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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
    		 2013-002653-30
    Trial protocol
    		 IT   GB   DE   ES   CZ   NL  
    Global end of trial date
    11 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Dec 2016
    First version publication date
    28 Dec 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    EVP-6124-025
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01969136
    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
    26 May 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 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
    23 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: 11
    Country: Number of subjects enrolled
    Argentina: 2
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Japan: 27
    Country: Number of subjects enrolled
    Mexico: 5
    Country: Number of subjects enrolled
    South Africa: 25
    Country: Number of subjects enrolled
    Korea, Republic of: 26
    Country: Number of subjects enrolled
    United States: 184
    Country: Number of subjects enrolled
    Netherlands: 17
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    Czech Republic: 40
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Italy: 6
    Worldwide total number of subjects
    403
    EEA total number of subjects
    115
    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)
    75
    From 65 to 84 years
    316
    85 years and over
    12

    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
    		 661 [1]
    Intermediate milestone: Number of subjects
    Run-in: 445
    Number of subjects completed
    		 403

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Other: 258
    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 (403) per country is indicated in the Trial information section. The number of screened subjects (661) 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, Monitor, 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
    134
    134
    135
    Completed
    55
    55
    55
    Not completed
    79
    79
    80
         Withdrawal by subject/caregiver
    4
    4
    4
         Due to Clinical Hold
    59
    60
    63
         Consent withdrawn by subject
    2
    -
    1
         Medication prohibited by protocol
    1
    -
    -
         Adverse event, non-fatal
    10
    10
    7
         Death
    1
    -
    1
         Administrative reasons
    -
    1
    -
         Other
    -
    3
    3
         Lost to follow-up
    2
    1
    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
    		 134 134 135 403
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 23 26 26 75
        From 65-84 years
    		 105 105 106 316
        85 years and over
    		 6 3 3 12
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 73.8 (55 to 85) 73.1 (55 to 85) 71.9 (55 to 85) -
    Gender categorical
    Units: Subjects
        Female
    		 86 67 80 233
        Male
    		 48 67 55 170

    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
    133
    133
    132
    Units: n/a
        arithmetic mean (full range (min-max))
    -0.1 (-13 to 20)
    0.4 (-19 to 19)
    0.9 (-18 to 18)
    No statistical analyses for this end point

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

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    End point title
    		 Clinical Dementia Rating Sum of the Boxes (CDR-SB) Score (change from baseline) [2]
    End point description
    End point type
    Primary
    End point timeframe
    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
    133
    133
    132
    Units: n/a
        arithmetic mean (full range (min-max))
    0.11 (-6 to 7)
    0.06 (-6 to 3)
    0.19 (-6 to 9)
    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
    134
    134
    135
    Units: Subjects reporting at least one TEAE
    79
    79
    79
    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
    Observed at 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
    134
    134
    135
    Units: Subjects reporting any serious TEAE
    8
    9
    7
    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 will be performed non-fasting at screening and Days 1 (predose), 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
    134
    134
    135
    Units: g/L
        arithmetic mean (full range (min-max))
    0.1 (-6 to 7)
    0.2 (-5 to 6)
    -0.6 (-7 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
    Routine clinical laboratory tests will be 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
    134
    134
    135
    Units: U/L
        arithmetic mean (full range (min-max))
    0.4 (-42 to 53)
    -2.9 (-33 to 32)
    -2.4 (-34 to 41)
    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 will be 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
    134
    134
    135
    Units: U/L
        arithmetic mean (full range (min-max))
    -1.9 (-48 to 18)
    -1.5 (-22 to 18)
    -1.1 (-48 to 18)
    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 will be performed non-fasting at screening and Days 1 (predose), 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
    134
    134
    135
    Units: U/L
        arithmetic mean (full range (min-max))
    -0.9 (-31 to 13)
    -0.4 (-13 to 42)
    0 (-42 to 24)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.36 (-7.1 to 7.1)
    -0.17 (-6.1 to 7)
    -0.43 (-7.7 to 5)
    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 will be performed non-fasting at screening and Days 1 (predose), 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
    134
    134
    135
    Units: umol/L
        arithmetic mean (full range (min-max))
    0.05 (-3.9 to 11.3)
    0.44 (-5.2 to 8.7)
    -0.56 (-12 to 4.6)
    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 will be 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
    134
    134
    135
    Units: MMOL UREA/L
        arithmetic mean (full range (min-max))
    -0.06 (-7.1 to 3.2)
    0.04 (-6 to 3.5)
    0.54 (-3.6 to 13.3)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.004 (-0.27 to 0.2)
    0.001 (-0.25 to 0.22)
    -0.01 (-0.25 to 0.17)
    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 will be 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
    134
    134
    135
    Units: U/L
        arithmetic mean (full range (min-max))
    1 (-532 to 192)
    2 (-357 to 315)
    24.6 (-133 to 1541)
    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 will be performed non-fasting at screening and Days 1 (predose), 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.1 (-8 to 7)
    -0.6 (-8 to 3)
    -0.2 (-11 to 5)
    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 will be 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
    134
    134
    135
    Units: umol/L
        arithmetic mean (full range (min-max))
    1.24 (-25.6 to 24.7)
    1.84 (-31 to 23)
    8 (-15 to 295.3)
    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 will be 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
    134
    134
    135
    Units: U/L
        arithmetic mean (full range (min-max))
    -2.2 (-52 to 26)
    -2.4 (-46 to 21)
    -0.4 (-39 to 25)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.066 (-6.66 to 3.28)
    0.264 (-3.66 to 7.6)
    0.09 (-5.28 to 3.83)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.05 (-1.9 to 1.5)
    0.1 (-1.3 to 1.3)
    0.08 (-1 to 0.7)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.0079 (-0.136 to 0.132)
    -0.0041 (-0.123 to 0.127)
    0.0024 (-0.14 to 0.124)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.0047 (-0.375 to 0.4)
    0.0277 (-0.452 to 0.798)
    0.0395 (-0.352 to 0.649)
    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 will be 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
    134
    134
    135
    Units: g/L
        arithmetic mean (full range (min-max))
    0.5 (-9 to 12)
    0.1 (-6 to 12)
    0.2 (-10 to 8)
    No statistical analyses for this end point

    Primary: Sodium (change fron baseline)

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    End point title
    		 Sodium (change fron baseline) [22]
    End point description
    End point type
    Primary
    End point timeframe
    The routine clinical laboratory tests will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    0.7 (-5 to 7)
    0.3 (-6 to 7)
    0.2 (-9 to 7)
    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 will be 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
    134
    134
    135
    Units: mmol/L
        arithmetic mean (full range (min-max))
    -0.005 (-0.15 to 0.16)
    0.001 (-0.26 to 0.11)
    0.019 (-0.08 to 0.35)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.255 (-3.76 to 9.74)
    -0.002 (-4.1 to 2.78)
    0.388 (-2.77 to 11.58)
    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 will be 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
    134
    134
    135
    Units: 10^12/L
        arithmetic mean (full range (min-max))
    0.022 (-0.52 to 1.42)
    0.029 (-0.41 to 0.6)
    -0.047 (-0.87 to 0.66)
    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 will be 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
    134
    134
    135
    Units: g/L
        arithmetic mean (full range (min-max))
    -0.8 (-23 to 30)
    0.1 (-16 to 20)
    -1.7 (-24 to 21)
    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 will be 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
    134
    134
    135
    Units: %(v/v)
        arithmetic mean (full range (min-max))
    0.0029 (-0.068 to 0.118)
    0.0078 (-0.07 to 0.09)
    0.0015 (-0.078 to 0.061)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0 (-153 to 60)
    6 (-56 to 62)
    8.7 (-72 to 302)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.002 (-0.05 to 0.03)
    0.002 (-0.04 to 0.04)
    0.001 (-0.07 to 0.06)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.015 (-0.57 to 0.22)
    -0.009 (-0.91 to 0.26)
    0.039 (-0.19 to 0.55)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.009 (-1.2 to 0.63)
    -0.024 (-1.12 to 0.68)
    0.051 (-0.87 to 0.73)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.013 (-0.61 to 0.61)
    -0.01 (-0.4 to 0.3)
    0.052 (-0.27 to 0.9)
    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 will be 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
    134
    134
    135
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.301 (-3.62 to 9.14)
    0.037 (-4.6 to 2.68)
    0.245 (-3.42 to 11.31)
    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 will be 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
    134
    134
    135
    Units: n/a
        arithmetic mean (full range (min-max))
    -0.2 (-2 to 3)
    0.1 (-2 to 3)
    0 (-2 to 3)
    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 will be 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
    134
    134
    135
    Units: n/a
        arithmetic mean (full range (min-max))
    0.0012 (-0.03 to 0.03)
    0.0008 (-0.015 to 0.02)
    -0.0003 (-0.02 to 0.02)
    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
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose 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
    134
    134
    134
    Units: beats/min
        arithmetic mean (full range (min-max))
    0.1 (-16 to 20)
    -0.4 (-34 to 27)
    1.8 (-17 to 16)
    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
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose 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
    134
    134
    135
    Units: msec
        arithmetic mean (full range (min-max))
    1.8 (-68 to 54)
    5.3 (-74 to 78)
    -4.8 (-72 to 38)
    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
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose 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
    134
    134
    135
    Units: msec
        arithmetic mean (full range (min-max))
    0.5 (-16 to 14)
    1.2 (-14 to 40)
    -0.3 (-18 to 16)
    No statistical analyses for this end point

    Primary: PR Duration (change from baseline)

    		 Close Top of page
    End point title
    		 PR Duration (change from baseline) [39]
    End point description
    End point type
    Primary
    End point timeframe
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose 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
    134
    134
    135
    Units: msec
        arithmetic mean (full range (min-max))
    -3.7 (-62 to 24)
    1.9 (-28 to 34)
    0.4 (-40 to 28)
    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
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose 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
    134
    134
    135
    Units: msec
        arithmetic mean (full range (min-max))
    2.2 (-41 to 40)
    4 (-45 to 49)
    -1 (-42 to 30)
    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
    Recorded at each clinic visit, including predose and within 3 hours postdose 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
    134
    134
    135
    Units: (c)
        arithmetic mean (full range (min-max))
    -1.8 (-61 to 62)
    2.7 (-62 to 61)
    -0.8 (-62 to 62)
    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
    Recorded at each clinic visit, including predose and within 3 hours postdose 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
    134
    134
    135
    Units: mmHg
        arithmetic mean (full range (min-max))
    -2.7 (-35 to 33)
    0.3 (-38 to 42)
    1.2 (-38 to 45)
    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
    Recorded at each clinic visit, including predose and within 3 hours postdose 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
    134
    134
    135
    Units: mmHg
        arithmetic mean (full range (min-max))
    -0.6 (-25 to 38)
    0.4 (-32 to 27)
    -2.3 (-26 to 24)
    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
    Standard 12-lead ECG tracings will be obtained at screening, predose and within 3 hours postdose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination.
    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
    134
    134
    134
    Units: bpm
        arithmetic mean (full range (min-max))
    -1.7 (-16 to 18)
    1.5 (-21 to 37)
    1.3 (-10 to 16)
    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
    Recorded at each clinic visit, including predose and within 3 hours postdose 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
    134
    134
    135
    Units: breaths/min
        arithmetic mean (full range (min-max))
    -0.3 (-6 to 4)
    -0.2 (-7 to 4)
    0.4 (-5 to 9)
    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 screening, predose on Day 1, and Days 28, 56, 84, 112, 140, and 182 or early termination.
    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
    134
    134
    134
    Units: kg
        arithmetic mean (full range (min-max))
    -0.2 (-88 to 92)
    2.2 (-78 to 91)
    -3.2 (-113 to 18)
    No statistical analyses for this end point

    Primary: Columbia Suicide Severity Rating Scale (C-SSRS) (Day 182)

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    End point title
    		 Columbia Suicide Severity Rating Scale (C-SSRS) (Day 182) [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
    134
    134
    135
    Units: Subjects wishing to be dead
    0
    0
    1
    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
    134
    134
    135
    Units: n/a
        arithmetic mean (full range (min-max))
    0.2 (-3 to 9)
    -0.1 (-5 to 5)
    0.4 (-2 to 9)
    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
    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
    133
    133
    132
    Units: n/a
        arithmetic mean (full range (min-max))
    -1 (-28 to 36)
    -1.7 (-35 to 33)
    -3.4 (-50 to 32)
    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
    8 / 134 (5.97%)
    9 / 134 (6.72%)
    7 / 135 (5.19%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant pleural effusion
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Tibia fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Large intestine perforation
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Peptic ulcer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary arterial hypertension
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Bipolar I disorder
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Bladder leukoplakia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
    1 / 7
         deaths causally related to treatment / all
    0 / 1
    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
    79 / 134 (58.96%)
    79 / 134 (58.96%)
    79 / 135 (58.52%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Malignant pleural effusion
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Mucinous breast carcinoma
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Prostate cancer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Haemorrhage
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hypertension
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Malaise
         subjects affected / exposed
    0 / 134 (0.00%)
    3 / 134 (2.24%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Fatigue
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Pyrexia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Asthenia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Chest discomfort
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Chest pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Device breakage
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Temperature intolerance
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Reproductive system and breast disorders
    Acquired hydrocele
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Prostatitis
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Bronchiectasis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dyspnoea
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Dyspnoea exertional
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Epistaxis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Hiccups
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Nasal congestion
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Oropharyngeal pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Pulmonary arterial hypertension
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Respiratory failure
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Rhinorrhoea
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Rhonchi
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Wheezing
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    2 / 134 (1.49%)
    3 / 134 (2.24%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Anxiety
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    3 / 135 (2.22%)
         occurrences all number
    79
    79
    79
    Depression
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Insomnia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Nervousness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Abnormal dreams
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Adjustment disorder with depressed mood
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Aggression
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Bipolar I disorder
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Confusional state
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Delirium
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Depressed mood
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Emotional disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hallucination
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hallucination, auditory
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hallucination, visual
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hyposomnia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Libido decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Mania
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Paranoia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Restlessness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Sleep disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Investigations
    Blood urea increased
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Blood creatinine increased
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood pressure increased
         subjects affected / exposed
    2 / 134 (1.49%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Weight decreased
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Weight increased
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    White blood cells urine
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood glucose increased
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Electrocardiogram abnormal
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Eosinophil count increased
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood albumin decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood magnesium decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood phosphorus increased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Blood pressure decreased
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Blood uric acid increased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Crystal urine present
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    ECG signs of myocardial ischaemia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Platelet count decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Protein total decreased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Protein urine present
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 134 (1.49%)
    4 / 134 (2.99%)
    4 / 135 (2.96%)
         occurrences all number
    79
    79
    79
    Laceration
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Rib fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Contusion
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Subdural haematoma
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Accidental overdose
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Ankle fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Arthropod bite
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Arthropod sting
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Back injury
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Excoriation
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Face injury
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Femur fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Foot fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hand fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Heat stroke
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hip fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Humerus fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Limb injury
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Muscle strain
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Post procedural complication
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Procedural pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Radius fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Scapula fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Scratch
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Tibia fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Tooth fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Toxicity to various agents
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Wound haemorrhage
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Angina pectoris
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Bradycardia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Cardiac failure
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Myocardial infarction
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Palpitations
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 134 (3.73%)
    3 / 134 (2.24%)
    3 / 135 (2.22%)
         occurrences all number
    79
    79
    79
    Headache
         subjects affected / exposed
    4 / 134 (2.99%)
    1 / 134 (0.75%)
    6 / 135 (4.44%)
         occurrences all number
    79
    79
    79
    Syncope
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Somnolence
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Tremor
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Amnesia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Ataxia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Cerebrovascular accident
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Cognitive disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Convulsion
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dementia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Parkinsonism
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Sciatica
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Anaemia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Haemolysis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Lymphadenopathy
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Deafness unilateral
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Tinnitus
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vertigo
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Vertigo positional
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Dry eye
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Ocular hyperaemia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Visual impairment
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    9 / 134 (6.72%)
    37 / 134 (27.61%)
    34 / 135 (25.19%)
         occurrences all number
    79
    79
    79
    Diarrhoea
         subjects affected / exposed
    9 / 134 (6.72%)
    17 / 134 (12.69%)
    8 / 135 (5.93%)
         occurrences all number
    79
    79
    79
    Abdominal pain
         subjects affected / exposed
    3 / 134 (2.24%)
    18 / 134 (13.43%)
    6 / 135 (4.44%)
         occurrences all number
    79
    79
    79
    Nausea
         subjects affected / exposed
    9 / 134 (6.72%)
    8 / 134 (5.97%)
    5 / 135 (3.70%)
         occurrences all number
    79
    79
    79
    Vomiting
         subjects affected / exposed
    3 / 134 (2.24%)
    4 / 134 (2.99%)
    6 / 135 (4.44%)
         occurrences all number
    79
    79
    79
    Faeces hard
         subjects affected / exposed
    1 / 134 (0.75%)
    2 / 134 (1.49%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Dyspepsia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Haemorrhoids
         subjects affected / exposed
    2 / 134 (1.49%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Toothache
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Abdominal distension
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Dental caries
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Faecal incontinence
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Rectal haemorrhage
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Abdominal tenderness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Cheilitis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Colitis ulcerative
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Diverticulum intestinal
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Dry mouth
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dyschezia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Eructation
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Flatulence
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Gastric ulcer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Gastritis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Haematochezia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Large intestine perforation
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Pancreatitis acute
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Peptic ulcer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Rectal prolapse
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Rectal tenesmus
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Rash
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Acne
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Drug eruption
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dry skin
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Ecchymosis
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Night sweats
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Skin lesion
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Skin ulcer
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vascular skin disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    3 / 134 (2.24%)
    3 / 134 (2.24%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Dysuria
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Renal failure
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Renal failure acute
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Urinary incontinence
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Bladder leukoplakia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Micturition urgency
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Proteinuria
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 134 (3.73%)
    1 / 134 (0.75%)
    3 / 135 (2.22%)
         occurrences all number
    79
    79
    79
    Arthralgia
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 134 (0.00%)
    3 / 135 (2.22%)
         occurrences all number
    79
    79
    79
    Muscle spasms
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Osteoarthritis
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Pain in extremity
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Bursitis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Fracture pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Muscular weakness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Myalgia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Neck pain
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Spinal pain
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vertebral wedging
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    5 / 134 (3.73%)
    3 / 134 (2.24%)
    6 / 135 (4.44%)
         occurrences all number
    79
    79
    79
    Nasopharyngitis
         subjects affected / exposed
    8 / 134 (5.97%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 134 (1.49%)
    3 / 134 (2.24%)
    3 / 135 (2.22%)
         occurrences all number
    79
    79
    79
    Influenza
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Bronchitis
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Cystitis
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Herpes zoster
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    2 / 135 (1.48%)
         occurrences all number
    79
    79
    79
    Tinea pedis
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Gastroenteritis
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Gastroenteritis viral
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Pneumonia
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Rhinitis
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Tooth abscess
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Bacteriuria
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Bronchopneumonia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Otitis media acute
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Paronychia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Periodontitis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Sinusitis
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Soft tissue infection
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Tooth infection
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Tracheitis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Viral infection
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 134 (0.00%)
    2 / 134 (1.49%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Decreased appetite
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Gout
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    79
    79
    79
    Hypokalaemia
         subjects affected / exposed
    1 / 134 (0.75%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Dyslipidaemia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Folate deficiency
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hyperlipidaemia
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 134 (0.75%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hyperuricaemia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Hypovitaminosis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79
    Vitamin D deficiency
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 134 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    79
    79
    79

    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
    11 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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