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    Clinical Trial Results:
    A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study with open label extension to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with active ulcerative colitis

    Summary
    EudraCT number
    		 2016-001833-29
    Trial protocol
    		 SE   GB   PL   NL  
    Global end of trial date
    17 Jun 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jun 2020
    First version publication date
    03 Jun 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    202152
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.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
    06 Sep 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jun 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the safety and tolerability of 60 mg three daily doses of GSK2982772 in subjects with moderate to severe ulcerative colitis
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Nov 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Poland: 7
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    United States: 4
    Worldwide total number of subjects
    36
    EEA total number of subjects
    18
    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)
    34
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study evaluated the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) or placebo three times daily (TID) in Part A (double blind [DB]) followed by GSK2982772 60 mg TID in Part B open label extension (OL) in active ulcerative colitis (UC) participants.

    Pre-assignment
    Screening details
    		 A total of 77 participants were screened, of which 36 eligible participants were enrolled (41 were screening failure). All 36 participants were randomized to receive GSK2982772 60 mg or Placebo in Part A of the study.

    Period 1
    Period 1 title
    Part A (Day 1 to 43)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo TID DB /GSK2982772 60 mg TID OL
    Arm description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Arm title
    		 GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Arm description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the pharmacokinetic (PK) profile is comparable for BID & TID regimen.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2982772
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase) and in Part B (open label phase).

    Number of subjects in period 1
    		Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Started
    12
    24
    Completed
    11
    24
    Not completed
    1
    0
         Adverse event, non-fatal
    1
    -
    Period 2
    Period 2 title
    Part B (Day 44 to 112)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo TID DB /GSK2982772 60 mg TID OL
    Arm description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Arm title
    		 GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Arm description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the pharmacokinetic (PK) profile is comparable for BID & TID regimen.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2982772
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase) and in Part B (open label phase).

    Number of subjects in period 2
    		Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Started
    11
    24
    Completed
    11
    22
    Not completed
    0
    2
         Consent withdrawn by subject
    -
    1
         Lack of efficacy
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo TID DB /GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112.

    Reporting group title
    GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the pharmacokinetic (PK) profile is comparable for BID & TID regimen.

    Reporting group values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL Total
    Number of subjects
    		 12 24 36
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 11 23 34
        From 65-84 years
    		 1 1 2
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 50.4 ( 11.17 ) 39.0 ( 13.69 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 6 8 14
        Male
    		 6 16 22
    Race/Ethnicity, Customized
    Units: Subjects
        White - Arabic/North African Heritage
    		 0 1 1
        White - White/Caucasian/European Heritage
    		 12 23 35

    End points

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    End points reporting groups
    Reporting group title
    Placebo TID DB /GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112.

    Reporting group title
    GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the pharmacokinetic (PK) profile is comparable for BID & TID regimen.
    Reporting group title
    Placebo TID DB /GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112.

    Reporting group title
    GSK2982772 60 mg TID DB/ GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the pharmacokinetic (PK) profile is comparable for BID & TID regimen.

    Subject analysis set title
    Part A: Placebo TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    Part A: GSK2982772 60 mg TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    Part B: GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part B (open label phase).

    Subject analysis set title
    Part A: Placebo TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    Part B: GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part B (open label phase).

    Subject analysis set title
    GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the PK profile is comparable for BID & TID regimen

    Subject analysis set title
    Part A: Placebo TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the PK profile is comparable for BID & TID regimen

    Subject analysis set title
    Part A: GSK2982772 60 mg TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    Part A: Placebo TID DB
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Subject analysis set title
    GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 1 to 43) in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days (from Day 44 to 85) in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the PK profile is comparable for BID & TID regimen

    Subject analysis set title
    GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase), followed by GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part B (open label phase). There was no wash out period in between Part A and B. All participants were followed up until Day 112. 1 participant was randomized to receive BID regimen instead of TID regimen prior to protocol amendment; however, BID and TID are presented in the same arm because the PK profile is comparable for BID & TID regimen

    Primary: Part A: Number of participants with common (>=5%) non-serious adverse events (non-SAEs) and any serious adverse events (SAEs)

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    End point title
    		 Part A: Number of participants with common (>=5%) non-serious adverse events (non-SAEs) and any serious adverse events (SAEs) [1]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. Safety population comprised of all participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    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: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [2]
    24 [3]
    Units: Participants
        Common non-SAEs
    7
    13
        Any SAEs
    1
    0
    Notes
    [2] - Safety population
    [3] - Safety population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with common (>=5%) non serious AEs and SAEs

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    End point title
    		 Part B: Number of participants with common (>=5%) non serious AEs and SAEs [4]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [5]
    Units: Participants
        Common non-SAEs
    7
        Any SAEs
    2
    Notes
    [5] - Safety population. Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst case abnormal clinical chemistry parameters by potential clinical importance (PCI) criteria

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    End point title
    		 Part A: Number of participants with worst case abnormal clinical chemistry parameters by potential clinical importance (PCI) criteria [6]
    End point description
    Clinical chemistry parameters with PCI ranges: aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) (high: >=2 times upper limit of normal [ULN] units per liter [U/L]); calcium (low: <2 millimoles per liter [mmol/L], high: >2.75 mmol/L); glucose (low: <3, high: >9 mmol/L); potassium (low: <3, high: >5.5 mmol/L); sodium (low: <130, high: >150 mmol/L); total bilirubin (high: >=1.5 times ULN micromoles per liter [µmol/L]); high density lipoproteins (HDL) 0.9 to 99.99 mmol/L; low density lipoprotein (LDL) 0 to 3.35 mmol/L; triglycerides 0 to 2.24 mmol/L and creatinine (high: change from Baseline [BL]>44.2 µmol/L). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change'
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [7]
    24 [8]
    Units: Participants
        AST, To Low
    0
    0
        AST, To within range or no change
    12
    24
        AST, To High
    0
    0
        ALT, To Low
    0
    0
        ALT, To within range or no change
    12
    24
        ALT, To High
    0
    0
        ALP, To Low
    0
    0
        ALP, To within range or no change
    12
    24
        ALP, To High
    0
    0
        Calcium, To Low
    0
    0
        Calcium, To within range or no change
    12
    24
        Calcium, To High
    0
    0
        Glucose, To Low
    0
    1
        Glucose, To within range or no change
    11
    23
        Glucose, To High
    1
    0
        Potassium, To Low
    0
    0
        Potassium, To within range or no change
    12
    24
        Potassium, To High
    0
    0
        Sodium, To Low
    0
    0
        Sodium, To within range or no change
    12
    24
        Sodium, To High
    0
    0
        Total Bilirubin, To Low
    0
    0
        Total Bilirubin, To within range or no change
    12
    24
        Total Bilirubin, To High
    0
    0
        HDL, To Low
    0
    0
        HDL, To within range or no change
    12
    24
        HDL, To High
    0
    0
        LDL, To Low
    0
    0
        LDL, To within range or no change
    10
    22
        LDL To High
    2
    2
        Triglycerides, To Low
    0
    0
        Triglycerides, To within range or no change
    12
    23
        Triglycerides, To High
    0
    1
        Creatinine, To Low
    0
    0
        Creatinine, To within range or no change
    12
    24
        Creatinine, To High
    0
    0
    Notes
    [7] - Safety population
    [8] - Safety population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst case abnormal clinical chemistry parameters by potential clinical importance (PCI) criteria

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    End point title
    		 Part B: Number of participants with worst case abnormal clinical chemistry parameters by potential clinical importance (PCI) criteria [9]
    End point description
    Clinical chemistry parameters with their PCI ranges were: AST, ALT, and ALP (high: >=2 ULN [U/L]); calcium (low: <2 mmol/L and high: >2.75 mmol/L); glucose (low: <3 and high: >9 mmol/L); potassium (low: <3 and high: >5.5 mmol/L); sodium (low: <130 and high: >150 mmol/L); total bilirubin (high: >=1.5 times ULN [µmol/L]); HDL 0.9 to 99.99 mmol/L; LDL 0.to 3.35 mmol/L; triglycerides 0 to 2.24 mmol/L, creatinine (high: change from BL >44.2 µmol/L). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [10]
    Units: Participants
        AST, To Low
    0
        AST, To within range or no change
    35
        AST, To High
    0
        ALT, To Low
    0
        ALT, To within range or no change
    35
        ALT, To High
    0
        ALP, To Low
    0
        ALP, To within range or no change
    35
        ALP, To High
    0
        Calcium, To Low
    0
        Calcium, To within range or no change
    35
        Calcium, To High
    0
        Glucose, To Low
    1
        Glucose, To within range or no change
    34
        Glucose, To High
    0
        Potassium, To Low
    0
        Potassium, To within range or no change
    33
        Potassium, To High
    2
        Sodium, To Low
    0
        Sodium, To within range or no change
    35
        Sodium, To High
    0
        Total Bilirubin, To Low
    0
        Total Bilirubin, To within range or no change
    34
        Total Bilirubin, To High
    1
        HDL, To Low
    2
        HDL, To within range or no change
    33
        HDL, To High
    0
        LDL, To Low
    0
        LDL, To within range or no change
    33
        LDL, To High
    2
        Triglycerides, To Low
    0
        Triglycerides, To within range or no change
    34
        Triglycerides, To High
    1
        Creatinine, To Low
    0
        Creatinine, To within range or no change
    35
        Creatinine, To High
    0
    Notes
    [10] - Safety Population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst case abnormal hematology parameters by PCI criteria

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    End point title
    		 Part A: Number of participants with worst case abnormal hematology parameters by PCI criteria [11]
    End point description
    Hematology parameters with their PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from BL<0.075); hemoglobin (high: >180 grams per liter [g/L] and low: change from BL<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell (WBC) count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [12]
    24 [13]
    Units: Participants
        Hematocrit, To Low
    0
    0
        Hematocrit, To within range or no change
    12
    24
        Hematocrit, To High
    0
    0
        Hemoglobin, To Low
    0
    0
        Hemoglobin, To within range or no change
    12
    24
        Hemoglobin, To High
    0
    0
        Lymphocytes, To Low
    1
    0
        Lymphocytes, To within range or no change
    11
    24
        Lymphocytes, To High
    0
    0
        Platelet count, To Low
    0
    0
        Platelet count, To within range or no change
    12
    22
        Platelet count, To High
    0
    2
        Neutrophil count, To Low
    0
    1
        Neutrophil count, To within range or no change
    12
    23
        Neutrophil count, To High
    0
    0
        WBC, To Low
    0
    2
        WBC To within range or no change
    12
    24
        WBC, To High
    0
    0
    Notes
    [12] - Safety Population
    [13] - Safety Population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst case abnormal hematology parameters by PCI criteria

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    End point title
    		 Part B: Number of participants with worst case abnormal hematology parameters by PCI criteria [14]
    End point description
    Hematology parameters with their PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from BL<0.075); hemoglobin (high: >180 g/L and low: change from BL<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); WBC count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [15]
    Units: Participants
        Hematocrit, To Low
    0
        Hematocrit, To within range or no change
    35
        Hematocrit, To High
    0
        Hemoglobin, To Low
    0
        Hemoglobin, To within range or no change
    35
        Hemoglobin, To High
    0
        Lymphocytes, To Low
    1
        Lymphocytes, To within range or no change
    34
        Lymphocytes, To High
    0
        Platelet count, To Low
    0
        Platelet count, To within range or no change
    35
        Platelet count, To High
    0
        Neutrophil count, To Low
    0
        Neutrophil count, To within range or no change
    35
        Neutrophil count, To High
    0
        WBC, To Low
    1
        WBC To within range or no change
    34
        WBC, To High
    0
    Notes
    [15] - Safety Population.Participants with data available at the specified time points were analyzed
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst case abnormal urinalysis results by dipstick method

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    End point title
    		 Part A: Number of participants with worst case abnormal urinalysis results by dipstick method [16]
    End point description
    Urine samples were collected for the assessment of following urine parameters by dipstick method: glucose, protein, blood and ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+, 4+, 5+ indicating proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'increase to trace' or 'increase to 1+, 2+, 3+, 4+, 5+' relative to BL (Day 1) value. Participants whose value was unchanged (e.g., Trace to Trace), or whose value was decreased, were recorded in the 'No change or Decreased' category. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [17]
    11 [18]
    Units: Participants
        Glucose, No change or decreased
    24
    11
        Glucose, Increase to Trace
    0
    0
        Glucose, Increase to 1+
    0
    0
        Glucose, Increase to 2+
    0
    0
        Glucose, Increase to 3+
    0
    0
        Glucose, Increase to 4+
    0
    0
        Glucose, Increase to 5+
    0
    0
        Ketones, No change or decreased
    16
    10
        Ketones, Increase to Trace
    3
    0
        Ketones, Increase to 1+
    3
    0
        Ketones, Increase to 2+
    1
    1
        Ketones, Increase to 3+
    1
    0
        Ketones, Increase to 4+
    0
    0
        Ketones, Increase to 5+
    0
    0
        Occult Blood, No change or decreased
    21
    7
        Occult Blood, Increase to Trace,
    2
    2
        Occult Blood, Increase to 1+
    1
    0
        Occult Blood, Increase to 2+
    0
    2
        Occult Blood, Increase to 3+
    0
    0
        Occult Blood, Increase to 4+
    0
    0
        Occult Blood, Increase to 5+
    0
    0
        Protein, No change or Decreased
    19
    8
        Protein, Increase to Trace
    4
    2
        Protein, Increase to 1+
    1
    1
        Protein, Increase to 2+
    0
    0
        Protein, Increase to 3+
    0
    0
        Protein, Increase to 4+
    0
    0
        Protein, Increase to 5+
    0
    0
    Notes
    [17] - Safety Population
    [18] - Safety Population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst case abnormal urinalysis results by dipstick method

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    End point title
    		 Part B: Number of participants with worst case abnormal urinalysis results by dipstick method [19]
    End point description
    Urine samples were collected for the assessment of following urine parameters by dipstick method: glucose, protein, blood and ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+, 4+, 5+ indicating proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'increase to trace' or 'increase to 1+, 2+, 3+, 4+, 5+' relative to BL (Day 1) value. Participants whose value was unchanged (e.g., Trace to Trace), or whose value was decreased, were recorded in the 'No change or Decreased' category. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    34 [20]
    Units: Participants
        Glucose, No change or Decreased
    34
        Glucose, Increase to Trace
    0
        Glucose, Increase to 1+
    0
        Glucose, Increase to 2+
    0
        Glucose, Increase to 3+
    0
        Glucose, Increase to 4+
    0
        Glucose, Increase to 5+
    0
        Ketones, No change or Decrease
    21
        Ketones, Increase to Trace
    9
        Ketones, Increase to 1+
    2
        Ketones, Increase to 2+
    2
        Ketones, Increase to 3+
    0
        Ketones, Increase to 4+
    0
        Ketones, Increase to 5+
    0
        Occult Blood, No change or Decreased
    30
        Occult Blood, Increase to Trace
    2
        Occult Blood, Increase to 1+
    1
        Occult Blood, Increase to 2+
    1
        Occult Blood, Increase to 3+
    0
        Occult Blood, Increase to 4+
    0
        Occult Blood, Increase to 5+
    0
        Protein, No change or Decreased
    30
        Protein, Increase to Trace
    3
        Protein, Increase to 1+
    1
        Protein, Increase to 2+
    0
        Protein, Increase to 3+
    0
        Protein, Increase to 4+
    0
        Protein, Increase to 5+
    0
    Notes
    [20] - Safety Population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst case abnormal blood pressure results by PCI criteria

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    End point title
    		 Part A: Number of participants with worst case abnormal blood pressure results by PCI criteria [21]
    End point description
    Vital signs were measured in a semi-supine position after 5 minutes rest and included body temperature, systolic and diastolic blood pressure. The clinical concern range for vital signs were: systolic blood pressure (SBP) (low: <85 and high: >160 millimeters of mercury [mmHg]); diastolic blood pressure (DBP) (low: <45 and high: >100 mmHg). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [22]
    24 [23]
    Units: Participants
        DBP, To Low
    0
    0
        DBP, To within range or no change
    12
    24
        DBP, To High
    0
    0
        SBP, To Low
    0
    0
        SBP, To within range or no change
    12
    24
        SBP, To High
    0
    0
    Notes
    [22] - Safety Population
    [23] - Safety Population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst case abnormal blood pressure results by PCI criteria

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    End point title
    		 Part B: Number of participants with worst case abnormal blood pressure results by PCI criteria [24]
    End point description
    Vital signs were measured in a semi-supine position after 5 minutes rest and included body temperature, systolic and diastolic blood pressure. The clinical concern range for vital signs were: SBP (low: <85 and high: >160 mmHg); DBP (low: <45 and high: >100 mmHg). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [25]
    Units: Participants
        DBP, To Low
    0
        DBP, To within range or no change
    34
        DBP, To High
    1
        SBP, To Low
    0
        SBP, To within range or no change
    33
        SBP, To High
    2
    Notes
    [25] - Safety Population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst case abnormal heart rate (HR) results by PCI criteria

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    End point title
    		 Part A: Number of participants with worst case abnormal heart rate (HR) results by PCI criteria [26]
    End point description
    Vital signs were measured in a semi-supine position after 5 minutes rest which included HR. The clinical concern range for HR (low <40 beats per min [bpm] and high >100 bpm). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [27]
    24 [28]
    Units: Participants
        HR, To Low
    0
    0
        HR, To within range or no change
    11
    24
        HR, To High
    1
    0
    Notes
    [27] - Safety Population
    [28] - Safety Population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst case abnormal HR results by PCI criteria

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    End point title
    		 Part B: Number of participants with worst case abnormal HR results by PCI criteria [29]
    End point description
    Vital signs were measured in a semi-supine position after 5 minutes rest which included HR. The clinical concern range for HR (low <40 bpm and high >100 bpm). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [30]
    Units: Participants
        HR, To Low
    0
        HR, To within range or no change
    35
        HR, To High
    0
    Notes
    [30] - Safety Population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Primary: Part A: Number of participants with worst-case abnormal Electrocardiogram (ECG) findings

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    End point title
    		 Part A: Number of participants with worst-case abnormal Electrocardiogram (ECG) findings [31]
    End point description
    12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
    End point type
    Primary
    End point timeframe
    Up to Day 43
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    12 [32]
    24 [33]
    Units: Participants
        Abnormal-not clinically significant
    5
    11
        Abnormal-clinically significant
    0
    0
    Notes
    [32] - Safety Population
    [33] - Safety Population
    No statistical analyses for this end point

    Primary: Part B: Number of participants with worst-case abnormal ECG findings

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    End point title
    		 Part B: Number of participants with worst-case abnormal ECG findings [34]
    End point description
    12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. All participants in Part B were presented in a single arm as they all received GSK2982772 60 mg in Part B (OL Phase).
    End point type
    Primary
    End point timeframe
    From Day 44 to Day 112
    Notes
    [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There is no statistical analysis to report.
    End point values
    		 Part B: GSK2982772 60 mg TID OL
    Number of subjects analysed
    35 [35]
    Units: Participants
        Abnormal-not clinically significant
    18
        Abnormal-clinically significant
    1
    Notes
    [35] - Safety Population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Part A: Percentage of participants who achieved an absolute mayo endoscopy subscore of 0 or 1 at Day 43

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    End point title
    		 Part A: Percentage of participants who achieved an absolute mayo endoscopy subscore of 0 or 1 at Day 43
    End point description
    The Mayo scoring system was used to assess UC disease activity, scoring ranges from 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal;2=3 to 4 stools/day more than normal;3= >4 stools/day more than normal);rectal bleeding (0=no blood seen;1=visible blood with stools less than half the time;2= visible blood with stool half the time or more;3=passing blood alone);findings at endoscopy (0=normal or inactive disease;1=mild disease [erythema, decreased vascular pattern, mild friability];2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions];3=severe disease [spontaneous bleeding, ulceration]); and physician's global assessment (PGA) (0=normal;1=mild;2=moderate;3=severe). Number of participants with Mayo endoscopic sub-score of 0 or 1 are presented. (range=0 to 3, higher scores indicating more severe disease).
    End point type
    Secondary
    End point timeframe
    Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [36]
    11 [37]
    Units: Percentage of participants
        Mayo endoscopy sub-score =0
    4
    0
        Mayo endoscopy sub-score=1
    8
    0
    Notes
    [36] - Safety population
    [37] - Safety population
    No statistical analyses for this end point

    Secondary: Part B: Percentage of participants who achieved an absolute Mayo endoscopy subscore of 0 or 1 at Day 85

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    End point title
    		 Part B: Percentage of participants who achieved an absolute Mayo endoscopy subscore of 0 or 1 at Day 85 [38]
    End point description
    The Mayo scoring system was used to assess UC disease activity, scoring ranges from 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores (0=normal number of stools;1=1 to 2 stools/day more than normal;2=3 to 4 stools/day more than normal;3= >4 stools/day more than normal);rectal bleeding (0=no blood seen;1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more;3=passing blood alone); findings at endoscopy (0=normal or inactive disease;1=mild disease [erythema, decreased vascular pattern, mild friability]; 2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions];3=severe disease [spontaneous bleeding, ulceration]); and PGA (0=normal;3=severe). Number of participants with Mayo endoscopic sub-score of 0 or 1 are presented. (range=0 to 3). Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Day 85
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [39]
    22 [40]
    Units: Percentage of participants
        Mayo endoscopy sub-score =0
    0
    5
        Mayo endoscopy sub-score=1
    11
    9
    Notes
    [39] - Safety Population.Participants with data available at the specified time points were analyzed.
    [40] - Safety population.Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Part A: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) total score

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    End point title
    		 Part A: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) total score
    End point description
    UCEIS was used as an additional tool to assess disease activity based on 3 sub-scales: 'endoscopic vascular pattern, bleeding, erosions and ulcerations'. UCEIS total score was calculated by sum of all 3 sub-scale scores. Total score ranges from 0 to 8, with higher scores indicating more severe disease. Individual sub-scales were vascular pattern (0=Normal, 1=Patchy loss, 2=Obliterated); bleeding (0=None, 1=Mucosal, 2=Luminal mild, 3=Luminal severe); erosions and ulcerations (0=None, 1=Erosions, 2=Superficial ulcer, 3=Deep ulcer). BL is defined as the latest pre-dose assessment at Screening (within 30 days prior to Day 1). Change from BL was calculated as post-BL visit value minus BL value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (screening - within 30 days prior to Day 1) and Day 43
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    11 [41]
    24 [42]
    Units: Scores on scale
        least squares mean (standard error)
    -0.24 ( 0.428 )
    -0.42 ( 0.289 )
    Notes
    [41] - Safety Population
    [42] - Safety Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a Mixed Models Repeated Measures (MMRM) model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 0.87

    Secondary: Part B: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) total score

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    End point title
    		 Part B: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) total score [43]
    End point description
    UCEIS was used as an additional tool to assess disease activity based on 3 sub-scales: 'endoscopic vascular pattern, bleeding, erosions and ulcerations'. UCEIS total score was calculated by sum of all 3 sub-scale scores. Total score ranges from 0 to 8, with higher scores indicating more severe disease. Individual sub-scales were vascular pattern (0=Normal, 1=Patchy loss, 2=Obliterated); bleeding (0=None, 1=Mucosal, 2=Luminal mild, 3=Luminal severe); erosions and ulcerations (0=None, 1=Erosions, 2=Superficial ulcer, 3=Deep ulcer). BL is defined as the latest pre-dose assessment at Screening (within 30 days prior to Day 1). Change from BL was calculated as post-BL visit value minus BL value. Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline (screening - within 30 days prior to Day 1) and Day 85
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [44]
    22 [45]
    Units: Scores on scale
        least squares mean (standard error)
    -0.84 ( 0.495 )
    -0.82 ( 0.318 )
    Notes
    [44] - Safety Population.Participants with data available at the specified time points were analyzed.
    [45] - Safety Population.Participants with data available at the specified time points were analyzed.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.18
         upper limit
    		 1.22

    Secondary: Part A: Change from Baseline in mean C reactive protein (CRP)

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    End point title
    		 Part A: Change from Baseline in mean C reactive protein (CRP)
    End point description
    Blood samples were collected to measure CRP. BL is defined as the latest pre-dose assessment on Day 1. Change from BL is the value at indicated time point minus BL value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Days 15, 29, 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [46]
    11 [47]
    Units: Milligrams per liter
    least squares mean (standard error)
        Day 15, n=11,24
    0.20 ( 1.112 )
    0.25 ( 1.648 )
        Day 29, n=11, 23
    -1.84 ( 0.782 )
    1.34 ( 1.119 )
        Day 43, n=11, 24
    -0.64 ( 1.251 )
    1.06 ( 1.854 )
    Notes
    [46] - Safety population
    [47] - Safety population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Day 15. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.11
         upper limit
    		 4.02
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Day 29. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -3.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.99
         upper limit
    		 -0.35
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Day 43. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.26
         upper limit
    		 2.88

    Secondary: Part B:Change from Baseline in mean CRP

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    End point title
    		 Part B:Change from Baseline in mean CRP [48]
    End point description
    Blood samples were collected to measure CRP. BL is defined as the latest pre-dose assessment on Day 1. Change from BL is the value at indicated time point minus BL value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). All participants in Part B received GSK2982772 60 mg in Part B (OL Phase), however they were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Days 57, 71, 85
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    11 [49]
    23 [50]
    Units: Milligrams per liter
    least squares mean (standard error)
        Day 57, n=11,23
    -2.61 ( 1.740 )
    -2.32 ( 1.186 )
        Day 71, n=11, 22
    -2.82 ( 1.510 )
    -2.71 ( 1.040 )
        Day 85, n=10, 22
    -2.77 ( 1.616 )
    -1.66 ( 1.092 )
    Notes
    [49] - Safety population
    [50] - Safety population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Day 57. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.01
         upper limit
    		 4.59
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Day 71. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.64
         upper limit
    		 3.85
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Day 85. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline value, and the treatment by visit and Baseline value by visit interactions
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.87
         upper limit
    		 5.1

    Secondary: Part A: Change from Baseline in fecal calprotectin (FCP)

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    End point title
    		 Part A: Change from Baseline in fecal calprotectin (FCP)
    End point description
    Fecal sample were collected to measure FCP. BL is defined as the latest pre-dose assessment on Day 1. Change from BL is the value at indicated time point minus BL value. Geometric Mean and Geometric Coefficient of Variation has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Days 15, 29, 43
    End point values
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    11 [51]
    23 [52]
    Units: Microgram per gram
    geometric mean (geometric coefficient of variation)
        Day 15, n=10, 23
    0.78 ( 39.2 )
    0.55 ( 25.1 )
        Day 29, n=11, 23
    1.23 ( 33.5 )
    0.54 ( 22.3 )
        Day 43, n=11, 22
    1.90 ( 40.7 )
    0.44 ( 27.1 )
    Notes
    [51] - Safety Population
    [52] - Safety Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Day 15. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.8
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Day 29. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 1
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Day 43. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.09
         upper limit
    		 0.62

    Secondary: Part B:Change from Baseline in fecal calprotectin (FCP)

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    End point title
    		 Part B:Change from Baseline in fecal calprotectin (FCP) [53]
    End point description
    Fecal sample were collected to measure FCP. BL is defined as the latest pre-dose assessment on Day 1. Change from BL is the value at indicated time point minus BL value. Geometric Mean and Geometric Coefficient of Variation has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). All participants in Part B received GSK2982772 60 mg in Part B (OL Phase), however they were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Days 57, 71, 85
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    11 [54]
    23 [55]
    Units: Microgram per gram
    geometric mean (geometric coefficient of variation)
        Day 57, n=11, 23
    1.13 ( 27.7 )
    0.56 ( 18.7 )
        Day 71, n=11, 22
    0.69 ( 42.1 )
    0.39 ( 28.9 )
        Day 85, n=11, 22
    0.48 ( 39.9 )
    0.40 ( 27.2 )
    Notes
    [54] - Safety Population
    [55] - Safety Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Day 57. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 0.97
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Day 71. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 1.57
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Day 85. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, log-transformed Baseline value, and the treatment by visit and log-transformed baseline value by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 2.18

    Secondary: Part A: Change from Baseline in Modified Riley Scale score (MRS)

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    End point title
    		 Part A: Change from Baseline in Modified Riley Scale score (MRS)
    End point description
    MRS is 4-point scale (none, mild, moderate and severe) which scores histologic activity based on localization and quantification of neutrophils in the mucosa, score ranges from 0 to 7, with higher scores indicates more severity. 0= Normal biopsy, 1= Lamina propria neutrophils only (Scattered individual neutrophils), 2= Lamina propria neutrophils only (Patchy collections of neutrophils), 3= Lamina propria neutrophils only (Diffuse neutrophils infiltrate), 4= Cryptitis/crypt abscesses (<25% crypts involved), 5= Cryptitis/crypt abscesses (25% to 74% crypts involved), 6= Cryptitis/crypt abscesses (>=75% crypts involved), 7= Erosion or ulceration present. Score 0 indicates normal condition; 1 to 3 mild condition; 4 to 6 moderate condition and score 7 severe condition. BL is defined as the latest pre-dose assessment. Change from BL is the value at indicated time point minus BL value. Only those participants with data available at the specified time points were analyzed
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    23 [56]
    10 [57]
    Units: Scores on scale
        least squares mean (standard error)
    0.04 ( 0.558 )
    0.04 ( 0.842 )
    Notes
    [56] - Safety Population.
    [57] - Safety Population.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.05
         upper limit
    		 2.07

    Secondary: Part B: Change from Baseline in MRS score

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    End point title
    		 Part B: Change from Baseline in MRS score [58]
    End point description
    MRS is 4-point scale (none, mild, moderate and severe) which scores histologic activity based on localization and quantification of neutrophils in the mucosa, score ranges from 0 to 7, with higher scores indicates more severity. 0=Normal biopsy, 1=Lamina propria neutrophils only (Scattered individual neutrophils), 2=Lamina propria neutrophils only (Patchy collections of neutrophils), 3=Lamina propria neutrophils only (Diffuse neutrophils infiltrate), 4=Cryptitis/crypt abscesses (<25% crypts involved), 5=Cryptitis/crypt abscesses (25% to 74% crypts involved), 6=Cryptitis/crypt abscesses (>=75% crypts involved), 7=Erosion or ulceration present. Score 0 indicates normal condition; 1 to 3 mild condition; 4 to 6 moderate condition and score 7 severe condition. BL is defined as the latest pre-dose assessment. Change from BL is the value at indicated time point minus BL value. Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, pre-dose) and Day 85
    Notes
    [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [59]
    21 [60]
    Units: Scores on scale
        least squares mean (standard error)
    -0.72 ( 0.894 )
    -0.65 ( 0.576 )
    Notes
    [59] - Safety Population. Participants with data available at the specified time points were analyzed.
    [60] - Safety Population. Participants with data available at the specified time points were analyzed.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 2.27

    Secondary: Part A: Change from Baseline in Geboes Index Total Score

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    End point title
    		 Part A: Change from Baseline in Geboes Index Total Score
    End point description
    Geboes score is a 7-items instrument which classifies histologic changes and generates a score from 0 to 5.4. The 7 items are: grade 0=structural-architectural changes (scored from 0.0 to 0.3); grade 1=chronic inflammatory infiltrate (scored from 1.0 to 1.3); grade 2A=lamina propria neutrophils (scored from 2.0 to 2.3), grade 2B= lamina propria eosinophils (scored from 2.0 to 2.3); 3=neutrophils in the epithelium (scored from 3.0 to 3.3); 4=crypt destruction (scored from 4.0 to 4.3); 5=erosions or ulceration (scored from 5.0 to 5.4). The most severe observation that the histopathologist sees on the slide is considered as the Geboes index total score, ranges from 0 to 5.4, with higher scores indicates severe disease. BL is defined as the latest pre-dose assessment before Day 1. Change from BL is the value at indicated time point minus BL value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    23 [61]
    10 [62]
    Units: Scores on scale
        least squares mean (standard error)
    0.28 ( 1.223 )
    1.04 ( 1.847 )
    Notes
    [61] - Safety Population
    [62] - Safety Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.29
         upper limit
    		 3.77

    Secondary: Part B: Change from Baseline in Geboes Index Total Score

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    End point title
    		 Part B: Change from Baseline in Geboes Index Total Score [63]
    End point description
    Geboes score is a 7-items instrument which classifies histologic changes and generates a score from 0 to 5.4. The 7 items are: grade 0=structural-architectural changes (scored from 0.0 to 0.3); grade 1=chronic inflammatory infiltrate (scored from 1.0 to 1.3); grade 2A=lamina propria neutrophils (scored from 2.0 to 2.3), grade 2B= lamina propria eosinophils (scored from 2.0 to 2.3); 3=neutrophils in the epithelium (scored from 3.0 to 3.3); 4=crypt destruction (scored from 4.0 to 4.3); 5=erosions or ulceration (scored from 5.0 to 5.4). The most severe observation that the histopathologist sees on the slide is considered as the Geboes index total score, ranges from 0 to 5.4, with higher scores indicates severe disease. BL is defined as the latest pre-dose assessment before Day 1. Change from BL is the value at indicated time point minus BL value. Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 85
    Notes
    [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [64]
    21 [65]
    Units: Scores on scale
        least squares mean (standard error)
    -0.67 ( 1.981 )
    -1.47 ( 1.286 )
    Notes
    [64] - Safety Population. Participants with data available at the specified time points were analyzed.
    [65] - Safety Population. Participants with data available at the specified time points were analyzed.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.68
         upper limit
    		 4.08

    Secondary: Part A: Number of participants who achieved Mayo clinical response

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    End point title
    		 Part A: Number of participants who achieved Mayo clinical response
    End point description
    Mayo Clinical Response defined as >=3 points or >=30% improvement from BL in Total Mayo Score, along with a decrease in the rectal bleeding sub-score of >= 1 point. Scoring ranges 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal; 2=3 to 4 stools/day more than normal; 3= >4 stools/day more than normal); rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more; 3=passing blood alone); findings at endoscopy (0=normal or inactive disease; 1=mild disease [erythema, decreased vascular pattern, mild friability]; 2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions]; 3=severe disease [spontaneous bleeding, ulceration]); and PGA (0=normal, 3=severe). Only those participants with data available at the specified time points were analyzed
    End point type
    Secondary
    End point timeframe
    Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [66]
    11 [67]
    Units: Participants
    9
    4
    Notes
    [66] - Safety Population
    [67] - Safety Population
    No statistical analyses for this end point

    Secondary: Part B: Number of participants who achieved Mayo clinical response

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    End point title
    		 Part B: Number of participants who achieved Mayo clinical response [68]
    End point description
    Mayo Clinical Response defined as >=3 points or >=30% improvement from BL in Total Mayo Score, along with a decrease in the rectal bleeding sub-score of >= 1 point. Scoring ranges 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools;1=1 to 2 stools/day more than normal;2=3 to 4 stools/day more than normal;3= >4 stools/day more than normal);rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time;2= visible blood with stool half the time or more;3=passing blood alone); findings at endoscopy (0=normal; 1=mild disease [erythema, decreased vascular pattern, mild friability];2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions];3=severe disease [spontaneous bleeding, ulceration]);and PGA (0=normal, 3=severe). Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Day 85
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [69]
    22 [70]
    Units: Participants
    5
    11
    Notes
    [69] - Safety Population. Participants with data available at the specified time points were analyzed.
    [70] - Safety Population. Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Part A: Number of participants who achieved Mayo clinical remission

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    End point title
    		 Part A: Number of participants who achieved Mayo clinical remission
    End point description
    Mayo clinical remission is defined as total mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Scoring ranges 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal; 2=3 to 4 stools/day more than normal; 3= >4 stools/day more than normal); rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more; 3=passing blood alone); findings at endoscopy (0=normal or inactive disease; 1=mild disease [erythema, decreased vascular pattern, mild friability]; 2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions]; 3=severe disease [spontaneous bleeding, ulceration]); and PGA (0=normal, 3=severe). Only those participants with data available at the specified time points were analyzed
    End point type
    Secondary
    End point timeframe
    Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [71]
    11 [72]
    Units: Participants
    0
    0
    Notes
    [71] - Safety Population
    [72] - Safety Population
    No statistical analyses for this end point

    Secondary: Part B: Number of participants who achieved Mayo clinical remission

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    End point title
    		 Part B: Number of participants who achieved Mayo clinical remission [73]
    End point description
    Mayo clinical remission is defined as total mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Score ranges from 0 to 12, calculated as sum of 4 sub-scores, higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal; 2=3 to 4 stools/day more than normal; 3= >4 stools/day more than normal); rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more; 3=passing blood alone); findings at endoscopy (0=normal or inactive disease; 1=mild disease [erythema, decreased vascular pattern, mild friability]; 2=moderate disease [marked erythema, lack of vascular pattern, friability, erosions]; 3=severe disease [spontaneous bleeding, ulceration]); and PGA(0=normal;1=mild;2=moderate;3=severe). Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Day 85
    Notes
    [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    9 [74]
    22 [75]
    Units: Participants
    1
    2
    Notes
    [74] - Safety Population. Participants with data available at the specified time points were analyzed.
    [75] - Safety Population. Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Part A: Change from Baseline in partial mayo score

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    End point title
    		 Part A: Change from Baseline in partial mayo score
    End point description
    Partial Mayo Score defined as total score of 3 domain subscores-stool frequency, rectal bleeding and PGA, ranges from 0 to 9, higher score indicate more severe disease. It has 4 sub-scores: Stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal; 2=3 to 4 stools/day more than normal; 3= >4 stools/day more than normal); rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more;3=passing blood alone); findings at endoscopy (0=normal or inactive disease;1=mild disease[erythema,decreased vascular pattern,mild friability];2=moderate disease[marked erythema,lack of vascular pattern,friability,erosions];3=severe disease [spontaneous bleeding,ulceration]);and PGA (0=normal, 3=severe). Change from BL=post-BL value minus BL value (screening-within 30 days prior to Day 1). Only those participants with data available at the specified time points were analyzed
    End point type
    Secondary
    End point timeframe
    Baseline (Screening - within 30 days prior to Day 1) and at Days 15, 29, 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB Part A: Placebo TID DB
    Number of subjects analysed
    24 [76]
    11 [77]
    Units: Scores on scale
    least squares mean (standard error)
        Day 15
    -1.04 ( 0.333 )
    -0.68 ( 0.493 )
        Day 29
    -1.16 ( 0.324 )
    -1.05 ( 0.480 )
        Day 43
    -1.64 ( 0.376 )
    -1.30 ( 0.557 )
    Notes
    [76] - Safety Population
    [77] - Safety Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Day 15. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.58
         upper limit
    		 0.86
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Day 29. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.29
         upper limit
    		 1.08
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Day 43. Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Part A: Placebo TID DB v Part A: GSK2982772 60 mg TID DB
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.72
         upper limit
    		 1.04

    Secondary: Part B: Change from Baseline in partial mayo score

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    End point title
    		 Part B: Change from Baseline in partial mayo score [78]
    End point description
    Partial Mayo Score defined as total score of 3 domain subscores-stool frequency, rectal bleeding and PGA, ranges from 0 to 9, higher score indicate more severe disease. It has 4 sub-scores: Stool frequency (0=normal number of stools; 1=1 to 2 stools/day more than normal; 2=3 to 4 stools/day more than normal; 3= >4 stools/day more than normal); rectal bleeding (0=no blood seen; 1=visible blood with stools less than half the time; 2= visible blood with stool half the time or more;3=passing blood alone); findings at endoscopy (0=normal or inactive disease;1=mild disease[erythema,decreased vascular pattern,mild friability];2=moderate disease[marked erythema,lack of vascular pattern, friability, erosions];3=severe disease [spontaneous bleeding,ulceration]);and PGA (0=normal, 3=severe). Change from BL=post-BL value minus BL value (screening-within 30 days prior to Day 1). Participants were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 85
    Notes
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    11 [79]
    22 [80]
    Units: Scores on scale
        least squares mean (standard error)
    -2.87 ( 0.728 )
    -2.93 ( 0.502 )
    Notes
    [79] - Safety Population. Participants with data available at the specified time points were analyzed
    [80] - Safety Population. Participants with data available at the specified time points were analyzed
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis performed using a MMRM model, adjusting for the following covariates: treatment, visit, Baseline score, and the treatment by visit and Baseline score by visit interactions.
    Comparison groups
    Placebo TID DB /GSK2982772 60 mg TID OL v GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.87
         upper limit
    		 1.75

    Secondary: Part A: Pre-dose plasma concentration of GSK2982772

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    End point title
    		 Part A: Pre-dose plasma concentration of GSK2982772
    End point description
    Pre-dose blood sample was collected on Day 43 for the measurement of plasma concentration of GSK2982772. PK Population is defined as the participants in the safety population who received an active dose and for whom a GSK2982772 pharmacokinetic sample was obtained and analyzed. All participants in Part B received GSK2982772 60 mg in Part B (OL Phase), however they were split into 2 arms as randomized in Part A to allow statistical comparison of efficacy outcomes.
    End point type
    Secondary
    End point timeframe
    Day 43
    End point values
    		 Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    23 [81]
    Units: Nanogram/milliliter
        arithmetic mean (standard deviation)
    131.749 ( 214.9127 )
    Notes
    [81] - PK Population. Participants with data available at the specified time points were analyzed
    No statistical analyses for this end point

    Secondary: Part A: Post-dose plasma concentrations of GSK2982772

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    End point title
    		 Part A: Post-dose plasma concentrations of GSK2982772
    End point description
    Post-dose blood sample were collected on Days 1 and 43 at 1, 2, 4 and 6 hours for the measurement of plasma concentration of GSK2982772. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Days 1 and 43: 1, 2, 4 and 6 hours post dose
    End point values
    		 Part A: GSK2982772 60 mg TID DB
    Number of subjects analysed
    23 [82]
    Units: Nanogram/milliliter
    arithmetic mean (standard deviation)
        Day 1, 1 hour
    674.588 ( 412.8928 )
        Day 1, 2 hours
    772.043 ( 378.5145 )
        Day 1, 4 hours
    474.248 ( 309.5524 )
        Day 1, 6 hours
    481.304 ( 679.5678 )
        Day 43, 1 hour
    918.926 ( 508.8658 )
        Day 43, 2 hours
    851.391 ( 340.6479 )
        Day 43, 4 hours
    472.132 ( 246.0718 )
        Day 43, 6 hours
    278.039 ( 187.2142 )
    Notes
    [82] - PK Population. Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Part B: Trough concentrations of GSK2982772 on Day 85

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    End point title
    		 Part B: Trough concentrations of GSK2982772 on Day 85 [83]
    End point description
    Blood samples were collected for the measurement of trough plasma concentration of GSK2982772 on Day 85. Only those participants with data available at the specified time points were analyzed. All participants in Part B received GSK2982772 60 mg in Part B (OL Phase), however they were split into 2 arms as randomized in Part A to compare trough concentrations.
    End point type
    Secondary
    End point timeframe
    Day 85
    Notes
    [83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical analysis to report.
    End point values
    		 Placebo TID DB /GSK2982772 60 mg TID OL GSK2982772 60 mg TID DB /GSK2982772 60 mg TID OL
    Number of subjects analysed
    10 [84]
    24 [85]
    Units: Nanogram/milliliter
        arithmetic mean (standard deviation)
    47.970 ( 78.9909 )
    150.642 ( 305.3144 )
    Notes
    [84] - PK Population. Participants with data available at the specified time points were analyzed.
    [85] - PK Population. Participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 43 in Part A and from Day 44 till follow up visit (Day 112) in Part B.
    Adverse event reporting additional description
    SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least one dose of study treatment. Adverse events are presented treatment wise.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Part A: Placebo TID DB
    Reporting group description
    		 Eligible participants with UC, received two tablets of placebo TID orally for 42 days in Part A (double blind phase).

    Reporting group title
    Part A: GSK2982772 60 mg TID DB
    Reporting group description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part A (double blind phase).

    Reporting group title
    Part B: GSK2982772 60 mg TID OL
    Reporting group description
    		 Eligible participants with UC, received GSK2982772 60 mg (given as 2 tablets of 30 mg) TID orally for 42 days in Part B (open label phase).

    Serious adverse events
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB Part B: GSK2982772 60 mg TID OL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    2 / 35 (5.71%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 24 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Comminuted fracture
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 24 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A: Placebo TID DB Part A: GSK2982772 60 mg TID DB Part B: GSK2982772 60 mg TID OL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 12 (58.33%)
    13 / 24 (54.17%)
    7 / 35 (20.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 12 (8.33%)
    6 / 24 (25.00%)
    6 / 35 (17.14%)
         occurrences all number
    1
    10
    7
    Dizziness
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 24 (4.17%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    1
    Dysgeusia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    0
    Tremor
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 24 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 24 (4.17%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 24 (12.50%)
    1 / 35 (2.86%)
         occurrences all number
    2
    3
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 24 (12.50%)
    1 / 35 (2.86%)
         occurrences all number
    0
    4
    2
    Abdominal distension
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 24 (8.33%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    0
    Abdominal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 24 (8.33%)
    1 / 35 (2.86%)
         occurrences all number
    0
    2
    1
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    1
    0
    1
    Constipation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 24 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Nasal ulcer
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 24 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Petechiae
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Nightmare
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 24 (8.33%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 24 (4.17%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    1
    Spinal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 24 (12.50%)
    2 / 35 (5.71%)
         occurrences all number
    1
    4
    2
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 24 (4.17%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    0
    Borrelia infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 24 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2017
    Protocol Amendment 1: Change in dosing regimen from 60 mg twice daily (BID) to 60 mg thrice daily (TID), updates to Inclusion criteria 3 and 6 and Exclusion criteria 3, 9, 21 and 22, allowance for rescreening, and addition of suicidality stopping criteria plus some minor protocol clarifications and administrative changes.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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