSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LEUKOPENIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LYMPHADENITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LYMPHOPENIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MYELOPROLIFERATIVE NEOPLASM
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    NORMOCYTIC ANAEMIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SCHWANNOMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SQUAMOUS CELL CARCINOMA OF SKIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    EAR PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    TINNITUS
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    5
    0
    VERTIGO
         subjects affected / exposed
    6 / 326 (1.84%)
    3 / 166 (1.81%)
         occurrences all number
    6
    3
    VERTIGO POSITIONAL
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    Eye disorders
    BORDERLINE GLAUCOMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CATARACT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    CONJUNCTIVAL HAEMORRHAGE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DIPLOPIA
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    DRY EYE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    ENTROPION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    EYE DISCHARGE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    EYE HAEMATOMA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    EYE INFLAMMATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    EYE IRRITATION
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    EYE PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    EYE SWELLING
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    EYELID CYST
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    GLAUCOMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    IRITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LACRIMATION INCREASED
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    MACULAR DEGENERATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VISION BLURRED
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    3 / 326 (0.92%)
    4 / 166 (2.41%)
         occurrences all number
    3
    4
    ABDOMINAL DISTENSION
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    12 / 326 (3.68%)
    2 / 166 (1.20%)
         occurrences all number
    13
    2
    ABDOMINAL PAIN LOWER
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    2
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    7 / 326 (2.15%)
    2 / 166 (1.20%)
         occurrences all number
    7
    2
    APHTHOUS ULCER
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CONSTIPATION
         subjects affected / exposed
    38 / 326 (11.66%)
    21 / 166 (12.65%)
         occurrences all number
    41
    22
    DENTAL CARIES
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    DENTAL DISCOMFORT
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    DIARRHOEA
         subjects affected / exposed
    26 / 326 (7.98%)
    14 / 166 (8.43%)
         occurrences all number
    31
    18
    DRY MOUTH
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    DYSPEPSIA
         subjects affected / exposed
    3 / 326 (0.92%)
    6 / 166 (3.61%)
         occurrences all number
    4
    7
    DYSPHAGIA
         subjects affected / exposed
    47 / 326 (14.42%)
    27 / 166 (16.27%)
         occurrences all number
    55
    31
    ENTERITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    ERUCTATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    FLATULENCE
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    FOOD POISONING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    GASTRIC HYPERMOTILITY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    GASTRIC ULCER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    GASTRITIS
         subjects affected / exposed
    3 / 326 (0.92%)
    2 / 166 (1.20%)
         occurrences all number
    3
    2
    GASTROINTESTINAL PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    7 / 326 (2.15%)
    3 / 166 (1.81%)
         occurrences all number
    7
    3
    HIATUS HERNIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPOAESTHESIA ORAL
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    IRRITABLE BOWEL SYNDROME
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    LIP SWELLING
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MOUTH ULCERATION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NAUSEA
         subjects affected / exposed
    29 / 326 (8.90%)
    15 / 166 (9.04%)
         occurrences all number
    35
    17
    ODYNOPHAGIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ORAL MUCOSAL BLISTERING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    RETCHING
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SALIVARY GLAND ENLARGEMENT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SALIVARY HYPERSECRETION
         subjects affected / exposed
    22 / 326 (6.75%)
    9 / 166 (5.42%)
         occurrences all number
    23
    10
    TONGUE ULCERATION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    TOOTHACHE
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    2
    VOMITING
         subjects affected / exposed
    2 / 326 (0.61%)
    5 / 166 (3.01%)
         occurrences all number
    2
    6
    Skin and subcutaneous tissue disorders
    ACNE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    ALOPECIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    BLISTER
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DECUBITUS ULCER
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    DERMATITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DERMATITIS CONTACT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    DRY SKIN
         subjects affected / exposed
    5 / 326 (1.53%)
    2 / 166 (1.20%)
         occurrences all number
    5
    2
    DYSHIDROTIC ECZEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    ECZEMA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    ERYTHEMA
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    HYPERHIDROSIS
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    INGROWING NAIL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MILIARIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NIGHT SWEATS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PIGMENTATION DISORDER
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PRURITUS
         subjects affected / exposed
    10 / 326 (3.07%)
    4 / 166 (2.41%)
         occurrences all number
    10
    4
    RASH
         subjects affected / exposed
    11 / 326 (3.37%)
    6 / 166 (3.61%)
         occurrences all number
    11
    8
    RASH MACULAR
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    RASH PAPULAR
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SEBORRHOEA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SEBORRHOEIC DERMATITIS
         subjects affected / exposed
    3 / 326 (0.92%)
    0 / 166 (0.00%)
         occurrences all number
    3
    0
    SKIN EXFOLIATION
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    SKIN IRRITATION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLADDER DYSFUNCTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BLADDER PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    BLADDER SPASM
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    CHROMATURIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HAEMATURIA
         subjects affected / exposed
    0 / 326 (0.00%)
    3 / 166 (1.81%)
         occurrences all number
    0
    4
    HYPERTONIC BLADDER
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    INCONTINENCE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    LEUKOCYTURIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MICTURITION URGENCY
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    NOCTURIA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    POLLAKIURIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    POLYURIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PROTEINURIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    RENAL COLIC
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    RENAL FAILURE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    RENAL PAIN
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    URGE INCONTINENCE
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    URINARY RETENTION
         subjects affected / exposed
    3 / 326 (0.92%)
    3 / 166 (1.81%)
         occurrences all number
    3
    3
    URINE ABNORMALITY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    DIABETES INSIPIDUS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    13 / 326 (3.99%)
    9 / 166 (5.42%)
         occurrences all number
    15
    9
    ARTHRITIS
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    BACK PAIN
         subjects affected / exposed
    14 / 326 (4.29%)
    7 / 166 (4.22%)
         occurrences all number
    16
    11
    BONE PAIN
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    BURSITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    COCCYDYNIA
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    3
    1
    EXOSTOSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    FRACTURE PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    GROIN PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    JOINT HYPEREXTENSION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    JOINT NOISE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    JOINT SWELLING
         subjects affected / exposed
    7 / 326 (2.15%)
    0 / 166 (0.00%)
         occurrences all number
    7
    0
    LIMB MASS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MOBILITY DECREASED
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences all number
    5
    1
    MUSCLE CONTRACTURE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MUSCLE FATIGUE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MUSCLE SPASMS
         subjects affected / exposed
    17 / 326 (5.21%)
    7 / 166 (4.22%)
         occurrences all number
    21
    8
    MUSCLE TIGHTNESS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MUSCLE TWITCHING
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    MUSCULAR WEAKNESS
         subjects affected / exposed
    31 / 326 (9.51%)
    18 / 166 (10.84%)
         occurrences all number
    39
    18
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    6 / 326 (1.84%)
    1 / 166 (0.60%)
         occurrences all number
    6
    1
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    14 / 326 (4.29%)
    8 / 166 (4.82%)
         occurrences all number
    17
    8
    MUSCULOSKELETAL STIFFNESS
         subjects affected / exposed
    4 / 326 (1.23%)
    1 / 166 (0.60%)
         occurrences all number
    4
    1
    MYALGIA
         subjects affected / exposed
    4 / 326 (1.23%)
    3 / 166 (1.81%)
         occurrences all number
    4
    3
    NECK PAIN
         subjects affected / exposed
    10 / 326 (3.07%)
    6 / 166 (3.61%)
         occurrences all number
    11
    6
    PAIN IN EXTREMITY
         subjects affected / exposed
    24 / 326 (7.36%)
    6 / 166 (3.61%)
         occurrences all number
    28
    6
    PAIN IN JAW
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    PERIARTHRITIS
         subjects affected / exposed
    3 / 326 (0.92%)
    1 / 166 (0.60%)
         occurrences all number
    4
    1
    POSTURE ABNORMAL
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    ROTATOR CUFF SYNDROME
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SPINAL PAIN
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    TENDONITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    TENOSYNOVITIS STENOSANS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    Infections and infestations
    ALVEOLAR OSTEITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BACTERIAL INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    BACTERIURIA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    BLASTOMYCOSIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    BRONCHITIS
         subjects affected / exposed
    7 / 326 (2.15%)
    4 / 166 (2.41%)
         occurrences all number
    8
    4
    CANDIDA INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    CATHETER SITE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CELLULITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CONJUNCTIVITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    COVID-19
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    CYSTITIS
         subjects affected / exposed
    4 / 326 (1.23%)
    4 / 166 (2.41%)
         occurrences all number
    6
    4
    EAR INFECTION
         subjects affected / exposed
    3 / 326 (0.92%)
    3 / 166 (1.81%)
         occurrences all number
    3
    3
    ERYSIPELAS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    EYE INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    FUNGAL INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    FUNGAL SKIN INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    FURUNCLE
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    GASTROENTERITIS
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    6 / 326 (1.84%)
    2 / 166 (1.20%)
         occurrences all number
    7
    2
    GASTROINTESTINAL INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    GENITOURINARY TRACT INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HELMINTHIC INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    HERPES ZOSTER
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    HORDEOLUM
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    IMPETIGO
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    INFECTED BITE
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    INFLUENZA
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    4
    0
    LARYNGITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    2
    LOCALISED INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    4 / 326 (1.23%)
    0 / 166 (0.00%)
         occurrences all number
    5
    0
    MALASSEZIA INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    MEDICAL DEVICE SITE INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NAIL INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    52 / 326 (15.95%)
    26 / 166 (15.66%)
         occurrences all number
    62
    31
    ORAL CANDIDIASIS
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    ORAL FUNGAL INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    ORAL HERPES
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    OROPHARYNGEAL CANDIDIASIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    OTITIS MEDIA CHRONIC
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    PERIODONTITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PHARYNGITIS
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    2
    PHARYNGITIS STREPTOCOCCAL
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    PNEUMONIA
         subjects affected / exposed
    2 / 326 (0.61%)
    5 / 166 (3.01%)
         occurrences all number
    2
    5
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    PULPITIS DENTAL
         subjects affected / exposed
    2 / 326 (0.61%)
    2 / 166 (1.20%)
         occurrences all number
    2
    3
    PYELITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    7 / 326 (2.15%)
    2 / 166 (1.20%)
         occurrences all number
    7
    2
    RHINITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    3
    ROOT CANAL INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    SIALOADENITIS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    SINUSITIS
         subjects affected / exposed
    8 / 326 (2.45%)
    3 / 166 (1.81%)
         occurrences all number
    8
    3
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    STOMA SITE INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    TONGUE FUNGAL INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    TONSILLITIS
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    TOOTH ABSCESS
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    TOOTH INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    13 / 326 (3.99%)
    5 / 166 (3.01%)
         occurrences all number
    16
    5
    URINARY TRACT INFECTION
         subjects affected / exposed
    25 / 326 (7.67%)
    17 / 166 (10.24%)
         occurrences all number
    31
    22
    URINARY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VIRAL INFECTION
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    1 / 166 (0.60%)
         occurrences all number
    2
    1
    VULVOVAGINAL MYCOTIC INFECTION
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    CACHEXIA
         subjects affected / exposed
    1 / 326 (0.31%)
    1 / 166 (0.60%)
         occurrences all number
    1
    1
    DECREASED APPETITE
         subjects affected / exposed
    10 / 326 (3.07%)
    5 / 166 (3.01%)
         occurrences all number
    10
    5
    DEHYDRATION
         subjects affected / exposed
    1 / 326 (0.31%)
    2 / 166 (1.20%)
         occurrences all number
    1
    2
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    GOUT
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 326 (0.00%)
    2 / 166 (1.20%)
         occurrences all number
    0
    3
    HYPERLIPIDAEMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPOKALAEMIA
         subjects affected / exposed
    3 / 326 (0.92%)
    2 / 166 (1.20%)
         occurrences all number
    3
    2
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 326 (0.61%)
    0 / 166 (0.00%)
         occurrences all number
    2
    0
    HYPOPHAGIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    HYPOVOLAEMIA
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    IRON DEFICIENCY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0
    MALNUTRITION
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    POLYDIPSIA
         subjects affected / exposed
    0 / 326 (0.00%)
    1 / 166 (0.60%)
         occurrences all number
    0
    1
    VITAMIN B12 DEFICIENCY
         subjects affected / exposed
    1 / 326 (0.31%)
    0 / 166 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jan 2018
    -Orthostatic test was added as requested by the FDA. -Instruction not to report day-to-day fluctuation in ALS signs/symptoms (e.g. dysphagia,muscular weakness) not indicating clinically significant progression of the disease as an AE was added. -Background was updated regarding new information on tirasemtiv and CK-2127101. -Number of centres was updated from 70-80 to approximately 100. -Primary and secondary efficacy evaluations were clarified to include all SVC measurements prior to 12 weeks in the statistical model. -Timing of vital sign assessments during baseline and treatment period was clarified. -Flexibility was added to timing of the second daily dose to best meet clinical needs of the subjects. -Objectives related to health care resource use were updated to be in line with home diary questions. -Data to be collected on subjects who have discontinued the study treatment were clarified, as well as the end-of-study visit assessments for these subjects
    17 Apr 2018
    -Borg scale was added to obtain subjects’ perception of the intensity of dyspnoea. -Use of edaravone was allowed as it was becoming standard of care in the USA. - CK-2127107 was replaced by the generic name reldesemtiv. -Discussion of cardiac safety and possible risks were added as requested by the Medical Products Agency (MPA) Sweden. -Exclusion of patients with severe renal impairment was added as requested by the MPA Sweden. -Lactating women were excluded as requested by the Medicines and Healthcare Products Regulatory Agency (MHRA) UK. -Use of highly effective contraceptive measures was added as requested by the Federal Agency for Medicines and Health Products (FAMPH) Belgium, Italian Medicines Agency (AIFA) Italy, Health Products Regulatory Authority (HPRA) Ireland and MPA Sweden. -ECG recording procedure was clarified and in order to verify that the measured HR represents genuine resting value, repeated 12-lead ECG recordings were added in connection with criteria on dose decrease. -Unblinding procedure was changed as requested by the MHRA UK. -Back-up system of the IWRS was added as requested by the MPA Sweden. -Pregnancy test was added to all physical visits except at week 2 as requested by the FAMPH Belgium and MHRA UK. -Re-screening procedure was clarified. -A mistake regarding PK sampling was corrected: at visits 4, 5, 6, and 7 only one blood sample was collected for levosimendan, OR-1855 and OR-1896 PK
    26 Mar 2020
    This amendment was written to describe how to perform visits 7 (week 36), 8 (week 48) and/or end-of-study visit (14-25 days after visit 8) remotely in case visit to the study centre was not possible due to restriction related to COVID-19 pandemic. The telephone visit was to include all protocol assessments that could be performed remotely and was to take place within the original visit window. In addition to the telephone visit, the investigator was to make reasonable efforts to obtain 12-lead ECG, laboratory safety assessments and vital signs for each visit. These measurements could include local practitioners and resources. In case these assessments, at least vital signs, could not be obtained within a reasonable time after the visit 7 telephone contact, the benefit-risk ratio for the subject to continue in the study was to be reassessed. The following assessments were not performed at telephone visits: SVC supine, weight, sitting or orthostatic changes in vital signs, blood sampling for levosimendan, OR-1855 and OR-1896 PK, for riluzole concentration and for exploratory biomarkers, and physical examination. Table 4. Study Procedures at remote visits was created.

    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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