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    Clinical Trial Results:
    Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Safety, Efficacy and Potential Pharmacokinetic Interaction of RDEA594 and Allopurinol in Gout Patients with an Inadequate Hypouricemic Response with Standard Doses of Allopurinol

    Summary
    EudraCT number
    		 2009-014660-19
    Trial protocol
    		 GB   ES   PL  
    Global end of trial date
    12 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Dec 2017
    First version publication date
    29 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RDEA594-203
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01001338
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ardea Biosciences, Inc.
    Sponsor organisation address
    9390 Towne Centre Dr., San Diego, United States,
    Public contact
    Nihar Bhakta, Ardea Biosciences, Inc., nbhakta@ardeabio.com
    Scientific contact
    Nihar Bhakta, MD, Ardea Biosciences, Inc., 1 8586526671, nbhakta@ardeabio.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 Aug 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Jul 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the percent reduction from baseline in serum urate levels following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response.
    Protection of trial subjects
    This study was conducted in accordance with the protocol, International Conference on Harmonisation (ICH) E6 Good Clinical Practice (GCP), the Declaration of Helsinki (2008), and all other applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Oct 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 28
    Country: Number of subjects enrolled
    Georgia: 32
    Country: Number of subjects enrolled
    Poland: 25
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Ukraine: 40
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 78
    Worldwide total number of subjects
    208
    EEA total number of subjects
    30
    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)
    17
    From 65 to 84 years
    191
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects who completed the Main Period could enter the optional Double-Blind Extension (DBE) Period. Subjects who completed the DBE Period could enter the optional OLE Period, with the Week 44 visit of the DBE Period serving as the Month 0 visit of the OLE Period.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Main Period Cohort 1: Lesinurad 200 mg
    Arm description
    		 Lesinurad 200 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    lesinurad
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg

    Arm title
    		 Main Period Cohort 2: Lesinurad 400 mg
    Arm description
    		 Lesinurad 400 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    lesinurad
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg

    Arm title
    		 Main Period Cohort 3: Lesinurad 600 mg
    Arm description
    		 Lesinurad 600 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    lesinurad
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg

    Arm title
    		 Main Period: Pooled Placebo
    Arm description
    		 Pooled placebo.
    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
    N/A

    Number of subjects in period 1
    		Main Period Cohort 1: Lesinurad 200 mg Main Period Cohort 2: Lesinurad 400 mg Main Period Cohort 3: Lesinurad 600 mg Main Period: Pooled Placebo
    Started
    46
    42
    48
    72
    Completed
    41
    40
    42
    66
    Not completed
    5
    2
    6
    6
         Consent withdrawn by subject
    3
    -
    2
    3
         Adverse event, non-fatal
    -
    1
    2
    1
         Prolonged QTc intervals
    1
    -
    -
    -
         Day 27 dose at home
    1
    -
    -
    -
         Lost to follow-up
    -
    1
    -
    1
         Protocol deviation
    -
    -
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Main Period Cohort 1: Lesinurad 200 mg
    Reporting group description
    		 Lesinurad 200 mg

    Reporting group title
    Main Period Cohort 2: Lesinurad 400 mg
    Reporting group description
    		 Lesinurad 400 mg

    Reporting group title
    Main Period Cohort 3: Lesinurad 600 mg
    Reporting group description
    		 Lesinurad 600 mg

    Reporting group title
    Main Period: Pooled Placebo
    Reporting group description
    		 Pooled placebo.

    Reporting group values
    		 Main Period Cohort 1: Lesinurad 200 mg Main Period Cohort 2: Lesinurad 400 mg Main Period Cohort 3: Lesinurad 600 mg Main Period: Pooled Placebo Total
    Number of subjects
    		 46 42 48 72 208
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 39 39 45 68 191
        From 65-84 years
    		 7 3 3 4 17
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 52.9 ( 10.11 ) 50.7 ( 10.38 ) 48.4 ( 11.03 ) 51.1 ( 9.21 ) -
    Sex/Gender, Customized
    Units: Subjects
        Male|
    		 44 41 48 71 204
        Female|
    		 2 1 0 1 4

    End points

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    End points reporting groups
    Reporting group title
    Main Period Cohort 1: Lesinurad 200 mg
    Reporting group description
    		 Lesinurad 200 mg

    Reporting group title
    Main Period Cohort 2: Lesinurad 400 mg
    Reporting group description
    		 Lesinurad 400 mg

    Reporting group title
    Main Period Cohort 3: Lesinurad 600 mg
    Reporting group description
    		 Lesinurad 600 mg

    Reporting group title
    Main Period: Pooled Placebo
    Reporting group description
    		 Pooled placebo.

    Subject analysis set title
    Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 (Lesinurad) 200 mg qd for 28 days. (N at Baseline = 46)

    Subject analysis set title
    Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days. (N at Baseline = 42)

    Subject analysis set title
    Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 7 days followed by 400 mg qd for 7 days followed by 600 mg qd for 14 days. (N at Baseline = 48)

    Subject analysis set title
    Pooled Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled place72 (N at Baseline = 72)

    Subject analysis set title
    Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 28 days

    Subject analysis set title
    Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days

    Subject analysis set title
    Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 7 days followed by 400 mg qd for 7 days followed by 600 mg qd for 14 days.

    Subject analysis set title
    Pooled Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pooled placebo

    Subject analysis set title
    Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 28 days.

    Subject analysis set title
    Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days.

    Subject analysis set title
    Total RDEA594
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants in the Double-Blind Extension remained on their randomized treatment (RDEA594 or placebo) plus allopurinol.

    Subject analysis set title
    Pooled Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants in the Double-Blind Extension remained on their randomized treatment (RDEA594 or placebo) plus allopurinol.

    Subject analysis set title
    Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants in the Double-Blind Extension remained on their randomized treatment (RDEA594 or placebo) plus allopurinol.

    Subject analysis set title
    Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants in the Double-Blind Extension remained on their randomized treatment (RDEA594 or placebo) plus allopurinol.

    Subject analysis set title
    Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants in the Double-Blind Extension remained on their randomized treatment (RDEA594 or placebo) plus allopurinol.

    Subject analysis set title
    ALLO-only
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects originally randomized to receive placebo plus allopurinol whose sUA values were <6.0 mg/dL continued on allopurinol alone in the OLE Period.

    Subject analysis set title
    ALLO-switch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Among subjects who continued on allopurinol alone, those whose sUA values later increased to ≥6.0 mg/dL in the OLE Period began dosing with lesinurad (starting at 200 mg and escalating to a maximum of 600 mg qd as necessary using 6.0 mg/dL as the target sUA level) in combination with their current dose of allopurinol.

    Subject analysis set title
    PBO-switch
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects originally randomized to receive placebo plus allopurinol whose sUA values were ≥6.0 mg/dL at Week 44 of the DBE Period began dosing with lesinurad (starting at 200 mg and escalating to a maximum of 600 mg qd as necessary using 6.0 mg/dL as the target sUA level) in combination with their current dose of allopurinol.

    Subject analysis set title
    Lesinurad
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to lesinurad in combination with allopurinol in the Main and DBE Periods began taking open-label lesinurad at the dose level they were taking at the end of the DBE Period (200, 400, or 600 mg qd) in combination with the dose of allopurinol they were taking at the end of the DBE Period.

    Subject analysis set title
    Total Lesinurad
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Total Lesinurad

    Primary: Percent reduction from Baseline in serum urate (sUA) following 4 weeks of treatment (Main Period).

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    End point title
    		 Percent reduction from Baseline in serum urate (sUA) following 4 weeks of treatment (Main Period).
    End point description
    The percent reduction from Baseline in sUA levels following 4 weeks of continuous treatment with lesinurad in combination with allopurinol compared to allopurinol alone (the placebo group) in participants with documented inadequate hypouricemic response with standard doses of allopurinol.
    End point type
    Primary
    End point timeframe
    4 Weeks
    End point values
    		 Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd Pooled Placebo
    Number of subjects analysed
    40
    40
    41
    72
    Units: Percent (%) Change
        arithmetic mean (standard deviation)
    -16.12 ( 18.89 )
    -22.07 ( 21.59 )
    -30.35 ( 14.03 )
    2.63 ( 21.12 )
    Statistical analysis title
    		 Cohort 1 vs. Placebo
    Comparison groups
    Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd v Pooled Placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -23.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.42
         upper limit
    		 -8.83
    Statistical analysis title
    		 Cohort 2 vs. Placebo
    Comparison groups
    Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd v Pooled Placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -23.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.71
         upper limit
    		 -17.09
    Statistical analysis title
    		 Cohort 3 vs. Placebo
    Comparison groups
    Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd v Pooled Placebo
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -29.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.08
         upper limit
    		 -22.41

    Secondary: Percentage of participants whose sUA level was < 6.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).

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    End point title
    		 Percentage of participants whose sUA level was < 6.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    64
    40
    39
    40
    Units: Percent (%) of Participants
        Day 28
    16
    29
    28
    33
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level was < 5.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).

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    End point title
    		 Percentage of participants whose sUA level was < 5.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    64
    40
    39
    40
    Units: Percent (%) of Participants
        Day 28
    4
    13
    14
    23
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level was < 4.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).

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    End point title
    		 Percentage of participants whose sUA level was < 4.0 mg/dL at Day 28 by treatment group in all participants and in participants who have an sUA ≥ 6.0 mg/dL at the Baseline visit (Main Period).
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    64
    40
    39
    40
    Units: Percent (%) of Participants
        Day 28
    1
    4
    6
    7
    No statistical analyses for this end point

    Secondary: Absolute reduction from Baseline in sUA levels at each visit. (Main Period)

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    End point title
    		 Absolute reduction from Baseline in sUA levels at each visit. (Main Period)
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    72
    46
    42
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline|
    6.70 ( 1.29 )
    6.37 ( 1.27 )
    6.89 ( 1.37 )
    7.30 ( 1.53 )
        Day 7|
    -0.05 ( 1.07 )
    -1.12 ( 1.08 )
    -1.12 ( 1.36 )
    -1.54 ( 1.45 )
        Day 14|
    -0.19 ( 1.13 )
    -0.81 ( 1.16 )
    -1.30 ( 1.45 )
    -1.88 ( 1.51 )
        Day 21|
    0.06 ( 1.50 )
    -0.93 ( 1.18 )
    -1.29 ( 1.63 )
    -1.89 ( 1.82 )
        Day 27|
    0.01 ( 1.14 )
    -1.19 ( 1.47 )
    -1.59 ( 1.53 )
    -2.29 ( 1.28 )
        Day 28|
    -0.10 ( 1.09 )
    -1.00 ( 1.31 )
    -1.38 ( 1.40 )
    -2.11 ( 1.45 )
    No statistical analyses for this end point

    Secondary: Percent reduction from Baseline in sUA levels at each visit. (Main Period).

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    End point title
    		 Percent reduction from Baseline in sUA levels at each visit. (Main Period).
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    72
    46
    42
    48
    Units: Percent (%) Reduction in sUA
    arithmetic mean (standard deviation)
        Day 7|
    2.15 ( 25.80 )
    -16.15 ( 14.62 )
    -15.66 ( 18.78 )
    -19.09 ( 17.37 )
        Day 14|
    -0.06 ( 22.73 )
    -10.94 ( 15.28 )
    -17.63 ( 20.49 )
    -24.22 ( 16.27 )
        Day 21|
    4.28 ( 30.86 )
    -12.73 ( 15.58 )
    -17.90 ( 23.94 )
    -23.19 ( 27.88 )
        Day 27|
    2.63 ( 21.12 )
    -16.12 ( 18.89 )
    -22.07 ( 21.59 )
    -30.35 ( 14.03 )
        Day 28|
    1.07 ( 21.51 )
    -13.57 ( 17.31 )
    -19.53 ( 20.74 )
    -27.86 ( 20.45 )
    No statistical analyses for this end point

    Secondary: Percent change in 24-hour urine urate excretion from Baseline to Day 28. (Main Period)

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    End point title
    		 Percent change in 24-hour urine urate excretion from Baseline to Day 28. (Main Period)
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    72
    46
    42
    48
    Units: mg/24hr
        arithmetic mean (standard deviation)
    6.7 ( 60.88 )
    22.3 ( 52.19 )
    33.5 ( 107.18 )
    38.3 ( 88.62 )
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced a gout flare (Main Period)

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    End point title
    		 Percentage of participants who experienced a gout flare (Main Period)
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    72
    46
    42
    48
    Units: Percent (%) of Participants
    15
    10
    13
    15
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level decreased to or is maintained at < 6.0 mg/dL at Week 44. (Double-Blind Extension Period)

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    End point title
    		 Percentage of participants whose sUA level decreased to or is maintained at < 6.0 mg/dL at Week 44. (Double-Blind Extension Period)
    End point description
    End point type
    Secondary
    End point timeframe
    44 Weeks
    End point values
    		 Total RDEA594 Pooled Placebo
    Number of subjects analysed
    61
    34
    Units: Percent (%) of Participants
        Week 44 Extension
    51
    25
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level decreased to or is maintained at < 5.0 mg/dL at Week 44. (Double-Blind Extension Period)

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    End point title
    		 Percentage of participants whose sUA level decreased to or is maintained at < 5.0 mg/dL at Week 44. (Double-Blind Extension Period)
    End point description
    End point type
    Secondary
    End point timeframe
    44 Weeks
    End point values
    		 Total RDEA594 Pooled Placebo
    Number of subjects analysed
    61
    34
    Units: Percent (%) of Participants
        Week 44 - Extension
    41
    9
    No statistical analyses for this end point

    Secondary: Absolute reduction from Baseline in sUA levels at each visit (Double-Blind Extension)

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    End point title
    		 Absolute reduction from Baseline in sUA levels at each visit (Double-Blind Extension)
    End point description
    End point type
    Secondary
    End point timeframe
    44 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    48
    18
    15
    45
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline|
    7.79 ( 1.675 )
    6.59 ( 1.333 )
    7.57 ( 2.611 )
    7.52 ( 1.708 )
        Week 2 - Extension|
    -0.83 ( 1.926 )
    -1.13 ( 1.627 )
    -2.07 ( 2.033 )
    -1.59 ( 1.936 )
        Week 4 - Extension|
    -1.51 ( 1.843 )
    -0.94 ( 1.664 )
    -1.56 ( 1.699 )
    -1.72 ( 2.162 )
        Week 6 - Extension|
    -1.12 ( 1.823 )
    -1.91 ( 1.797 )
    -2.27 ( 2.822 )
    -1.76 ( 1.824 )
        Week 8 - Extension|
    -1.12 ( 1.674 )
    -1.80 ( 1.905 )
    -2.29 ( 3.159 )
    -1.69 ( 2.049 )
        Week 10 - Extension|
    -1.21 ( 1.823 )
    -1.60 ( 0 )
    -2.80 ( 0 )
    -2.20 ( 2.286 )
        Week 12 - Extension|
    -1.38 ( 1.786 )
    -1.95 ( 1.635 )
    -2.74 ( 2.651 )
    -1.68 ( 2.564 )
        Week 14 - Extension|
    -1.04 ( 1.494 )
    0 ( 0 )
    0 ( 0 )
    -1.00 ( 2.047 )
        Week 16 - Extension|
    -1.61 ( 2.064 )
    -2.18 ( 1.834 )
    -2.21 ( 2.581 )
    -2.11 ( 2.535 )
        Week 18 - Extension|
    -1.37 ( 1.405 )
    -0.60 ( 0 )
    .50 ( 0 )
    -2.06 ( 2.238 )
        Week 20 - Extension|
    -1.40 ( 1.998 )
    -2.31 ( 1.591 )
    -2.48 ( 3.131 )
    -1.93 ( 2.150 )
        Week 22 - Extension|
    -1.53 ( 1.688 )
    0 ( 0 )
    -4.17 ( 3.580 )
    -0.75 ( 2.836 )
        Week 24 - Extension|
    -2.50 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Week 28 - Extension|
    -1.33 ( 1.922 )
    -2.03 ( 1.493 )
    -2.71 ( 2.695 )
    -2.12 ( 1.840 )
        Week 36 - Extension|
    -2.06 ( 1.655 )
    -2.03 ( 2.147 )
    -2.68 ( 2.898 )
    -2.04 ( 2.042 )
        Week 44 - Extension|
    -2.10 ( 1.710 )
    -2.31 ( 1.639 )
    -2.55 ( 3.052 )
    -2.03 ( 2.154 )
    No statistical analyses for this end point

    Secondary: Percent reduction from Baseline in sUA levels at each visit (Double-Blind Extension)

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    End point title
    		 Percent reduction from Baseline in sUA levels at each visit (Double-Blind Extension)
    End point description
    End point type
    Secondary
    End point timeframe
    44 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    48
    18
    15
    45
    Units: Percent (%) of Participants
    arithmetic mean (standard deviation)
        Baseline|
    7.79 ( 1.675 )
    6.59 ( 1.333 )
    7.57 ( 2.611 )
    7.52 ( 1.708 )
        Week 2 - Extension|
    -7.75 ( 24.484 )
    -15.85 ( 21.576 )
    -25.12 ( 17.303 )
    -17.70 ( 21.909 )
        Week 4 - Extension|
    -9.67 ( 18.734 )
    -21.17 ( 20.475 )
    -19.16 ( 18.955 )
    -17.74 ( 20.824 )
        Week 6 - Extension|
    -11.60 ( 19.573 )
    -25.56 ( 21.483 )
    -23.14 ( 23.962 )
    -20.97 ( 19.995 )
        Week 8 - Extension|
    -11.82 ( 17.999 )
    -24.14 ( 22.498 )
    -23.04 ( 29.376 )
    -18.77 ( 25.88 )
        Week 10 - Extension|
    -13.05 ( 20.267 )
    -25.40 ( 0 )
    -41.18 ( 0 )
    -25.49 ( 33.216 )
        Week 12 - Extension|
    -15.48 ( 18.189 )
    -26.25 ( 19.959 )
    -31.30 ( 20.792 )
    -18.25 ( 35.377 )
        Week 14 - Extension|
    -11.65 ( 34.933 )
    0 ( 0 )
    0 ( 0 )
    -11.65 ( 34.933 )
        Week 16 - Extension|
    -17.55 ( 21.420 )
    -29.49 ( 20.642 )
    -24.27 ( 25.706 )
    -24.06 ( 35.250 )
        Week 18 - Extension|
    -17.83 ( 17.100 )
    -11.32 ( 0 )
    7.04 ( 0 )
    -24.84 ( 31.399 )
        Week 20 - Extension|
    15.63 ( 21.872 )
    -31.76 ( 17.488 )
    -25.28 ( 30.392 )
    -22.97 ( 27.814 )
        Week 22 - Extension|
    -19.64 ( 20.032 )
    -19.64 ( 20.032 )
    0 ( 0 )
    -46.47 ( 25.079 )
        Week 24 - Extension|
    -29.41 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Week 28 - Extension|
    -1.33 ( 1.922 )
    -27.99 ( 18.002 )
    -30.52 ( 24.583 )
    -26.32 ( 26.541 )
        Week 36 - Extension|
    -25.24 ( 17.434 )
    -26.18 ( 29.565 )
    -30.56 ( 23.603 )
    -26.31 ( 26.460 )
        Week 44 - Extension|
    -25.68 ( 16.126 )
    -31.59 ( 18.047 )
    -27.37 ( 28.450 )
    -25.66 ( 30.065 )
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced a gout flare (Double-Blind Extension)

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    End point title
    		 Percentage of participants who experienced a gout flare (Double-Blind Extension)
    End point description
    End point type
    Secondary
    End point timeframe
    4 Weeks
    End point values
    		 Pooled Placebo Cohort 1: Lesinurad 200 mg qd + Allopurinol 300 mg qd Cohort 2: Lesinurad 400 mg qd + Allopurinol 300 mg qd Cohort 3: Lesinurad 600 mg + Allopurinol 300 mg qd
    Number of subjects analysed
    48
    18
    15
    45
    Units: Percent (%) of Participants
    19
    4
    4
    29
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level decreased to or is maintained at < 6.0 mg/dL at Month 36. (Open-Label Extension Period)

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    End point title
    		 Percentage of participants whose sUA level decreased to or is maintained at < 6.0 mg/dL at Month 36. (Open-Label Extension Period)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 60 Months
    End point values
    		 ALLO-only ALLO-switch PBO-switch Lesinurad Total Lesinurad
    Number of subjects analysed
    4
    3
    12
    28
    43
    Units: Percent (%) of Participants
        Month 36 - OLE Extension
    4
    2
    9
    27
    38
    No statistical analyses for this end point

    Secondary: Percentage of participants whose sUA level decreased to or is maintained at < 5.0 mg/dL at Month 36. (Open-Label Extension Period)

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    End point title
    		 Percentage of participants whose sUA level decreased to or is maintained at < 5.0 mg/dL at Month 36. (Open-Label Extension Period)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 60 Months
    End point values
    		 ALLO-only ALLO-switch PBO-switch Lesinurad Total Lesinurad
    Number of subjects analysed
    4
    3
    12
    28
    43
    Units: Percent (%) of Participants
        Month 36 - OLE Extension
    4
    2
    9
    25
    36
    No statistical analyses for this end point

    Secondary: Percent reduction from Baseline in sUA levels at each visit (Open-Label Extension Period).

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    End point title
    		 Percent reduction from Baseline in sUA levels at each visit (Open-Label Extension Period).
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 60 Months
    End point values
    		 ALLO-only ALLO-switch PBO-switch Lesinurad Total Lesinurad
    Number of subjects analysed
    8
    5
    20
    54
    79
    Units: Percent (%)
    arithmetic mean (standard deviation)
        Baseline - OLE Extension
    4.29 ( 0.853 )
    5.04 ( 0.699 )
    6.16 ( 1.225 )
    4.92 ( 1.477 )
    5.24 ( 1.470 )
        Month 2 - OLE Extension
    2.05 ( 3.065 )
    -5.57 ( 24.901 )
    -20.24 ( 19.323 )
    0.61 ( 35.536 )
    -5.01 ( 32.589 )
        Month 4 - OLE Extension
    3.01 ( 13.001 )
    -5.52 ( 22.037 )
    -14.18 ( 24.297 )
    -1.13 ( 36.777 )
    -4.60 ( 33.490 )
        Month 6 - OLE Extension|
    0.06 ( 16.962 )
    -7.66 ( 25.335 )
    -23.13 ( 9.942 )
    -3.69 ( 32.608 )
    -8.69 ( 29.247 )
        Month 9 - OLE Extension
    6.13 ( 16.282 )
    20.02 ( 49.012 )
    -26.38 ( 17.833 )
    -1.55 ( 27.492 )
    -5.85 ( 29.801 )
        Month 12 - OLE Extension
    3.57 ( 15.923 )
    -0.45 ( 31.900 )
    -16.02 ( 32.121 )
    -1.75 ( 28.975 )
    -5.07 ( 30.134 )
        Month 15 - OLE Extension
    20.95 ( 47.880 )
    -39.05 ( 15.549 )
    -21.12 ( 39.352 )
    -3.31 ( 30.808 )
    -9.25 ( 33.729 )
        Month 18 - OLE Extension
    2.94 ( 14.276 )
    -3.90 ( 23.734 )
    -25.95 ( 16.229 )
    1.64 ( 27.272 )
    -5.41 ( 27.268 )
        Month 21 - OLE Extension
    3.30 ( 6.092 )
    -10.45 ( 3.900 )
    -9.74 ( 30.567 )
    -3.51 ( 29.581 )
    -5.47 ( 29.215 )
        Month 24 - OLE Extension
    4.17 ( 9.420 )
    -25.59 ( 30.147 )
    -12.00 ( 43.066 )
    -6.56 ( 30.364 )
    -8.89 ( 33.561 )
        Month 27 - OLE Extension
    -1.04 ( 6.635 )
    -16.17 ( 19.180 )
    -30.04 ( 19.773 )
    -1.37 ( 32.387 )
    -8.99 ( 31.404 )
        Month 30 - OLE Extension
    7.64 ( 10.486 )
    9.50 ( 65.700 )
    -27.28 ( 25.489 )
    -8.50 ( 27.604 )
    -12.23 ( 30.720 )
        Month 32 - OLE Extension
    6.22 ( 13.247 )
    -24.53 ( 0 )
    -25.98 ( 26.936 )
    -5.51 ( 36.135 )
    -12.25 ( 33.348 )
        Month 33 - OLE Extension
    0.00 ( 0 )
    -15.69 ( 0 )
    -28.93 ( 29.062 )
    -7.08 ( 22.807 )
    -13.41 ( 25.725 )
        Month 34 - OLE Extension
    7.94 ( 4.490 )
    -18.34 ( 11.426 )
    -27.52 ( 18.439 )
    -9.57 ( 25.251 )
    -14.93 ( 23.319 )
        Month 36 - OLE Extension
    -2.01 ( 5.490 )
    6.41 ( 19.146 )
    -23.07 ( 25.086 )
    -11.61 ( 24.349 )
    -13.55 ( 24.905 )
        Month 38 - OLE Extension
    3.50 ( 5.166 )
    -8.80 ( 20.195 )
    -21.04 ( 32.691 )
    -8.01 ( 19.273 )
    -11.65 ( 23.821 )
        Month 40 - OLE Extension
    5.31 ( 15.925 )
    -26.90 ( 19.391 )
    -17.91 ( 27.938 )
    2.08 ( 31.297 )
    -5.59 ( 31.054 )
        Month 42 - OLE Extension
    2.00 ( 6.558 )
    -5.31 ( 20.237 )
    -26.35 ( 21.386 )
    -2.62 ( 33.778 )
    -8.91 ( 31.442 )
        Month 44 - OLE Extension
    -4.04 ( 12.042 )
    21.64 ( 41.488 )
    -15.75 ( 24.242 )
    -3.86 ( 28.528 )
    -5.69 ( 28.447 )
        Month 46 - OLE Extension
    13.27 ( 22.891 )
    -17.35 ( 28.156 )
    -19.24 ( 32.838 )
    2.62 ( 29.863 )
    -4.36 ( 31.478 )
        Month 48 - OLE Extension
    -5.76 ( 13.184 )
    -12.82 ( 0 )
    -26.63 ( 25.675 )
    2.57 ( 28.594 )
    -5.97 ( 30.093 )
        Month 50 - OLE Extension
    -3.29 ( 5.998 )
    -37.18 ( 41.701 )
    -24.88 ( 29.375 )
    0.66 ( 37.373 )
    -7.83 ( 37.149 )
        Month 52 - OLE Extension
    -16.7 ( 0 )
    -25.04 ( 17.278 )
    -7.60 ( 50.400 )
    8.35 ( 43.554 )
    1.98 ( 44.594 )
        Month 54 - OLE Extension
    0 ( 0 )
    -23.08 ( 14.505 )
    -17.81 ( 23.967 )
    13.78 ( 35.494 )
    3.89 ( 35.097 )
        Month 56 - OLE Extension
    0 ( 0 )
    -22.40 ( 9.919 )
    -32.88 ( 23.681 )
    1.74 ( 21.235 )
    -10.37 ( 26.221 )
        Month 58 - OLE Extension
    0 ( 0 )
    -2.56 ( 0 )
    -9.62 ( 36.096 )
    3.35 ( 25.674 )
    -0.05 ( 27.008 )
        Month 60 - OLE Extension
    0 ( 0 )
    0 ( 0 )
    -36.77 ( 6.084 )
    3.13 ( 14.530 )
    -4.85 ( 21.243 )
        Month 62 - OLE Extension
    0 ( 0 )
    0 ( 0 )
    57.14 ( 0 )
    48.38 ( 65.750 )
    51.30 ( 46.767 )
        Follow-Up - OLE Extension
    29.33 ( 57.288 )
    9.26 ( 16.155 )
    25.46 ( 36.841 )
    44.58 ( 38.853 )
    38.14 ( 38.502 )
    No statistical analyses for this end point

    Secondary: Absolute reduction from Baseline in sUA levels at each visit (Open-Label Extension Period).

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    End point title
    		 Absolute reduction from Baseline in sUA levels at each visit (Open-Label Extension Period).
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 60 Months
    End point values
    		 ALLO-only ALLO-switch PBO-switch Lesinurad Total Lesinurad
    Number of subjects analysed
    8
    5
    20
    54
    79
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline - OLE Extension
    4.29 ( 0.853 )
    5.04 ( 0.699 )
    6.16 ( 1.225 )
    4.92 ( 1.477 )
    5.24 ( 1.470 )
        Month 2 - OLE Extension
    0.10 ( 0.163 )
    -0.38 ( 1.190 )
    -1.25 ( 1.331 )
    -0.22 ( 1.877 )
    -0.49 ( 1.760 )
        Month 4 - OLE Extension
    0.07 ( 0.610 )
    -0.40 ( 1.037 )
    -0.89 ( 1.486 )
    -0.35 ( 1.933 )
    -0.49 ( 1.785 )
        Month 6 - OLE Extension
    -0.10 ( 0.852 )
    -0.50 ( 1.317 )
    -1.44 ( 0.683 )
    -0.36 ( 1.619 )
    -0.63 ( 1.619 )
        Month 9 - OLE Extension
    0.16 ( 0.842 )
    0.76 ( 2.110 )
    -1.65 ( 1.231 )
    -0.26 ( 1.555 )
    -0.51 ( 1.651 )
        Month 12 - OLE Extension
    0.10 ( 0.543 )
    -0.04 ( 1.635 )
    -0.90 ( 1.991 )
    -0.27 ( 1.702 )
    -0.41 ( 1.768 )
        Month 15 - OLE Extension
    0.68 ( 1.590 )
    -1.90 ( 0.917 )
    -1.37 ( 2.177 )
    -0.35 ( 1.672 )
    -0.67 ( 1.834 )
        Month 18 - OLE Extension
    0.10 ( 0.548 )
    -0.30 ( 1.058 )
    -1.56 ( 1.027 )
    -0.06 ( 1.562 )
    -0.44 ( 1.554 )
        Month 21 - OLE Extension
    0.13 ( 0.222 )
    -0.50 ( 0.283 )
    -0.64 ( 1.813 )
    -0.38 ( 1.770 )
    -0.46 ( 1.739 )
        Month 24 - OLE Extension
    0.17 ( 0.377 )
    -1.23 ( 1.570 )
    -0.93 ( 2.433 )
    -0.56 ( 1.660 )
    -0.69 ( 1.850 )
        Month 27 - OLE Extension
    -0.05 ( 0.252 )
    -0.87 ( 0.971 )
    -1.83 ( 1.177 )
    -0.24 ( 1.668 )
    -0.65 ( 1.659 )
        Month 30 - OLE Extension
    0.30 ( 0.408 )
    0.13 ( 2.779 )
    -1.61 ( 1.620 )
    -0.52 ( 1.411 )
    -0.76 ( 1.603 )
        Month 32 - OLE Extension
    0.27 ( 0.551 )
    -1.30 ( 0 )
    -1.58 ( 1.579 )
    -0.48 ( 1.814 )
    -0.83 ( 1.726 )
        Month 33 - OLE Extension
    0.00 ( 0 )
    -0.80 ( 0 )
    -1.74 ( 1.745 )
    -0.39 ( 1.159 )
    -0.77 ( 1.430 )
        Month 34 - OLE Extension
    0.30 ( 0.141 )
    -0.90 ( 0.707 )
    -1.60 ( 1.111 )
    -0.62 ( 1.424 )
    -0.90 ( 1.322 )
        Month 36 - OLE Extension
    -0.08 ( 0.206 )
    0.27 ( 0.929 )
    -1.33 ( 1.559 )
    -0.67 ( 1.535 )
    -0.79 ( 1.539 )
        Month 38 - OLE Extension
    0.13 ( 0.208 )
    -0.43 ( 1.041 )
    -1.35 ( 1.978 )
    -0.45 ( 1.133 )
    -0.69 ( 1.431 )
        Month 40 - OLE Extension
    0.20 ( 0.656 )
    -1.33 ( 1.041 )
    -1.00 ( 1.860 )
    0.00 ( 1.514 )
    -0.37 ( 1.640 )
        Month 42 - OLE Extension|
    0.07 ( 0.252 )
    -0.30 ( 1.058 )
    -1.66 ( 1.360 )
    -0.26 ( 1.606 )
    -0.62 ( 1.605 )
        Month 44 - OLE Extension
    -0.17 ( 0.503 )
    1.15 ( 2.051 )
    -1.02 ( 1.522 )
    -0.27 ( 1.505 )
    -0.40 ( 1.568 )
        Month 46 - OLE Extension
    0.53 ( 0.945 )
    -0.90 ( 1.414 )
    -1.22 ( 2.013 )
    0.04 ( 1.485 )
    -0.35 ( 1.694 )
        Month 48 - OLE Extension
    -0.23 ( 0.551 )
    -0.50 ( 0 )
    -1.70 ( 1.559 )
    0.11 ( 1.510 )
    -0.41 ( 1.690 )
        Month 50 - OLE Extension
    -0.13 ( 0.252 )
    -1.85 ( 2.192 )
    -1.53 ( 1.764 )
    -0.06 ( 1.771 )
    -0.53 ( 1.876 )
        Month 52 - OLE Extension
    -0.70 ( 0 )
    -1.20 ( 0.990 )
    -0.67 ( 2.595 )
    0.33 ( 1.956 )
    -0.04 ( 2.124 )
        Month 54 - OLE Extension
    0 ( 0 )
    -1.10 ( 0.849 )
    -1.11 ( 1.415 )
    0.60 ( 1.720 )
    0.08 ( 1.768 )
        Month 56 - OLE Extension
    0 ( 0 )
    -1.05 ( 0.636 )
    -2.13 ( 1.619 )
    0.03 ( 0.934 )
    -0.69 ( 1.486 )
        Month 58 - OLE Extension
    0 ( 0 )
    -0.10 ( 0 )
    -0.75 ( 2.278 )
    -0.15 ( 1.918 )
    -0.29 ( 1.890 )
        Month 60 - OLE Extension
    0 ( 0 )
    0 ( 0 )
    -2.40 ( 0.141 )
    0.16 ( 0.635 )
    -0.35 ( 1.218 )
        Month 62 - OLE Extension
    0 ( 0 )
    0 ( 0 )
    3.20 ( 0 )
    1.90 ( 2.546 )
    2.33 ( 1.950 )
        Follow-Up - OLE Extension
    1.03 ( 2.290 )
    0.42 ( 0.760 )
    1.38 ( 2.232 )
    1.96 ( 1.616 )
    1.73 ( 1.736 )
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced a gout flare (Open-Label Extension)

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    End point title
    		 Percentage of participants who experienced a gout flare (Open-Label Extension)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 60 months.
    End point values
    		 ALLO-only ALLO-switch PBO-switch Lesinurad Total Lesinurad
    Number of subjects analysed
    8
    5
    20
    54
    79
    Units: Percent (%) of Participants
    2
    2
    11
    18
    31
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Main Period: 4 Weeks; Double-Blind Extension Period: 44 Weeks; Open-Label Extension Period: Up to 60 Months.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    Main Period Cohort 2: Lesinurad 400 mg
    Reporting group description
    		 Lesinurad 400 mg

    Reporting group title
    Main Period Cohort 1: Lesinurad 200 mg
    Reporting group description
    		 Lesinurad 200 mg

    Reporting group title
    Main Period: Pooled Placebo
    Reporting group description
    		 Pooled placebo

    Reporting group title
    Main Period Cohort 3: Lesinurad 600 mg
    Reporting group description
    		 Lesinurad 600 mg

    Reporting group title
    Double-Blind Extension Period: Lesinurad 200 mg
    Reporting group description
    		 Lesinurad 200 mg

    Reporting group title
    Double-Blind Extension Period: Lesinurad 400 mg
    Reporting group description
    		 Lesinurad 400 mg

    Reporting group title
    Double-Blind Extension Period: Lesinurad 600 mg
    Reporting group description
    		 Lesinurad 600 mg

    Reporting group title
    Double-Blind Extension Period: Pooled Placebo
    Reporting group description
    		 Pooled Placebo

    Reporting group title
    Open-Label Extension Period: Pooled Lesinurad
    Reporting group description
    		 Pooled Lesinurad

    Reporting group title
    Open-Label Extension Period: ALLO-only
    Reporting group description
    		 ALLO-only

    Serious adverse events
    		 Main Period Cohort 2: Lesinurad 400 mg Main Period Cohort 1: Lesinurad 200 mg Main Period: Pooled Placebo Main Period Cohort 3: Lesinurad 600 mg Double-Blind Extension Period: Lesinurad 200 mg Double-Blind Extension Period: Lesinurad 400 mg Double-Blind Extension Period: Lesinurad 600 mg Double-Blind Extension Period: Pooled Placebo Open-Label Extension Period: Pooled Lesinurad Open-Label Extension Period: ALLO-only
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    1 / 60 (1.67%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    7 / 79 (8.86%)
    1 / 8 (12.50%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    WEIGHT INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    THYROID CANCER METASTATIC
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    MUSCLE RUPTURE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANGINA PECTORIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    CAUDA EQUINA SYNDROME
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL ARTERY EMBOLISM
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    COSTOCHONDRITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    BURSITIS INFECTIVE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DIABETIC KETOACIDOSIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OBESITY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Main Period Cohort 2: Lesinurad 400 mg Main Period Cohort 1: Lesinurad 200 mg Main Period: Pooled Placebo Main Period Cohort 3: Lesinurad 600 mg Double-Blind Extension Period: Lesinurad 200 mg Double-Blind Extension Period: Lesinurad 400 mg Double-Blind Extension Period: Lesinurad 600 mg Double-Blind Extension Period: Pooled Placebo Open-Label Extension Period: Pooled Lesinurad Open-Label Extension Period: ALLO-only
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 42 (47.62%)
    23 / 46 (50.00%)
    35 / 72 (48.61%)
    26 / 48 (54.17%)
    44 / 78 (56.41%)
    26 / 60 (43.33%)
    26 / 45 (57.78%)
    35 / 48 (72.92%)
    60 / 79 (75.95%)
    6 / 8 (75.00%)
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    4 / 78 (5.13%)
    2 / 60 (3.33%)
    2 / 45 (4.44%)
    1 / 48 (2.08%)
    9 / 79 (11.39%)
    1 / 8 (12.50%)
         occurrences all number
    0
    2
    0
    1
    4
    2
    2
    1
    9
    1
    HYPERTENSIVE CRISIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    VARICOSE VEIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Surgical and medical procedures
    KNEE ARTHROPLASTY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    1
    0
    FATIGUE
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    2 / 72 (2.78%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    3
    0
    0
    0
    0
    1
    4
    0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    INFLAMMATION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    7
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    0
    0
    2
    0
    SWELLING
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Immune system disorders
    SERUM SICKNESS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    EPIDIDYMAL CYST
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    ERECTILE DYSFUNCTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    2
    1
    0
    1
    1
    0
    1
    0
    1
    EPISTAXIS
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    2
    0
    NASAL CONGESTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    0
    1
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    SINUS CONGESTION
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 46 (4.35%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    1
    3
    0
    1
    0
    0
    1
    0
    1
    0
    SLEEP APNOEA SYNDROME
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    UPPER RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    2 / 48 (4.17%)
    5 / 78 (6.41%)
    3 / 60 (5.00%)
    0 / 45 (0.00%)
    2 / 48 (4.17%)
    9 / 79 (11.39%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    3
    6
    3
    0
    2
    18
    1
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    DEPRESSION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    INSOMNIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    4 / 79 (5.06%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    5
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    4 / 79 (5.06%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    4
    0
    BLOOD AMYLASE INCREASED
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    1
    0
    BLOOD CREATINE PHOSPHOKINASE ABNORMAL
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    1 / 48 (2.08%)
    2 / 78 (2.56%)
    2 / 60 (3.33%)
    0 / 45 (0.00%)
    3 / 48 (6.25%)
    5 / 79 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    1
    2
    2
    2
    0
    4
    5
    0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    2 / 78 (2.56%)
    2 / 60 (3.33%)
    3 / 45 (6.67%)
    1 / 48 (2.08%)
    12 / 79 (15.19%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    0
    1
    3
    2
    3
    1
    15
    2
    BLOOD GLUCOSE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    BLOOD PRESSURE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    BLOOD UREA INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    CREATININE RENAL CLEARANCE DECREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    2 / 45 (4.44%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    ELECTROCARDIOGRAM ST SEGMENT DEPRESSION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    2 / 78 (2.56%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    3
    0
    LIPASE INCREASED
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    2 / 48 (4.17%)
    4 / 79 (5.06%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    7
    0
    EXPOSURE TO TOXIC AGENT
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    JOINT SPRAIN
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    3 / 78 (3.85%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    4 / 79 (5.06%)
    0 / 8 (0.00%)
         occurrences all number
    2
    2
    0
    0
    3
    0
    0
    0
    4
    0
    MOUTH INJURY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    MUSCLE INJURY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    MUSCLE RUPTURE
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    MUSCLE STRAIN
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    5 / 79 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    1
    0
    0
    7
    0
    POST-TRAUMATIC PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PROCEDURAL PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    SKIN LACERATION
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    0
    0
    0
    0
    SOFT TISSUE INJURY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    2
    0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Nervous system disorders
    CARPAL TUNNEL SYNDROME
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    2
    0
    DIZZINESS
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    2 / 48 (4.17%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    4 / 79 (5.06%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    4
    0
    0
    0
    0
    4
    0
    HEADACHE
         subjects affected / exposed
    2 / 42 (4.76%)
    4 / 46 (8.70%)
    1 / 72 (1.39%)
    1 / 48 (2.08%)
    2 / 78 (2.56%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    2 / 48 (4.17%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    4
    6
    1
    1
    2
    1
    0
    3
    1
    0
    HYPOREFLEXIA
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    PARAESTHESIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    PRESYNCOPE
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    RESTLESS LEGS SYNDROME
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    EOSINOPHILIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    1
    0
    0
    0
    LEUKOPENIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    NEUTROPENIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Eye disorders
    CATARACT
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    SCLERAL PIGMENTATION
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    1
    0
    0
    2
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    1
    0
    CONSTIPATION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    3
    0
    DIARRHOEA
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 46 (4.35%)
    4 / 72 (5.56%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    2 / 45 (4.44%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    1
    3
    4
    0
    1
    0
    2
    1
    1
    0
    DRY MOUTH
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    3
    2
    0
    0
    0
    0
    0
    0
    0
    DUODENITIS
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    DYSPEPSIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    2
    1
    0
    0
    2
    0
    0
    FLATULENCE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    GASTRITIS
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    1
    1
    0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    2 / 78 (2.56%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    2
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    HERNIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    HIATUS HERNIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    NAUSEA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    2 / 72 (2.78%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    0
    2
    0
    PYREXIA
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    VOMITING
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Hepatobiliary disorders
    HEPATIC STEATOSIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    LIVER DISORDER
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    DERMATITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    0
    0
    0
    DERMATITIS CONTACT
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    2 / 45 (4.44%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    3
    1
    1
    0
    ECZEMA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    1
    0
    ERYTHEMA
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    TINEA CRURIS
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    URTICARIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    2 / 48 (4.17%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    VITILIGO
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    CALCULUS URINARY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    HAEMATURIA
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    3 / 72 (4.17%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    3
    0
    0
    0
    0
    2
    4
    0
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    3
    0
    PROTEINURIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    1
    PYURIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    RENAL FAILURE CHRONIC
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    Endocrine disorders
    HYPERPARATHYROIDISM
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HYPOTHYROIDISM
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 42 (2.38%)
    3 / 46 (6.52%)
    4 / 72 (5.56%)
    2 / 48 (4.17%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    2 / 48 (4.17%)
    2 / 79 (2.53%)
    1 / 8 (12.50%)
         occurrences all number
    1
    11
    9
    3
    2
    0
    1
    2
    2
    1
    BACK PAIN
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    3 / 72 (4.17%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    2 / 48 (4.17%)
    8 / 79 (10.13%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    0
    1
    3
    8
    0
    FLANK PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    JOINT SWELLING
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    1 / 60 (1.67%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    2
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    2 / 45 (4.44%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    MUSCULOSKELETAL STIFFNESS
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    1
    0
    0
    MYALGIA
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    2 / 72 (2.78%)
    0 / 48 (0.00%)
    2 / 78 (2.56%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    3
    0
    2
    0
    0
    0
    4
    0
    NECK PAIN
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    2
    0
    0
    1
    0
    0
    0
    0
    0
    NODULE ON EXTREMITY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    OSTEOARTHRITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    1
    3
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    7 / 79 (8.86%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    7
    0
    SYNOVIAL CYST
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    2
    0
    0
    0
    0
    0
    TENDON DISORDER
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    1 / 79 (1.27%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    TENDONITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 46 (4.35%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    4
    0
    2
    0
    0
    0
    0
    2
    0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    5 / 79 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    5
    0
    EAR INFECTION
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    INFLUENZA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    2
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    4 / 46 (8.70%)
    1 / 72 (1.39%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    2 / 48 (4.17%)
    4 / 79 (5.06%)
    1 / 8 (12.50%)
         occurrences all number
    0
    7
    1
    1
    1
    0
    0
    3
    5
    1
    ORAL HERPES
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    PHARYNGITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    1 / 79 (1.27%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    0
    1
    1
    0
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    SINUSITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    2 / 45 (4.44%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    0
    2
    0
    TONSILLITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    2
    0
    TOOTH INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    1 / 78 (1.28%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    1
    0
    2
    0
    TRACHEITIS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    2 / 48 (4.17%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    2 / 78 (2.56%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    0 / 79 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    0
    0
    0
    0
    GOUT
         subjects affected / exposed
    13 / 42 (30.95%)
    11 / 46 (23.91%)
    16 / 72 (22.22%)
    17 / 48 (35.42%)
    25 / 78 (32.05%)
    14 / 60 (23.33%)
    16 / 45 (35.56%)
    19 / 48 (39.58%)
    31 / 79 (39.24%)
    2 / 8 (25.00%)
         occurrences all number
    30
    29
    22
    43
    42
    20
    39
    37
    99
    3
    HYPERCHOLESTEROLAEMIA
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    2
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 72 (1.39%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    0
    1
    2
    0
    HYPERLIPIDAEMIA
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
    2 / 79 (2.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    HYPERTRIGLYCERIDAEMIA
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 72 (0.00%)
    0 / 48 (0.00%)
    0 / 78 (0.00%)
    0 / 60 (0.00%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    3 / 79 (3.80%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    1
    1
    3
    0
    TYPE 2 DIABETES MELLITUS
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 72 (0.00%)
    1 / 48 (2.08%)
    2 / 78 (2.56%)
    2 / 60 (3.33%)
    1 / 45 (2.22%)
    1 / 48 (2.08%)
    5 / 79 (6.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    2
    1
    1
    6
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jan 2010
    To remove the 300 mg dose level of RDEA594 from the study based on data that has recently become available from Cohort 2 of the completed RDEA594-201 pilot pharmacodynamic study.
    12 Feb 2010
    To allow for extended dosing of subjects by adding an optional double-blind Extension Period for subjects who successfully complete the 4-week Double-Blind Treatment Period and attend the follow-up visit.
    29 Mar 2010
    To broaden the age range for study participants from a maximum of 75 years to a maximum of 80 years of age and to allow a shorter minimum duration for prior allopurinol use for entry into the study.
    01 Apr 2010
    To add a 600 mg dose level of RDEA594 to the study based on a preliminary analysis of the recently concluded 28-day, randomized, double-blind, placebo-controlled, monotherapy, dose-response study, study RDEA594-202.
    29 Apr 2010
    To modify the primary study endpoint and to increase the sample size of Cohorts 2 and 3 of the study based on this new primary endpoint.
    27 May 2010
    The study entry criteria amended to better reflect the gout population under treatment by allowing patients to enter receiving a daily dose of allopurinol between 200 mg and 600 mg instead of only 300 mg per day, rheumatoid arthritis or other autoimmune disease are only excluded if they require treatment, a history of malignancy is only excluded if within 5 years, and a Body Mass Index up to 48 kg/m2 is permitted.
    12 Aug 2010
    To extend the duration of treatment with RDEA594 in the Extension Period from 5 months to 11 months.
    17 Jan 2011
    To allow for an open label extension to further extend the duration of treatment with RDEA594 in combination with allopurinol as long as the investigator judges that the patient continues to benefit from treatment.
    22 Nov 2011
    To amend the target serum urate (sUA) value for dose escalation to 6.0 mg/dL in the Open-Label Extension Period.
    25 Jul 2013
    To expand guidance on subject hydration and to expand the management algorithm if a subject experiences an elevated serum creatinine or kidney stone.
    10 Jan 2014
    To modify the lesinurad and allopurinol combination Study RDEA594-203 in all countries where the study is ongoing to ensure patient safety.
    07 Oct 2015
    To require all active subjects who are receiving lesinurad 400 mg or 600 mg in combination with allopurinol to have their dose of lesinurad reduced to 200 mg.

    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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