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    Clinical Trial Results:
    A Phase 2 Single-Center, Proof-of-Concept Safety and Efficacy Study of Orally Administered OLT1177 Capsules with Successive, Result-Dependent Dose Adaptation in Subjects with an Acute Gout Flare

    Summary
    EudraCT number
    2016-000943-14
    Trial protocol
    NL  
    Global end of trial date
    04 Feb 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Jun 2022
    First version publication date
    25 Jun 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    OLT1177-05
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Olatec Therapeutics LLC
    Sponsor organisation address
    800 Fifth Avenue, Fl 25, New York, United States,
    Public contact
    Clinical Trials Inquiries, Olatec Therapeutics LLC, +1 833-652-8321, inquiries@olatec.com
    Scientific contact
    Clinical Trials Inquiries, Olatec Therapeutics LLC, +1 833-652-8321, inquiries@olatec.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
    27 Feb 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Feb 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Feb 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety and tolerability of OLT1177 Capsule after oral administration in subjects with an acute gout flare
    Protection of trial subjects
    The OLT1177-05 Study Protocol and associated documents, including the Investigator Brochure, Informed Consent Form and any informational documentation given to study subjects, were reviewed by an appropriately constituted Institutional Review Board (IRB), or Ethics Committee (EC). Proposed changes to the conduct of the study were documented in Protocol Amendments and submitted to and reviewed and approved by the EC before implementation. If at any time during the study a subject was unable to tolerate his/her pain and wished to receive standard medical intervention for their gout flare, the subject was withdrawn from the study, considered a Treatment Failure and treated with either methylprednisolone 500 mg IV, prednisolone (30 mg PO QD), or colchicine (0.5 mg PO TID). Subjects were also given Rescue Medication (paracetamol, 1 g/dose or up to 4 g/day) at the Baseline Visit to use if needed following the first 12 hours post-initial dose of Investigational Product. Additionally, a Data Monitoring Committee (DMC) was convened to review all relevant safety and efficacy data for all subjects in a cohort to determine if an increase or decrease in total daily exposure was warranted for the subsequent cohort.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    18 May 2017
    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
    Netherlands: 34
    Worldwide total number of subjects
    34
    EEA total number of subjects
    34
    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)
    21
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were recruited for the study directly from the Investigator’s clinic as well as by referral from general practitioners in the Netherlands and by local and internet advertisements. The first subject was enrolled in May 2017 and the last subject completed the final study visit in February 2019.

    Pre-assignment
    Screening details
    Subjects had to meet all inclusion and no exclusion criteria to be eligible for enrollment. Presence of monosodium urate in synovial fluid of the target joint at Baseline with confirmed gout flare starting within 96 hours of Baseline Visit were required for enrollment. Both first-time gout and recurrent gout patients were included in the study.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1
    Arm description
    500 mg BID for 8 days (1000 mg total/day)
    Arm type
    Experimental

    Investigational medicinal product name
    OLT1177 Capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg twice daily (BID) for 8 days

    Arm title
    Cohort 2
    Arm description
    500 mg QID for 8 days (2000 mg total/day)
    Arm type
    Experimental

    Investigational medicinal product name
    OLT1177 Capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg four times daily (QID) for 8 days

    Arm title
    Cohort 3
    Arm description
    200 mg (am) and 100 mg (pm) BID for 8 days (300 mg total/day)
    Arm type
    Experimental

    Investigational medicinal product name
    OLT1177 Capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg (am) and 100 mg (pm) for 8 days

    Arm title
    Cohort 4
    Arm description
    100 mg QD for 8 days (100 mg total/day)
    Arm type
    Experimental

    Investigational medicinal product name
    OLT1177 Capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg once daily (QD) for 8 days

    Number of subjects in period 1
    Cohort 1 Cohort 2 Cohort 3 Cohort 4
    Started
    10
    8
    8
    8
    Completed
    6
    8
    8
    8
    Not completed
    4
    0
    0
    0
         Worsening condition as determined by Investigator
    2
    -
    -
    -
         Adverse event, non-fatal
    2
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    500 mg BID for 8 days (1000 mg total/day)

    Reporting group title
    Cohort 2
    Reporting group description
    500 mg QID for 8 days (2000 mg total/day)

    Reporting group title
    Cohort 3
    Reporting group description
    200 mg (am) and 100 mg (pm) BID for 8 days (300 mg total/day)

    Reporting group title
    Cohort 4
    Reporting group description
    100 mg QD for 8 days (100 mg total/day)

    Reporting group values
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total
    Number of subjects
    10 8 8 8 34
    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)
    5 7 5 4 21
        From 65-84 years
    5 1 3 4 13
        85 years and over
    0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.4 ± 10.77 50.9 ± 11.83 61.8 ± 11.39 62.9 ± 8.61 -
    Gender categorical
    Units: Subjects
        Female
    0 1 0 0 1
        Male
    10 7 8 8 33
    Target Joint
    The acutely inflamed and tender joint
    Units: Subjects
        Ankle
    3 0 4 3 10
        Knee
    1 1 0 0 2
        Forefoot/Toe
    6 7 4 5 22
    Target Joint - Side
    The acutely inflamed and tender joint, side affected. MTP1 = first metatarsophalangeal joint TMT1 = first tarsometatarsal joint
    Units: Subjects
        Knee - Left
    1 0 0 0 1
        Knee - Right
    0 1 0 0 1
        MTP1 - Left
    2 2 1 3 8
        MTP1- Right
    4 5 2 2 13
        TMT1 - Right
    0 0 1 0 1
        Ankle - Left
    1 0 4 1 6
        Ankle - Right
    2 0 0 2 4
    Duration from Gout Flare to Treatment
    Time in hours from gout flare to treatment with OLT1177 Capsules
    Units: hours
        arithmetic mean (standard deviation)
    54.5 ± 25.88 45.0 ± 29.24 32.9 ± 14.76 63.1 ± 16.85 -
    Body Mass Index
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    28.99 ± 3.409 29.14 ± 4.031 27.98 ± 3.275 28.53 ± 2.004 -
    Subject analysis sets

    Subject analysis set title
    Cohort 1 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. Four subjects in Cohort 1 were excluded from the PP due to major protocol deviations.

    Subject analysis set title
    Cohort 2 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor.

    Subject analysis set title
    Cohort 3 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. One subject in Cohort 3 was excluded from the PP set due to a major protocol deviation.

    Subject analysis set title
    Cohort 4 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor.

    Subject analysis set title
    Overall - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. Overall, five subjects were excluded from the PP set due to major protocol deviations.

    Subject analysis sets values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects
    6
    8
    7
    8
    29
    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)
    2
    7
    4
    4
    17
        From 65-84 years
    4
    1
    3
    4
    12
        85 years and over
    0
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    66.7 ± 11.62
    50.9 ± 11.83
    62.1 ± 12.24
    62.9 ± 8.61
    60.2 ± 12.10
    Gender categorical
    Units: Subjects
        Female
    0
    1
    0
    0
    1
        Male
    6
    7
    7
    8
    28
    Target Joint
    The acutely inflamed and tender joint
    Units: Subjects
        Ankle
    1
    0
    3
    3
    7
        Knee
    1
    1
    0
    0
    2
        Forefoot/Toe
    4
    7
    4
    5
    20
    Target Joint - Side
    The acutely inflamed and tender joint, side affected. MTP1 = first metatarsophalangeal joint TMT1 = first tarsometatarsal joint
    Units: Subjects
        Knee - Left
    1
    0
    0
    0
    1
        Knee - Right
    0
    1
    0
    0
    1
        MTP1 - Left
    1
    2
    1
    3
    7
        MTP1- Right
    3
    5
    2
    2
    12
        TMT1 - Right
    0
    0
    1
    0
    1
        Ankle - Left
    1
    0
    3
    1
    5
        Ankle - Right
    0
    0
    0
    2
    2
    Duration from Gout Flare to Treatment
    Time in hours from gout flare to treatment with OLT1177 Capsules
    Units: hours
        arithmetic mean (standard deviation)
    58.3 ± 20.68
    45.0 ± 29.24
    33.3 ± 15.89
    63.1 ± 16.85
    49.9 ± 23.58
    Body Mass Index
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    28.73 ± 3.303
    29.14 ± 4.031
    28.05 ± 3.530
    28.53 ± 2.004
    28.62 ± 3.138

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    500 mg BID for 8 days (1000 mg total/day)

    Reporting group title
    Cohort 2
    Reporting group description
    500 mg QID for 8 days (2000 mg total/day)

    Reporting group title
    Cohort 3
    Reporting group description
    200 mg (am) and 100 mg (pm) BID for 8 days (300 mg total/day)

    Reporting group title
    Cohort 4
    Reporting group description
    100 mg QD for 8 days (100 mg total/day)

    Subject analysis set title
    Cohort 1 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. Four subjects in Cohort 1 were excluded from the PP due to major protocol deviations.

    Subject analysis set title
    Cohort 2 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor.

    Subject analysis set title
    Cohort 3 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. One subject in Cohort 3 was excluded from the PP set due to a major protocol deviation.

    Subject analysis set title
    Cohort 4 - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor.

    Subject analysis set title
    Overall - Per-Protocol
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The Per-Protocol (PP) set consists of all subjects who took 80% or more of the total expected doses of investigational product and had no major protocol violations as determined by the Medical Monitor. Overall, five subjects were excluded from the PP set due to major protocol deviations.

    Primary: Change in Pain Intensity Score from Baseline to Day 3 and from Baseline to Day 7

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    End point title
    Change in Pain Intensity Score from Baseline to Day 3 and from Baseline to Day 7 [1]
    End point description
    Target joint pain was measured using a 100-mm Visual Analog Scale (VAS).
    End point type
    Primary
    End point timeframe
    Baseline, Day 3, and Day 7
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical inference tests were not conducted. The purpose of the study was to assess, on an unblinded basis, a small number of subjects exposed for safety, tolerability, and clinical and inflammatory biomarker activity of oral OLT1177 Capsules in the treatment of acute gout flare. As such, the study was not powered to achieve significance.
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    Units: millimetre(s)
    arithmetic mean (standard deviation)
        Baseline (Pre-dose)
    82.2 ± 14.82
    68.9 ± 9.52
    70.6 ± 5.88
    64.1 ± 9.61
    70.7 ± 11.57
        Day 3 (pm)
    40.2 ± 42.14
    29.4 ± 27.31
    22.4 ± 24.07
    29.8 ± 19.96
    30.0 ± 27.64
        Day 3 (pm) - Change from Baseline
    -42.0 ± 32.63
    -39.5 ± 27.37
    -48.1 ± 24.17
    -34.4 ± 22.72
    -40.7 ± 25.64
        Day 7
    28.8 ± 33.91
    11.1 ± 10.96
    11.3 ± 11.69
    9.7 ± 11.67
    14.8 ± 19.24
        Day 7 - Change from Baseline
    -53.3 ± 24.25
    -57.8 ± 13.42
    -59.3 ± 12.16
    -51.3 ± 19.20
    -55.7 ± 16.65
    No statistical analyses for this end point

    Secondary: Subject-reported Global Evaluation of Treatment on Day 7

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    End point title
    Subject-reported Global Evaluation of Treatment on Day 7
    End point description
    The Global Evaluation of Treatment was used to measure overall perceived quality of the investigational product in treating the subject's symptoms and was completed at the Day 7 visit. A 5-point Likert scale, with numerical values assigned as follows, was used: 0 = poor, 1 = reasonable, 2 = good, 3 = very good and 4 = excellent.
    End point type
    Secondary
    End point timeframe
    Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6
    8
    7
    8
    29
    Units: Subjects
        Poor
    0
    2
    0
    3
    5
        Fair
    1
    1
    2
    1
    5
        Good
    1
    2
    1
    1
    5
        Very Good
    2
    0
    4
    1
    7
        Excellent
    1
    3
    0
    2
    6
        Not Done
    1
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Subject-reported Pain Intensity Score

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    End point title
    Subject-reported Pain Intensity Score
    End point description
    Subjects reported pain in target joint from Baseline to Day 14 using a 100 mm Visual Analog Scale (VAS).
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose) to Day 14
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6
    8
    7
    8
    29
    Units: millimetre(s)
    arithmetic mean (standard deviation)
        Baseline (pre-dose)
    82.2 ± 14.82
    68.9 ± 9.52
    70.6 ± 5.88
    64.1 ± 9.61
    70.7 ± 11.57
        2 hours (post-dose)
    59.3 ± 30.22
    61.8 ± 17.81
    58.6 ± 30.12
    65.1 ± 14.55
    61.4 ± 22.28
        2 hours (post-dose) - Change from Baseline
    -22.8 ± 26.39
    -7.1 ± 18.56
    -12.0 ± 29.73
    1.0 ± 14.54
    -9.3 ± 22.92
        4 hours (post-dose)
    62.2 ± 28.85
    58.3 ± 20.67
    55.9 ± 30.57
    60.5 ± 8.96
    59.1 ± 21.94
        4 hours (post-dose) - Change from Baseline
    -20.0 ± 22.45
    -10.6 ± 22.21
    -14.7 ± 30.14
    -3.6 ± 9.96
    -11.6 ± 21.65
        6 hours (post-dose)
    62.8 ± 28.96
    49.8 ± 24.74
    55.4 ± 31.42
    61.3 ± 14.87
    57.0 ± 24.45
        6 hours (post-dose) - Change from Baseline
    -19.3 ± 21.90
    -19.1 ± 24.71
    -15.1 ± 31.65
    -2.9 ± 16.65
    -13.7 ± 23.90
        12 hours (post-dose)
    70.3 ± 31.51
    54.5 ± 25.57
    45.3 ± 33.80
    65.1 ± 18.00
    58.5 ± 27.52
        12 hours (post-dose) - Change from Baseline
    -11.8 ± 22.89
    -14.4 ± 22.80
    -25.3 ± 33.64
    1.0 ± 19.49
    -12.2 ± 25.59
        Day 1 (am)
    60.0 ± 34.18
    43.5 ± 26.86
    43.0 ± 33.66
    61.1 ± 18.99
    51.7 ± 28.29
        Day 1 (am) - Change from Baseline
    -22.2 ± 23.94
    -25.4 ± 23.18
    -27.6 ± 32.95
    -3.0 ± 20.59
    -19.1 ± 26.09
        Day 1 (pm)
    55.5 ± 36.06
    54.1 ± 30.92
    42.3 ± 29.32
    51.5 ± 18.45
    50.8 ± 27.69
        Day 1 (pm) - Change from Baseline
    -26.7 ± 25.63
    -14.8 ± 27.90
    -28.3 ± 29.51
    -12.6 ± 21.93
    -19.9 ± 25.86
        Day 2 (am)
    47.2 ± 38.57
    44.1 ± 26.80
    32.0 ± 25.42
    39.8 ± 20.62
    40.6 ± 26.86
        Day 2 (am) - Change from Baseline
    -35.0 ± 28.40
    -24.8 ± 27.67
    -38.6 ± 24.99
    -24.4 ± 20.65
    -30.1 ± 24.83
        Day 2 (pm)
    43.7 ± 42.58
    38.1 ± 26.27
    27.3 ± 26.35
    38.9 ± 27.45
    36.8 ± 29.53
        Day 2 (pm) - Change from Baseline
    -38.5 ± 32.29
    -30.8 ± 27.09
    -43.3 ± 25.75
    -26.0 ± 29.02
    -34.4 ± 27.65
        Day 3 (am)
    42.8 ± 40.69
    31.4 ± 24.85
    25.4 ± 27.50
    33.3 ± 23.7
    32.8 ± 28.23
        Day 3 (am) - Change from Baseline
    -39.3 ± 31.25
    -37.5 ± 26.12
    -45.1 ± 27.56
    -31.6 ± 26.89
    -38.3 ± 26.67
        Day 3 (pm)
    40.2 ± 42.14
    29.4 ± 27.31
    22.4 ± 24.07
    29.8 ± 19.96
    30.0 ± 27.64
        Day 3 (pm) - Change from Baseline
    -42.0 ± 32.63
    -39.5 ± 27.37
    -48.1 ± 24.17
    -34.4 ± 22.72
    -40.7 ± 25.64
        Day 4 (am)
    38.5 ± 43.45
    27.8 ± 23.90
    19.1 ± 22.52
    25.1 ± 20.97
    27.2 ± 27.27
        Day 4 (am) - Change from Baseline
    -43.7 ± 34.13
    -41.1 ± 26.88
    -51.4 ± 23.39
    -39.0 ± 22.77
    -43.6 ± 25.66
        Day 4 (pm)
    37.0 ± 44.01
    29.9 ± 26.10
    17.7 ± 19.62
    21.9 ± 20.93
    26.2 ± 27.58
        Day 4 (pm) - Change from Baseline
    -45.2 ± 34.94
    -39.0 ± 31.80
    -52.9 ± 20.53
    -42.3 ± 23.61
    -44.5 ± 26.98
        Day 5 (am)
    40.0 ± 44.37
    30.7 ± 24.83
    17.9 ± 19.16
    25.0 ± 29.80
    27.9 ± 29.61
        Day 5 (am) - Change from Baseline
    -42.2 ± 33.61
    -36.6 ± 23.20
    -52.7 ± 19.96
    -39.1 ± 34.39
    -42.5 ± 27.63
        Day 5 (pm)
    37.5 ± 42.18
    21.6 ± 18.51
    10.7 ± 12.45
    23.3 ± 28.67
    23.1 ± 27.23
        Day 5 (pm) - Change from Baseline
    -44.7 ± 32.38
    -47.3 ± 24.45
    -60.3 ± 12.85
    -40.9 ± 32.83
    -47.7 ± 26.66
        Day 6 (am)
    35.2 ± 40.95
    17.0 ± 12.49
    18.3 ± 19.99
    24.5 ± 28.86
    23.3 ± 26.26
        Day 6 (am) - Change from Baseline
    -47.0 ± 31.00
    -51.9 ± 17.35
    -52.7 ± 19.70
    -39.6 ± 33.34
    -47.5 ± 25.42
        Day 6 (pm)
    36.5 ± 44.28
    18.1 ± 15.31
    17.1 ± 17.11
    17.8 ± 25.34
    21.9 ± 26.36
        Day 6 (pm) - Change from Baseline
    -45.7 ± 34.78
    -50.8 ± 18.85
    -53.4 ± 17.66
    -43.2 ± 30.45
    -48.6 ± 24.39
        Day 7 (am)
    36.3 ± 37.88
    13.3 ± 11.39
    15.7 ± 17.90
    13.7 ± 19.00
    19.1 ± 23.31
        Day 7 (am) - Change from Baseline
    -45.8 ± 27.01
    -55.6 ± 16.54
    -54.9 ± 18.07
    -47.3 ± 25.11
    -51.4 ± 20.74
        Day 7 (pm)
    17.8 ± 22.90
    9.7 ± 11.03
    11.4 ± 12.01
    11.4 ± 12.16
    12.3 ± 14.14
        Day 7 (pm) - Change from Baseline
    -60.8 ± 17.81
    -58.9 ± 14.10
    -59.4 ± 13.46
    -50.0 ± 21.15
    -57.4 ± 15.95
        Day 8 (am)
    13.0 ± 14.72
    8.4 ± 11.13
    9.6 ± 7.92
    10.2 ± 13.29
    10.0 ± 11.09
        Day 8 (am) - Change from Baseline
    -65.8 ± 5.74
    -60.1 ± 15.44
    -61.2 ± 10.47
    -50.8 ± 20.67
    -58.9 ± 14.99
        Day 14
    6.2 ± 8.38
    11.9 ± 11.62
    2.4 ± 3.41
    13.9 ± 27.12
    9.0 ± 15.95
        Day 14 - Change from Baseline
    -76.0 ± 11.05
    -57.0 ± 16.80
    -68.1 ± 6.57
    -50.3 ± 23.91
    -61.8 ± 18.51
    No statistical analyses for this end point

    Secondary: Subject-reported General Disability Score

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    End point title
    Subject-reported General Disability Score
    End point description
    Subjects recorded their level of general disability on a 100 mm Visual Analog Scale (VAS) in response to the question "How limited do you feel right now, this [insert time of day,] in your daily activities as a result of this gout attack?". The scale went from 0 (I can do everything I was able to do before this gout attack started) to 100 (I cannot do anything).
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose) to Day 14
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6
    8
    7
    8
    29
    Units: millimetre(s)
    arithmetic mean (standard deviation)
        Baseline (pre-dose)
    60.7 ± 24.47
    68.3 ± 16.20
    63.6 ± 27.81
    62.8 ± 18.11
    64.0 ± 20.70
        2 hours (post-dose)
    63.7 ± 31.30
    62.6 ± 20.62
    55.9 ± 30.97
    69.6 ± 12.37
    63.1 ± 23.46
        2 hours (post-dose) - Change from Baseline
    3.0 ± 14.72
    -5.6 ± 10.84
    -7.7 ± 16.15
    6.9 ± 12.94
    -0.9 ± 14.30
        4 hours (post-dose)
    63.8 ± 27.76
    56.6 ± 18.81
    52.4 ± 34.07
    63.4 ± 7.91
    59.0 ± 22.66
        4 hours (post-dose) - Change from Baseline
    3.2 ± 13.50
    -11.6 ± 10.95
    -11.1 ± 22.33
    0.6 ± 10.56
    -5.1 ± 15.57
        6 hours (post-dose)
    65.0 ± 27.52
    47.4 ± 22.48
    59.0 ± 30.19
    62.4 ± 19.33
    58.0 ± 24.47
        6 hours (post-dose) - Change from Baseline
    4.3 ± 17.53
    -20.9 ± 14.73
    -4.6 ± 21.78
    -0.4 ± 9.84
    -6.1 ± 18.18
        12 hours (post-dose)
    69.2 ± 29.82
    50.5 ± 22.39
    49.9 ± 37.34
    64.6 ± 23.95
    58.1 ± 28.25
        12 hours (post-dose) - Change from Baseline
    8.5 ± 21.89
    -17.8 ± 17.79
    -13.7 ± 24.49
    1.9 ± 13.45
    -5.9 ± 21.34
        Day 1 (am)
    59.2 ± 36.34
    40.1 ± 23.74
    45.9 ± 34.55
    59.6 ± 23.93
    50.8 ± 29.18
        Day 1 (am) - Change from Baseline
    -1.5 ± 28.91
    -28.1 ± 21.06
    -17.7 ± 22.23
    -3.1 ± 17.64
    -13.2 ± 23.89
        Day 1 (pm)
    55.0 ± 36.71
    49.4 ± 29.79
    45.7 ± 34.45
    53.8 ± 21.93
    50.9 ± 29.16
        Day 1 (pm) - Change from Baseline
    -5.7 ± 31.40
    -18.9 ± 27.48
    -17.9 ± 24.99
    -9.0 ± 13.94
    -13.2 ± 24.07
        Day 2 (am)
    48.3 ± 39.64
    43.1 ± 26.37
    38.1 ± 31.49
    44.1 ± 21.37
    43.3 ± 28.17
        Day 2 (am) - Change from Baseline
    -12.3 ± 33.89
    -25.1 ± 27.94
    -25.4 ± 22.17
    -18.6 ± 15.12
    -20.8 ± 24.29
        Day 2 (pm)
    42.8 ± 42.96
    39.4 ± 28.67
    37.6 ± 32.16
    44.4 ± 27.32
    40.9 ± 30.95
        Day 2 (pm) - Change from Baseline
    -17.8 ± 35.91
    -28.9 ± 28.26
    -26.0 ± 25.59
    -19.3 ± 22.57
    -23.4 ± 26.95
        Day 3 (am)
    42.2 ± 41.22
    31.6 ± 27.70
    33.6 ± 34.69
    35.3 ± 23.48
    35.3 ± 30.31
        Day 3 (am) - Change from Baseline
    -18.5 ± 34.72
    -36.6 ± 26.03
    -30.0 ± 29.50
    -28.4 ± 19.80
    -29.0 ± 26.86
        Day 3 (pm)
    38.8 ± 42.32
    30.5 ± 26.50
    31.9 ± 33.70
    31.0 ± 23.07
    32.7 ± 29.70
        Day 3 (pm) - Change from Baseline
    -21.8 ± 35.56
    -37.8 ± 21.94
    -31.7 ± 28.14
    -31.8 ± 17.51
    -31.3 ± 24.97
        Day 4 (am)
    36.8 ± 39.95
    31.0 ± 26.42
    27.7 ± 31.20
    27.8 ± 23.03
    30.5 ± 28.52
        Day 4 (am) - Change from Baseline
    -23.8 ± 32.93
    -37.3 ± 24.45
    -35.9 ± 27.03
    -35.0 ± 17.06
    -33.5 ± 24.46
        Day 4 (pm)
    38.0 ± 43.92
    30.5 ± 30.13
    24.4 ± 26.22
    24.8 ± 22.34
    29.0 ± 29.53
        Day 4 (pm) - Change from Baseline
    -22.7 ± 36.98
    -37.8 ± 29.79
    -39.1 ± 23.19
    -38.0 ± 17.22
    -35.0 ± 26.40
        Day 5 (am)
    39.7 ± 44.52
    28.7 ± 25.84
    23.9 ± 26.18
    27.1 ± 31.59
    29.4 ± 30.98
        Day 5 (am) - Change from Baseline
    -21.0 ± 38.68
    -42.6 ± 25.05
    -39.7 ± 22.70
    -35.6 ± 24.78
    -35.3 ± 27.47
        Day 5 (pm)
    36.5 ± 43.13
    24.3 ± 28.60
    18.8 ± 24.05
    26.0 ± 30.66
    26.2 ± 30.73
        Day 5 (pm) - Change from Baseline
    -24.2 ± 36.95
    -44.0 ± 26.37
    -43.2 ± 24.35
    -36.8 ± 23.40
    -37.5 ± 27.28
        Day 6 (am)
    34.2 ± 42.78
    19.8 ± 27.69
    22.7 ± 23.46
    26.8 ± 30.87
    25.5 ± 30.26
        Day 6 (am) - Change from Baseline
    -26.5 ± 36.26
    -48.5 ± 24.73
    -39.3 ± 22.11
    -36.0 ± 23.91
    -38.3 ± 26.54
        Day 6 (pm)
    34.8 ± 44.48
    21.5 ± 28.09
    22.9 ± 21.11
    21.2 ± 26.17
    24.7 ± 29.29
        Day 6 (pm) - Change from Baseline
    -25.8 ± 37.35
    -46.8 ± 23.16
    -40.7 ± 19.76
    -44.5 ± 21.79
    -40.0 ± 25.68
        Day 7 (am)
    36.3 ± 37.59
    19.8 ± 27.03
    20.7 ± 22.68
    16.0 ± 20.57
    22.9 ± 26.93
        Day 7 (am) - Change from Baseline
    -24.3 ± 31.00
    -48.5 ± 22.42
    -42.9 ± 23.50
    -49.7 ± 18.05
    -41.9 ± 24.68
        Day 7 (pm)
    20.6 ± 27.96
    14.4 ± 22.44
    14.2 ± 14.02
    13.8 ± 15.82
    15.6 ± 19.64
        Day 7 (pm) - Change from Baseline
    -34.6 ± 29.38
    -53.0 ± 17.04
    -54.4 ± 14.99
    -53.8 ± 15.71
    -49.3 ± 20.11
        Day 8 (am)
    12.8 ± 15.00
    14.1 ± 20.71
    12.0 ± 9.59
    13.3 ± 18.46
    13.2 ± 15.94
        Day 8 (am) - Change from Baseline
    -40.0 ± 26.26
    -53.3 ± 17.48
    -56.6 ± 13.59
    -52.3 ± 16.05
    -51.4 ± 17.75
        Day 14
    11.2 ± 19.68
    14.0 ± 15.25
    2.9 ± 3.13
    14.1 ± 26.61
    10.8 ± 18.12
        Day 14 - Change from Baseline
    -49.5 ± 19.99
    -54.3 ± 14.83
    -60.7 ± 26.04
    -48.6 ± 36.53
    -53.3 ± 25.07
    No statistical analyses for this end point

    Secondary: Subject-reported Walking Disability Score

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    End point title
    Subject-reported Walking Disability Score
    End point description
    Subjects were instructed to record their level of walking disability on a 100-mm Visual Analog Scale (VAS) in response to the question "How are you walking now, this [insert time of day]?" The scale went from 0 ("I am not experiencing any deterioration in walking") to 100 ("I can absolutely not walk").
    End point type
    Secondary
    End point timeframe
    Baseline (pre-dose) to Day 14
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6
    8
    7
    8
    29
    Units: millimetre(s)
    arithmetic mean (standard deviation)
        Baseline (pre-dose)
    79.5 ± 31.37
    73.0 ± 20.11
    70.3 ± 14.68
    71.9 ± 18.45
    73.4 ± 20.48
        2 hours (post-dose)
    74.5 ± 31.57
    66.5 ± 21.53
    56.1 ± 27.53
    65.1 ± 21.31
    65.3 ± 24.68
        2-hours (post-dose) - Change from Baseline
    -5.0 ± 7.40
    -6.5 ± 8.28
    -14.1 ± 18.59
    -6.8 ± 9.54
    -8.1 ± 11.67
        4 hours (post-dose)
    66.5 ± 36.36
    58.5 ± 21.20
    59.4 ± 28.58
    62.6 ± 19.78
    61.5 ± 25.11
        4 hours (post-dose) - Change from Baseline
    -13.0 ± 20.92
    -14.5 ± 15.40
    -10.9 ± 19.63
    -9.3 ± 9.68
    -11.9 ± 15.75
        6 hours (post-dose)
    67.5 ± 36.45
    48.3 ± 23.90
    56.1 ± 29.95
    62.6 ± 20.78
    58.1 ± 27.09
        6 hours (post-dose) - Change from Baseline
    -12.0 ± 20.81
    -24.8 ± 18.19
    -14.1 ± 21.33
    -9.3 ± 10.50
    -15.3 ± 17.99
        12 hours (post-dose)
    75.3 ± 33.10
    51.6 ± 25.64
    51.9 ± 34.98
    65.4 ± 23.74
    60.4 ± 29.29
        12 hours (post-dose) - Change from Baseline
    -4.2 ± 12.50
    -21.4 ± 17.67
    -18.4 ± 30.65
    -6.5 ± 12.35
    -13.0 ± 20.04
        Day 1 (am)
    71.0 ± 35.66
    42.6 ± 25.07
    46.9 ± 33.01
    58.3 ± 23.21
    53.8 ± 29.48
        Day 1 (am) - Change from Baseline
    -8.5 ± 11.73
    -30.4 ± 21.53
    -23.4 ± 26.37
    -13.6 ± 10.11
    -19.6 ± 19.71
        Day 1 (pm)
    66.3 ± 33.33
    48.8 ± 31.23
    46.4 ± 37.14
    53.1 ± 21.68
    53.0 ± 30.15
        Day 1 (pm) - Change from Baseline
    -13.2 ± 9.75
    -24.3 ± 26.00
    -23.9 ± 27.66
    -18.8 ± 7.98
    -20.3 ± 19.62
        Day 2 (am)
    57.7 ± 37.16
    48.0 ± 29.36
    41.7 ± 34.22
    47.5 ± 23.66
    48.3 ± 29.71
        Day 2 (am) - Change from Baseline
    -21.8 ± 20.72
    -25.0 ± 25.96
    -28.6 ± 25.62
    -24.4 ± 10.01
    -25.0 ± 20.40
        Day 2 (pm)
    47.8 ± 39.80
    43.1 ± 29.99
    39.9 ± 32.74
    46.9 ± 30.31
    44.3 ± 31.29
        Day 2 (pm) - Change from Baseline
    -31.7 ± 28.73
    -29.9 ± 25.81
    -30.4 ± 24.07
    -26.7 ± 17.34
    -29.6 ± 22.90
        Day 3 (am)
    47.0 ± 40.48
    35.5 ± 27.66
    35.3 ± 37.19
    35.1 ± 23.36
    37.8 ± 30.89
        Day 3 (am) - Change from Baseline
    -32.5 ± 30.83
    -37.5 ± 26.67
    -35.0 ± 26.78
    -38.4 ± 12.82
    -36.0 ± 23.69
        Day 3 (pm)
    42.3 ± 43.05
    35.9 ± 31.74
    32.1 ± 35.00
    37.4 ± 22.88
    36.7 ± 31.44
        Day 3 (pm) - Change from Baseline
    -37.2 ± 35.11
    -37.1 ± 26.63
    -38.1 ± 25.28
    -34.5 ± 16.54
    -36.7 ± 24.59
        Day 4 (am)
    39.5 ± 42.95
    37.6 ± 32.05
    28.7 ± 31.10
    30.8 ± 24.92
    34.0 ± 31.13
        Day 4 (am) - Change from Baseline
    -40.0 ± 37.12
    -35.4 ± 30.93
    -41.6 ± 20.46
    -41.1 ± 14.68
    -39.4 ± 25.21
        Day 4 (pm)
    38.7 ± 43.79
    37.4 ± 31.65
    27.9 ± 31.48
    26.4 ± 23.03
    32.3 ± 31.13
        Day 4 (pm) - Change from Baseline
    -40.8 ± 37.95
    -35.6 ± 32.56
    -42.4 ± 20.48
    -45.5 ± 14.70
    -41.1 ± 26.09
        Day 5 (am)
    39.2 ± 44.01
    35.7 ± 27.17
    26.9 ± 28.73
    29.4 ± 33.23
    32.4 ± 31.88
        Day 5 (am) - Change from Baseline
    -40.3 ± 39.02
    -38.4 ± 28.32
    -43.4 ± 18.44
    -42.5 ± 24.84
    -41.3 ± 26.45
        Day 5 (pm)
    38.0 ± 43.31
    31.1 ± 31.51
    18.7 ± 24.13
    26.6 ± 31.37
    28.6 ± 31.82
        Day 5 (pm) - Change from Baseline
    -41.5 ± 37.85
    -41.9 ± 31.11
    -50.3 ± 13.95
    -45.3 ± 24.16
    -44.6 ± 26.75
        Day 6 (am)
    34.3 ± 40.50
    29.3 ± 31.62
    24.3 ± 25.22
    27.4 ± 33.21
    28.8 ± 31.28
        Day 6 (am) - Change from Baseline
    -45.2 ± 36.21
    -43.8 ± 31.62
    -44.7 ± 24.64
    -44.5 ± 25.55
    -44.5 ± 28.00
        Day 6 (pm)
    34.7 ± 42.91
    26.3 ± 31.83
    22.1 ± 19.93
    22.5 ± 29.53
    26.2 ± 30.17
        Day 6 (pm) - Change from Baseline
    -44.8 ± 37.93
    -46.8 ± 28.09
    -48.1 ± 17.43
    -46.7 ± 20.71
    -46.7 ± 25.36
        Day 7 (am)
    36.8 ± 36.80
    24.1 ± 28.38
    23.9 ± 23.29
    16.8 ± 20.61
    25.3 ± 27.06
        Day 7 (am) - Change from Baseline
    -42.7 ± 33.11
    -48.9 ± 25.97
    -46.4 ± 24.64
    -52.3 ± 14.80
    -47.6 ± 24.22
        Day 7 (pm)
    20.4 ± 27.90
    16.1 ± 23.74
    15.0 ± 12.88
    13.4 ± 14.52
    16.2 ± 19.68
        Day 7 (pm) - Change from Baseline
    -55.0 ± 31.87
    -54.6 ± 23.33
    -50.6 ± 12.03
    -57.6 ± 16.20
    -54.5 ± 20.80
        Day 8 (am)
    13.0 ± 14.72
    14.1 ± 19.60
    12.0 ± 9.92
    14.0 ± 19.04
    13.4 ± 15.70
        Day 8 (am) - Change from Baseline
    -60.3 ± 35.06
    -56.6 ± 22.84
    -53.6 ± 10.41
    -55.2 ± 15.68
    -56.2 ± 20.22
        Day 14
    10.0 ± 19.02
    18.3 ± 22.34
    7.4 ± 15.34
    16.1 ± 26.77
    13.3 ± 20.96
        Day 14 - Change from Baseline
    -69.5 ± 29.51
    -54.8 ± 21.04
    -62.9 ± 11.13
    -55.8 ± 27.37
    -60.0 ± 22.68
    No statistical analyses for this end point

    Secondary: Investigator-assessed Index Joint Score - Joint Tenderness

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    End point title
    Investigator-assessed Index Joint Score - Joint Tenderness
    End point description
    investigator assessment of index joint tenderness from 0 to 3 with the following categories: 0 = no pain, 1 = mild pain , 2 = moderate pain, 3 = severe pain.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-dose and post-dose), Day 3, Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [2]
    8
    7
    8
    29 [3]
    Units: Subjects
        Day 0 (pre-dose) - No Pain
    0
    0
    0
    0
    0
        Day 0 (pre-dose) - Mild Pain
    1
    1
    0
    0
    2
        Day 0 (pre-dose) - Moderate Pain
    0
    2
    3
    3
    8
        Day 0 (pre-dose) - Severe Pain
    5
    5
    4
    5
    19
        Day 0 (post-dose) - No Pain
    0
    0
    1
    0
    1
        Day 0 (post-dose) - Mild Pain
    2
    3
    1
    1
    7
        Day 0 (post-dose) - Moderate Pain
    2
    3
    3
    5
    13
        Day 0 (post-dose) - Severe Pain
    2
    2
    2
    2
    8
        Day 3 - No Pain
    1
    2
    1
    1
    5
        Day 3 - Mild Pain
    2
    3
    3
    2
    10
        Day 3 - Moderate Pain
    1
    3
    2
    3
    9
        Day 3 - Severe Pain
    1
    0
    1
    2
    4
        Day 7 - No Pain
    3
    5
    2
    6
    16
        Day 7 - Mild Pain
    1
    3
    4
    0
    8
        Day 7 - Moderate Pain
    2
    0
    1
    1
    4
        Day 7 - Severe Pain
    0
    0
    0
    1
    1
    Notes
    [2] - At Day 3, only 5 subjects were analyzed.
    [3] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Secondary: Investigator-assessed Index Joint Score - Joint Swelling

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    End point title
    Investigator-assessed Index Joint Score - Joint Swelling
    End point description
    Investigator assessment of index joint swelling, with numerical values assigned as follows: 0 = no swelling; 1 = mild swelling; 2 = moderate swelling; 3 = severe swelling (or bulging beyond joint margins).
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-dose and post-dose), Day 3, Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [4]
    8
    7
    8
    29 [5]
    Units: Subjects
        Day 0 (pre-dose) - No Swelling
    0
    0
    0
    0
    0
        Day 0 (pre-dose) - Mild Swelling
    0
    1
    1
    1
    3
        Day 0 (pre-dose) - Moderate Swelling
    4
    3
    4
    4
    15
        Day 0 (pre-dose) - Severe Swelling
    2
    4
    2
    3
    11
        Day 0 (post-dose) - No Swelling
    1
    0
    0
    0
    1
        Day 0 (post-dose) - Mild Swelling
    1
    3
    3
    2
    9
        Day 0 (post-dose) - Moderate Swelling
    2
    4
    2
    4
    12
        Day 0 (post-dose) - Severe Swelling
    2
    1
    2
    2
    7
        Day 3 - No Swelling
    1
    3
    1
    1
    6
        Day 3 - Mild Swelling
    2
    2
    4
    2
    10
        Day 3 - Moderate Swelling
    2
    3
    2
    2
    9
        Day 3 - Severe Swelling
    0
    0
    0
    3
    3
        Day 7 - No Swelling
    4
    3
    3
    5
    15
        Day 7 - Mild Swelling
    1
    5
    4
    2
    12
        Day 7 - Moderate Swelling
    1
    0
    0
    1
    2
        Day 7 - Severe Swelling
    0
    0
    0
    0
    0
    Notes
    [4] - At Day 3, only 5 subjects were analyzed.
    [5] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Secondary: Investigator-assessed Index Joint Score - Erythema

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    End point title
    Investigator-assessed Index Joint Score - Erythema
    End point description
    Investigator assessment of index joint erythema, with values assigned as follows: present, absent, and non-assessable.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-dose and post-dose), Day 3, Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [6]
    8
    7
    8
    29 [7]
    Units: Subjects
        Day 0 (pre-dose) - Absent
    1
    2
    1
    0
    4
        Day 0 (pre-dose) - Present
    5
    6
    6
    8
    25
        Day 0 (pre-dose) - Non-assessable
    0
    0
    0
    0
    0
        Day 0 (post-dose) - Absent
    2
    1
    2
    0
    5
        Day 0 (post-dose) - Present
    4
    7
    5
    8
    24
        Day 0 (post-dose) - Non-assessable
    0
    0
    0
    0
    0
        Day 3 - Absent
    3
    2
    4
    1
    10
        Day 3 - Present
    2
    6
    3
    7
    18
        Day 3 - Non-assessable
    0
    0
    0
    0
    0
        Day 7 - Absent
    4
    3
    5
    4
    16
        Day 7 - Present
    2
    5
    2
    4
    13
        Day 7 - Non-assessable
    0
    0
    0
    0
    0
    Notes
    [6] - At Day 3, only 5 subjects were analyzed.
    [7] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Secondary: Investigator-assessed Index Joint Score - Warmth

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    End point title
    Investigator-assessed Index Joint Score - Warmth
    End point description
    Investigator assessment of index joint warmth, with values assigned as follows: present, absent, and non-assessable.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-dose and post-dose), Day 3, Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [8]
    8
    7
    8
    29 [9]
    Units: Subjects
        Day 0 (pre-dose) - Absent
    0
    0
    0
    0
    0
        Day 0 (pre-dose) - Present
    6
    8
    7
    8
    29
        Day 0 (pre-dose) - Non-assessable
    0
    0
    0
    0
    0
        Day 0 (post-dose) - Absent
    1
    0
    1
    0
    2
        Day 0 (post-dose) - Present
    5
    8
    6
    8
    27
        Day 0 (post-dose) - Non-assessable
    0
    0
    0
    0
    0
        Day 3 - Absent
    4
    4
    4
    1
    13
        Day 3 - Present
    1
    4
    3
    7
    15
        Day 3 - Non-assessable
    0
    0
    0
    0
    0
        Day 7 - Absent
    4
    5
    3
    5
    17
        Day 7 - Present
    2
    3
    4
    3
    12
        Day 7 - Non-assessable
    0
    0
    0
    0
    0
    Notes
    [8] - At Day 3, only 5 subjects were analyzed.
    [9] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Secondary: Investigator-assessed Global Rating of Disease

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    End point title
    Investigator-assessed Global Rating of Disease
    End point description
    Global Rating of Disease was one general question the Investigator was asked to answer about the overall perceived status of the subject’s symptoms. The Investigator responded to the following question: "Considering all of the patient’s signs and symptoms, how well are they doing?" The Global Rating of Disease was assessed on a 5-point Likert scale, with numerical values to assigned as follows: (0 = poor, 1 = fair, 2 = good, 3 = very good and 4 = excellent).
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-dose and post-dose), Day 3, Day 7
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [10]
    8
    7
    8
    29 [11]
    Units: Subjects
        Day 0 (pre-dose) - Poor
    1
    3
    3
    2
    9
        Day 0 (pre-dose) - Fair
    4
    4
    1
    6
    15
        Day 0 (pre-dose) - Good
    1
    1
    3
    0
    5
        Day 0 (pre-dose) - Very Good
    0
    0
    0
    0
    0
        Day 0 (pre-dose) - Excellent
    0
    0
    0
    0
    0
        Day 0 (post-dose) - Poor
    1
    2
    3
    1
    7
        Day 0 (post-dose) - Fair
    3
    4
    0
    5
    12
        Day 0 (post-dose) - Good
    1
    2
    4
    2
    9
        Day 0 (post-dose) - Very Good
    1
    0
    0
    0
    1
        Day 0 (post-dose) - Excellent
    0
    0
    0
    0
    0
        Day 3 - Poor
    0
    0
    0
    2
    2
        Day 3 - Fair
    2
    3
    2
    4
    11
        Day 3 - Good
    2
    2
    3
    2
    9
        Day 3 - Very Good
    0
    1
    1
    0
    2
        Day 3 - Excellent
    1
    2
    1
    0
    4
        Day 7 - Poor
    0
    0
    0
    0
    0
        Day 7 - Fair
    2
    0
    1
    2
    5
        Day 7 - Good
    1
    3
    3
    1
    8
        Day 7 - Very Good
    1
    1
    0
    2
    4
        Day 7 - Excellent
    2
    4
    3
    3
    12
    Notes
    [10] - At Day 3, only 5 subjects were analyzed
    [11] - At Day 3, only 28 subjects were analyzed
    No statistical analyses for this end point

    Secondary: Blood Levels of C-reactive Protein

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    End point title
    Blood Levels of C-reactive Protein
    End point description
    Blood levels of the inflammatory biomarker C-reactive protein (CRP) were analyzed for changes from Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 3, Day 7, Day 14
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [12]
    8
    7
    8
    29 [13]
    Units: milligram(s)/litre
    arithmetic mean (standard deviation)
        Baseline
    22.78 ± 31.204
    11.06 ± 8.565
    19.60 ± 16.271
    30.53 ± 63.836
    20.92 ± 36.373
        Day 3
    39.54 ± 58.100
    9.18 ± 7.052
    41.01 ± 49.548
    39.94 ± 57.478
    31.35 ± 46.035
        Day 3 - Change from Baseline
    15.60 ± 24.172
    -1.89 ± 9.985
    21.41 ± 40.099
    9.41 ± 26.785
    10.29 ± 27.151
        Day 7
    6.10 ± 3.863
    4.93 ± 3.848
    9.90 ± 11.422
    32.56 ± 52.535
    13.99 ± 29.391
        Day 7 - Change from Baseline
    -16.68 ± 28.922
    -6.14 ± 8.632
    -9.70 ± 11.128
    2.04 ± 34.898
    -6.92 ± 23.334
        Day 14
    1.33 ± 0.596
    4.43 ± 1.695
    6.56 ± 8.831
    2.96 ± 2.331
    3.90 ± 4.728
        Day 14 - Change from Baseline
    -21.45 ± 31.246
    -6.64 ± 9.234
    -13.04 ± 20.021
    -27.56 ± 62.144
    -17.02 ± 36.301
    Notes
    [12] - At Day 3, only 5 subjects were analyzed.
    [13] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Secondary: Blood Levels of Serum Amyloid A Protein

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    End point title
    Blood Levels of Serum Amyloid A Protein
    End point description
    Blood levels of inflammatory biomarker serum amyloid A protein (SAA) were analyzed for changes from Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 3, Day 7, Day 14
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6 [14]
    8
    7
    8
    29 [15]
    Units: milligram(s)/litre
    arithmetic mean (standard deviation)
        Baseline
    96.20 ± 192.716
    15.25 ± 14.116
    49.26 ± 63.862
    228.51 ± 614.857
    99.04 ± 330.885
        Day 3
    275.38 ± 502.153
    15.35 ± 17.418
    259.11 ± 397.833
    293.15 ± 508.943
    202.10 ± 392.922
        Day 3 - Change from Baseline
    164.12 ± 291.205
    0.10 ± 16.980
    209.86 ± 337.459
    64.64 ± 359.248
    100.27 ± 280.396
        Day 7
    9.88 ± 7.323
    7.01 ± 7.360
    6.84 ± 6.183
    216.19 ± 381.395
    65.27 ± 213.037
        Day 7 - Change from Baseline
    -86.32 ± 187.345
    -8.24 ± 8.619
    -42.41 ± 59.364
    -12.33 ± 362.927
    -33.77 ± 202.233
        Day 14
    2.68 ± 1.778
    5.91 ± 2.892
    10.83 ± 19.053
    6.78 ± 7.631
    6.67 ± 10.144
        Day 14 - Change from Baseline
    -93.52 ± 192.751
    -9.34 ± 14.410
    -38.43 ± 69.613
    -221.74 ± 615.038
    -92.37 ± 331.318
    Notes
    [14] - At Day 3, only 5 subjects were analyzed.
    [15] - At Day 3, only 28 subjects were analyzed.
    No statistical analyses for this end point

    Other pre-specified: Treatment Failures

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    End point title
    Treatment Failures
    End point description
    Subjects unable to tolerate his/her pain who wished to receive standard medical intervention for an acute gout flare could withdraw from the study. These subjects were considered a Treatment Failure and were treated with either prednisolone (30 mg QD) or colchicine (0.5 mg TID). No subjects were considered a treatment failure.
    End point type
    Other pre-specified
    End point timeframe
    Baseline through Day 35
    End point values
    Cohort 1 - Per-Protocol Cohort 2 - Per-Protocol Cohort 3 - Per-Protocol Cohort 4 - Per-Protocol Overall - Per-Protocol
    Number of subjects analysed
    6
    8
    7
    8
    29
    Units: Subjects
        Treatment Failures
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from time of informed consent form signature through Day 14. Serious adverse events were reported from time of informed consent signature through Day 35.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    500 mg BID for 8 days

    Reporting group title
    Cohort 2
    Reporting group description
    500 mg QID for 8 days

    Reporting group title
    Cohort 3
    Reporting group description
    BID (am and pm dosing) for 8 days

    Reporting group title
    Cohort 4
    Reporting group description
    100 mg QD for 8 days

    Reporting group title
    All Subjects
    Reporting group description
    Includes all subjects in the Safety Population (n=34).

    Serious adverse events
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 All Subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 34 (5.88%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Post procedural myocardial infarction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Cohort 1 Cohort 2 Cohort 3 Cohort 4 All Subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 10 (80.00%)
    7 / 8 (87.50%)
    4 / 8 (50.00%)
    6 / 8 (75.00%)
    25 / 34 (73.53%)
    Injury, poisoning and procedural complications
    Joint injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    1
    1
    Post procedural myocardial infarction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    0
    1
    Serum amyloid A protein increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    3 / 34 (8.82%)
         occurrences all number
    2
    1
    0
    0
    3
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    3 / 34 (8.82%)
         occurrences all number
    3
    0
    0
    0
    3
    Flatulence
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    3 / 34 (8.82%)
         occurrences all number
    2
    1
    0
    0
    3
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    0
    0
    2
    Nausea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Gout
         subjects affected / exposed
    4 / 10 (40.00%)
    2 / 8 (25.00%)
    3 / 8 (37.50%)
    5 / 8 (62.50%)
    14 / 34 (41.18%)
         occurrences all number
    4
    2
    3
    6
    15
    Hyponatraemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    0
    1
    Myringitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Sep 2017
    Key revisions included change of prohibited use of paracetamol before Baseline Visit to within 4 hours (from within 12 hours of Baseline Visit).
    11 Apr 2018
    Key revisions included added exclusion criteria for known diagnosis of chronic kidney disease or known history of renal impairment, change of Cohort 2 dose administration to 500 mg QID (from 1000 mg BID), change of urate-lowering therapy (a prohibited concomitant medication/therapy) stable dosing condition to 1 month (from 3 months), allowance of usage of medical data from synovial fluid collection/analysis from within 24 hours prior to Baseline Visit as part of standard medical diagnosis to be used and reported in study case report forms, addition of discretionary replacement of any subject who did not complete dosing through the Day 7 Visit, removal of requirement that at least three subjects per cohort be enrolled with a gout flare that began within 36 hours of the Baseline Visit, and addition of optional, suggested subject contact for dosing compliance.
    10 Oct 2018
    Key revisions included addition of Cohort 4 with 8 patients dosing at 100 mg per day thereby changing total enrollment to approximately 32 eligible subjects (from approximately 24 eligible subjects), and removal of decision tree for determination of dose schedules and replacement with a table to reflect actual trial dosages.

    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.
    This proof-of-concept trial was conducted in a small number subjects, therefore no statistical analyses between groups were conducted.

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/33005902
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