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    Clinical Trial Results:
    A randomized, double-blind, multi-dose, placebo-controlled study to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus in patients with primary biliary cholangitis (GLIMMER: GSK2330672 triaL of Ibat inhibition with Multidose Measurement for Evaluation of Response)

    Summary
    EudraCT number
    2016-002416-41
    Trial protocol
    ES   GB   PL   IT  
    Global end of trial date
    15 Apr 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Apr 2021
    First version publication date
    24 Apr 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    201000
    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
    30 Jul 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Apr 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the dose response of oral GSK2330672 on itch in primary biliary cholangitis (PBC) participants with moderate to severe pruritus at Baseline
    Protection of trial subjects
    Not applicable
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Jan 2017
    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
    Australia: 4
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 13
    Country: Number of subjects enrolled
    Japan: 38
    Country: Number of subjects enrolled
    Poland: 17
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    United States: 20
    Worldwide total number of subjects
    147
    EEA total number of subjects
    49
    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)
    111
    From 65 to 84 years
    36
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This study was conducted across 66 centers in 10 countries. The 40 milligrams (mg) twice daily dose group was added and recruitment into the 20 mg twice daily dose group was discontinued following the pre-specified interim analysis.

    Pre-assignment
    Screening details
    A total of 147 adult participants were randomized in this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 16 weeks including the Main Study Period and Final Study period. Participants were then followed up for 4 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Arm title
    GSK2330672 20 mg QD
    Arm description
    Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period followed by matching placebo for 4 weeks in the Final Study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK2330672
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Arm title
    GSK2330672 90 mg QD
    Arm description
    Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks. All doses were administered via oral route.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK2330672
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Arm title
    GSK2330672 180 mg QD
    Arm description
    Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK2330672
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Arm title
    GSK2330672 40 mg BID
    Arm description
    Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK2330672
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Arm title
    GSK2330672 90 mg BID
    Arm description
    Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks All doses were administered via oral route.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as white-film coated tablets to be administered orally.

    Investigational medicinal product name
    GSK2330672
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2330672 was available as white-film coated tablets at unit dose strength of 10 and 45 milligrams (mg) to be administered orally.

    Number of subjects in period 1
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Started
    36
    16
    23
    27
    23
    22
    Completed
    35
    16
    22
    22
    22
    21
    Not completed
    1
    0
    1
    5
    1
    1
         Consent withdrawn by subject
    -
    -
    -
    2
    -
    -
         Adverse event, non-fatal
    -
    -
    1
    2
    1
    1
         Lack of efficacy
    1
    -
    -
    -
    -
    -
         Protocol deviation
    -
    -
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 16 weeks including the Main Study Period and Final Study period. Participants were then followed up for 4 weeks.

    Reporting group title
    GSK2330672 20 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period followed by matching placebo for 4 weeks in the Final Study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 90 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 180 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 40 mg BID
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 90 mg BID
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks All doses were administered via oral route.

    Reporting group values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID Total
    Number of subjects
    36 16 23 27 23 22 147
    Age categorical
    Units: Subjects
        All participants
    36 16 23 27 23 22 147
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    54.4 ± 11.06 58.5 ± 7.35 52.5 ± 12.32 58.9 ± 11.10 55.6 ± 11.23 56.2 ± 11.32 -
    Sex: Female, Male
    Units: Participants
        Female
    34 16 21 25 22 20 138
        Male
    2 0 2 2 1 2 9
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    0 0 0 0 1 0 1
        Asian - Japanese Heritage
    8 6 6 7 4 7 38
        White - White/Caucasian/European Heritage
    26 10 17 19 16 15 103
        Multiple
    0 0 0 1 0 0 1
        Unknown
    2 0 0 0 2 0 4

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 16 weeks including the Main Study Period and Final Study period. Participants were then followed up for 4 weeks.

    Reporting group title
    GSK2330672 20 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period followed by matching placebo for 4 weeks in the Final Study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 90 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 180 mg QD
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 40 mg BID
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final study period. Participants were then followed up for 4 weeks. All doses were administered via oral route.

    Reporting group title
    GSK2330672 90 mg BID
    Reporting group description
    Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period followed by matching placebo for 4 weeks in the Final Study Period. Participants were then followed up for 4 weeks All doses were administered via oral route.

    Subject analysis set title
    Placebo -Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 12 weeks in Main Study Period.

    Subject analysis set title
    GSK2330672 20 mg QD - Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 20 milligrams (mg) once daily (QD) for 12 weeks in the Main Study period.

    Subject analysis set title
    GSK2330672 90 mg QD - Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 90 mg QD for 12 weeks in the Main study period.

    Subject analysis set title
    GSK2330672 180 mg QD - Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 180 mg QD for 12 weeks in the Main study period.

    Subject analysis set title
    GSK2330672 40 mg BID - Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 40 mg twice daily (BID) for 12 weeks in the Main study period.

    Subject analysis set title
    GSK2330672 90 mg BID - Main Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 90 mg BID for 12 weeks in the Main study period

    Subject analysis set title
    Placebo - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period.

    Subject analysis set title
    GSK2330672 20 mg QD - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 20 mg QD during Main study period.

    Subject analysis set title
    GSK2330672 90 mg QD - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 90 mg QD during Main study period.

    Subject analysis set title
    GSK2330672 180 mg QD - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 180 mg QD during Main study period.

    Subject analysis set title
    GSK2330672 40 mg BID - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 40 mg BID during Main study period.

    Subject analysis set title
    GSK2330672 90 mg BID - Final Study Period
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Eligible participants were randomized to receive GSK2330672 matching placebo via oral route for 4 weeks in Final Study Period. Participants received GSK2330672 90 mg BID during Main study period.

    Subject analysis set title
    Placebo - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received GSK2330672 matching placebo in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Subject analysis set title
    GSK2330672 20 mg QD - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Subject analysis set title
    GSK2330672 90 mg QD - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Subject analysis set title
    GSK2330672 180 mg QD - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Subject analysis set title
    GSK2330672 40 mg BID - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Subject analysis set title
    GSK2330672 90 mg BID - Follow-up
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received treatment (active or placebo) in Main study period and Final study period entered in a 4-week no-treatment follow-up period.

    Primary: Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score

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    End point title
    Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score
    End point description
    Participants were required to score the severity of their itching using a 0-10 numerical rating scale (NRS) where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the average of the scores in the 7 days prior to the Week 4 (Visit 3 [V3]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was done using Analysis of covariance (ANCOVA) including treatment group and centered Mean Worst Daily Itch score at Baseline. Intent-to-Treat (ITT) Population comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one on-treatment assessment. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline and Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [1]
    16 [2]
    20 [3]
    22 [4]
    22 [5]
    21 [6]
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -1.73 (-2.44 to -1.01)
    -2.19 (-3.26 to -1.12)
    -2.60 (-3.55 to -1.65)
    -2.60 (-3.51 to -1.70)
    -2.86 (-3.76 to -1.95)
    -2.25 (-3.19 to -1.32)
    Notes
    [1] - ITT Population
    [2] - ITT Population
    [3] - ITT Population
    [4] - ITT Population
    [5] - ITT Population
    [6] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.75
         upper limit
    0.82
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.07
         upper limit
    0.31
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.03
         upper limit
    0.28
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.29
         upper limit
    0.03
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.71
         upper limit
    0.65

    Secondary: Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale

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    End point title
    Mean change from Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) scale
    End point description
    PBC-40 questionnaire consists of 40 questions arranged in 6 domains with 3 to 11 questions in each domain. Each question is scored from 1 (least impact) to 5 (greatest impact). All questions within a domain are summed to obtain individual domain score. Domains were: Symptoms (7 questions) with score range 7-35, Itch (3 questions) with score range 3-15, Fatigue (11 questions) with score range 11-55, Cognitive (6 questions) with score range 6-30, Emotional (3 questions) with score range 3-15, and Social (10 questions) with score range 10-50. Higher scores for individual domains represent a poor quality of life. Baseline is the assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [7]
    16 [8]
    21 [9]
    22 [10]
    22 [11]
    20 [12]
    Units: Scores on a scale
    least squares mean (confidence interval 95%)
        Symptoms
    0.2 (-1.0 to 1.4)
    0.4 (-1.3 to 2.2)
    0.7 (-0.8 to 2.3)
    -0.9 (-2.4 to 0.6)
    0.3 (-1.2 to 1.8)
    0.2 (-1.4 to 1.8)
        Itch
    -2.3 (-3.3 to -1.4)
    -1.9 (-3.3 to -0.4)
    -2.6 (-3.9 to -1.3)
    -2.7 (-3.9 to -1.4)
    -3.4 (-4.6 to -2.1)
    -2.7 (-4.0 to -1.4)
        Fatigue
    -1.8 (-4.0 to 0.4)
    -2.4 (-5.6 to 0.7)
    -1.1 (-3.8 to 1.7)
    1.7 (-1.0 to 4.5)
    -0.1 (-2.8 to 2.6)
    -1.8 (-4.6 to 1.1)
        Cognitive
    -0.3 (-1.7 to 1.1)
    -0.3 (-2.4 to 1.8)
    -0.9 (-2.7 to 0.9)
    -0.1 (-1.9 to 1.6)
    0.1 (-1.6 to 1.9)
    -0.1 (-2.0 to 1.7)
        Emotional
    -0.5 (-1.2 to 0.1)
    -1.4 (-2.4 to -0.4)
    -0.4 (-1.3 to 0.5)
    -0.6 (-1.5 to 0.3)
    -1.4 (-2.2 to -0.5)
    -0.6 (-1.5 to 0.3)
        Social
    -0.8 (-2.3 to 0.8)
    -0.5 (-2.7 to 1.8)
    0.4 (-1.5 to 2.4)
    -0.6 (-2.5 to 1.3)
    -3.1 (-5.1 to -1.2)
    -1.0 (-3.0 to 1.0)
    Notes
    [7] - ITT Population
    [8] - ITT Population
    [9] - ITT Population
    [10] - ITT Population
    [11] - ITT Population
    [12] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Symptoms
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    2.3
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Symptoms
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    2.5
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Symptoms
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    0.8
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Symptoms
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    2
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Symptoms
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    1.9
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Itch
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    2.2
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Itch
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    1.3
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Itch
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    1.2
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Itch
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.6
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Itch
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    1.3
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Fatigue
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.5
         upper limit
    3.2
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Fatigue
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Median difference (net)
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    4.2
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Fatigue
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    3.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    7
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Fatigue
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    5.1
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Fatigue
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.6
         upper limit
    3.6
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Cognitive
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    2.6
    Statistical analysis title
    Statistical Analysis 17
    Statistical analysis description
    Cognitive
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    1.7
    Statistical analysis title
    Statistical Analysis 18
    Statistical analysis description
    Cognitive
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    2.5
    Statistical analysis title
    Statistical Analysis 19
    Statistical analysis description
    Cognitive
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    2.8
    Statistical analysis title
    Statistical Analysis 20
    Statistical analysis description
    Cognitive
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    2.5
    Statistical analysis title
    Statistical Analysis 21
    Statistical analysis description
    Emotional
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    0.4
    Statistical analysis title
    Statistical Analysis 22
    Statistical analysis description
    Emotional
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    1.3
    Statistical analysis title
    Statistical Analysis 23
    Statistical analysis description
    Emotional
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    1.1
    Statistical analysis title
    Statistical Analysis 24
    Statistical analysis description
    Emotional
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 25
    Statistical analysis description
    Emotional
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    1.1
    Statistical analysis title
    Statistical Analysis 26
    Statistical analysis description
    Social
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    3
    Statistical analysis title
    Statistical Analysis 27
    Statistical analysis description
    Social
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    3.7
    Statistical analysis title
    Statistical Analysis 28
    Statistical analysis description
    Social
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3
         upper limit
    2.7
    Statistical analysis title
    Statistical Analysis 29
    Statistical analysis description
    Social
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -2.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.8
         upper limit
    0.1
    Statistical analysis title
    Statistical Analysis 30
    Statistical analysis description
    Social
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    2.4

    Secondary: Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in serum alkaline phosphatase (ALP) concentrations, in participants with high risk of PBC progression
    End point description
    Criteria for high risk of PBC progression is defined as serum ALP concentrations more than or equal to (>=)1.67 times upper limit of normal (ULN) range and/or total bilirubin concentrations more than (>)ULN at Day 1. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. High Risk Population comprised of subset of the ITT population who were assigned to the High Risk stratum for randomization (based upon serum ALP concentrations >=1.67 times ULN and/or total bilirubin concentrations >ULN at Day 1 (Visit 2). Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [13]
    5 [14]
    11 [15]
    7 [16]
    6 [17]
    5 [18]
    Units: International units per Liter
        least squares mean (confidence interval 95%)
    49.1 (-29.3 to 127.6)
    -57.7 (-179.6 to 64.3)
    -38.2 (-117.0 to 40.5)
    49.6 (-49.1 to 148.2)
    -29.2 (-136.7 to 78.3)
    19.1 (-97.7 to 136.0)
    Notes
    [13] - High Risk Population
    [14] - High Risk Population
    [15] - High Risk Population
    [16] - High Risk Population
    [17] - High Risk Population
    [18] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -106.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -251.7
         upper limit
    38.2
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -87.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -198.5
         upper limit
    23.8
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -125.6
         upper limit
    126.5
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -78.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -211.5
         upper limit
    54.8
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -30
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -170.7
         upper limit
    110.7

    Secondary: Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16

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    End point title
    Number of participants with serum ALP concentrations less than (<)1.67 times ULN and total bilirubin concentrations less than or equal to (<=) ULN at Week 16
    End point description
    Number of participants with ALP < 1.67 times ULN and total bilirubin <= ULN at Week 16 is presented. The endpoint was analyzed in Restricted High Risk Population. Restricted High Risk Population comprised of a subset of the High Risk population, i.e. all those participants assigned to the High Risk stratum for randomization who met the ALP/bilirubin criteria at both Visit 2 (Day 1) and Visit 3 (Week 4).
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [19]
    5 [20]
    9 [21]
    9 [22]
    6 [23]
    7 [24]
    Units: Participants
    0
    0
    0
    0
    0
    1
    Notes
    [19] - Restricted High Risk Population
    [20] - Restricted High Risk Population
    [21] - Restricted High Risk Population
    [22] - Restricted High Risk Population
    [23] - Restricted High Risk Population
    [24] - Restricted High Risk Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in serum alanine aminotransferase (ALT) among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [25]
    5 [26]
    11 [27]
    7 [28]
    6 [29]
    5 [30]
    Units: International Units per Liter
        least squares mean (confidence interval 95%)
    13.0 (-7.9 to 33.9)
    -8.4 (-39.5 to 22.7)
    0.3 (-20.7 to 21.2)
    -2.0 (-29.0 to 25.1)
    -13.5 (-42.8 to 15.9)
    13.2 (-17.4 to 43.7)
    Notes
    [25] - High Risk Population
    [26] - High Risk Population
    [27] - High Risk Population
    [28] - High Risk Population
    [29] - High Risk Population
    [30] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -21.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -58.4
         upper limit
    15.5
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -12.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -41.9
         upper limit
    16.4
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -49.9
         upper limit
    20
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -26.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -63.3
         upper limit
    10.4
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -36.7
         upper limit
    37.1

    Secondary: Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in serum aspartate aminotransferase (AST) among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including Treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [31]
    5 [32]
    11 [33]
    7 [34]
    6 [35]
    5 [36]
    Units: International Units per Liter
        least squares mean (confidence interval 95%)
    13.96 (-4.55 to 32.46)
    -6.04 (-34.20 to 22.12)
    -10.75 (-28.90 to 7.40)
    -8.66 (-32.24 to 14.93)
    -17.72 (-42.77 to 7.34)
    8.16 (-18.72 to 35.04)
    Notes
    [31] - High Risk Population
    [32] - High Risk Population
    [33] - High Risk Population
    [34] - High Risk Population
    [35] - High Risk Population
    [36] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -20
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -52.73
         upper limit
    12.74
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -24.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -50.8
         upper limit
    1.39
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -22.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -53.39
         upper limit
    8.16
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -31.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -63.44
         upper limit
    0.09
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -5.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -38.33
         upper limit
    26.74

    Secondary: Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in serum gamma glutamyl transferase (GGT), among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [37]
    5 [38]
    11 [39]
    7 [40]
    6 [41]
    5 [42]
    Units: International Units per Liter
        least squares mean (confidence interval 95%)
    47.5 (-9.9 to 104.8)
    -58.5 (-142.5 to 25.5)
    -18.0 (-74.9 to 38.9)
    4.6 (-66.5 to 75.8)
    -18.4 (-93.6 to 56.8)
    -6.7 (-89.1 to 75.8)
    Notes
    [37] - High Risk Population
    [38] - High Risk Population
    [39] - High Risk Population
    [40] - High Risk Population
    [41] - High Risk Population
    [42] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -106
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -205.1
         upper limit
    -6.8
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -65.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -148.5
         upper limit
    17.6
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -42.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -136.5
         upper limit
    50.9
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -65.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -161.2
         upper limit
    29.5
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -54.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -153.6
         upper limit
    45.3

    Secondary: Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in total bilirubin concentration, among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [43]
    5 [44]
    11 [45]
    7 [46]
    6 [47]
    5 [48]
    Units: Micromoles per Liter
        least squares mean (confidence interval 95%)
    1.258 (-2.068 to 4.583)
    -4.841 (-9.693 to 0.011)
    -1.079 (-4.345 to 2.187)
    -0.975 (-5.150 to 3.201)
    -0.234 (-4.914 to 4.446)
    6.494 (1.622 to 11.365)
    Notes
    [43] - High Risk Population
    [44] - High Risk Population
    [45] - High Risk Population
    [46] - High Risk Population
    [47] - High Risk Population
    [48] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -6.099
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.929
         upper limit
    -0.268
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -2.337
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.962
         upper limit
    2.289
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -2.232
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.679
         upper limit
    3.215
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1.492
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.413
         upper limit
    4.43
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    5.236
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.591
         upper limit
    11.063

    Secondary: Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in albumin concentration, among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    11 [49]
    5 [50]
    11 [51]
    7 [52]
    6 [53]
    5 [54]
    Units: Grams per Liter
        least squares mean (confidence interval 95%)
    0.0 (-1.2 to 1.3)
    -0.5 (-2.3 to 1.3)
    0.3 (-1.0 to 1.6)
    0.8 (-0.8 to 2.3)
    0.0 (-1.7 to 1.7)
    0.7 (-1.1 to 2.5)
    Notes
    [49] - High Risk Population
    [50] - High Risk Population
    [51] - High Risk Population
    [52] - High Risk Population
    [53] - High Risk Population
    [54] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    1.6
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    2.1
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    2.7
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    2
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    2.9

    Secondary: Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in prothrombin international normalized ratio (INR), among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    9 [55]
    5 [56]
    11 [57]
    6 [58]
    7 [59]
    5 [60]
    Units: Ratio
        least squares mean (confidence interval 95%)
    0.01 (-0.03 to 0.05)
    -0.01 (-0.06 to 0.04)
    -0.03 (-0.06 to 0.00)
    0.01 (-0.04 to 0.05)
    -0.02 (-0.07 to 0.02)
    -0.03 (-0.08 to 0.02)
    Notes
    [55] - High Risk Population
    [56] - High Risk Population
    [57] - High Risk Population
    [58] - High Risk Population
    [59] - High Risk Population
    [60] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.08
         upper limit
    0.04
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.09
         upper limit
    0.01
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.06
         upper limit
    0.05
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.09
         upper limit
    0.02
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.1
         upper limit
    0.02

    Secondary: Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression

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    End point title
    Mean change from Baseline at Week 16 in prothrombin time, among those with a high risk of PBC progression
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    9 [61]
    5 [62]
    11 [63]
    6 [64]
    7 [65]
    5 [66]
    Units: Seconds
        least squares mean (confidence interval 95%)
    -0.10 (-0.40 to 0.20)
    0.05 (-0.33 to 0.44)
    -0.21 (-0.47 to 0.05)
    0.02 (-0.33 to 0.37)
    -0.18 (-0.51 to 0.15)
    -0.17 (-0.55 to 0.22)
    Notes
    [61] - High Risk Population
    [62] - High Risk Population
    [63] - High Risk Population
    [64] - High Risk Population
    [65] - High Risk Population
    [66] - High Risk Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.33
         upper limit
    0.63
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.51
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.34
         upper limit
    0.58
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.54
         upper limit
    0.38
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.54
         upper limit
    0.41

    Secondary: Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period

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    End point title
    Number of participants with non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) -Main study period
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE. Safety Population comprised of all randomized participants who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    Placebo -Main Study Period GSK2330672 20 mg QD - Main Study Period GSK2330672 90 mg QD - Main Study Period GSK2330672 180 mg QD - Main Study Period GSK2330672 40 mg BID - Main Study Period GSK2330672 90 mg BID - Main Study Period
    Number of subjects analysed
    36 [67]
    16 [68]
    23 [69]
    27 [70]
    23 [71]
    22 [72]
    Units: Participants
        Any non-SAE
    17
    11
    19
    24
    16
    18
        Any SAE
    0
    0
    1
    0
    0
    0
    Notes
    [67] - Safety Population
    [68] - Safety Population
    [69] - Safety Population
    [70] - Safety Population
    [71] - Safety Population
    [72] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with non-SAEs and SAEs -Final study period

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    End point title
    Number of participants with non-SAEs and SAEs -Final study period
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
    End point type
    Secondary
    End point timeframe
    Up to 4 weeks
    End point values
    Placebo - Final Study Period GSK2330672 20 mg QD - Final Study Period GSK2330672 90 mg QD - Final Study Period GSK2330672 180 mg QD - Final Study Period GSK2330672 40 mg BID - Final Study Period GSK2330672 90 mg BID - Final Study Period
    Number of subjects analysed
    35 [73]
    16 [74]
    19 [75]
    19 [76]
    21 [77]
    17 [78]
    Units: Participants
        Any non-SAE
    2
    6
    8
    2
    2
    2
        Any SAE
    0
    0
    0
    0
    0
    0
    Notes
    [73] - Safety Population
    [74] - Safety Population
    [75] - Safety Population
    [76] - Safety Population
    [77] - Safety Population
    [78] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with non-SAEs and SAEs - Follow-up period

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    End point title
    Number of participants with non-SAEs and SAEs - Follow-up period
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
    End point type
    Secondary
    End point timeframe
    Up to 4 weeks
    End point values
    Placebo - Follow-up GSK2330672 20 mg QD - Follow-up GSK2330672 90 mg QD - Follow-up GSK2330672 180 mg QD - Follow-up GSK2330672 40 mg BID - Follow-up GSK2330672 90 mg BID - Follow-up
    Number of subjects analysed
    35 [79]
    16 [80]
    23 [81]
    27 [82]
    22 [83]
    22 [84]
    Units: Participants
        Any non-SAE
    0
    0
    0
    0
    0
    0
        Any SAE
    0
    1
    0
    1
    0
    0
    Notes
    [79] - Safety Population
    [80] - Safety Population
    [81] - Safety Population
    [82] - Safety Population
    [83] - Safety Population
    [84] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with clinical chemistry data of potential clinical importance

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    End point title
    Number of participants with clinical chemistry data of potential clinical importance
    End point description
    Blood samples were collected to measure analyze the following parameters: albumin, calcium, Glomerular filtration rate (GFR) from creatinine, glucose, potassium and sodium. Participants were counted in the worst case category that their value changes to (low, within range [w/in] or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100 percent (%). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Only “To Low” and/or “To High” categories with potential clinical importance data have been presented.
    End point type
    Secondary
    End point timeframe
    At Weeks 8, 12, 16 and 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [85]
    16 [86]
    23 [87]
    27 [88]
    23 [89]
    22 [90]
    Units: Participants
        Albumin, To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Albumin, To Low, Week 12, n=35, 16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Albumin, To Low, Week 16, n=35, 16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Albumin, To Low, Week 20, n=35, 16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
        Calcium, To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Calcium, To High, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Calcium, To Low, Week 12, n=35, 16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Calcium, To High, Week 12, n=35, 16, 21, 23, 22,21
    0
    0
    0
    0
    0
    0
        Calcium, To Low, Week 16, n=35, 16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Calcium, To High, Week 16,n=35, 16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Calcium, To Low, Week 20, n=35,16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
        Calcium, To High, Week 20, n=35,16, 22, 22, 22, 21
    1
    0
    0
    0
    0
    0
        GFR, To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        GFR, To Low, Week 12, n=35, 15, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        GFR, To Low, Week 16, n=35, 16, 21, 22, 21, 21
    0
    0
    0
    0
    0
    0
        GFR, To Low, Week 20, n=35, 16, 22, 22, 22, 21
    0
    0
    0
    1
    0
    0
        Glucose ,To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Glucose ,To High, Week 8, n=36, 16, 21, 21, 22, 19
    1
    0
    0
    0
    0
    1
        Glucose ,To Low, Week 12, n=35, 16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Glucose, To High, Week 12, n=35,16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Glucose ,To Low, Week 16, n=35, 16, 21, 22, 21,20
    0
    0
    0
    0
    0
    0
        Glucose, To High, Week 16, n=35,16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Glucose ,To Low, Week 20, n=35, 16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
        Glucose, To High, Week 20, n=35,16, 22, 22, 22, 21
    1
    0
    0
    0
    0
    0
        Potassium,To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Potassium, To High, Week 8, n=36,16, 21, 21, 22,19
    0
    0
    0
    0
    0
    0
        Potassium,To Low, Week 12, n=35,16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Potassium,To High, Week 12,n=35,16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Potassium,To Low, Week 16, n=35,16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Potassium, To High, Week 16, n=35,16,21, 22, 21,20
    0
    0
    0
    0
    0
    0
        Potassium,To Low, Week 20, n=35,16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
        Potassium, To High,Week 20, n=35,16, 22,22, 22, 21
    0
    0
    0
    0
    0
    0
        Sodium, To Low, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Sodium, To High, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Sodium, To Low, Week 12, n=35, 16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Sodium, To High, Week 12, n=35,16, 21, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Sodium, To Low, Week 16, n=35, 16, 21, 22, 21, 20
    0
    0
    0
    0
    0
    0
        Sodium, To High, Week 16, n=35,16, 21, 22, 21, 20
    0
    0
    1
    0
    0
    0
        Sodium, To Low, Week 20, n=35, 16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
        Sodium, To High, Week 20, n=35,16, 22, 22, 22, 21
    0
    0
    0
    0
    0
    0
    Notes
    [85] - Safety Population
    [86] - Safety Population
    [87] - Safety Population
    [88] - Safety Population
    [89] - Safety Population
    [90] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with hematology data of potential clinical importance

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    End point title
    Number of participants with hematology data of potential clinical importance
    End point description
    Blood samples were collected to analyze the following parameters: hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Participants were counted in the worst case category that their value changes to (low, w/in or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., high to high), or whose value became within range, were recorded in the "To w/in Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Only “To Low” and/or “To High” categories with potential clinical importance data have been presented.
    End point type
    Secondary
    End point timeframe
    At Weeks 8, 12, 16 and 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [91]
    16 [92]
    23 [93]
    27 [94]
    23 [95]
    22 [96]
    Units: Participants
        Hematocrit, To High, Week 8,n=36,16,21, 21, 22, 19
    0
    0
    0
    0
    0
    0
        Hematocrit,To High, Week 12, n=33,15,21, 23, 22,20
    0
    0
    0
    0
    0
    0
        Hematocrit,To High, Week 16, n=35,15,21,22,21,21
    0
    0
    0
    0
    0
    0
        Hematocrit,To High, Week 20, n=34,16,22,22,22,20
    0
    0
    0
    0
    0
    0
        Hemoglobin, To High, Week 8,n=36,16, 21,21, 22,19
    0
    0
    0
    0
    0
    0
        Hemoglobin, To High, Week 12, n=33,15,21,23,22,20
    0
    0
    0
    0
    0
    0
        Hemoglobin, To High, Week 16, n=35,15,21,22,21,21
    0
    0
    0
    0
    0
    0
        Hemoglobin, To High, Week 20, n=34,16, 22,22,22,20
    0
    0
    0
    0
    0
    0
        Leukocytes, To Low, Week 8, n=36,15, 21,21, 22,19
    1
    0
    0
    0
    1
    0
        Leukocytes,To High, Week 8, n=36,15,21,21,22,19
    0
    0
    0
    0
    0
    0
        Leukocytes,To Low,Week 12, n=33,15,21,23,22,20
    1
    1
    1
    0
    0
    0
        Leukocytes,To High, Week 12, n=33,15,21,23, 22,20
    0
    0
    0
    0
    0
    0
        Leukocytes, To Low, Week 16, n=34,15,21, 22, 20,21
    1
    0
    3
    1
    1
    0
        Leukocytes,To High, Week 16, n=34,15,21,22, 20,21
    0
    0
    0
    0
    0
    0
        Leukocytes, To Low, Week 20, n=34,16,22,21,22,19
    0
    1
    1
    0
    0
    0
        Leukocytes, To High, Week 20, n=34,16,22,21,22,19
    0
    0
    0
    0
    0
    0
        Lymphocytes, To Low, Week 8, n=35,15,21,21,22,19
    2
    0
    0
    0
    0
    0
        Lymphocytes, To Low, Week 12, n=32,15,21,23,22,20
    1
    0
    0
    2
    0
    0
        Lymphocytes, To Low, Week 16, n=34,15,21,22,20,21
    0
    0
    0
    1
    0
    0
        Lymphocytes, To Low, Week 20, n=34,16,22,21,22,19
    0
    0
    1
    0
    0
    0
        Neutrophils, To Low, Week 8,n=35,15,21,21,22,19
    1
    1
    0
    1
    1
    1
        Neutrophils, To Low, Week 12, n=32,15,21,23,22,20
    0
    1
    0
    1
    0
    1
        Neutrophils, To Low, Week 16, n=34,15,21,22,20,21
    1
    0
    2
    0
    1
    0
        Neutrophils, To Low, Week 20, n=34,16,22,21,22,19
    0
    0
    1
    0
    0
    0
        Platelets, To Low, Week 8,n=36,15,20,21,22,19
    0
    0
    0
    0
    0
    0
        Platelets, To High, Week 8,n=36,15,20,21,22,19
    0
    0
    0
    0
    0
    0
        Platelets, To Low, Week 12, n=33,14,19,23,22,20
    0
    0
    0
    0
    0
    1
        Platelets,To High, Week 12, n=33,14,19,23,22,20
    0
    0
    0
    0
    0
    0
        Platelets, To Low, Week 16, n=35,14,19,22, 21,21
    1
    0
    0
    0
    0
    1
        Platelets,To High, Week 16, n=35,14,19,22, 21,21
    1
    0
    0
    0
    0
    0
        Platelets, To Low, Week 20, n=33,16,21,21,22,20
    0
    0
    0
    0
    0
    0
        Platelets,To High, Week 20, n=33,16,21,21,22,20
    0
    0
    0
    0
    0
    0
    Notes
    [91] - Safety Population
    [92] - Safety Population
    [93] - Safety Population
    [94] - Safety Population
    [95] - Safety Population
    [96] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters

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    End point title
    Number of participants with abnormal 12-Lead Electrocardiogram (ECG) parameters
    End point description
    A 12-lead ECG was recorded with the participant in a semi-supine position. 12-lead ECGs were obtained by using an automated ECG machine. Data for abnormal, not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS 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. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    At Weeks 8, 12, 16 and 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [97]
    16 [98]
    23 [99]
    27 [100]
    23 [101]
    22 [102]
    Units: Participants
        Abnormal, NCS, Week 8, n=36, 16, 21, 21, 22,19
    10
    2
    1
    7
    8
    4
        Abnormal, CS, Week 8, n=36, 16, 21, 21, 22, 19
    0
    0
    0
    1
    0
    0
        Abnormal, NCS, Week 12, n= 35, 16, 20, 23, 22, 21
    9
    3
    3
    8
    8
    4
        Abnormal, CS, Week 12, n=35, 16, 20, 23, 22, 21
    0
    0
    0
    0
    0
    0
        Abnormal, NCS, Week 16, n= 35, 16, 21, 21, 22 ,21
    9
    3
    2
    5
    7
    4
        Abnormal, CS, Week 16, n=35, 16, 21, 21, 22, 21
    0
    0
    0
    0
    0
    0
        Abnormal, NCS, Week 20, n=35, 16, 22, 22, 22, 20
    8
    3
    2
    7
    8
    3
        Abnormal, CS, Week 20, n=35, 16, 22, 22, 22, 20
    0
    0
    0
    0
    0
    0
    Notes
    [97] - Safety Population
    [98] - Safety Population
    [99] - Safety Population
    [100] - Safety Population
    [101] - Safety Population
    [102] - Safety Population
    No statistical analyses for this end point

    Secondary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

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    End point title
    Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
    End point description
    SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [103]
    16 [104]
    22 [105]
    22 [106]
    22 [107]
    21 [108]
    Units: Millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP
    -3.3 ± 13.33
    -2.1 ± 11.47
    0.1 ± 12.78
    0.7 ± 10.42
    -0.3 ± 15.16
    2.0 ± 15.43
        DBP
    -1.3 ± 8.99
    0.3 ± 7.75
    -0.3 ± 9.16
    -0.7 ± 5.51
    2.5 ± 8.64
    2.3 ± 7.23
    Notes
    [103] - Safety Population
    [104] - Safety Population
    [105] - Safety Population
    [106] - Safety Population
    [107] - Safety Population
    [108] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pulse Rate

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    End point title
    Change from Baseline in Pulse Rate
    End point description
    Pulse rate was measured in a semi-supine position after 5 minutes of rest. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [109]
    16 [110]
    22 [111]
    22 [112]
    22 [113]
    21 [114]
    Units: Beats per minute
        arithmetic mean (standard deviation)
    1.5 ± 7.19
    -2.6 ± 10.35
    1.2 ± 10.91
    -0.2 ± 7.93
    3.4 ± 8.92
    0.5 ± 8.03
    Notes
    [109] - Safety Population
    [110] - Safety Population
    [111] - Safety Population
    [112] - Safety Population
    [113] - Safety Population
    [114] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment

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    End point title
    Change from Baseline in Gastrointestinal Symptom Rating Scale (GSRS) assessment
    End point description
    GSRS was measured for all 5 domains: Average Diarrhea Syndrome Score, Average Indigestion Syndrome Score, Average Constipation Syndrome Score, Average Abdominal Pain Syndrome Score, Average Reflux Syndrome Score. All individual domains are scored on a 7-point Likert scale ranging from 1(not at all) to 7(extremely). Higher score indicate more severe symptoms. The Average Total GSRS score was mean of these 5 domains and ranges from 1 to 7. Higher score indicates worst possible degree of symptoms. The responses summarized at each visit are those given during the week prior to the visit, with exception of Day 1. Baseline is the most recent assessment completed by participant prior to randomization. Change from Baseline was calculated as post-Baseline value minus the Baseline value. Data has been presented for each domain along with the average Total GSRS score. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 20
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    33 [115]
    16 [116]
    20 [117]
    21 [118]
    22 [119]
    20 [120]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Average Diarrhea Syndrome Score
    0.22 ± 1.343
    0.15 ± 1.587
    0.23 ± 1.180
    -0.13 ± 0.637
    -0.23 ± 1.729
    0.22 ± 1.565
        Average Indigestion Syndrome Score
    -0.01 ± 1.138
    0.09 ± 0.865
    -0.03 ± 0.811
    -0.14 ± 0.820
    -0.31 ± 1.046
    -0.54 ± 1.007
        Average Constipation Syndrome Score
    -0.03 ± 1.045
    -0.15 ± 0.989
    0.32 ± 1.370
    -0.02 ± 0.934
    -0.32 ± 1.215
    -0.37 ± 0.772
        Average Abdominal Pain Syndrome Score
    -0.05 ± 1.074
    0.06 ± 0.712
    -0.02 ± 1.000
    -0.06 ± 0.629
    -0.08 ± 0.885
    -0.25 ± 0.904
        Average Reflux Syndrome Score
    -0.09 ± 1.208
    -0.13 ± 0.619
    -0.20 ± 1.332
    -0.26 ± 0.664
    -0.16 ± 0.762
    -0.43 ± 0.847
        Average Total Score
    0.01 ± 0.830
    0.02 ± 0.668
    0.07 ± 0.802
    -0.11 ± 0.433
    -0.23 ± 0.690
    -0.28 ± 0.695
    Notes
    [115] - Safety Population
    [116] - Safety Population
    [117] - Safety Population
    [118] - Safety Population
    [119] - Safety Population
    [120] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with Mean Worst Daily Itch Score of <4 at Week 16

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    End point title
    Number of participants with Mean Worst Daily Itch Score of <4 at Week 16
    End point description
    Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Number of participants with Mean Worst Daily Itch Score of <4 at Week 16 is presented.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [121]
    16 [122]
    23 [123]
    27 [124]
    23 [125]
    22 [126]
    Units: Participants
    21
    13
    14
    18
    18
    14
    Notes
    [121] - ITT Population
    [122] - ITT Population
    [123] - ITT Population
    [124] - ITT Population
    [125] - ITT Population
    [126] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    12.02
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.48
         upper limit
    5.02
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    10.76
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    10.76
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.43
         upper limit
    4.13

    Secondary: Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline

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    End point title
    Number of participants with improvement of >= 30 percent (%) in the Mean Worst Daily Itch Score at Week 16 from Baseline
    End point description
    Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
    End point type
    Secondary
    End point timeframe
    Baseline and At Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [127]
    16 [128]
    23 [129]
    27 [130]
    23 [131]
    22 [132]
    Units: Participants
    17
    9
    15
    14
    15
    14
    Notes
    [127] - ITT Population
    [128] - ITT Population
    [129] - ITT Population
    [130] - ITT Population
    [131] - ITT Population
    [132] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.41
         upper limit
    4.47
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    3.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.95
         upper limit
    10.65
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.62
         upper limit
    5.53
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    6.92
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    6.51

    Secondary: Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

    Close Top of page
    End point title
    Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline
    End point description
    Participants were required to score the severity of their itching using a 0-10 NRS where 0 represents no itching and 10 indicates the worst imaginable itching. The Worst Daily Itch Score is the most severe (highest) NRS recorded on a given day. Mean Worst Daily Itch score was calculated as the average of the worst daily itch scores provided in the 7 days prior to the Week 16 visit. Baseline is the most recent assessment completed by the participant prior to randomization. Number of participants with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
    End point type
    Secondary
    End point timeframe
    Baseline and At Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [133]
    16 [134]
    23 [135]
    27 [136]
    23 [137]
    22 [138]
    Units: Participants
    14
    6
    12
    9
    13
    12
    Notes
    [133] - ITT Population
    [134] - ITT Population
    [135] - ITT Population
    [136] - ITT Population
    [137] - ITT Population
    [138] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.27
         upper limit
    3.04
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    6.91
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.35
         upper limit
    3.08
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    6.42
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis was performed using Logistic regression. No covariates were used.
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.67
         upper limit
    5.99

    Secondary: Percentage of responder days with Worst Daily Itch Score of <4

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    End point title
    Percentage of responder days with Worst Daily Itch Score of <4
    End point description
    Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Percentage of responder days with Worst Daily Itch Score of <4 is presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [139]
    16 [140]
    23 [141]
    27 [142]
    23 [143]
    22 [144]
    Units: Percentage of days
        least squares mean (confidence interval 95%)
    40.32 (28.79 to 51.86)
    58.53 (41.23 to 75.83)
    51.38 (36.95 to 65.81)
    58.76 (45.45 to 72.08)
    65.80 (51.37 to 80.23)
    53.58 (38.83 to 68.34)
    Notes
    [139] - ITT Population
    [140] - ITT Population
    [141] - ITT Population
    [142] - ITT Population
    [143] - ITT Population
    [144] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    18.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.59
         upper limit
    39
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    11.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.42
         upper limit
    29.53
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    18.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.82
         upper limit
    36.06
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    25.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7
         upper limit
    43.95
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    13.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.47
         upper limit
    31.99

    Secondary: Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline

    Close Top of page
    End point title
    Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline
    End point description
    Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [145]
    16 [146]
    23 [147]
    27 [148]
    23 [149]
    22 [150]
    Units: Percentage of days
        least squares mean (confidence interval 95%)
    38.46 (27.30 to 49.61)
    53.44 (36.71 to 70.18)
    45.43 (31.47 to 59.39)
    50.23 (37.35 to 63.12)
    60.29 (46.33 to 74.25)
    60.03 (45.76 to 74.31)
    Notes
    [145] - ITT Population
    [146] - ITT Population
    [147] - ITT Population
    [148] - ITT Population
    [149] - ITT Population
    [150] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    14.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.13
         upper limit
    35.1
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    6.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.9
         upper limit
    24.84
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    11.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.27
         upper limit
    28.82
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    21.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.96
         upper limit
    39.7
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    21.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.46
         upper limit
    39.69

    Secondary: Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline

    Close Top of page
    End point title
    Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline
    End point description
    Percentage of Responder Days with Worst Daily Itch score was calculated as: (number of days response from Visit 3+1 to Visit 6-1 divided by number of days from Visit 3+1 to Visit 6-1 with worst daily itch scores available) times 100. Days for which no worst daily itch score was available did not contribute to either the numerator or the denominator. Analysis was performed using ANCOVA model including treatment group. Baseline is the most recent assessment completed by the participant prior to randomization. Percentage of responder days with improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 from Baseline is presented.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [151]
    16 [152]
    23 [153]
    27 [154]
    23 [155]
    22 [156]
    Units: Percentage of days
        least squares mean (confidence interval 95%)
    31.56 (19.96 to 43.16)
    37.71 (20.31 to 55.11)
    38.82 (24.31 to 53.33)
    40.69 (27.29 to 54.08)
    51.49 (36.98 to 66.00)
    58.60 (43.76 to 73.43)
    Notes
    [151] - ITT Population
    [152] - ITT Population
    [153] - ITT Population
    [154] - ITT Population
    [155] - ITT Population
    [156] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    6.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.76
         upper limit
    27.06
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    7.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.32
         upper limit
    25.84
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    9.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.59
         upper limit
    26.85
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    19.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.36
         upper limit
    38.51
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    27.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.2
         upper limit
    45.87

    Secondary: Change from Baseline in the Mean Daily Sleep Score at Week 16

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    End point title
    Change from Baseline in the Mean Daily Sleep Score at Week 16
    End point description
    Mean Daily Sleep Score is defined as the average of the daily sleep scores provided in the 7 days prior to the relevant visit. Participants sleep quality was recorded in an electronic diary each morning using a 0-10 NRS in which 0: good sleep to 10:worst possible sleep. Higher score indicates worse possible sleep. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [157]
    16 [158]
    20 [159]
    22 [160]
    22 [161]
    20 [162]
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -1.39 (-2.06 to -0.72)
    -1.66 (-2.64 to -0.67)
    -1.87 (-2.75 to -0.99)
    -1.85 (-2.69 to -1.01)
    -2.35 (-3.19 to -1.50)
    -1.69 (-2.57 to -0.81)
    Notes
    [157] - ITT Population
    [158] - ITT Population
    [159] - ITT Population
    [160] - ITT Population
    [161] - ITT Population
    [162] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.46
         upper limit
    0.92
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.58
         upper limit
    0.62
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.53
         upper limit
    0.61
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.03
         upper limit
    0.12
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.8

    Secondary: Change from Baseline in the Mean Daily Fatigue Score at Week 16

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    End point title
    Change from Baseline in the Mean Daily Fatigue Score at Week 16
    End point description
    Mean Daily Fatigue Score is defined as the average of the daily fatigue scores provided in the 7 days prior to the relevant visit. Participants fatigue level was recorded in an electronic diary each evening using a 0-10 NRS in which 0: no fatigue to 10:worst possible fatigue. Higher score indicates worse possible fatigue. Baseline is the average of the scores in the 7 days prior to the Week 4 (V3) visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Analysis was performed using ANCOVA model including treatment group and Baseline. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [163]
    16 [164]
    20 [165]
    22 [166]
    22 [167]
    21 [168]
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -0.79 (-1.39 to -0.18)
    -1.18 (-2.08 to -0.27)
    -1.19 (-2.00 to -0.37)
    -1.04 (-1.81 to -0.28)
    -1.20 (-1.97 to -0.44)
    -1.07 (-1.86 to -0.29)
    Notes
    [163] - ITT Population
    [164] - ITT Population
    [165] - ITT Population
    [166] - ITT Population
    [167] - ITT Population
    [168] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.49
         upper limit
    0.71
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.41
         upper limit
    0.61
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.24
         upper limit
    0.72
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.39
         upper limit
    0.56
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.28
         upper limit
    0.7

    Secondary: Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16

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    End point title
    Change from Baseline in the Five Dimensional (5-D) Itch Scale at Week 16
    End point description
    The 5-D itch scale is instrument for multidimensional quantification of itch that is sensitive to change over time. It has data to support its validity in pruritus participants and covers five dimensions of itch: duration, degree, direction, disability and distribution. Each domain was scored on a 5-point scale, ranging from 1 (Not present/resolved/never) to 5 (unbearable/getting worse/always), higher scores indicates worst itching. The scores of each of five domains were achieved separately and then summed together to obtain a total 5-D score. A total 5-D scores ranged between 5 (no pruritus) and 25 (most severe pruritus) where higher score indicates worse possible itching. Baseline is assessment performed at Week 4 (V3) which is conducted prior to first dosing of randomized medication that evening. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [169]
    16 [170]
    21 [171]
    21 [172]
    22 [173]
    20 [174]
    Units: Scores on a scale
    least squares mean (confidence interval 95%)
        Duration
    -0.8 (-1.1 to -0.4)
    -0.9 (-1.3 to -0.4)
    -0.4 (-0.8 to 0.0)
    -1.2 (-1.6 to -0.8)
    -0.6 (-1.0 to -0.2)
    -0.7 (-1.1 to -0.3)
        Degree
    -0.7 (-1.0 to -0.4)
    -0.9 (-1.4 to -0.5)
    -0.7 (-1.1 to -0.3)
    -0.7 (-1.2 to -0.3)
    -0.9 (-1.3 to -0.5)
    -0.8 (-1.2 to -0.4)
        Direction
    -0.7 (-1.1 to -0.3)
    -0.7 (-1.3 to -0.1)
    -0.7 (-1.2 to -0.2)
    -0.9 (-1.4 to -0.4)
    -1.1 (-1.6 to -0.6)
    -0.7 (-1.2 to -0.2)
        Disability
    -0.4 (-0.7 to 0.0)
    -0.8 (-1.4 to -0.2)
    -0.5 (-1.0 to 0.0)
    -0.7 (-1.2 to -0.2)
    -0.7 (-1.2 to -0.2)
    -0.7 (-1.2 to -0.1)
        Distribution
    -0.4 (-0.7 to -0.1)
    -0.7 (-1.2 to -0.2)
    -0.7 (-1.1 to -0.3)
    -0.9 (-1.3 to -0.5)
    -0.7 (-1.2 to -0.3)
    -0.6 (-1.0 to -0.2)
        5-D Itch Total Score
    -3.0 (-4.2 to -1.7)
    -4.0 (-5.9 to -2.0)
    -3.0 (-4.7 to -1.3)
    -4.4 (-6.0 to -2.7)
    -3.8 (-5.4 to -2.2)
    -3.5 (-5.2 to -1.8)
    Notes
    [169] - ITT Population
    [170] - ITT Population
    [171] - ITT Population
    [172] - ITT Population
    [173] - ITT Population
    [174] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Duration
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Duration
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    0.9
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Duration
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.1
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Duration
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0.7
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Duration
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0.6
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Degree
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Degree
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Degree
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Degree
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Degree
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Median difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.4
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Direction
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.7
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Direction
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.6
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Direction
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Direction
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.2
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Direction
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.6
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Disability
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 17
    Statistical analysis description
    Disability
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.5
    Statistical analysis title
    Statistical Analysis 18
    Statistical analysis description
    Disability
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 19
    Statistical analysis description
    Disability
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 20
    Statistical analysis description
    Disability
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 21
    Statistical analysis description
    Distribution
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 22
    Statistical analysis description
    Distribution
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Median difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.2
    Statistical analysis title
    Statistical Analysis 23
    Statistical analysis description
    Distribution
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0
    Statistical analysis title
    Statistical Analysis 24
    Statistical analysis description
    Distribution
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.2
    Statistical analysis title
    Statistical Analysis 25
    Statistical analysis description
    Distribution
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.3
    Statistical analysis title
    Statistical Analysis 26
    Statistical analysis description
    5-D Itch Total Score
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.3
         upper limit
    1.3
    Statistical analysis title
    Statistical Analysis 27
    Statistical analysis description
    5-D Itch Total Score
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    2.1
    Statistical analysis title
    Statistical Analysis 28
    Statistical analysis description
    5-D Itch Total Score
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.5
         upper limit
    0.7
    Statistical analysis title
    Statistical Analysis 29
    Statistical analysis description
    5-D Itch Total Score
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    1.2
    Statistical analysis title
    Statistical Analysis 30
    Statistical analysis description
    5-D Itch Total Score
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    1.6

    Secondary: Mean change from Baseline at Week 16 in serum total bile acid concentration

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    End point title
    Mean change from Baseline at Week 16 in serum total bile acid concentration
    End point description
    Blood samples were collected for evaluating total bile acid concentration as a biomarker of PBC. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [175]
    16 [176]
    20 [177]
    22 [178]
    21 [179]
    21 [180]
    Units: Micromoles per Liter
        arithmetic mean (standard deviation)
    -4.274 ± 20.0163
    -0.469 ± 6.5466
    -3.878 ± 40.1857
    -1.114 ± 6.9359
    -2.133 ± 8.9308
    7.379 ± 38.8282
    Notes
    [175] - ITT Population
    [176] - ITT Population
    [177] - ITT Population
    [178] - ITT Population
    [179] - ITT Population
    [180] - ITT Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)

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    End point title
    Mean change from Baseline at Week 16 in serum 7-alpha hydroxy-4-cholesten-3-one (C4)
    End point description
    Blood samples were collected for evaluating C4 concentration as a marker of bile acid synthesis. Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 or Visit 1, excluding unscheduled visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    35 [181]
    15 [182]
    21 [183]
    22 [184]
    22 [185]
    20 [186]
    Units: Micrograms per Liter
        arithmetic mean (standard deviation)
    4.746 ± 11.5644
    10.703 ± 24.6045
    11.452 ± 16.6371
    29.488 ± 38.7584
    58.674 ± 59.4833
    40.629 ± 36.2769
    Notes
    [181] - ITT Population
    [182] - ITT Population
    [183] - ITT Population
    [184] - ITT Population
    [185] - ITT Population
    [186] - ITT Population
    No statistical analyses for this end point

    Secondary: Plasma concentration of GSK2330672 after sparse sampling

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    End point title
    Plasma concentration of GSK2330672 after sparse sampling [187]
    End point description
    Blood samples were collected for measurement of plasma GSK2330672 concentration at Week 4 (between [B/W] 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose. "99999" indicates standard deviation could not be calculated as >30% of samples were below the limit of quantification. Pharmacokinetic (PK) Population consisted of any randomized participant who had at least one PK sample. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    At Week 4 (between 1 and 3 hours post-dose) and At Weeks 8, 12 and 16 (between 1 and 3 hours post-dose, and between 5 and 8 hours post-dose)
    Notes
    [187] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    16 [188]
    23 [189]
    27 [190]
    23 [191]
    22 [192]
    Units: Picograms per milliliter
    arithmetic mean (standard deviation)
        Week 4, B/W 1 and 3 hours post-dose, n=6, 2,7, 0,4
    5.00 ± 99999
    5.00 ± 99999
    32.71 ± 73.325
    99999 ± 99999
    5.00 ± 99999
        Week8, B/W 1 and 3 hour post-dose,n=16,21,20,22,17
    358.04 ± 665.685
    958.81 ± 1563.265
    2327.58 ± 3737.965
    453.45 ± 967.424
    2908.06 ± 5106.895
        Week8, B/W 5 and 8hour post-dose,n=14, 17,18,21,16
    300.04 ± 356.268
    820.87 ± 1143.023
    2234.28 ± 3420.442
    339.74 ± 357.914
    1990.89 ± 4061.978
        Week12,B/W 1 and 3 hours post-dose,n=14,1917,20,14
    447.88 ± 1160.518
    1594.16 ± 3133.370
    2060.51 ± 2888.033
    419.47 ± 774.321
    3531.36 ± 6296.828
        Week12,B/W 5 and 8 hour post-dose,n=14,16,17,20,13
    341.39 ± 638.359
    1084.00 ± 1353.089
    2569.00 ± 3727.883
    303.83 ± 300.716
    2197.16 ± 3604.704
        Week16,B/W 1 and 3hours post-dose,n=3, 5, 4, 2, 5
    394.00 ± 162.151
    864.26 ± 1045.467
    3328.50 ± 3185.646
    338.50 ± 236.881
    703.60 ± 756.010
        Week16,B/W 5 and 8 hour post-dose,n=3, 3, 4, 2, 5
    296.33 ± 118.154
    578.00 ± 651.263
    1940.50 ± 1128.203
    364.50 ± 217.082
    869.40 ± 1148.331
    Notes
    [188] - PK Population
    [189] - PK Population
    [190] - PK Population
    [191] - PK Population. 99999 indicates data was not available.
    [192] - PK Population. 99999 indicates data was not available.
    No statistical analyses for this end point

    Post-hoc: Mean change from Baseline in Monthly Itch Score

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    End point title
    Mean change from Baseline in Monthly Itch Score
    End point description
    Participants were required to score severity of their itching each morning and evening using a 0-10 NRS where 0(no itching) and 10(worst imaginable itching). The worst of these 2 scores was Worst Daily Itch Score. For each week, mean Worst Daily Itch Score was calculated to form Mean Worst Daily Itch Score. The Monthly Itch Score was defined as worst weekly score (e.g., Mean Worst Daily Itch Score) for that month. The monthly itch score ranges from 0 to 10, higher score indicates worst imaginable itching. Baseline is average of scores in the 7 days prior to Week 4 (Visit 3 [V3]). Change from Baseline was calculated as post-Baseline value minus Baseline value. Analysis was performed on change in Monthly Itch Scores over 12 week treatment period using Mixed model repeated measures (MMRM) with Baseline itch, treatment group, visit and a treatment group*visit interaction as covariates in the model. Only those participants with data available at the specified data points were analyzed.
    End point type
    Post-hoc
    End point timeframe
    Baseline and up to Week 12
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [193]
    16 [194]
    23 [195]
    24 [196]
    22 [197]
    22 [198]
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -0.46 (-1.01 to 0.08)
    -1.17 (-1.99 to -0.35)
    -1.08 (-1.77 to -0.39)
    -1.36 (-2.03 to -0.69)
    -1.63 (-2.32 to -0.93)
    -1.41 (-2.13 to -0.7)
    Notes
    [193] - ITT Population
    [194] - ITT Population
    [195] - ITT Population
    [196] - ITT Population
    [197] - ITT Population
    [198] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.69
         upper limit
    0.28
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    59
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.49
         upper limit
    0.26
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    60
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.76
         upper limit
    -0.03
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -1.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.05
         upper limit
    -0.28
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Mean difference (net)
    Point estimate
    -0.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.85
         upper limit
    -0.06

    Post-hoc: Ratio to Baseline in Total Serum Bile Acid Concentration

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    End point title
    Ratio to Baseline in Total Serum Bile Acid Concentration
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Ratio to Baseline was defined as the geometric mean of post-Baseline visit value divided by the geometric mean of Baseline value. Values were log-transformed and mean change from Baseline on the log-scale was calculated over the 12 week treatment period. Analysis was performed on change in total serum bile acid concentration on the log-scale over the 12 week treatment period using MMRM with log-transformed Baseline total serum bile acid, visit, treatment group, a log-transformed Baseline total serum bile acid*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were back-transformed to the original scale. Ratios of geometric means are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Post-hoc
    End point timeframe
    Baseline and up to Week 12
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [199]
    16 [200]
    22 [201]
    24 [202]
    22 [203]
    22 [204]
    Units: Ratio
        least squares mean (confidence interval 95%)
    1.01 (0.801 to 1.273)
    0.977 (0.688 to 1.386)
    1.182 (0.874 to 1.6)
    0.918 (0.687 to 1.226)
    0.697 (0.519 to 0.938)
    0.833 (0.616 to 1.127)
    Notes
    [199] - ITT Population
    [200] - ITT Population
    [201] - ITT Population
    [202] - ITT Population
    [203] - ITT Population
    [204] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    Least Square (LS) mean ratio
    Point estimate
    0.967
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.635
         upper limit
    1.471
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    1.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.712
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    60
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    0.909
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.627
         upper limit
    1.316
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    0.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.474
         upper limit
    1.005
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    0.825
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.564
         upper limit
    1.207

    Post-hoc: Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration

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    End point title
    Ratio to Baseline in serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Concentration
    End point description
    Baseline is the assessment performed at Week 4 (V3), or if missing then Visit 2 (Day 1) or Visit 1 (Screening), excluding unscheduled visits. Ratio to Baseline was defined as the geometric mean of post-Baseline visit value divided by the geometric mean of Baseline value. Values were log-transformed and mean change from Baseline on the log-scale was calculated over the 12 week treatment period. Analysis was performed on change in C4 on the log-scale over the 12 week treatment period using Mixed model repeated measures (MMRM) with log-transformed Baseline C4, visit, treatment group, a log-transformed Baseline C4*visit interaction, and a treatment group*visit interaction used as covariates in the model. Afterwards, values were back-transformed to the original scale. Ratios of geometric means are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Post-hoc
    End point timeframe
    Baseline and up to Week 12
    End point values
    Placebo GSK2330672 20 mg QD GSK2330672 90 mg QD GSK2330672 180 mg QD GSK2330672 40 mg BID GSK2330672 90 mg BID
    Number of subjects analysed
    36 [205]
    16 [206]
    22 [207]
    24 [208]
    22 [209]
    22 [210]
    Units: Ratio
        least squares mean (confidence interval 95%)
    1.158 (0.937 to 1.431)
    1.579 (1.151 to 2.166)
    2.374 (1.812 to 3.109)
    2.846 (2.192 to 3.694)
    3.622 (2.753 to 4.764)
    3.127 (2.385 to 4.101)
    Notes
    [205] - ITT Population
    [206] - ITT Population
    [207] - ITT Population
    [208] - ITT Population
    [209] - ITT Population
    [210] - ITT Population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v GSK2330672 20 mg QD
    Number of subjects included in analysis
    52
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    1.363
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.932
         upper limit
    1.995
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo v GSK2330672 90 mg QD
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    2.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.456
         upper limit
    2.887
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    Placebo v GSK2330672 180 mg QD
    Number of subjects included in analysis
    60
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    2.457
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.758
         upper limit
    3.436
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    Placebo v GSK2330672 40 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    3.128
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.206
         upper limit
    4.435
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    Placebo v GSK2330672 90 mg BID
    Number of subjects included in analysis
    58
    Analysis specification
    Post-hoc
    Analysis type
    other
    Method
    Parameter type
    LS mean ratio
    Point estimate
    2.701
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.915
         upper limit
    3.81

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to 12 weeks during Main study period; up to 4 weeks during Final study period and up to 4 weeks during Follow-up period.
    Adverse event reporting additional description
    Safety Population consisted of all randomized participants who received at least 1 dose of study intervention.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Placebo - Main Study Period
    Reporting group description
    Placebo - Main Study Period

    Reporting group title
    GSK2330672 20 mg QD - Main Study Period
    Reporting group description
    GSK2330672 20 mg QD - Main Study Period

    Reporting group title
    GSK2330672 90 mg QD - Main Study Period
    Reporting group description
    GSK2330672 90 mg QD - Main Study Period

    Reporting group title
    GSK2330672 180 mg QD - Main Study Period
    Reporting group description
    GSK2330672 180 mg QD - Main Study Period

    Reporting group title
    GSK2330672 40 mg BID - Main Study Period
    Reporting group description
    GSK2330672 40 mg BID - Main Study Period

    Reporting group title
    GSK2330672 90 mg BID - Main Study Period
    Reporting group description
    GSK2330672 90 mg BID - Main Study Period

    Reporting group title
    Placebo - Final Study Period
    Reporting group description
    Placebo - Final Study Period

    Reporting group title
    GSK2330672 20 mg QD - Final Study Period
    Reporting group description
    GSK2330672 20 mg QD - Final Study Period

    Reporting group title
    GSK2330672 90 mg QD - Final Study Period
    Reporting group description
    GSK2330672 90 mg QD - Final Study Period

    Reporting group title
    GSK2330672 180 mg QD - Final Study Period
    Reporting group description
    GSK2330672 180 mg QD - Final Study Period

    Reporting group title
    GSK2330672 40 mg BID - Final Study Period
    Reporting group description
    GSK2330672 40 mg BID - Final Study Period

    Reporting group title
    GSK2330672 90 mg BID - Final Study Period
    Reporting group description
    GSK2330672 90 mg BID - Final Study Period

    Reporting group title
    Placebo - Follow-up
    Reporting group description
    Placebo - Follow-up

    Reporting group title
    GSK2330672 20 mg QD - Follow-up
    Reporting group description
    GSK2330672 20 mg QD - Follow-up

    Reporting group title
    GSK2330672 90 mg QD - Follow-up
    Reporting group description
    GSK2330672 90 mg QD - Follow-up

    Reporting group title
    GSK2330672 180 mg QD - Follow-up
    Reporting group description
    GSK2330672 180 mg QD - Follow-up

    Reporting group title
    GSK2330672 40 mg BID - Follow-up
    Reporting group description
    GSK2330672 40 mg BID - Follow-up

    Reporting group title
    GSK2330672 90 mg BID - Follow-up
    Reporting group description
    GSK2330672 90 mg BID - Follow-up

    Serious adverse events
    Placebo - Main Study Period GSK2330672 20 mg QD - Main Study Period GSK2330672 90 mg QD - Main Study Period GSK2330672 180 mg QD - Main Study Period GSK2330672 40 mg BID - Main Study Period GSK2330672 90 mg BID - Main Study Period Placebo - Final Study Period GSK2330672 20 mg QD - Final Study Period GSK2330672 90 mg QD - Final Study Period GSK2330672 180 mg QD - Final Study Period GSK2330672 40 mg BID - Final Study Period GSK2330672 90 mg BID - Final Study Period Placebo - Follow-up GSK2330672 20 mg QD - Follow-up GSK2330672 90 mg QD - Follow-up GSK2330672 180 mg QD - Follow-up GSK2330672 40 mg BID - Follow-up GSK2330672 90 mg BID - Follow-up
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 23 (0.00%)
    0 / 22 (0.00%)
    0 / 35 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 21 (0.00%)
    0 / 17 (0.00%)
    0 / 35 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 23 (0.00%)
    0 / 22 (0.00%)
    0 / 35 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 21 (0.00%)
    0 / 17 (0.00%)
    0 / 35 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0