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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled, Parallel, 26 Week, Phase 3 Study of 2 Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo as an Adjunctive Pro-cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy

    Summary
    EudraCT number
    		 2012-003208-10
    Trial protocol
    		 DE   ES   PL  
    Global end of trial date
    12 Jan 2016

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

    Trial information

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    Trial identification
    Sponsor protocol code
    EVP-6124-015
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND Number: 076939
    Sponsors
    Sponsor organisation name
    Forum Pharmaceuticals Inc.
    Sponsor organisation address
    225 Second Avenue, Waltham, MA, United States, 02451
    Public contact
    SSU & Regulatory Lead, INC Research , valerie.desaedeleer@incresearch.com
    Scientific contact
    SSU & Regulatory Lead, INC Research , valerie.desaedeleer@incresearch.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
    12 May 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Jan 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study are to assess the safety and the efficacy of 2 doses of once daily EVP-6124 tablets (1 and 2 mg) as an adjunctive pro-cognitive treatment, versus placebo, when added to chronic, stable, atypical antipsychotic therapy in subjects with schizophrenia. Safety will be determined by clinical and laboratory safety assessments. Efficacy will be determined by cognitive function as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™) Consensus Cognitive Battery (MCCB™) Neurocognitive Composite Score, and by clinical function as measured by the interview-based Schizophrenia Cognition Rating Scale (SCoRS).
    Protection of trial subjects
    Measures to minimize pain and discomfort secondary to phlebotomy were used on an as-needed basis. As there were no other invasive measures in this study, additional interventions were not needed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Dec 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 30
    Country: Number of subjects enrolled
    Spain: 53
    Country: Number of subjects enrolled
    Germany: 23
    Country: Number of subjects enrolled
    Argentina: 53
    Country: Number of subjects enrolled
    Brazil: 25
    Country: Number of subjects enrolled
    Canada: 38
    Country: Number of subjects enrolled
    Mexico: 40
    Country: Number of subjects enrolled
    Russian Federation: 57
    Country: Number of subjects enrolled
    Serbia: 24
    Country: Number of subjects enrolled
    Singapore: 5
    Country: Number of subjects enrolled
    Ukraine: 56
    Country: Number of subjects enrolled
    United States: 349
    Worldwide total number of subjects
    753
    EEA total number of subjects
    106
    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)
    753
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects will be screened for eligibility within 28 days of entry into the single-blind placebo Run-in Period. On Day -14 subjects will be dispensed a 32-day supply of single-blind, placebo study medication.

    Pre-assignment period milestones
    Number of subjects started
    		 1078 [1]
    Number of subjects completed
    		 753

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screen Fails Prior to Run-In: 282
    Reason: Number of subjects
    		 Withdrawn Prior to Randomization: 43
    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 worldwide number corresponds to the number of patients randomized (753) and not to the number of patients screened (1078).
    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 EVP-6124, 1 mg
    Arm description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).
    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 of study medication once daily at the same time each day, preferably between 8 to 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 in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).
    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 of study medication once daily at the same time each day, preferably between 8 to 10 AM, with or without food, and with an adequate amount of water.

    Arm title
    		 Placebo
    Arm description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).
    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 of study medication once daily at the same time each day, preferably between 8 to 10 AM, with or without food, and with an adequate amount of water.

    Number of subjects in period 1
    		EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Started
    252
    248
    253
    Completed
    199
    185
    200
    Not completed
    53
    63
    53
         Consent withdrawn by subject
    18
    14
    13
         Physician decision
    -
    1
    1
         Medication prohibited by protocol
    -
    1
    2
         Adverse event, non-fatal
    12
    11
    15
         Administrative reasons
    2
    -
    1
         Other
    3
    5
    1
         Substance Abuse
    8
    6
    3
         Lost to follow-up
    4
    16
    8
         Protocol deviation
    6
    9
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    EVP-6124, 1 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo Total
    Number of subjects
    		 252 248 253 753
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 252 248 253 753
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 37 (18 to 50) 36.8 (18 to 50) 37.1 (18 to 51) -
    Gender categorical
    Units: Subjects
        Female
    		 86 79 90 255
        Male
    		 166 169 163 498

    End points

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    End points reporting groups
    Reporting group title
    EVP-6124, 1 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Primary: MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite T-Score with Imputation of missing components (Change from Baseline)

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    End point title
    		 MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite T-Score with Imputation of missing components (Change from Baseline)
    End point description
    End point type
    Primary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (standard error)
    3.9 ( 0.41 )
    4 ( 0.47 )
    3.2 ( 0.42 )
    Statistical analysis title
    		 Hochberg method adjustment
    Comparison groups
    EVP-6124, 1 mg v EVP-6124, 2 mg v Placebo
    Number of subjects included in analysis
    731
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Hochberg method adjustment
    Confidence interval

    Primary: Schizophrenia Cognition Rating Scale (SCoRS) Total Scores (Change from Baseline)

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    End point title
    		 Schizophrenia Cognition Rating Scale (SCoRS) Total Scores (Change from Baseline)
    End point description
    End point type
    Primary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: N/A
        arithmetic mean (full range (min-max))
    -4.4 (-26 to 14)
    -5 (-33 to 21)
    -3.9 (-42 to 21)
    Statistical analysis title
    		 Hochberg method adjustment
    Comparison groups
    EVP-6124, 1 mg v EVP-6124, 2 mg v Placebo
    Number of subjects included in analysis
    731
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Hochberg method adjustment
    Confidence interval

    Primary: MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite T-Score without Imputation of missing components (Change from Baseline)

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    End point title
    		 MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite T-Score without Imputation of missing components (Change from Baseline)
    End point description
    End point type
    Primary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    4 (-10 to 35)
    4.2 (-9 to 27)
    3.1 (-17 to 21)
    Statistical analysis title
    		 Hochberg method adjustment
    Comparison groups
    EVP-6124, 1 mg v EVP-6124, 2 mg v Placebo
    Number of subjects included in analysis
    731
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Hochberg method adjustment
    Confidence interval

    Primary: Summary of Treatment-Emergent Adverse Events (TEAE)

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    End point title
    		 Summary of Treatment-Emergent Adverse Events (TEAE) [1]
    End point description
    End point type
    Primary
    End point timeframe
    Any time after the subject signs the ICF through the follow-up period of the study (Day 182, 189, or ET, as applicable)
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: Subjects with any TEAE
    135
    127
    140
    No statistical analyses for this end point

    Primary: Basophils (Change from baseline)

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    End point title
    		 Basophils (Change from baseline) [2]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0 (-0.07 to 0.04)
    0.001 (-0.06 to 0.08)
    -0.003 (-0.11 to 0.04)
    No statistical analyses for this end point

    Primary: Basophils/Leukocytes (Change from baseline)

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    End point title
    		 Basophils/Leukocytes (Change from baseline) [3]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    0 (-1 to 1)
    0.1 (-1 to 1)
    -0.1 (-2 to 1)
    No statistical analyses for this end point

    Primary: Eosinophils (Change from baseline)

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    End point title
    		 Eosinophils (Change from baseline) [4]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.003 (-0.55 to 0.64)
    0.003 (-0.57 to 0.86)
    -0.002 (-0.7 to 0.6)
    No statistical analyses for this end point

    Primary: Eosinophils/Leukocytes (Change from baseline)

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    End point title
    		 Eosinophils/Leukocytes (Change from baseline) [5]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    -0.1 (-7 to 9)
    0.1 (-9 to 10)
    0 (-12 to 7)
    No statistical analyses for this end point

    Primary: Erythrocytes (Change from baseline)

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    End point title
    		 Erythrocytes (Change from baseline) [6]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^12/L
        arithmetic mean (full range (min-max))
    0.037 (-0.56 to 1.57)
    0.017 (-0.77 to 0.75)
    -0.005 (-1.12 to 1.35)
    No statistical analyses for this end point

    Primary: Hematocrit (Change from baseline)

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    End point title
    		 Hematocrit (Change from baseline) [7]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    0.28 (-5.2 to 8)
    0.25 (-8 to 8.3)
    -0.12 (-9.7 to 10.2)
    No statistical analyses for this end point

    Primary: Hemoglobin (Change from baseline)

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    End point title
    		 Hemoglobin (Change from baseline) [8]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: g/dL
        arithmetic mean (full range (min-max))
    0.01 (-1.9 to 3.2)
    0 (-3.3 to 2.7)
    -0.09 (-4.1 to 3.1)
    No statistical analyses for this end point

    Primary: Leukocytes (Change from baseline)

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    End point title
    		 Leukocytes (Change from baseline) [9]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.117 (-5.98 to 8)
    0.018 (-5.8 to 6.6)
    -0.046 (-14.92 to 8.4)
    No statistical analyses for this end point

    Primary: Lymphocytes (Change from Baseline)

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    End point title
    		 Lymphocytes (Change from Baseline) [10]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.016 (-1.99 to 3.19)
    -0.002 (-1.89 to 2.27)
    -0.016 (-2.27 to 1.77)
    No statistical analyses for this end point

    Primary: Lymphocytes/Leukocytes (Change from baseline)

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    End point title
    		 Lymphocytes/Leukocytes (Change from baseline) [11]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    -0.1 (-33 to 18)
    -0.2 (-21 to 27)
    -0.6 (-30 to 33)
    No statistical analyses for this end point

    Primary: Monocytes (Change from baseline)

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    End point title
    		 Monocytes (Change from baseline) [12]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    -0.002 (-0.43 to 0.78)
    0.01 (-0.45 to 0.65)
    -0.026 (-0.97 to 0.45)
    No statistical analyses for this end point

    Primary: Monocytes/Leukocytes (Change from Baseline)

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    End point title
    		 Monocytes/Leukocytes (Change from Baseline) [13]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    -0.1 (-6 to 7)
    0.1 (-11 to 12)
    -0.3 (-9 to 7)
    No statistical analyses for this end point

    Primary: Neutrophils (Change from Baseline)

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    End point title
    		 Neutrophils (Change from Baseline) [14]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    0.114 (-5.87 to 7.87)
    -0.016 (-5.5 to 3.85)
    0.006 (-14.06 to 8.9)
    No statistical analyses for this end point

    Primary: Neutrophils/Leukocytes (Change from Baseline)

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    End point title
    		 Neutrophils/Leukocytes (Change from Baseline) [15]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: percent
        arithmetic mean (full range (min-max))
    0.4 (-19 to 39)
    -0.2 (-28 to 25)
    0.9 (-37 to 36)
    No statistical analyses for this end point

    Primary: Platelets (Change from Baseline)

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    End point title
    		 Platelets (Change from Baseline) [16]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: 10^9/L
        arithmetic mean (full range (min-max))
    3.6 (-94 to 112)
    4.4 (-127 to 137)
    0.9 (-183 to 112)
    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) [17]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: IU/L
        arithmetic mean (full range (min-max))
    0.9 (-43 to 52)
    -2.3 (-146 to 48)
    -0.6 (-47 to 53)
    No statistical analyses for this end point

    Primary: Albumin (Change from Baseline)

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    End point title
    		 Albumin (Change from Baseline) [18]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: g/dL
        arithmetic mean (full range (min-max))
    -0.01 (-0.7 to 0.6)
    0.03 (-1 to 0.9)
    -0.03 (-0.7 to 0.6)
    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) [19]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: IU/L
        arithmetic mean (full range (min-max))
    -0.6 (-39 to 61)
    -0.7 (-69 to 36)
    -0.5 (-41 to 48)
    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) [20]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: IU/L
        arithmetic mean (full range (min-max))
    1.5 (-30 to 116)
    -2.9 (-273 to 33)
    -1 (-94 to 64)
    No statistical analyses for this end point

    Primary: Bicarbonate (Change from Baseline)

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    End point title
    		 Bicarbonate (Change from Baseline) [21]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mEq/L
        arithmetic mean (full range (min-max))
    -0.4 (-7 to 7)
    -0.3 (-7 to 7)
    -0.6 (-8 to 8)
    No statistical analyses for this end point

    Primary: Bilirubin (Change from Baseline)

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    End point title
    		 Bilirubin (Change from Baseline) [22]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    0 (-0.8 to 1.2)
    0.01 (-0.6 to 1.3)
    -0.03 (-0.9 to 1)
    No statistical analyses for this end point

    Primary: Blood Urea Nitrogen (Change from Baseline)

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    End point title
    		 Blood Urea Nitrogen (Change from Baseline) [23]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    0.1 (-9 to 10)
    0 (-7 to 9)
    -0.2 (-11 to 11)
    No statistical analyses for this end point

    Primary: Calcium (Change from Baseline)

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    End point title
    		 Calcium (Change from Baseline) [24]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    -0.04 (-1.3 to 0.8)
    0.01 (-1 to 1.2)
    -0.05 (-1.4 to 1)
    No statistical analyses for this end point

    Primary: Chloride (Change from Baseline)

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    End point title
    		 Chloride (Change from Baseline) [25]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mEq/L
        arithmetic mean (full range (min-max))
    -0.4 (-7 to 5)
    -0.7 (-8 to 6)
    0.1 (-8 to 8)
    No statistical analyses for this end point

    Primary: Creatine Phosphokinase (Change from Baseline)

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    End point title
    		 Creatine Phosphokinase (Change from Baseline) [26]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: IU/L
        arithmetic mean (full range (min-max))
    38.7 (-1954 to 4393)
    -37.6 (-4953 to 1096)
    -13.6 (-3903 to 4776)
    No statistical analyses for this end point

    Primary: Creatinine (Change from Baseline)

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    End point title
    		 Creatinine (Change from Baseline) [27]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    0.023 (-0.26 to 0.46)
    0.008 (-0.34 to 0.75)
    -0.004 (-0.62 to 0.37)
    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) [28]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: IU/L
        arithmetic mean (full range (min-max))
    -0.2 (-168 to 146)
    -0.3 (-148 to 101)
    0 (-462 to 297)
    No statistical analyses for this end point

    Primary: Glucose (Change from Baseline)

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    End point title
    		 Glucose (Change from Baseline) [29]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    1.3 (-138 to 222)
    0.2 (-207 to 179)
    2 (-97 to 138)
    No statistical analyses for this end point

    Primary: Magnesium (Change from Baseline)

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    End point title
    		 Magnesium (Change from Baseline) [30]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    -0.01 (-0.5 to 0.5)
    -0.02 (-0.4 to 0.4)
    0 (-0.6 to 1)
    No statistical analyses for this end point

    Primary: Phosphate (Change from Baseline)

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    End point title
    		 Phosphate (Change from Baseline) [31]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    -0.04 (-1.6 to 1.8)
    -0.01 (-1.8 to 1.5)
    -0.15 (-2.3 to 1.8)
    No statistical analyses for this end point

    Primary: Potassium (Change from Baseline)

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    End point title
    		 Potassium (Change from Baseline) [32]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mEq/L
        arithmetic mean (full range (min-max))
    0 (-1.1 to 1.6)
    0.05 (-2.2 to 1.1)
    0 (-1.3 to 1)
    No statistical analyses for this end point

    Primary: Protein (Change from Baseline)

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    End point title
    		 Protein (Change from Baseline) [33]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: g/dL
        arithmetic mean (full range (min-max))
    -0.04 (-1.2 to 1)
    0 (-1.7 to 1.6)
    -0.06 (-1 to 1.3)
    No statistical analyses for this end point

    Primary: Sodium (Change from Baseline)

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    End point title
    		 Sodium (Change from Baseline) [34]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mEq/L
        arithmetic mean (full range (min-max))
    -0.1 (-11 to 7)
    -0.2 (-8 to 8)
    0 (-10 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) [35]
    End point description
    End point type
    Primary
    End point timeframe
    The non-fasting laboratory tests will be performed at the screening visit and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mg/dL
        arithmetic mean (full range (min-max))
    0.05 (-3.3 to 3)
    0.01 (-2.2 to 3.8)
    -0.16 (-3.6 to 2.9)
    No statistical analyses for this end point

    Primary: Systolic Blood Pressure (Change from Baseline)

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    End point title
    		 Systolic Blood Pressure (Change from Baseline) [36]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mmHg
        arithmetic mean (full range (min-max))
    -0.2 (-40 to 33)
    -0.2 (-26 to 32)
    0.3 (-42 to 42)
    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) [37]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: mmHg
        arithmetic mean (full range (min-max))
    0.2 (-27 to 23)
    -0.8 (-25 to 26)
    0.1 (-25 to 25)
    No statistical analyses for this end point

    Primary: Pulse Rate (Change from Baseline)

    		 Close Top of page
    End point title
    		 Pulse Rate (Change from Baseline) [38]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: BEATS/MIN
        arithmetic mean (full range (min-max))
    -0.7 (-36 to 30)
    -0.3 (-30 to 26)
    1.4 (-25 to 40)
    No statistical analyses for this end point

    Primary: Respiratory Rate (Change from Baseline)

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    End point title
    		 Respiratory Rate (Change from Baseline) [39]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    252
    Units: BREATHS/MIN
        arithmetic mean (full range (min-max))
    -0.1 (-12 to 8)
    0 (-7 to 10)
    0 (-8 to 6)
    No statistical analyses for this end point

    Primary: Temperature (Change from Baseline)

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    End point title
    		 Temperature (Change from Baseline) [40]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: celsius
        arithmetic mean (full range (min-max))
    0.02 (-1.6 to 1.5)
    0.01 (-1 to 1.1)
    -0.05 (-1.7 to 1)
    No statistical analyses for this end point

    Primary: Weight (Change from Baseline)

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    End point title
    		 Weight (Change from Baseline) [41]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, Day 1 (pre-dose) and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: kg
        arithmetic mean (full range (min-max))
    1.01 (-14 to 14.9)
    1 (-17.7 to 17.3)
    0.07 (-15.3 to 9.9)
    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) [42]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: BEATS/MIN
        arithmetic mean (full range (min-max))
    -0.4 (-38 to 32)
    0.9 (-30 to 28)
    1 (-31 to 45)
    No statistical analyses for this end point

    Primary: QT Duration (Change from Baseline)

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    End point title
    		 QT Duration (Change from Baseline) [43]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: msec
        arithmetic mean (full range (min-max))
    -0.4 (-67 to 82)
    0.1 (-54 to 82)
    -2.1 (-105 to 75)
    No statistical analyses for this end point

    Primary: QTcB - Bazett's Correction Formula (Change from baseline)

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    End point title
    		 QTcB - Bazett's Correction Formula (Change from baseline) [44]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: msec
        arithmetic mean (full range (min-max))
    -1.2 (-59 to 73)
    2.5 (-50 to 65)
    0.8 (-79 to 50)
    No statistical analyses for this end point

    Primary: QTcF - Fridericia's Correction Formula (Change from baseline)

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    End point title
    		 QTcF - Fridericia's Correction Formula (Change from baseline) [45]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: msec
        arithmetic mean (full range (min-max))
    -0.9 (-50 to 53)
    1.6 (-41 to 50)
    -0.3 (-68 to 38)
    No statistical analyses for this end point

    Primary: QRS Duration (Change from Baseline)

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    End point title
    		 QRS Duration (Change from Baseline) [46]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: msec
        arithmetic mean (full range (min-max))
    -1.1 (-21 to 16)
    -0.6 (-22 to 19)
    -0.6 (-25 to 30)
    No statistical analyses for this end point

    Primary: PR Duration (Change from Baseline)

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    End point title
    		 PR Duration (Change from Baseline) [47]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, on Day 1 pre-dose and within 3 hours post-dose, and on Days 28, 56, 84, 112, 140, and 182 (± 2 days) or ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: msec
        arithmetic mean (full range (min-max))
    2.8 (-46 to 58)
    -0.8 (-32 to 44)
    -0.5 (-29 to 41)
    No statistical analyses for this end point

    Primary: Calgary Depression Severity in Schizophrenia (CDSS) (Day 182)

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    End point title
    		 Calgary Depression Severity in Schizophrenia (CDSS) (Day 182) [48]
    End point description
    End point type
    Primary
    End point timeframe
    Screening visit, Day 1 (Pre-dose), Day 182 and on ET.
    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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: n/a
        arithmetic mean (full range (min-max))
    1.3 (0 to 9)
    1.2 (0 to 13)
    1.1 (0 to 9)
    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) [49]
    End point description
    End point type
    Primary
    End point timeframe
    Screening, Days 1 (pre-dose), 14 (telephone call), 28, 56, 84, 112, 140, and 182 (± 2 days) or early termination.
    Notes
    [49] - 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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: Subjects with suicidal behavior/ideation
    5
    1
    4
    No statistical analyses for this end point

    Primary: Simpson-Angus Total Scores (SAS) (Change from baseline)

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    End point title
    		 Simpson-Angus Total Scores (SAS) (Change from baseline) [50]
    End point description
    End point type
    Primary
    End point timeframe
    Screening and on Days 1 (pre-dose), 28, 56, 84, 112, 140, and 182 (± 2 days) or ET
    Notes
    [50] - 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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: n/a
        arithmetic mean (full range (min-max))
    -0.2 (-9 to 4)
    0 (-6 to 4)
    -0.1 (-4 to 4)
    No statistical analyses for this end point

    Primary: Positive and Negative Syndrome Scale (PANSS) Positive Symptom Scores (Change from baseline)

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    End point title
    		 Positive and Negative Syndrome Scale (PANSS) Positive Symptom Scores (Change from baseline) [51]
    End point description
    End point type
    Primary
    End point timeframe
    Days -14, 1 (pre-dose), and 28, 56, 84, 112, 140, and 182.
    Notes
    [51] - 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: Statistical tests were not performed on safety parameters.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    252
    248
    253
    Units: n/a
        arithmetic mean (full range (min-max))
    -1.5 (-9 to 13)
    -1.2 (-9 to 8)
    -1 (-7 to 9)
    No statistical analyses for this end point

    Secondary: Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor (Marder Factor) (Change from Baseline)

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    End point title
    		 Positive and Negative Syndrome Scale (PANSS) Negative Symptom Factor (Marder Factor) (Change from Baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    Days -14, 1 (pre-dose), and 28, 56, 84, 112, 140, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    -2.6 (-12 to 8)
    -2.1 (-13 to 8)
    -1.8 (-14 to 9)
    Statistical analysis title
    		 Hochberg method adjustment
    Comparison groups
    EVP-6124, 1 mg v EVP-6124, 2 mg v Placebo
    Number of subjects included in analysis
    731
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Hochberg method adjustment
    Confidence interval

    Secondary: MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Scores with Imputation of missing components (Change from Baseline)

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    End point title
    		 MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Scores with Imputation of missing components (Change from Baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (standard error)
    3.6 ( 0.41 )
    3.5 ( 0.49 )
    2.8 ( 0.45 )
    No statistical analyses for this end point

    Secondary: MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Scores without Imputation of missing components (Change from Baseline)

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    End point title
    		 MATRICS Consensus Cognitive Battery (MCCB) Overall Composite T-Scores without Imputation of missing components (Change from Baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    3.7 (-14 to 33)
    3.7 (-10 to 29)
    2.7 (-18 to 22)
    No statistical analyses for this end point

    Secondary: Schizophrenia Cognition Rating Scale (SCoRS) Global rating (Change from Baseline)

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    End point title
    		 Schizophrenia Cognition Rating Scale (SCoRS) Global rating (Change from Baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    Day -14 (training and practice) and testing on Days 1 (pre-dose), 28, 56, 84, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    -0.8 (-5 to 2)
    -1 (-5 to 3)
    -0.9 (-6 to 3)
    No statistical analyses for this end point

    Secondary: Positive and Negative Syndrome Scale (PANSS) Negative Symptom Scores (Change from baseline)

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    End point title
    		 Positive and Negative Syndrome Scale (PANSS) Negative Symptom Scores (Change from baseline)
    End point description
    End point type
    Secondary
    End point timeframe
    Days -14, 1 (pre-dose), and 28, 56, 84, 112, 140, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    -2.5 (-13 to 7)
    -1.7 (-11 to 9)
    -1.6 (-15 to 10)
    No statistical analyses for this end point

    Secondary: Clinical Global Impression – Severity scale (CGI-S) (Day 182)

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    End point title
    		 Clinical Global Impression – Severity scale (CGI-S) (Day 182)
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 (pre-dose, baseline), and 28, 56, 84, 112, 140, and 182.
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    3.2 (1 to 5)
    3.2 (2 to 5)
    3.3 (1 to 5)
    No statistical analyses for this end point

    Secondary: Clinical Global Impression – Change scale (CGI-C) (Day 182)

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    End point title
    		 Clinical Global Impression – Change scale (CGI-C) (Day 182)
    End point description
    End point type
    Secondary
    End point timeframe
    Days 28, 56, 84, 112, 140, and 182
    End point values
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Number of subjects analysed
    247
    238
    246
    Units: n/a
        arithmetic mean (full range (min-max))
    3.1 (1 to 5)
    3.1 (1 to 6)
    3.2 (1 to 5)
    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 informed consent through the follow-up period of the study (Day 182, 189, or ET, 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
    EVP-6124, 1 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    EVP-6124, 2 mg
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Reporting group title
    Placebo
    Reporting group description
    		 Eligible subjects will be randomized in a 1:1:1 allocation to 1 of 3 double-blind treatment groups: once daily EVP-6124 tablets (1 or 2 mg) or placebo for 26 weeks (Days 1 to 182).

    Serious adverse events
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 252 (2.38%)
    3 / 248 (1.21%)
    7 / 253 (2.77%)
         number of deaths (all causes)
    1
    1
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychiatric decompensation
         subjects affected / exposed
    3 / 252 (1.19%)
    2 / 248 (0.81%)
    3 / 253 (1.19%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed mood
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination, auditory
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Tuberculosis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 EVP-6124, 1 mg EVP-6124, 2 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    135 / 252 (53.57%)
    127 / 248 (51.21%)
    140 / 253 (55.34%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Thyroid neoplasm
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 252 (0.79%)
    4 / 248 (1.61%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Hot flush
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    6 / 252 (2.38%)
    5 / 248 (2.02%)
    5 / 253 (1.98%)
         occurrences all number
    135
    127
    140
    Oedema peripheral
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Pain
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Pyrexia
         subjects affected / exposed
    3 / 252 (1.19%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Chest pain
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Cyst
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Discomfort
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Feeling abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Feeling hot
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Peripheral swelling
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Temperature intolerance
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Seasonal allergy
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Social circumstances
    Substance use
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Ovarian cyst
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Breast calcifications
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Breast disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Breast hyperplasia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Breast swelling
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dysmenorrhoea
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Erectile dysfunction
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gynaecomastia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Lactation disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Menstrual disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nipple pain
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Premenstrual pain
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Sexual dysfunction
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 252 (1.19%)
    3 / 248 (1.21%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Oropharyngeal pain
         subjects affected / exposed
    2 / 252 (0.79%)
    4 / 248 (1.61%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Epistaxis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Nasal congestion
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Rhinorrhoea
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Allergic sinusitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Asthma
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Bradypnoea
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Bronchitis chronic
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Catarrh
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dyspnoea
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Productive cough
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Respiratory disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Rhinitis allergic
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Snoring
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Upper respiratory tract congestion
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Wheezing
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    12 / 252 (4.76%)
    9 / 248 (3.63%)
    10 / 253 (3.95%)
         occurrences all number
    135
    127
    140
    Anxiety
         subjects affected / exposed
    8 / 252 (3.17%)
    5 / 248 (2.02%)
    12 / 253 (4.74%)
         occurrences all number
    135
    127
    140
    Psychiatric decompensation
         subjects affected / exposed
    6 / 252 (2.38%)
    7 / 248 (2.82%)
    8 / 253 (3.16%)
         occurrences all number
    135
    127
    140
    Suicidal ideation
         subjects affected / exposed
    2 / 252 (0.79%)
    3 / 248 (1.21%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hallucination, auditory
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Irritability
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Psychotic disorder
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Depressed mood
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Psychomotor retardation
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Thinking abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Agitation
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Bruxism
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Confusional state
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Delusion
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    124
    140
    Depression
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Hallucination
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Initial insomnia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Libido decreased
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Middle insomnia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Panic attack
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Paranoia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Restlessness
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Sleep disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Somnambulism
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Suicide attempt
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    5 / 252 (1.98%)
    12 / 248 (4.84%)
    16 / 253 (6.32%)
         occurrences all number
    135
    123
    140
    Weight increased
         subjects affected / exposed
    12 / 252 (4.76%)
    11 / 248 (4.44%)
    7 / 253 (2.77%)
         occurrences all number
    135
    127
    140
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 252 (1.59%)
    1 / 248 (0.40%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 252 (1.98%)
    0 / 248 (0.00%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Weight decreased
         subjects affected / exposed
    0 / 252 (0.00%)
    6 / 248 (2.42%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Blood glucose increased
         subjects affected / exposed
    0 / 252 (0.00%)
    6 / 248 (2.42%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blood uric acid increased
         subjects affected / exposed
    3 / 252 (1.19%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blood pressure increased
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Neutrophil count increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    White blood cell count increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Blood bilirubin increased
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood urea increased
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Urine leukocyte esterase positive
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    White blood cell count decreased
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Alanine aminotransferase abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Aspartate aminotransferase abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blood alcohol increased
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood cholesterol increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blood creatinine increased
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood glucose decreased
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood potassium decreased
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood pressure diastolic decreased
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood prolactin increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blood urine present
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Gamma-glutamyltransferase abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Glucose urine present
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Haemoglobin decreased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Nitrite urine present
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Platelet count increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Protein total increased
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Protein urine present
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Red blood cell count increased
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Urinary casts
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Urine ketone body present
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 252 (2.38%)
    2 / 248 (0.81%)
    5 / 253 (1.98%)
         occurrences all number
    135
    127
    140
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Thermal burn
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Ligament sprain
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Limb injury
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Toxicity to various agents
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Accidental overdose
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Alcohol poisoning
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Excoriation
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Eye contusion
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Multiple fractures
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Muscle injury
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Muscle strain
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Radius fracture
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Road traffic accident
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Scar
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Skin abrasion
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Soft tissue injury
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Sunburn
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Arthropod bite
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Cardiac disorders
    Defect conduction intraventricular
         subjects affected / exposed
    3 / 252 (1.19%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Bradycardia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Bundle branch block left
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Sinus bradycardia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Sinus tachycardia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Tachycardia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nervous system disorders
    Headache
         subjects affected / exposed
    24 / 252 (9.52%)
    16 / 248 (6.45%)
    15 / 253 (5.93%)
         occurrences all number
    135
    127
    140
    Somnolence
         subjects affected / exposed
    2 / 252 (0.79%)
    2 / 248 (0.81%)
    6 / 253 (2.37%)
         occurrences all number
    135
    127
    140
    Tremor
         subjects affected / exposed
    4 / 252 (1.59%)
    2 / 248 (0.81%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Dizziness
         subjects affected / exposed
    4 / 252 (1.59%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Disturbance in attention
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Sedation
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Akathisia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Extrapyramidal disorder
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Hypersomnia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hypoaesthesia
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Dysgeusia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dyskinesia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Extensor plantar response
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Glabellar reflex abnormal
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hyporeflexia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Hypotonia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Migraine
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Paraesthesia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Radial nerve compression
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Restless legs syndrome
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Sinus headache
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Stupor
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Tension headache
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    VIIth nerve paralysis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Lymphadenopathy
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Eosinophilia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Leukocytosis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Neutrophilia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Vertigo
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Eye disorders
    Ocular hyperaemia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Vision blurred
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Blepharospasm
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Eye irritation
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    14 / 252 (5.56%)
    19 / 248 (7.66%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Diarrhoea
         subjects affected / exposed
    3 / 252 (1.19%)
    7 / 248 (2.82%)
    5 / 253 (1.98%)
         occurrences all number
    135
    127
    140
    Nausea
         subjects affected / exposed
    4 / 252 (1.59%)
    4 / 248 (1.61%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Toothache
         subjects affected / exposed
    5 / 252 (1.98%)
    3 / 248 (1.21%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dyspepsia
         subjects affected / exposed
    3 / 252 (1.19%)
    3 / 248 (1.21%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Abdominal pain
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Abdominal pain upper
         subjects affected / exposed
    2 / 252 (0.79%)
    2 / 248 (0.81%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Vomiting
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Abdominal discomfort
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Faeces hard
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dry mouth
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gastritis
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Haematochezia
         subjects affected / exposed
    0 / 252 (0.00%)
    2 / 248 (0.81%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Rectal haemorrhage
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Abdominal distension
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Anal fissure
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Abdominal pain lower
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Aphthous stomatitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Chronic gastritis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Dental caries
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Flatulence
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Gingival pain
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Gingival swelling
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Haemorrhoids
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Oesophagitis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Painful defaecation
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Salivary gland calculus
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Stomatitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Rash
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Alopecia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Dermatitis contact
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Eczema asteatotic
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Erythema
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hyperhidrosis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nail bed disorder
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nail disorder
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Pain of skin
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Petechiae
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Photosensitivity reaction
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Pruritus
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Psoriasis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Skin disorder
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Skin fissures
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Skin hypopigmentation
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Skin lesion
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Skin mass
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Skin ulcer
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Urticaria
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 252 (0.00%)
    3 / 248 (1.21%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Dysuria
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Proteinuria
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Glycosuria
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Ketonuria
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nephrolithiasis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 252 (2.38%)
    5 / 248 (2.02%)
    10 / 253 (3.95%)
         occurrences all number
    135
    127
    140
    Arthralgia
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Pain in extremity
         subjects affected / exposed
    1 / 252 (0.40%)
    5 / 248 (2.02%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Musculoskeletal pain
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Myalgia
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Muscle spasms
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Neck pain
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Arthritis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Muscle rigidity
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Muscle twitching
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Muscular weakness
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Nuchal rigidity
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Osteitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Torticollis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    11 / 252 (4.37%)
    17 / 248 (6.85%)
    14 / 253 (5.53%)
         occurrences all number
    135
    127
    140
    Bronchitis
         subjects affected / exposed
    4 / 252 (1.59%)
    2 / 248 (0.81%)
    4 / 253 (1.58%)
         occurrences all number
    135
    127
    140
    Influenza
         subjects affected / exposed
    3 / 252 (1.19%)
    4 / 248 (1.61%)
    3 / 253 (1.19%)
         occurrences all number
    135
    127
    140
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 252 (0.79%)
    4 / 248 (1.61%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Pharyngitis
         subjects affected / exposed
    4 / 252 (1.59%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Ear infection
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gastroenteritis
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Conjunctivitis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Respiratory tract infection
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Tooth infection
         subjects affected / exposed
    2 / 252 (0.79%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Urinary tract infection
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Cystitis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Gastroenteritis viral
         subjects affected / exposed
    2 / 252 (0.79%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Gingivitis
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Hordeolum
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Sinusitis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Subcutaneous abscess
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Tonsillitis
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Acarodermatitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Eye infection
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Fungal infection
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Genital infection fungal
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Herpes simplex
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Localised infection
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Pneumonia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Pulpitis dental
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Rhinitis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Tinea pedis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Tooth abscess
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Tuberculosis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Varicella
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Viral infection
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Viral rhinitis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Wound infection
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Metabolism and nutrition disorders
    Increased appetite
         subjects affected / exposed
    1 / 252 (0.40%)
    2 / 248 (0.81%)
    2 / 253 (0.79%)
         occurrences all number
    135
    127
    140
    Hyperglycaemia
         subjects affected / exposed
    3 / 252 (1.19%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Diabetes mellitus
         subjects affected / exposed
    1 / 252 (0.40%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Dehydration
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Dyslipidaemia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Gout
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hyperlipidaemia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 248 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    135
    127
    140
    Hypoglycaemia
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 248 (0.40%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140
    Obesity
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 248 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    135
    127
    140

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Feb 2013
    Protocol Amendment 1
    08 Jul 2013
    Protocol Amendment 2
    05 Dec 2013
    Protocol Amendment 2.1
    26 Aug 2014
    Protocol Amendment 2.2
    30 Sep 2015
    Protocol Amendment 3
    01 Oct 2015
    Protocol Amendment 3.1

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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

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