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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 26-Week, Phase 3 Study of Two Doses of EVP-6124 or Placebo in Subjects with Mild to Moderate Alzheimer?s Disease Currently or Previously Receiving an Acetylcholinesterase Inhibitor Medication

    Summary
    EudraCT number
    		 2013-002618-10
    Trial protocol
    		 IT   DE   BE   ES  
    Global end of trial date
    20 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jan 2017
    First version publication date
    04 Jan 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    EVP-6124-024
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01969123
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND Number: 102623
    Sponsors
    Sponsor organisation name
    FORUM Pharmaceuticals Inc.
    Sponsor organisation address
    225 Second Avenue, Waltham, MA, United States, 02451
    Public contact
    Franz Buchholzer, inVentiv Health Clinical UK Ltd, RegOpsEurope@inventivhealth.com
    Scientific contact
    Franz Buchholzer, inVentiv Health Clinical UK Ltd, RegOpsEurope@inventivhealth.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
    24 May 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Nov 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives are to evaluate the safety and efficacy of 2 fixed doses of EVP-6124 HCl (2 or 3 mg daily) compared to placebo for 26 weeks in subjects with mild to moderate dementia due to AD currently receiving stable treatment or previously treated with an AChEI (donepezil, rivastigmine, or galantamine). The primary efficacy response will be an assessment of the change from baseline in cognitive, (ADAS-Cog-13) and functional/global (CDR-SB) endpoints.
    Protection of trial subjects
    There were no invasive or potentially pain-inducing procedures in this study except blood sampling. If patients experience pain, analgesic treatment was allowed per the physician discretion.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Oct 2013
    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
    Australia: 15
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Japan: 17
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    South Africa: 52
    Country: Number of subjects enrolled
    Korea, Republic of: 26
    Country: Number of subjects enrolled
    United States: 251
    Country: Number of subjects enrolled
    Poland: 43
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Italy: 11
    Worldwide total number of subjects
    474
    EEA total number of subjects
    86
    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)
    61
    From 65 to 84 years
    395
    85 years and over
    18

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 On Day -14, eligible subjects will enter a single-blind run-in period to assess compliance with placebo study drug. To qualify for randomization at baseline, subjects must return unused study drug, be ≥75% compliant with study drug, considered capable of completing the study assessments, and meet all eligibility requirements.

    Pre-assignment period milestones
    Number of subjects started
    		 832 [1]
    Intermediate milestone: Number of subjects
    Run-in: 543
    Number of subjects completed
    		 474

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Other: 358
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of randomized subjects (474) per country is indicated in the Trial information section. The number of screened subjects (832) is reported in the pre-assignment period.
    Period 1
    Period 1 title
    Double-blind period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be instructed to take 1 tablet once daily at the same time each day, preferably between 8 and 10 AM, with or without food, and with an adequate amount of water.

    Arm title
    		 EVP-6124, 2 mg
    Arm description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Encenicline
    Investigational medicinal product code
    EVP-6124
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be instructed to take 1 tablet once daily at the same time each day, preferably between 8 and 10 AM, with or without food, and with an adequate amount of water.

    Arm title
    		 EVP-6124, 3 mg
    Arm description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Encenicline
    Investigational medicinal product code
    EVP-6124
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be instructed to take 1 tablet once daily at the same time each day, preferably between 8 and 10 AM, with or without food, and with an adequate amount of water.

    Number of subjects in period 1
    		Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Started
    156
    157
    161
    Completed
    85
    78
    72
    Not completed
    71
    79
    89
         Consent withdrawn by subject
    2
    -
    6
         Adverse event, non-fatal
    3
    11
    6
         Other
    -
    3
    3
         Death
    -
    -
    1
         Withdrawal by Subject/Caregiver
    2
    4
    7
         Due to Clinical hold
    64
    60
    64
         Lost to follow-up
    -
    1
    1
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 3 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg Total
    Number of subjects
    		 156 157 161 474
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 19 15 27 61
        From 65-84 years
    		 132 131 132 395
        85 years and over
    		 5 11 2 18
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 74.3 (57 to 85) 74 (55 to 85) 73.3 (55 to 85) -
    Gender categorical
    Units: Subjects
        Female
    		 93 81 99 273
        Male
    		 63 76 62 201

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 3 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Primary: Cognitive Subscale 13-item (ADAS-Cog-13) (change from baseline)

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    End point title
    		 Cognitive Subscale 13-item (ADAS-Cog-13) (change from baseline) [1]
    End point description
    End point type
    Primary
    End point timeframe
    On Day -14 (run-in), baseline (predose on Day 1) and Days 84, 140, and 182 or early termination.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed. An analysis of the available data at the time of halting the trial was conducted to determine of there was any indication of a clinical response. However, these exploratory analyses were negative.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    150
    157
    Units: n/a
        arithmetic mean (full range (min-max))
    2.4 (-14 to 29)
    1.7 (-15 to 19)
    2.5 (-11 to 19)
    No statistical analyses for this end point

    Primary: Clinical Dementia Rating Sum of the Boxes (CDR-SB) (change from baseline)

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    End point title
    		 Clinical Dementia Rating Sum of the Boxes (CDR-SB) (change from baseline) [2]
    End point description
    End point type
    Primary
    End point timeframe
    At baseline (predose on Day 1) and Days 84, 140, and 182 or early termination.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    150
    157
    Units: n/a
        arithmetic mean (full range (min-max))
    0.64 (-3 to 9)
    0.81 (-4 to 6)
    0.71 (-2.5 to 7)
    No statistical analyses for this end point

    Primary: Summary of adverse events

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    End point title
    		 Summary of adverse events [3]
    End point description
    End point type
    Primary
    End point timeframe
    Any time after the subject signs the ICF through the safety follow-up visit (Day 189 or early termination, as applicable)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: Subjects reporting at least one TEAE
    101
    105
    102
    No statistical analyses for this end point

    Primary: Summary of serious adverse events

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    End point title
    		 Summary of serious adverse events [4]
    End point description
    End point type
    Primary
    End point timeframe
    Any time after the subject signs the ICF through the safety follow-up visit (Day 189 or early termination, as applicable)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: subjects reporting any serious TEAE
    12
    18
    16
    No statistical analyses for this end point

    Primary: Albumin (change from baseline)

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    End point title
    		 Albumin (change from baseline) [5]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: g/L
        arithmetic mean (full range (min-max))
    -0.4 (-6 to 6)
    -0.8 (-7 to 4)
    -0.3 (-6 to 6)
    No statistical analyses for this end point

    Primary: Alkaline phosphatase (change from baseline)

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    End point title
    		 Alkaline phosphatase (change from baseline) [6]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: U/L
        arithmetic mean (full range (min-max))
    -1.2 (-97 to 66)
    -2.1 (-24 to 20)
    -3.1 (-71 to 33)
    No statistical analyses for this end point

    Primary: Alanine Aminotransferase (change from baseline)

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    End point title
    		 Alanine Aminotransferase (change from baseline) [7]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: U/L
        arithmetic mean (full range (min-max))
    -1.1 (-18 to 24)
    -0.3 (-20 to 47)
    -6.8 (-476 to 22)
    No statistical analyses for this end point

    Primary: Aspartate Aminotransferase (change from baseline)

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    End point title
    		 Aspartate Aminotransferase (change from baseline) [8]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: U/L
        arithmetic mean (full range (min-max))
    -0.5 (-15 to 11)
    -1.1 (-42 to 11)
    -3.6 (-281 to 16)
    No statistical analyses for this end point

    Primary: Bicarbonate (change from baseline)

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    End point title
    		 Bicarbonate (change from baseline) [9]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.67 (-6.9 to 7.7)
    -0.37 (-5.1 to 8)
    -0.66 (-9.2 to 7.8)
    No statistical analyses for this end point

    Primary: Bilirubin (change from baseline)

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    End point title
    		 Bilirubin (change from baseline) [10]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: umol/L
        arithmetic mean (full range (min-max))
    0.07 (-6.2 to 9.2)
    -0.17 (-12 to 7.2)
    -1.07 (-75.9 to 9.1)
    No statistical analyses for this end point

    Primary: Blood Urea Nitrogen (change from baseline)

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    End point title
    		 Blood Urea Nitrogen (change from baseline) [11]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: MMOL UREA/L
        arithmetic mean (full range (min-max))
    0.42 (-3.2 to 7.5)
    -0.08 (-4.6 to 4.2)
    0.11 (-7.1 to 4.3)
    No statistical analyses for this end point

    Primary: Calcium (change from baseline)

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    End point title
    		 Calcium (change from baseline) [12]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.006 (-0.2 to 0.15)
    -0.016 (-0.27 to 0.18)
    -0.014 (-0.23 to 0.27)
    No statistical analyses for this end point

    Primary: Creatine kinase (change from baseline)

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    End point title
    		 Creatine kinase (change from baseline) [13]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: U/L
        arithmetic mean (full range (min-max))
    -6.2 (-206 to 125)
    -49.7 (-3564 to 185)
    14.8 (-143 to 330)
    No statistical analyses for this end point

    Primary: Chloride (change from baseline)

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    End point title
    		 Chloride (change from baseline) [14]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0 (-6 to 12)
    -0.4 (-8 to 5)
    0 (-5 to 8)
    No statistical analyses for this end point

    Primary: Creatinine (change from baseline)

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    End point title
    		 Creatinine (change from baseline) [15]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: umol/L
        arithmetic mean (full range (min-max))
    4.64 (-25.6 to 168.8)
    1.59 (-24.7 to 32.7)
    2.09 (-28.2 to 21.2)
    No statistical analyses for this end point

    Primary: Gamma Glutamyl Transferase (change from baseline)

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    End point title
    		 Gamma Glutamyl Transferase (change from baseline) [16]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: U/L
        arithmetic mean (full range (min-max))
    0.3 (-18 to 36)
    -0.4 (-18 to 39)
    -3.5 (-207 to 23)
    No statistical analyses for this end point

    Primary: Glucose (change from baseline)

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    End point title
    		 Glucose (change from baseline) [17]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.29 (-6.1 to 6.72)
    0.458 (-2.61 to 4.44)
    0.206 (-7.22 to 6.32)
    No statistical analyses for this end point

    Primary: Potassium (change from baseline)

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    End point title
    		 Potassium (change from baseline) [18]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.07 (-1 to 1.8)
    0.02 (-1.7 to 1.4)
    0.11 (-0.9 to 1.4)
    No statistical analyses for this end point

    Primary: Magnesium (change from baseline)

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    End point title
    		 Magnesium (change from baseline) [19]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.0024 (-0.139 to 0.103)
    -0.0079 (-0.246 to 0.123)
    -0.003 (-0.103 to 0.206)
    No statistical analyses for this end point

    Primary: Inorganic phosphate (change from baseline)

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    End point title
    		 Inorganic phosphate (change from baseline) [20]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.0012 (-0.33 to 0.281)
    0.0069 (-0.41 to 0.381)
    0.0076 (-0.465 to 0.578)
    No statistical analyses for this end point

    Primary: Protein (change from baseline)

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    End point title
    		 Protein (change from baseline) [21]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: g/L
        arithmetic mean (full range (min-max))
    -0.6 (-10 to 7)
    -0.3 (-8 to 7)
    -0.1 (-8 to 12)
    No statistical analyses for this end point

    Primary: Sodium (change from baseline)

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    End point title
    		 Sodium (change from baseline) [22]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.2 (-6 to 11)
    -0.4 (-9 to 6)
    0.2 (-5 to 8)
    No statistical analyses for this end point

    Primary: Urate (change from baseline)

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    End point title
    		 Urate (change from baseline) [23]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: mmol/l
        arithmetic mean (full range (min-max))
    0.006 (-0.09 to 0.14)
    0.003 (-0.08 to 0.21)
    0.004 (-0.14 to 0.09)
    No statistical analyses for this end point

    Primary: Leukocytes (change from baseline)

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    End point title
    		 Leukocytes (change from baseline) [24]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.235 (-4.62 to 7.23)
    -0.009 (-4.4 to 3.33)
    -0.279 (-4.68 to 5.13)
    No statistical analyses for this end point

    Primary: Erythrocytes (change from baseline)

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    End point title
    		 Erythrocytes (change from baseline) [25]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^12/L
        arithmetic mean (full range (min-max))
    -0.036 (-0.61 to 0.51)
    -0.024 (-0.7 to 0.51)
    -0.062 (-2.88 to 0.53)
    No statistical analyses for this end point

    Primary: Hemoglobin (change from baseline)

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    End point title
    		 Hemoglobin (change from baseline) [26]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: g/L
        arithmetic mean (full range (min-max))
    -1.6 (-27 to 19)
    -0.9 (-16 to 29)
    -3.2 (-91 to 13)
    No statistical analyses for this end point

    Primary: Hematocrit (change from baseline)

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    End point title
    		 Hematocrit (change from baseline) [27]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: %(v/v)
        arithmetic mean (full range (min-max))
    0.0038 (-0.093 to 0.066)
    0.0032 (-0.06 to 0.088)
    0.0026 (-0.108 to 0.068)
    No statistical analyses for this end point

    Primary: Platelets (change from baseline)

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    End point title
    		 Platelets (change from baseline) [28]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    3.9 (-122 to 168)
    -2.2 (-111 to 87)
    8.3 (-105 to 167)
    No statistical analyses for this end point

    Primary: Basophils (change from baseline)

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    End point title
    		 Basophils (change from baseline) [29]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.001 (-0.14 to 0.05)
    -0.001 (-0.15 to 0.04)
    0.001 (-0.08 to 0.14)
    No statistical analyses for this end point

    Primary: Eosinophils (change from baseline)

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    End point title
    		 Eosinophils (change from baseline) [30]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.009 (-0.51 to 0.39)
    0.012 (-0.24 to 0.7)
    -0.008 (-0.34 to 0.61)
    No statistical analyses for this end point

    Primary: Lymphocytes (change from baseline)

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    End point title
    		 Lymphocytes (change from baseline) [31]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.03 (-1.48 to 1.41)
    0.083 (-0.59 to 1.25)
    -0.06 (-2.25 to 0.97)
    No statistical analyses for this end point

    Primary: Monocytes (change from baseline)

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    End point title
    		 Monocytes (change from baseline) [32]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.011 (-0.41 to 0.68)
    -0.001 (-0.41 to 0.43)
    -0.013 (-0.34 to 0.49)
    No statistical analyses for this end point

    Primary: Neutrophils (change from baseline)

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    End point title
    		 Neutrophils (change from baseline) [33]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (10^9/L)
        arithmetic mean (full range (min-max))
    0.186 (-4.48 to 6.07)
    -0.104 (-4.18 to 3.08)
    -0.196 (-3.66 to 4.13)
    No statistical analyses for this end point

    Primary: pH (change from baseline)

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    End point title
    		 pH (change from baseline) [34]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: n/a
        arithmetic mean (full range (min-max))
    -0.1 (-3 to 2)
    0.1 (-3 to 3)
    0.1 (-2 to 2)
    No statistical analyses for this end point

    Primary: Specific gravity (change from baseline)

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    End point title
    		 Specific gravity (change from baseline) [35]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests performed non-fasting at screening and Days 1 (predose), 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: n/a
        arithmetic mean (full range (min-max))
    0.0011 (-0.02 to 0.02)
    -0.0006 (-0.025 to 0.02)
    0.0007 (-0.025 to 0.025)
    No statistical analyses for this end point

    Primary: Heart rate (change from baseline)

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    End point title
    		 Heart rate (change from baseline) [36]
    End point description
    End point type
    Primary
    End point timeframe
    Screening, pre-dose and within 3 hours post-dose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: beats/min
        arithmetic mean (full range (min-max))
    1.5 (-23 to 52)
    -0.3 (-25 to 23)
    0.1 (-20 to 23)
    No statistical analyses for this end point

    Primary: QT Duration (change from baseline)

    		 Close Top of page
    End point title
    		 QT Duration (change from baseline) [37]
    End point description
    End point type
    Primary
    End point timeframe
    Screening, pre-dose and within 3 hours post-dose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: msec
        arithmetic mean (full range (min-max))
    -1.3 (-96 to 92)
    1.1 (-60 to 68)
    1.3 (-64 to 52)
    No statistical analyses for this end point

    Primary: QRS Duration (change from baseline)

    		 Close Top of page
    End point title
    		 QRS Duration (change from baseline) [38]
    End point description
    End point type
    Primary
    End point timeframe
    Screening, predose and within 3 hours, post-dose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination
    Notes
    [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: msec
        arithmetic mean (full range (min-max))
    0.5 (-26 to 80)
    0.1 (-20 to 30)
    0.4 (-40 to 48)
    No statistical analyses for this end point

    Primary: PR Duration (change from baseline)

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    End point title
    		 PR Duration (change from baseline) [39]
    End point description
    End point type
    Primary
    End point timeframe
    Screening, pre-dose and within 3 hours post-dose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: msec
        arithmetic mean (full range (min-max))
    0.7 (-76 to 42)
    -0.5 (-30 to 36)
    -3.3 (-48 to 38)
    No statistical analyses for this end point

    Primary: QTcF Fridericia's correction formula (change from baseline)

    		 Close Top of page
    End point title
    		 QTcF Fridericia's correction formula (change from baseline) [40]
    End point description
    End point type
    Primary
    End point timeframe
    At screening, pre-dose and within 3 hours post-dose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination.
    Notes
    [40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: msec
        arithmetic mean (full range (min-max))
    1.4 (-45 to 92)
    0.3 (-40 to 41)
    1.1 (-38 to 46)
    No statistical analyses for this end point

    Primary: Temperature (change from baseline)

    		 Close Top of page
    End point title
    		 Temperature (change from baseline) [41]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1.
    Notes
    [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (c)
        arithmetic mean (full range (min-max))
    -0.04 (-61.5 to 61.7)
    -3.25 (-62.5 to 3)
    2.15 (-61.7 to 62.2)
    No statistical analyses for this end point

    Primary: Systolic Blood Pressure (change from baseline)

    		 Close Top of page
    End point title
    		 Systolic Blood Pressure (change from baseline) [42]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1.
    Notes
    [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (mmHg)
        arithmetic mean (full range (min-max))
    0.2 (-36 to 40)
    -2.5 (-53 to 47)
    -0.9 (-51 to 48)
    No statistical analyses for this end point

    Primary: Diastolic Blood Pressure (change from baseline)

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    End point title
    		 Diastolic Blood Pressure (change from baseline) [43]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1.
    Notes
    [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (mmHg)
        arithmetic mean (full range (min-max))
    -1.5 (-27 to 20)
    0.1 (-22 to 26)
    -1.5 (-24 to 21)
    No statistical analyses for this end point

    Primary: Heart Rate (change from baseline)

    		 Close Top of page
    End point title
    		 Heart Rate (change from baseline) [44]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1
    Notes
    [44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (bpm)
        arithmetic mean (full range (min-max))
    0.9 (-22 to 49)
    0.7 (-37 to 25)
    0.2 (-19 to 26)
    No statistical analyses for this end point

    Primary: Respiratory Rate (change from baseline)

    		 Close Top of page
    End point title
    		 Respiratory Rate (change from baseline) [45]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1.
    Notes
    [45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (breaths/min)
        arithmetic mean (full range (min-max))
    -0.3 (-8 to 6)
    -0.4 (-6 to 7)
    0.1 (-9 to 6)
    No statistical analyses for this end point

    Primary: Weight (change from baseline)

    		 Close Top of page
    End point title
    		 Weight (change from baseline) [46]
    End point description
    End point type
    Primary
    End point timeframe
    At each clinic visit, including pre-dose and within 3 hours post-dose on Day 1.
    Notes
    [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: (kg)
        arithmetic mean (full range (min-max))
    2.38 (-85.2 to 99.5)
    -0.04 (-76.5 to 101.1)
    0.16 (-74.8 to 129.2)
    No statistical analyses for this end point

    Primary: Columbia Suicide Severity Rating Scale (C-SSRS)

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    End point title
    		 Columbia Suicide Severity Rating Scale (C-SSRS) [47]
    End point description
    End point type
    Primary
    End point timeframe
    At screening (lifetime history version) and Days 1 (predose), 28, 56, 84, 112, 140, 182 or early termination (symptoms since the last study visit)
    Notes
    [47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: Subjects wishing to be dead
    3
    1
    0
    No statistical analyses for this end point

    Primary: Geriatric Depression Scale (GDS) (change from baseline)

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    End point title
    		 Geriatric Depression Scale (GDS) (change from baseline) [48]
    End point description
    End point type
    Primary
    End point timeframe
    At screening and Days 1 (predose), 84, and 182 or early termination
    Notes
    [48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the premature termination of the studies, a full statistical analysis could not be performed.
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    156
    159
    Units: n/a
        arithmetic mean (full range (min-max))
    0.1 (-6 to 7)
    0.3 (-4 to 9)
    0.1 (-4 to 4)
    No statistical analyses for this end point

    Secondary: Disability assessment for dementia (DAD) (change from baseline)

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    End point title
    		 Disability assessment for dementia (DAD) (change from baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    At baseline (predose on Day 1), and Days 84, 140, and 182 or early termination
    End point values
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Number of subjects analysed
    155
    150
    157
    Units: n/a
        arithmetic mean (full range (min-max))
    -3.9 (-64 to 21)
    -4.3 (-38 to 30)
    -5 (-52 to 35)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events observed at any time after the subject signs the ICF through the safety follow-up visit (Day 189 or early termination, as applicable) are to be recorded.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Reporting group title
    EVP-6124, 3 mg
    Reporting group description
    		 Eligible subjects will be randomized to 1 of 3 groups, 2 or 3 mg EVP-6124 or placebo, for 26 weeks.

    Serious adverse events
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 155 (7.74%)
    18 / 156 (11.54%)
    16 / 159 (10.06%)
         number of deaths (all causes)
    1
    1
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Sick sinus syndrome
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain stem infarction
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dementia of the Alzheimer's type, with delusions
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia, obstructive
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Placebo EVP-6124, 2 mg EVP-6124, 3 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    101 / 155 (65.16%)
    105 / 156 (67.31%)
    102 / 159 (64.15%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    3 / 155 (1.94%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lung cancer metastatic
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Benign ear neoplasm
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Cancer pain
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Colon cancer
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lipoma
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Metastases to liver
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Pituitary tumour benign
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 155 (1.94%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Hypotension
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    102
    Deep vein thrombosis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Aortic arteriosclerosis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Aortic dilatation
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hot flush
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hypertensive crisis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Varicose vein
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 156 (1.28%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Irritability
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    103
    Asthenia
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    102
    105
    101
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Oedema peripheral
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    103
    Pain
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Local swelling
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Chest discomfort
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Feeling cold
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Inflammation
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Malaise
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Pyrexia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Vessel puncture site bruise
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Contrast media allergy
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Vulvovaginal discomfort
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 155 (3.87%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Dyspnoea
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Pulmonary embolism
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Productive cough
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Pulmonary mass
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Respiratory tract congestion
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Asthma
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dyspnoea exertional
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Oropharyngeal pain
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Pneumonia aspiration
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rhinitis allergic
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rhinorrhoea
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Sinus congestion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Upper respiratory tract inflammation
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    4 / 155 (2.58%)
    7 / 156 (4.49%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Confusional state
         subjects affected / exposed
    4 / 155 (2.58%)
    2 / 156 (1.28%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Depression
         subjects affected / exposed
    1 / 155 (0.65%)
    4 / 156 (2.56%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Anxiety
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Delusion
         subjects affected / exposed
    3 / 155 (1.94%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Insomnia
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Aggression
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Delirium
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Depressed mood
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Hallucination
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Nervousness
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Psychotic disorder
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Suicidal ideation
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abnormal behaviour
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abnormal dreams
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Apathy
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Hallucination, visual
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Hypersexuality
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Restlessness
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Somnambulism
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Stress
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 155 (0.65%)
    3 / 156 (1.92%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    White blood cells urine
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Blood urea increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Protein urine
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    White blood cells urine positive
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Blood calcium increased
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Blood creatinine increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Blood glucose increased
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Blood phosphorus increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Blood pressure increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Body temperature increased
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Electrocardiogram abnormal
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Glucose urine
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    2
    Platelet count decreased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Precancerous cells present
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Specific gravity urine increased
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Transaminases increased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Urinary sediment present
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Urine ketone body present
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Vitamin D decreased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Weight decreased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 155 (3.23%)
    2 / 156 (1.28%)
    6 / 159 (3.77%)
         occurrences all number
    101
    105
    102
    Contusion
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Excoriation
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Laceration
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Animal bite
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Arthropod bite
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Bone contusion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Clavicle fracture
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Epicondylitis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Femoral neck fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Femur fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Forearm fracture
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hand fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hip fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Injury
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Intentional overdose
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Joint injury
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Limb injury
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lip injury
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Meniscus injury
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Muscle strain
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Pelvic fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Periorbital contusion
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Procedural complication
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Procedural pain
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Scar
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Spinal compression fracture
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Thermal burn
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Toxicity to various agents
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Wrist fracture
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Atrial fibrillation
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Bradycardia
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Sinus bradycardia
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Atrioventricular block first degree
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Cardiac failure
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Myocardial infarction
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Palpitations
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Bundle branch block left
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Bundle branch block right
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Coronary artery disease
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Diastolic dysfunction
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Mitral valve incompetence
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Myocardial ischaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Sick sinus syndrome
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Tachycardia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 155 (4.52%)
    6 / 156 (3.85%)
    5 / 159 (3.14%)
         occurrences all number
    101
    105
    102
    Dizziness
         subjects affected / exposed
    4 / 155 (2.58%)
    5 / 156 (3.21%)
    4 / 159 (2.52%)
         occurrences all number
    101
    105
    102
    Dementia Alzheimer's type
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 156 (1.28%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    102
    Somnolence
         subjects affected / exposed
    4 / 155 (2.58%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Apraxia
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Cognitive disorder
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Sciatica
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Syncope
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Transient ischaemic attack
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Tremor
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Amnesia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Aphasia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Ataxia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Balance disorder
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Brain stem infarction
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Convulsion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Decreased vibratory sense
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dementia of the Alzheimer's type, with delusions
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dysarthria
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Essential tremor
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hemiparesis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Memory impairment
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Movement disorder
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Myoclonus
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Neuropathy peripheral
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Nystagmus
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Paraesthesia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Presyncope
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Restless legs syndrome
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Sinus headache
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Upper motor neurone lesion
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Coagulopathy
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Eosinophilia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Leukocytosis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Leukopenia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Lymphadenopathy
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lymphopenia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Thrombocytopenia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Motion sickness
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Vertigo
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Vertigo positional
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Glaucoma
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Cataract
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Conjunctivitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Eye allergy
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Eye haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Eye pruritus
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Lacrimation increased
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Visual impairment
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    17 / 155 (10.97%)
    49 / 156 (31.41%)
    50 / 159 (31.45%)
         occurrences all number
    101
    105
    102
    Diarrhoea
         subjects affected / exposed
    15 / 155 (9.68%)
    21 / 156 (13.46%)
    20 / 159 (12.58%)
         occurrences all number
    101
    105
    102
    Abdominal pain
         subjects affected / exposed
    8 / 155 (5.16%)
    16 / 156 (10.26%)
    15 / 159 (9.43%)
         occurrences all number
    101
    105
    102
    Nausea
         subjects affected / exposed
    9 / 155 (5.81%)
    10 / 156 (6.41%)
    6 / 159 (3.77%)
         occurrences all number
    101
    105
    102
    Vomiting
         subjects affected / exposed
    5 / 155 (3.23%)
    4 / 156 (2.56%)
    5 / 159 (3.14%)
         occurrences all number
    101
    105
    102
    Faeces hard
         subjects affected / exposed
    0 / 155 (0.00%)
    7 / 156 (4.49%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Haemorrhoids
         subjects affected / exposed
    1 / 155 (0.65%)
    3 / 156 (1.92%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    102
    Haematochezia
         subjects affected / exposed
    0 / 155 (0.00%)
    4 / 156 (2.56%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rectal tenesmus
         subjects affected / exposed
    0 / 155 (0.00%)
    4 / 156 (2.56%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Inguinal hernia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    102
    Rectal haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Abdominal distension
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abdominal pain upper
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abnormal faeces
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dyschezia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Dyspepsia
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Faecal incontinence
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Flatulence
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Gastritis
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abdominal discomfort
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Abdominal tenderness
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Barrett's oesophagus
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Diverticulum
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Dry mouth
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dysphagia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Faecaloma
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Faeces discoloured
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Food poisoning
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gastrointestinal motility disorder
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Inguinal hernia, obstructive
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Large intestine perforation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Proctalgia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rectal discharge
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rectal polyp
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rectal ulcer
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Swollen tongue
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Toothache
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Cholelithiasis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Cholecystitis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Jaundice
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 155 (1.29%)
    4 / 156 (2.56%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Actinic keratosis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Dermatitis
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dermatitis allergic
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Eczema
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Eczema asteatotic
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hyperhidrosis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Night sweats
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Pruritus
         subjects affected / exposed
    0 / 155 (0.00%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Acne
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Dermal cyst
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Dry skin
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Ecchymosis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Erythema
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Precancerous skin lesion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Psoriasis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rash maculo-papular
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Rash papular
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rash pruritic
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rash vesicular
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Scar pain
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Skin exfoliation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Skin irritation
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Skin lesion
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Skin ulcer
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    103
    Stasis dermatitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    2 / 155 (1.29%)
    8 / 156 (5.13%)
    4 / 159 (2.52%)
         occurrences all number
    101
    105
    102
    Leukocyturia
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Urinary retention
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Dysuria
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Proteinuria
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Renal impairment
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Urinary incontinence
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Azotaemia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Chromaturia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Pollakiuria
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Renal failure
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Renal failure acute
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 155 (3.23%)
    2 / 156 (1.28%)
    4 / 159 (2.52%)
         occurrences all number
    101
    105
    102
    Arthralgia
         subjects affected / exposed
    1 / 155 (0.65%)
    3 / 156 (1.92%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    103
    Muscle spasms
         subjects affected / exposed
    1 / 155 (0.65%)
    2 / 156 (1.28%)
    4 / 159 (2.52%)
         occurrences all number
    101
    105
    102
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    103
    Pain in extremity
         subjects affected / exposed
    2 / 155 (1.29%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    102
    105
    Musculoskeletal pain
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Neck pain
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Costochondritis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Groin pain
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Joint range of motion decreased
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Myalgia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Osteitis deformans
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Osteoarthritis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Osteoporosis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Torticollis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Trigger finger
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    9 / 155 (5.81%)
    6 / 156 (3.85%)
    8 / 159 (5.03%)
         occurrences all number
    101
    105
    102
    Nasopharyngitis
         subjects affected / exposed
    2 / 155 (1.29%)
    4 / 156 (2.56%)
    7 / 159 (4.40%)
         occurrences all number
    101
    105
    102
    Bronchitis
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 156 (1.28%)
    3 / 159 (1.89%)
         occurrences all number
    101
    105
    102
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 155 (3.23%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Gastroenteritis viral
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Pneumonia
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Bacteriuria
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Pharyngitis
         subjects affected / exposed
    1 / 155 (0.65%)
    2 / 156 (1.28%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Sinusitis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Cellulitis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Cystitis
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Diverticulitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Fungal skin infection
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Herpes zoster
         subjects affected / exposed
    1 / 155 (0.65%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Oral herpes
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Periodontitis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Tooth infection
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Abscess
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Acute sinusitis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Clostridium difficile infection
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Gastroenteritis
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Gingivitis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Helicobacter infection
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Impetigo
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Influenza
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Oropharyngitis fungal
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Respiratory tract infection
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Rhinitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Sinobronchitis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Tooth abscess
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Viral infection
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 156 (1.28%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Dehydration
         subjects affected / exposed
    3 / 155 (1.94%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Hypokalaemia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    2 / 159 (1.26%)
         occurrences all number
    101
    105
    102
    Diabetes mellitus
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hypoglycaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Gout
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hyperglycaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 156 (0.64%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Hyperkalaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102
    Hypocalcaemia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Increased appetite
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 156 (0.00%)
    0 / 159 (0.00%)
         occurrences all number
    101
    105
    102
    Vitamin D deficiency
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 156 (0.00%)
    1 / 159 (0.63%)
         occurrences all number
    101
    105
    102

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jun 2014
    Protocol Amendment 1, Version 2.0 (dated 30 June 2014)

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    20 Nov 2015
    The Phase 3 Alzheimer's disease studies (EVP-6124-024, EVP-6124-025 and EVP-6124-026) were placed on complete clinical hold by the FDA due to potential gastrointestinal safety concern(s) around September 1st, 2015. Subsequent to this time, they were terminated to analyze the available data around January 1st, 2016.
    -

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

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