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    Clinical Trial Results:
    An adaptive Phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184 in patients with mild to moderate systemic lupus erythematosus.

    Summary
    EudraCT number
    		 2012-001645-41
    Trial protocol
    		 DE   HU   SE   ES   GR   EE   CZ   PL  
    Global end of trial date
    31 Mar 2014

    Results information
    Results version number
    		 v2(current)
    This version publication date
    26 Mar 2016
    First version publication date
    01 Jul 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Minor corrections required.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    JAK115919
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01777256
    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, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    09 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Mar 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    • To estimate the relationship between dose of GSK2586184 and pharmacodynamic effect on expression of selected messenger ribonucleic acid (mRNA) transcripts following 2 weeks of treatment in SLE patients • To estimate the relationship between dose of GSK2586184 and clinical response as assessed by SELENA SLEDAI score following 12 weeks of treatment in SLE patients • To evaluate the safety and tolerability of repeat doses of GSK2586184 in SLE patients.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Mar 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Czech Republic: 2
    Country: Number of subjects enrolled
    Estonia: 3
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Hungary: 9
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Peru: 14
    Worldwide total number of subjects
    50
    EEA total number of subjects
    32
    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)
    50
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants (par) with a clinical diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology classification criteria were enrolled. Enrolled par with clinically active SLE were randomised in a 1:1:1:1:1 ratio to receive twice daily doses of GSK2586184 (50 milligram (mg), 100 mg, 200 mg, 400 mg) or placebo.

    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, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK2586184 50 mg BID
    Arm description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 50 milligram (mg) of GSK2586184, twice daily (BID) with food for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586184
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Either 50mg or 200mg oral tablets taken twice daily with food

    Arm title
    		 GSK2586184 100 mg BID
    Arm description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 100 mg of GSK2586184, BID with food for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586184
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Either 50mg or 200mg oral tablets taken twice daily with food

    Arm title
    		 GSK2586184 200 mg BID
    Arm description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 200 mg of GSK2586184, BID with food for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586184
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Either 50mg or 200mg oral tablets taken twice daily with food

    Arm title
    		 GSK2586184 400 mg BID
    Arm description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 400 mg of GSK2586184, BID with food for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586184
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Either 50mg or 200mg oral tablets taken twice daily with food

    Arm title
    		 Placebo
    Arm description
    		 Participants received a combination of 2 film coated tablets of GSK2586184 matching placebo, BID with food for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo - Either 50mg or 200mg oral tablets taken twice daily with food

    Number of subjects in period 1
    		GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Started
    9
    10
    10
    10
    11
    Completed
    4
    5
    4
    4
    5
    Not completed
    5
    5
    6
    6
    6
         Study closed/terminated
    4
    4
    -
    3
    5
         Consent withdrawn by subject
    -
    -
    1
    1
    -
         Physician decision
    -
    -
    -
    1
    -
         Adverse event, non-fatal
    1
    1
    4
    1
    -
         Lost to follow-up
    -
    -
    -
    -
    1
         Protocol deviation
    -
    -
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    GSK2586184 50 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 50 milligram (mg) of GSK2586184, twice daily (BID) with food for 12 weeks.

    Reporting group title
    GSK2586184 100 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 100 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 200 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 200 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 400 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 400 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a combination of 2 film coated tablets of GSK2586184 matching placebo, BID with food for 12 weeks.

    Reporting group values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo Total
    Number of subjects
    		 9 10 10 10 11 50
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 38 ( 12.55 ) 43.1 ( 11.23 ) 37.3 ( 7.15 ) 47.5 ( 10.99 ) 36.9 ( 10.14 ) -
    Gender categorical
    Units: Subjects
        Female
    		 9 10 10 10 11 50
        Male
    		 0 0 0 0 0 0
    Race
    Units: Subjects
        American Indian or Alaskan Native
    		 2 2 3 1 4 12
        Asian - Central/South Asian Heritage
    		 1 0 0 0 0 1
        Asian - East Asian Heritage
    		 0 0 0 1 0 1
        White - White/Caucasian/European Heritage
    		 6 6 7 8 7 34
        Mixed Race
    		 0 2 0 0 0 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    GSK2586184 50 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 50 milligram (mg) of GSK2586184, twice daily (BID) with food for 12 weeks.

    Reporting group title
    GSK2586184 100 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 100 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 200 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 200 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 400 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 400 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a combination of 2 film coated tablets of GSK2586184 matching placebo, BID with food for 12 weeks.

    Primary: Percentage Inhibition from Baseline of interferon (IFN) Transcriptional Biomarkers at Week 2

    		 Close Top of page
    End point title
    		 Percentage Inhibition from Baseline of interferon (IFN) Transcriptional Biomarkers at Week 2
    End point description
    Mean reduction (40%) from Baseline of the IFN transcriptional signature biomarker was monitored at Week 2. Percentage (Per) inhibition (=[(Day x–Baseline)/Baseline]*-100), was the Per reduction from baseline (Day1) and evaluated in any pre-designated panels of genes i.e. Addenbrookes 1, Addenbrookes 2, JAK439, PD, Panel Stripping, Flare and Transcription. Analysis was performed using a repeated measures model with covariates of treatment, baseline, Day, Day by baseline and Day by treatment interactions. Only those Par available at the specified time points were analysed (n=X,X,X,X,X). Different Par may have been analysed at different time points, so the overall number of Par analysed reflects everyone in the Intent To Treat (ITT) Population i.e. Par randomised to treatment, received >=1 dose of study medication and had >=1 valid post dose assessment
    End point type
    Primary
    End point timeframe
    Baseline and Week 2
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    8 [1]
    10 [2]
    9 [3]
    9 [4]
    9 [5]
    Units: Percentage
    arithmetic mean (standard deviation)
        Panel1
    1.55 ( 7.621 )
    0.53 ( 8.048 )
    0.15 ( 11.338 )
    4.83 ( 6.315 )
    -1.21 ( 7.543 )
        Panel2
    1.1 ( 8.526 )
    0.64 ( 7.804 )
    0.38 ( 11.696 )
    4.48 ( 6.697 )
    -1.05 ( 7.657 )
        Panel3
    0.31 ( 6.814 )
    0.49 ( 5.147 )
    1.22 ( 12.014 )
    3.98 ( 5.847 )
    -0.46 ( 5.36 )
        Panel4
    -0.48 ( 5.215 )
    -0.27 ( 4.461 )
    -1.91 ( 11.685 )
    2.08 ( 5.586 )
    -1.02 ( 5.182 )
        Panel5
    0.73 ( 7.682 )
    0.29 ( 7.789 )
    0.16 ( 12.227 )
    5.29 ( 6.825 )
    -1.14 ( 7.242 )
        Panel6
    1.07 ( 6.419 )
    0.82 ( 6.428 )
    1.24 ( 10.849 )
    5.64 ( 6.008 )
    -0.94 ( 6.425 )
        Panel7
    0.77 ( 1.835 )
    -1 ( 2.318 )
    -1.06 ( 6.948 )
    0.6 ( 1.503 )
    -0.3 ( 1.645 )
    Notes
    [1] - ITT Population
    [2] - ITT Population
    [3] - ITT Population
    [4] - ITT Population
    [5] - ITT Population
    Statistical analysis title
    		 Analysis 1
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.31
         upper limit
    		 9.81
    Notes
    [6] - Panel 1: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 2
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.19
         upper limit
    		 8.3
    Notes
    [7] - Panel 1: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 3
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.37
         upper limit
    		 6.56
    Notes
    [8] - Panel 1: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 4
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.46
         upper limit
    		 12.25
    Notes
    [9] - Panel 1: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 5
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.52
         upper limit
    		 9.56
    Notes
    [10] - Panel 2: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 6
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.86
         upper limit
    		 8.54
    Notes
    [11] - Panel 2: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 7
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.95
         upper limit
    		 6.99
    Notes
    [12] - Panel 2: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 8
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.55
         upper limit
    		 12.11
    Notes
    [13] - Panel 2: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 9
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 7.16
    Notes
    [14] - Panel 3: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 10
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.13
         upper limit
    		 6.65
    Notes
    [15] - Panel 3: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 11
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.06
         upper limit
    		 6.19
    Notes
    [16] - Panel 3: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 12
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.99
         upper limit
    		 10.03
    Notes
    [17] - Panel 3: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 13
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.42
         upper limit
    		 5.87
    Notes
    [18] - Panel 4: Placebo vs GSK25865184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 14
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.32
         upper limit
    		 5.46
    Notes
    [19] - Panel 4: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 15
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.41
         upper limit
    		 2.76
    Notes
    [20] - Panel 4: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 16
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.01
         upper limit
    		 8
    Notes
    [21] - Panel 4: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 17
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.53
         upper limit
    		 9.42
    Notes
    [22] - Panel 5: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 18
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.85
         upper limit
    		 8.41
    Notes
    [23] - Panel 5: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 19
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 7.04
    Notes
    [24] - Panel 5: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 20
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.45
         upper limit
    		 13.06
    Notes
    [25] - Panel 5: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 21
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.56
         upper limit
    		 8.61
    Notes
    [26] - Panel 6: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 22
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.71
         upper limit
    		 7.86
    Notes
    [27] - Panel 6: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 23
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.84
         upper limit
    		 7.15
    Notes
    [28] - Panel 6: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 24
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.46
         upper limit
    		 12.32
    Notes
    [29] - Panel 6: Placebo vs GSK2586184 400 mg BID at Week 2
    Statistical analysis title
    		 Analysis 25
    Comparison groups
    Placebo v GSK2586184 50 mg BID
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.18
         upper limit
    		 3.45
    Notes
    [30] - Panel 7: Placebo vs GSK2586184 50 mg BID at Week 2
    Statistical analysis title
    		 Analysis 26
    Comparison groups
    Placebo v GSK2586184 100 mg BID
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 2.17
    Notes
    [31] - Panel 7: Placebo vs GSK2586184 100 mg BID at Week 2
    Statistical analysis title
    		 Analysis 27
    Comparison groups
    Placebo v GSK2586184 200 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.85
         upper limit
    		 1.68
    Notes
    [32] - Panel 7: Placebo vs GSK2586184 200 mg BID at Week 2
    Statistical analysis title
    		 Analysis 28
    Comparison groups
    Placebo v GSK2586184 400 mg BID
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.41
         upper limit
    		 3.09
    Notes
    [33] - Panel 7: Placebo vs GSK2586184 400 mg BID at Week 2

    Primary: Change from Baseline of SELENA SLEDAI score at indicated timepoints up to Week 16.

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    End point title
    		 Change from Baseline of SELENA SLEDAI score at indicated timepoints up to Week 16. [34]
    End point description
    The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a validated index for assessing SLE disease activity. It is a weighted index in which signs and symptoms, laboratory tests, and physician’s assessment for each of 9 organ systems are given a weighted score and summed, if present at the time of the visit or in the preceding 10 days. Modified version of SLEDAI is Safety of Estrogen in Lupus National Assessment (SELENA) SLEDAI where the maximum theoretical score for the SELENA SLEDAI was 105 with 0 indicating inactive disease. Baseline value is defined as Day 1 (pre-dose) SELENA SLEDAI score. Only those Par available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different Par may have been analysed at different time points, so the overall number of Par analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    Notes
    [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [35]
    10 [36]
    10 [37]
    10 [38]
    11 [39]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week2, n=9,8,9,9,9
    -2 ( 3.43 )
    -1 ( 3.02 )
    0.3 ( 3.46 )
    -2.4 ( 2.19 )
    -1.3 ( 3.46 )
        Week4, n=7,8,7,8,8
    -1.9 ( 4.85 )
    -1.5 ( 2.33 )
    -0.6 ( 2.99 )
    -3.5 ( 3.16 )
    -2.8 ( 3.69 )
        Week6, n=7,7,6,8,8
    -3.3 ( 3.3 )
    -1.9 ( 2.61 )
    -2 ( 5.66 )
    -3 ( 3.55 )
    -2.8 ( 3.2 )
        Week8, n=6,7,4,7,7
    -4.2 ( 2.86 )
    -3 ( 2.65 )
    -3.5 ( 5.74 )
    -3.4 ( 3.21 )
    -4 ( 3.83 )
        Week10, n=5,6,4,6,6
    -3.6 ( 3.29 )
    -4.2 ( 1.33 )
    -2 ( 6.93 )
    -3.7 ( 3.44 )
    -5.2 ( 3.82 )
        Week12, n=4,5,4,5,5
    -4.5 ( 4.43 )
    -6.2 ( 6.1 )
    -3 ( 6.83 )
    -4.6 ( 4.98 )
    -3.6 ( 3.58 )
        Week16, n=9,10,9,8,10
    -3.7 ( 4.42 )
    -4.9 ( 4.72 )
    -3.7 ( 6.08 )
    -7 ( 3.55 )
    -3.4 ( 3.66 )
    Notes
    [35] - ITT Population.
    [36] - ITT Population.
    [37] - ITT Population.
    [38] - ITT Population.
    [39] - ITT Population.
    No statistical analyses for this end point

    Primary: Change from Baseline in systolic blood pressure and diastolic blood pressure at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in systolic blood pressure and diastolic blood pressure at the indicated time points up to Week 16 [40]
    End point description
    Change from Baseline in systolic blood pressure (BP) and diastolic BP is summarised for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    Notes
    [40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [41]
    10 [42]
    10 [43]
    10 [44]
    11 [45]
    Units: Millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        Sitting Systolic BP, Week2, n=8,8,6,8,7
    -1.25 ( 6.944 )
    -1.13 ( 7.624 )
    3.5 ( 11.895 )
    -2.25 ( 7.573 )
    -0.29 ( 5.09 )
        Sitting Systolic BP, Week4, n=6,6,7,8,7
    3.33 ( 10.838 )
    -2.83 ( 11.737 )
    -0.57 ( 5.318 )
    -6.75 ( 12.43 )
    7.14 ( 7.448 )
        Sitting Systolic BP, Week6, n=6,8,5,8,8
    3.83 ( 8.841 )
    -2.25 ( 7.421 )
    5 ( 11.225 )
    0.5 ( 7.728 )
    12.63 ( 16.151 )
        Sitting Systolic BP, Week8, n=7,5,8,8,7
    -3.57 ( 4.65 )
    -1.4 ( 11.546 )
    -0.38 ( 10.309 )
    -4.75 ( 12.556 )
    4.14 ( 11.067 )
        Sitting Systolic BP, Week10, n=5,6,3,5,7
    -1.2 ( 11.692 )
    -1.5 ( 16.159 )
    2 ( 8.185 )
    -1.4 ( 18.064 )
    6.29 ( 15.649 )
        Sitting Systolic BP, Week12, n=6,5,6,7,6
    -2.5 ( 10.895 )
    -1.8 ( 9.176 )
    2.5 ( 8.118 )
    -2.57 ( 13.477 )
    2.17 ( 10.265 )
        Sitting Systolic BP, Week16, n=4,5,2,4,5
    -0.75 ( 9.215 )
    -2.8 ( 8.758 )
    7 ( 2.828 )
    -10.75 ( 19.276 )
    7.2 ( 14.957 )
        Supine Systolic BP, Week2, n=1,2,3,1,3
    0 ( 99999 )
    -10 ( 0 )
    -9.67 ( 8.963 )
    5 ( 99999 )
    11 ( 18.248 )
        Supine Systolic BP, Week4, n=2,2,1,0,3
    0 ( 7.071 )
    -15 ( 7.071 )
    0 ( 99999 )
    99999 ( 99999 )
    11.67 ( 25.658 )
        Supine Systolic BP, Week6, n=1,2,1,1,0
    9 ( 99999 )
    -10 ( 0 )
    0 ( 99999 )
    2 ( 99999 )
    99999 ( 99999 )
        Supine Systolic BP, Week8, n=1,2,1,1,2
    5 ( 99999 )
    -10 ( 14.142 )
    -10 ( 99999 )
    0 ( 99999 )
    7.5 ( 17.678 )
        Supine Systolic BP, Week10, n=2,2,1,1,1
    10 ( 14.142 )
    -5 ( 7.071 )
    0 ( 99999 )
    0 ( 99999 )
    10 ( 99999 )
        Supine Systolic BP, Week12, n=1,2,1,1,1
    5 ( 99999 )
    -10 ( 0 )
    -10 ( 99999 )
    -2 ( 99999 )
    20 ( 99999 )
        Supine Systolic BP, Week16, n=1,1,1,1,1
    0 ( 99999 )
    -10 ( 99999 )
    0 ( 99999 )
    2 ( 99999 )
    18 ( 99999 )
        Sitting Diastolic BP, Week2, n=8,8,6,8,7
    -0.63 ( 8.667 )
    0.25 ( 6.944 )
    -0.33 ( 7.202 )
    -8.5 ( 10.268 )
    2.57 ( 4.826 )
        Sitting Diastolic BP, Week4, n=6,6,7,8,7
    5.17 ( 6.824 )
    -1.83 ( 8.773 )
    -0.43 ( 5.94 )
    -6.63 ( 12.094 )
    7 ( 8.813 )
        Sitting Diastolic BP, Week6, n=6,8,5,8,8
    -1.67 ( 3.933 )
    4 ( 3.817 )
    -1.6 ( 3.782 )
    -0.38 ( 8.331 )
    2.25 ( 8.155 )
        Sitting Diastolic BP, Week8, n=7,5,8,8,7
    1 ( 11.255 )
    -2 ( 8.276 )
    -0.38 ( 4.596 )
    -2 ( 10.515 )
    3.43 ( 4.685 )
        Sitting Diastolic BP, Week10, n=5,6,3,5,7
    -2.8 ( 6.419 )
    -2.17 ( 12.073 )
    4.33 ( 3.786 )
    1 ( 11.662 )
    6.71 ( 10.812 )
        Sitting Diastolic BP, Week12, n=6,5,6,7,6
    -2 ( 5.06 )
    -1.2 ( 3.271 )
    -2 ( 4.98 )
    -1 ( 9.539 )
    1.5 ( 3.507 )
        Sitting Diastolic BP, Week16, n=4,5,2,4,5
    -2.5 ( 2.646 )
    -3.6 ( 8.792 )
    2 ( 7.071 )
    -0.25 ( 16.681 )
    11.4 ( 12.422 )
        Supine Diastolic BP, Week2, n=1,2,3,1,3
    -10 ( 99999 )
    -5 ( 7.071 )
    -3.67 ( 5.508 )
    -5 ( 99999 )
    5 ( 8.66 )
        Supine Diastolic BP, Week4, n=2,2,1,0,3
    -5 ( 7.071 )
    -6 ( 5.657 )
    -20 ( 99999 )
    99999 ( 99999 )
    1.33 ( 12.662 )
        Supine Diastolic BP, Week6, n=1,2,1,1,0
    0 ( 99999 )
    -10 ( 2.828 )
    -10 ( 99999 )
    -10 ( 99999 )
    99999 ( 99999 )
        Supine Diastolic BP, Week8, n=1,2,1,1,2
    0 ( 99999 )
    -6 ( 5.657 )
    -10 ( 99999 )
    5 ( 99999 )
    5 ( 7.071 )
        Supine Diastolic BP, Week10, n=2,2,1,1,1
    2.5 ( 10.607 )
    -11 ( 1.414 )
    -10 ( 99999 )
    -15 ( 99999 )
    10 ( 99999 )
        Supine Diastolic BP, Week12, n=1,2,1,1,1
    0 ( 99999 )
    -6 ( 8.485 )
    -20 ( 99999 )
    -5 ( 99999 )
    5 ( 99999 )
        Supine Diastolic BP, Week16, n=1,1,1,1,1
    -5 ( 99999 )
    -12 ( 99999 )
    -10 ( 99999 )
    0 ( 99999 )
    8 ( 99999 )
    Notes
    [41] - ITT Population. “Not available (NA)” data is presented as “99999”
    [42] - ITT Population. “Not available (NA)” data is presented as “99999”
    [43] - ITT Population. “Not available (NA)” data is presented as “99999”
    [44] - ITT Population. “Not available (NA)” data is presented as “99999”
    [45] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in heart rate at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in heart rate at the indicated time points up to Week 16 [46]
    End point description
    Change from Baseline in sitting and supine heart rate is summarised for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    Notes
    [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [47]
    10 [48]
    10 [49]
    10 [50]
    11 [51]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Sitting Heart Rate, Week2, n=8,8,6,8,7
    5.25 ( 6.541 )
    -2.13 ( 7.357 )
    -0.5 ( 10.035 )
    -2.38 ( 9.68 )
    6.29 ( 13.45 )
        Sitting Heart Rate, Week4, n=6,6,7,8,7
    2 ( 8.786 )
    -0.67 ( 12.58 )
    3.43 ( 11.574 )
    -2.75 ( 8.924 )
    3.86 ( 15.869 )
        Sitting Heart Rate, Week6, n=6,8,5,8,8
    1.17 ( 4.07 )
    -3.13 ( 9.094 )
    -0.4 ( 6.58 )
    -2.38 ( 10.474 )
    4.88 ( 12.933 )
        Sitting Heart Rate, Week8, n=7,5,8,8,7
    7.43 ( 10.907 )
    -5.6 ( 10.139 )
    -1 ( 7.151 )
    2 ( 16.318 )
    3.43 ( 19.372 )
        Sitting Heart Rate, Week10, n=5,6,3,5,7
    2.2 ( 8.228 )
    -5.33 ( 7.866 )
    0.67 ( 5.686 )
    2.2 ( 6.87 )
    1.43 ( 17.116 )
        Sitting Heart Rate, Week12, n=6,5,6,7,6
    1 ( 10.881 )
    -6 ( 6 )
    5 ( 9.529 )
    -2.14 ( 9.668 )
    -2 ( 19.463 )
        Sitting Heart Rate, Week16, n=4,5,2,4,5
    -5.5 ( 8.737 )
    -3.8 ( 3.194 )
    -3 ( 2.828 )
    9.5 ( 13.229 )
    8 ( 19.3 )
        Supine Heart Rate, Week2, n=1,2,3,1,3
    7 ( 99999 )
    -1 ( 2.828 )
    2.67 ( 5.774 )
    1 ( 99999 )
    -6.33 ( 6.658 )
        Supine Heart Rate, Week4, n=2,2,1,0,3
    -2 ( 1.414 )
    0 ( 1.414 )
    4 ( 99999 )
    99999 ( 99999 )
    -3.33 ( 7.638 )
        Supine Heart Rate, Week6, n=1,2,1,1,0
    4 ( 99999 )
    -1.5 ( 0.707 )
    6 ( 99999 )
    -8 ( 99999 )
    99999 ( 99999 )
        Supine Heart Rate, Week8, n=1,2,1,1,2
    -8 ( 99999 )
    -0.5 ( 3.536 )
    12 ( 99999 )
    -11 ( 99999 )
    -4 ( 1.414 )
        Supine Heart Rate, Week10, n=2,2,1,1,1
    -4.5 ( 9.192 )
    -0.5 ( 0.707 )
    10 ( 99999 )
    -8 ( 99999 )
    -7 ( 99999 )
        Supine Heart Rate, Week12, n=1,2,1,1,1
    0 ( 99999 )
    -1 ( 1.414 )
    7 ( 99999 )
    -9 ( 99999 )
    -1 ( 99999 )
        Supine Heart Rate, Week16, n=1,1,1,1,1
    -8 ( 99999 )
    -2 ( 99999 )
    8 ( 99999 )
    -6 ( 99999 )
    0 ( 99999 )
    Notes
    [47] - ITT Population. “Not available (NA)” data is presented as “99999”
    [48] - ITT Population. “Not available (NA)” data is presented as “99999”
    [49] - ITT Population. “Not available (NA)” data is presented as “99999”
    [50] - ITT Population. “Not available (NA)” data is presented as “99999”
    [51] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in temperature at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in temperature at the indicated time points up to Week 16 [52]
    End point description
    Change from Baseline in temperature is summarised for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    Notes
    [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [53]
    10 [54]
    10 [55]
    10 [56]
    11 [57]
    Units: Celsius
    arithmetic mean (standard deviation)
        Temperature, Week2, n=9,10,9,9,10
    0.04 ( 0.279 )
    0.26 ( 0.556 )
    -0.01 ( 0.271 )
    -0.08 ( 0.299 )
    0.15 ( 0.331 )
        Temperature, Week4, n=8,8,8,8,10
    -0.06 ( 0.316 )
    0.34 ( 0.59 )
    0.19 ( 0.352 )
    0.09 ( 0.125 )
    -0.02 ( 0.326 )
        Temperature, Week6, n=7,10,6,9,8
    -0.01 ( 0.273 )
    0.12 ( 0.162 )
    0.2 ( 0.253 )
    0.18 ( 0.244 )
    0.24 ( 0.389 )
        Temperature, Week8, n=8,7,9,9,9
    0.04 ( 0.119 )
    0.06 ( 0.611 )
    0.07 ( 0.212 )
    0.04 ( 0.159 )
    0.18 ( 0.319 )
        Temperature, Week10, n=7,8,4,6,8
    0.04 ( 0.207 )
    0.11 ( 0.275 )
    0.23 ( 0.189 )
    0.07 ( 0.151 )
    0.18 ( 0.238 )
        Temperature, Week12, n=7,7,7,8,7
    0.09 ( 0.241 )
    0.3 ( 0.733 )
    0.1 ( 0.258 )
    0.08 ( 0.292 )
    0.09 ( 0.308 )
        Temperature, Week16, n=5,6,3,5,6
    -0.1 ( 0.1 )
    0.2 ( 0.369 )
    -0.13 ( 0.379 )
    0.04 ( 0.261 )
    0.05 ( 0.235 )
    Notes
    [53] - ITT Population. “Not available (NA)” data is presented as “99999”
    [54] - ITT Population. “Not available (NA)” data is presented as “99999”
    [55] - ITT Population. “Not available (NA)” data is presented as “99999”
    [56] - ITT Population. “Not available (NA)” data is presented as “99999”
    [57] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in albumin, globulin and protein at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in albumin, globulin and protein at the indicated time points up to Week 16 [58]
    End point description
    Change from Baseline in the albumin, globulin and protein values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [58] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [59]
    10 [60]
    10 [61]
    10 [62]
    11 [63]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        Albumin; Week2; n=9,9,9,9,10
    -0.4 ( 1.88 )
    0.2 ( 2.22 )
    -0.6 ( 2.19 )
    0.9 ( 2.2 )
    -1.2 ( 2.15 )
        Albumin; Week3; n=1,1,1,0,0
    -2 ( 99999 )
    -4 ( 99999 )
    1 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Albumin; Week4; n=8,9,8,9,9
    1.3 ( 2.05 )
    0.4 ( 2.55 )
    -1 ( 1.36 )
    1.1 ( 2.09 )
    -1.4 ( 3.09 )
        Albumin; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    2 ( 99999 )
    -3 ( 99999 )
    2 ( 99999 )
        Albumin; Week6; n=7,10,6,10,8
    -1 ( 2 )
    0.7 ( 2.31 )
    2.3 ( 2.5 )
    1 ( 3.13 )
    -0.9 ( 2.85 )
        Albumin; Week8; n=8,7,9,9,9
    1.3 ( 2.55 )
    -0.1 ( 2.34 )
    0.2 ( 1.79 )
    1.8 ( 4.02 )
    -2.1 ( 1.9 )
        Albumin; Week10; n=7,8,4,7,8
    -0.4 ( 2.15 )
    0.3 ( 2.82 )
    -0.3 ( 0.96 )
    1.7 ( 3.73 )
    -2.1 ( 1.55 )
        Albumin; Week12; n=7,7,7,8,7
    -0.4 ( 1.51 )
    0.6 ( 3.21 )
    -0.4 ( 2.57 )
    1 ( 3.66 )
    -2.6 ( 3.1 )
        Albumin; Week16; n=5,6,3,6,6
    -1.4 ( 2.88 )
    -1.5 ( 3.33 )
    -3 ( 1.73 )
    0.3 ( 3.01 )
    -2.5 ( 2.74 )
        Globulin; Week2; n=9,9,9,9,10
    -1.7 ( 3.2 )
    -0.6 ( 2.55 )
    0.2 ( 2.28 )
    -1.6 ( 2.96 )
    1.1 ( 1.79 )
        Globulin; Week3; n=1,1,1,0,0
    2 ( 99999 )
    0 ( 99999 )
    -6 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Globulin; Week4; n=8,9,8,9,9
    -2.1 ( 3.44 )
    -1.1 ( 3.18 )
    -1.8 ( 3.06 )
    -2.6 ( 1.67 )
    0.3 ( 2.92 )
        Globulin; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -0.7 ( 99999 )
    -3 ( 99999 )
    3 ( 99999 )
        Globulin; Week6; n=7,10,6,10,8
    -1 ( 1.83 )
    -0.3 ( 2.11 )
    -1.5 ( 3.33 )
    -3.4 ( 3.24 )
    1.5 ( 2 )
        Globulin; Week8; n=8,7,9,9,9
    -1.6 ( 3.78 )
    -1.7 ( 1.7 )
    -2.6 ( 3.13 )
    -2.6 ( 2.3 )
    -0.7 ( 2.29 )
        Globulin; Week10; n=7,8,4,7,8
    -2.1 ( 2.79 )
    -0.5 ( 2.27 )
    -0.8 ( 1.26 )
    -3.1 ( 1.46 )
    0.1 ( 1.64 )
        Globulin; Week12; n=7,7,7,8,7
    -0.3 ( 2.29 )
    -0.6 ( 3.46 )
    -0.7 ( 5.15 )
    -1.5 ( 3.02 )
    -0.4 ( 1.62 )
        Globulin; Week16; n=5,6,3,6,6
    -0.6 ( 1.67 )
    0.3 ( 2.34 )
    -0.7 ( 1.15 )
    -2 ( 4.1 )
    0.8 ( 2.23 )
        Protein; Week2; n=9,9,9,9,10
    -2.1 ( 3.95 )
    -0.3 ( 3.81 )
    -0.3 ( 3.81 )
    -0.7 ( 4.82 )
    -0.1 ( 3.14 )
        Protein; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -4 ( 99999 )
    -5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Protein; Week4; n=8,9,8,9,9
    -0.9 ( 2.9 )
    -0.7 ( 4.44 )
    -1.9 ( 2.23 )
    -1.4 ( 3.4 )
    -1.1 ( 3.52 )
        Protein; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -5 ( 99999 )
    -6 ( 99999 )
    5 ( 99999 )
        Protein; Week6; n=7,10,6,10,8
    -2 ( 3.46 )
    0.4 ( 2.8 )
    0.8 ( 2.93 )
    -2.4 ( 5.8 )
    0.6 ( 2.83 )
        Protein; Week8; n=8,7,9,9,9
    -0.4 ( 3.29 )
    -1.9 ( 2.54 )
    -2.3 ( 3.84 )
    -0.8 ( 5.21 )
    -2.8 ( 3.42 )
        Protein; Week10; n=7,8,4,7,8
    -2.6 ( 4.47 )
    -0.3 ( 3.69 )
    -1 ( 1.15 )
    -1.4 ( 4.39 )
    -2 ( 2.45 )
        Protein; Week12; n=7,7,7,8,7
    -0.7 ( 3.68 )
    0 ( 3.42 )
    -1.1 ( 3.53 )
    -0.5 ( 4 )
    -3 ( 3.32 )
        Protein; Week16; n=5,6,3,6,6
    -2 ( 4.36 )
    -1.2 ( 3.25 )
    -3.7 ( 1.53 )
    -1.7 ( 4.5 )
    -1.7 ( 3.44 )
    Notes
    [59] - ITT Population. “Not available (NA)” data is presented as “99999”
    [60] - ITT Population. “Not available (NA)” data is presented as “99999”
    [61] - ITT Population. “Not available (NA)” data is presented as “99999”
    [62] - ITT Population. “Not available (NA)” data is presented as “99999”
    [63] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase, gamma glutamyl transferase and lactate dehydrogenase at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase, gamma glutamyl transferase and lactate dehydrogenase at the indicated time points up to Week 16 [64]
    End point description
    Change from Baseline in the alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), creatine kinase (CK), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [64] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [65]
    10 [66]
    10 [67]
    10 [68]
    11 [69]
    Units: International units per liter
    arithmetic mean (standard deviation)
        ALP; Week2; n=9,9,9,9,10
    -4.2 ( 6.2 )
    1.7 ( 16.53 )
    -5.8 ( 13.64 )
    -4.1 ( 5.64 )
    -3.7 ( 9.33 )
        ALP; Week3; n=1,1,1,0,0
    5 ( 99999 )
    -10 ( 99999 )
    -59 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        ALP; Week4; n=8,9,8,9,9
    -0.9 ( 7.47 )
    -4.4 ( 6.52 )
    24.6 ( 102.06 )
    -3 ( 11.64 )
    0.3 ( 20.46 )
        ALP; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    27.7 ( 122.66 )
    12 ( 99999 )
    4 ( 99999 )
        ALP; Week6; n=7,10,7,10,8
    -3.1 ( 7.27 )
    -5.1 ( 4.95 )
    -4.4 ( 35.58 )
    -6.9 ( 10.76 )
    -2 ( 10.94 )
        ALP; Week8; n=9,7,9,9,9
    -5.3 ( 7.89 )
    -8.1 ( 5.87 )
    -13 ( 26 )
    -5.9 ( 7.06 )
    -3.3 ( 10.7 )
        ALP; Week10; n=7,8,4,7,8
    -5.3 ( 12.62 )
    -7.8 ( 7.83 )
    -16.3 ( 9.29 )
    -12.4 ( 10.66 )
    0.6 ( 13.32 )
        ALP; Week12; n=7,7,7,8,7
    -2.7 ( 9.07 )
    -6.4 ( 12.99 )
    -19.6 ( 24.23 )
    -10.4 ( 8.75 )
    -3.6 ( 8.14 )
        ALP; Week16; n=5,6,3,6,6
    1.2 ( 6.42 )
    -9.8 ( 9.83 )
    -8.3 ( 2.52 )
    -9.2 ( 16.75 )
    11.7 ( 37.75 )
        ALT; Week2; n=9,9,9,9,10
    10.4 ( 28.1 )
    24.1 ( 65.25 )
    35.3 ( 68.85 )
    10.7 ( 23.49 )
    1.4 ( 4.06 )
        ALT; Week3; n=1,1,1,0,0
    5 ( 99999 )
    -2 ( 99999 )
    5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        ALT; Week4; n=8,9,8,9,9
    0 ( 5.63 )
    1.8 ( 13.71 )
    67.3 ( 156.91 )
    7.7 ( 17.15 )
    1.1 ( 6.83 )
        ALT; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    40 ( 67.18 )
    17 ( 99999 )
    0 ( 99999 )
        ALT; Week6; n=7,10,7,10,8
    56.1 ( 149.97 )
    1 ( 4.67 )
    9.3 ( 27.37 )
    27.37 ( 4.36 )
    0.3 ( 4.65 )
        ALT; Week8; n=9,7,9,9,9
    -0.4 ( 4.98 )
    1.3 ( 9.95 )
    -2.3 ( 13.02 )
    0.8 ( 3.11 )
    1 ( 5.63 )
        ALT; Week10; n=7,8,4,7,8
    4.3 ( 13.31 )
    -2.4 ( 6.99 )
    1.8 ( 4.27 )
    1.3 ( 3.9 )
    -1.9 ( 4.94 )
        ALT; Week12; n=7,7,7,8,7
    9.6 ( 24.79 )
    -1.6 ( 6.16 )
    -5.3 ( 11.87 )
    4 ( 5.32 )
    -0.9 ( 3.85 )
        ALT; Week16; n=5,6,3,6,6
    2 ( 6.44 )
    3.5 ( 14.45 )
    2.3 ( 3.79 )
    -1.2 ( 5.31 )
    -0.7 ( 3.67 )
        AST; Week2; n=9,9,9,9,10
    9.7 ( 21.6 )
    37.6 ( 106.14 )
    37.7 ( 61.72 )
    14.8 ( 23.69 )
    2 ( 3.02 )
        AST; Week3; n=1,1,1,0,0
    6 ( 99999 )
    2 ( 99999 )
    -24 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        AST; Week4; n=8,9,8,9,9
    -2.8 ( 5.85 )
    -0.1 ( 3.14 )
    25.9 ( 68.92 )
    5 ( 3.04 )
    0.8 ( 4.74 )
        AST; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -4.3 ( 16.92 )
    -1 ( 99999 )
    0 ( 99999 )
        AST; Week6; n=7,10,7,10,8
    25.6 ( 66.39 )
    1.4 ( 4.2 )
    5 ( 23.47 )
    2.5 ( 7.49 )
    -0.5 ( 2 )
        AST; Week8; n=9,7,9,9,9
    1 ( 6.71 )
    2.7 ( 7.48 )
    -3.2 ( 10.8 )
    4 ( 4.66 )
    0.3 ( 4.12 )
        AST; Week10; n=7,8,4,7,8
    4.4 ( 7.61 )
    -0.9 ( 5.22 )
    2.5 ( 5 )
    4.9 ( 3.29 )
    -0.6 ( 4.57 )
        AST; Week12; n=7,7,7,8,7
    8 ( 17.95 )
    1.1 ( 5.79 )
    -2 ( 11.55 )
    8.5 ( 7.03 )
    0 ( 2.31 )
        AST; Week16; n=5,6,3,6,6
    1.6 ( 6.66 )
    0.3 ( 9.52 )
    2.3 ( 3.06 )
    -0.2 ( 3.25 )
    0.7 ( 2.58 )
        CK; Week2; n=9,9,9,9,10
    7.4 ( 10.51 )
    287.9 ( 809.45 )
    38.9 ( 53.16 )
    41.9 ( 31.62 )
    0.3 ( 6.58 )
        CK; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -27 ( 99999 )
    -30 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        CK; Week4; n=8,9,8,9,9
    2.6 ( 15.18 )
    25.1 ( 15.14 )
    19.3 ( 26.12 )
    55.9 ( 54.49 )
    4.7 ( 13.72 )
        CK; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    83 ( 154.15 )
    -19 ( 99999 )
    -5 ( 99999 )
        CK; Week6; n=7,10,7,10,8
    21.3 ( 30.6 )
    16.8 ( 17.16 )
    26.3 ( 37.3 )
    59.9 ( 125.28 )
    7.6 ( 22.19 )
        CK; Week8; n=9,7,9,9,9
    12.5 ( 17.03 )
    27.6 ( 26.79 )
    21.4 ( 53.68 )
    68.4 ( 57.07 )
    4.9 ( 13.36 )
        CK; Week10; n=7,8,4,7,8
    18.7 ( 20.25 )
    34.5 ( 31 )
    53.3 ( 45.68 )
    81.1 ( 63.2 )
    9.6 ( 34.85 )
        CK; Week12; n=7,7,7,8,7
    21.7 ( 24.56 )
    28.9 ( 20.36 )
    12.9 ( 50.7 )
    173.6 ( 265.21 )
    24.9 ( 52.2 )
        CK; Week16; n=5,6,3,6,6
    25.6 ( 39.6 )
    15.7 ( 10.52 )
    -4.3 ( 19.14 )
    18.5 ( 25.56 )
    -1.8 ( 18.45 )
        GGT; Week2; n=9,9,9,9,10
    1 ( 4.74 )
    15.7 ( 45.96 )
    5.9 ( 18.1 )
    0.2 ( 4.92 )
    -0.6 ( 7.26 )
        GGT; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -2 ( 99999 )
    19 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        GGT; Week4; n=8,9,8,9,9
    0.5 ( 4.14 )
    4.6 ( 25.5 )
    82.8 ( 197.06 )
    6.4 ( 25.04 )
    4 ( 16.12 )
        GGT; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -25 ( 99999 )
    42 ( 99999 )
    -2 ( 99999 )
        GGT; Week6; n=7,10,7,10,8
    5 ( 14.05 )
    1.2 ( 12.74 )
    1.2 ( 20.68 )
    3.1 ( 8.17 )
    -0.1 ( 7.3 )
        GGT; Week8; n=9,7,9,9,9
    -1.5 ( 8.67 )
    -0.3 ( 11.25 )
    7.2 ( 29.11 )
    0.9 ( 5.62 )
    -0.7 ( 6.26 )
        GGT; Week10; n=7,8,4,7,8
    -0.3 ( 3.73 )
    -4.1 ( 8.53 )
    0.8 ( 6.18 )
    -2.6 ( 2.76 )
    -1.9 ( 6.38 )
        GGT; Week12; n=7,7,7,8,7
    3.4 ( 13.2 )
    -4.3 ( 8.86 )
    -5.3 ( 16.5 )
    -1.5 ( 3.93 )
    -2.6 ( 4.79 )
        GGT; Week16; n=5,6,3,6,6
    0.8 ( 3.96 )
    -2.5 ( 5.09 )
    2 ( 5.2 )
    -1.3 ( 4.27 )
    6.3 ( 20.55 )
        LDH; Week2; n=9,9,9,9,10
    7.7 ( 21.75 )
    61.3 ( 148.63 )
    73.1 ( 70.39 )
    49.3 ( 62.86 )
    5.9 ( 20.62 )
        LDH; Week3; n=1,1,1,0,0
    18 ( 99999 )
    6 ( 99999 )
    -2 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        LDH; Week4; n=8,9,8,9,9
    -17.6 ( 55.64 )
    11.6 ( 12.85 )
    80.5 ( 160.09 )
    31.8 ( 32.28 )
    -7.7 ( 17.93 )
        LDH; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    45 ( 82.02 )
    43 ( 99999 )
    -1 ( 99999 )
        LDH; Week6; n=7,10,7,10,8
    18.7 ( 49.19 )
    10.1 ( 20.43 )
    21.3 ( 31.78 )
    36.8 ( 36.43 )
    -5.4 ( 15.68 )
        LDH; Week8; n=9,7,9,9,9
    -11.8 ( 36.81 )
    3.7 ( 18.59 )
    14.8 ( 21.62 )
    40.4 ( 25.95 )
    -1.6 ( 20.43 )
        LDH; Week10; n=7,8,4,7,8
    -3.7 ( 25.92 )
    22.4 ( 25.05 )
    23.8 ( 22.91 )
    41.3 ( 31.37 )
    -1.1 ( 11.92 )
        LDH; Week12; n=7,7,7,8,7
    0.6 ( 27.16 )
    18.4 ( 16.92 )
    9.7 ( 32.91 )
    46 ( 34.33 )
    3.9 ( 22.3 )
        LDH; Week16; n=5,6,3,6,6
    -2.2 ( 28.59 )
    9.3 ( 18.91 )
    4.3 ( 14.05 )
    17.7 ( 18.11 )
    -1.5 ( 30.33 )
    Notes
    [65] - ITT Population. “Not available (NA)” data is presented as “99999”
    [66] - ITT Population. “Not available (NA)” data is presented as “99999”
    [67] - ITT Population. “Not available (NA)” data is presented as “99999”
    [68] - ITT Population. “Not available (NA)” data is presented as “99999”
    [69] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in anion gap, calcium, cholesterol, chloride, carbon dioxide, glucose, HDL cholesterol, potassium, LDL cholesterol, magnesium, phosphate, sodium, triglycerides, urea, VLDL cholesterol at the indicated time points up to Week 16.

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    End point title
    		 Change from Baseline in anion gap, calcium, cholesterol, chloride, carbon dioxide, glucose, HDL cholesterol, potassium, LDL cholesterol, magnesium, phosphate, sodium, triglycerides, urea, VLDL cholesterol at the indicated time points up to Week 16. [70]
    End point description
    Change from Baseline in the anion gap, calcium, ionised calcium, cholesterol, chloride, carbon dioxide, glucose, high density lipoprotein (HDL) cholesterol (fasted and not fasted), potassium, low density lipoprotein (LDL) cholesterol (fasted and not fasted), magnesium, phosphate, sodium, triglycerides (fasted and not fasted), urea and very low density lipoprotein (VLDL) cholesterol values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (n=X,X,X,X,X). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [70] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [71]
    10 [72]
    10 [73]
    10 [74]
    11 [75]
    Units: Millimoles per liter
    arithmetic mean (standard deviation)
        Anion Gap; Week2; n=9,9,9,9,10
    -1.8 ( 2.49 )
    -0.8 ( 2.39 )
    -1 ( 3.71 )
    -0.1 ( 2.37 )
    -1.1 ( 3.48 )
        Anion Gap; Week3; n=1,1,1,0,0
    -3 ( 99999 )
    -3 ( 99999 )
    -5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Anion Gap; Week4; n=8,9,8,9,9
    0 ( 3.55 )
    -0.8 ( 3.15 )
    -0.6 ( 4.57 )
    -1 ( 4.06 )
    -0.7 ( 2.69 )
        Anion Gap; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -9 ( 99999 )
    -3 ( 99999 )
    -2 ( 99999 )
        Anion Gap; Week6; n=6,10,6,9,7
    0 ( 1.67 )
    -1 ( 3.09 )
    -1.7 ( 2.66 )
    -1.7 ( 2.5 )
    0 ( 1 )
        Anion Gap; Week8; n=8,7,8,9,9
    -0.5 ( 2.56 )
    -0.9 ( 3.93 )
    -0.5 ( 3.93 )
    -0.3 ( 3.87 )
    -1.4 ( 1.51 )
        Anion Gap; Week10; n=7,8,4,7,8
    0 ( 2.94 )
    -1.3 ( 3.62 )
    -1.3 ( 2.5 )
    0 ( 2.08 )
    -1 ( 1.51 )
        Anion Gap; Week12; n=6,7,7,8,7
    2.3 ( 2.5 )
    -0.9 ( 3.08 )
    -1.3 ( 4.54 )
    -0.3 ( 2.82 )
    -2.4 ( 3.1 )
        Anion Gap; Week16; n=5,6,3,6,6
    -0.8 ( 2.77 )
    0.8 ( 3.19 )
    -2.3 ( 3.06 )
    -0.3 ( 2.88 )
    -0.7 ( 3.5 )
        Calcium; Week2; n=9,9,9,9,10
    -0.036 ( 0.0654 )
    -0.011 ( 0.0842 )
    -0.029 ( 0.0985 )
    -0.034 ( 0.0814 )
    -0.03 ( 0.1111 )
        Calcium; Week3; n=1,1,1,0,0
    -0.12 ( 99999 )
    -0.06 ( 99999 )
    0.01 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Calcium; Week4; n=8,9,8,9,9
    -0.001 ( 0.0517 )
    -0.007 ( 0.0667 )
    -0.01 ( 0.0404 )
    -0.02 ( 0.061 )
    -0.006 ( 0.0843 )
        Calcium; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.08 ( 99999 )
    0.19 ( 99999 )
    0.11 ( 99999 )
        Calcium; Week6; n=7,10,7,10,8
    -0.033 ( 0.0596 )
    0.023 ( 0.0952 )
    0.043 ( 0.1108 )
    -0.02 ( 0.0833 )
    -0.049 ( 0.1166 )
        Calcium; Week8; n=9,7,9,9,9
    -0.051 ( 0.1109 )
    -0.02 ( 0.0728 )
    0.028 ( 0.0992 )
    0.002 ( 0.0856 )
    -0.059 ( 0.1125 )
        Calcium; Week10; n=7,8,4,7,8
    -0.053 ( 0.0692 )
    -0.032 ( 0.0794 )
    0 ( 0.0606 )
    -0.013 ( 0.0685 )
    -0.046 ( 0.0825 )
        Calcium; Week12; n=7,7,7,8,7
    -0.053 ( 0.0783 )
    -0.023 ( 0.105 )
    0.003 ( 0.0665 )
    -0.055 ( 0.0644 )
    -0.027 ( 0.072 )
        Calcium; Week16; n=5,6,3,6,6
    -0.02 ( 0.1288 )
    -0.065 ( 0.0779 )
    -0.03 ( 0.0755 )
    -0.04 ( 0.0654 )
    -0.027 ( 0.1046 )
        Calcium ionised; Week2; n=9,9,9,9,10
    0.003 ( 0.032 )
    0.001 ( 0.0448 )
    -0.011 ( 0.0183 )
    -0.011 ( 0.0306 )
    -0.012 ( 0.0326 )
        Calcium ionised; Week3; n=1,1,1,0,0
    -0.05 ( 99999 )
    0.01 ( 99999 )
    0.04 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Calcium ionised; Week4; n=8,9,8,9,9
    0.009 ( 0.0314 )
    -0.002 ( 0.0268 )
    0.011 ( 0.0217 )
    0.001 ( 0.0392 )
    0.003 ( 0.0274 )
        Calcium ionised; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.08 ( 99999 )
    0.14 ( 99999 )
    0 ( 99999 )
        Calcium ionised; Week6; n=6,10,6,9,7
    0.007 ( 0.0356 )
    0.004 ( 0.0357 )
    0.013 ( 0.0327 )
    0.01 ( 0.0456 )
    -0.023 ( 0.0446 )
        Calcium ionised; Week8; n=8,7,8,9,9
    -0.019 ( 0.0491 )
    0.009 ( 0.0302 )
    0.03 ( 0.0283 )
    0.009 ( 0.0293 )
    -0.003 ( 0.0433 )
        Calcium ionised; Week10; n=7,8,4,7,8
    0.003 ( 0.0359 )
    -0.01 ( 0.0351 )
    0.01 ( 0.0216 )
    0.006 ( 0.0315 )
    -0.001 ( 0.0356 )
        Calcium ionised; Week12; n=7,7,7,8,7
    -0.016 ( 0.0506 )
    -0.013 ( 0.0427 )
    0.011 ( 0.0334 )
    -0.021 ( 0.0348 )
    0.013 ( 0.039 )
        Calcium ionised; Week16; n=5,6,3,6,6
    0.012 ( 0.0396 )
    -0.018 ( 0.0382 )
    0.017 ( 0.0379 )
    -0.007 ( 0.0398 )
    0.007 ( 0.0372 )
        Cholesterol; Week2; n=9,9,9,9,10
    -0.126 ( 0.5514 )
    0.167 ( 0.4644 )
    -0.039 ( 0.4517 )
    0.316 ( 0.6995 )
    0.079 ( 0.3626 )
        Cholesterol; Week3; n=1,1,1,0,0
    -0.56 ( 99999 )
    -0.15 ( 99999 )
    1.51 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Cholesterol; Week4; n=8,9,8,9,9
    0.197 ( 0.8224 )
    0.197 ( 0.7258 )
    0.519 ( 0.9386 )
    0.322 ( 0.6854 )
    -0.023 ( 0.3443 )
        Cholesterol; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.98 ( 99999 )
    -0.55 ( 99999 )
    0.92 ( 99999 )
        Cholesterol; Week6; n=7,10,6,10,8
    -0.023 ( 0.7105 )
    0.325 ( 0.5219 )
    0.472 ( 0.8739 )
    0.559 ( 0.7808 )
    -0.103 ( 0.5727 )
        Cholesterol; Week8; n=8,7,9,9,9
    0.146 ( 0.5702 )
    -0.039 ( 0.3315 )
    0.466 ( 0.5557 )
    0.688 ( 0.8384 )
    -0.171 ( 0.3699 )
        Cholesterol; Week10; n=7,8,4,7,8
    -0.061 ( 0.5494 )
    0.26 ( 0.5641 )
    0.195 ( 0.3747 )
    0.551 ( 0.6929 )
    -0.549 ( 0.2554 )
        Cholesterol; Week12; n=7,7,7,8,7
    0.173 ( 0.5702 )
    0.147 ( 0.384 )
    0.119 ( 0.3293 )
    0.601 ( 0.5253 )
    -0.176 ( 0.348 )
        Cholesterol; Week16; n=5,6,3,6,6
    -0.472 ( 0.4219 )
    0.04 ( 0.3043 )
    0.133 ( 0.0569 )
    0.223 ( 0.4871 )
    -0.26 ( 0.3636 )
        Chloride; Week2; n=9,9,9,9,10
    0.3 ( 2.6 )
    1 ( 1.73 )
    0.1 ( 3.22 )
    -1.3 ( 2.12 )
    0.1 ( 2.42 )
        Chloride; Week3; n=1,1,1,0,0
    3 ( 99999 )
    -1 ( 99999 )
    -3 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Chloride; Week4; n=8,9,8,9,9
    99999 ( 99999 )
    0.7 ( 1.94 )
    -0.9 ( 2.3 )
    -0.4 ( 2.4 )
    0.7 ( 1.73 )
        Chloride; Week5; n=0,0,1,1,1
    -1.3 ( 1.39 )
    99999 ( 99999 )
    -1 ( 99999 )
    -3 ( 99999 )
    -6 ( 99999 )
        Chloride; Week6; n=7,10,6,10,8
    -0.3 ( 1.11 )
    -0.8 ( 2.53 )
    -0.3 ( 1.51 )
    -0.3 ( 2.06 )
    0.3 ( 1.67 )
        Chloride; Week8; n=8,7,9,9,9
    -0.5 ( 2.33 )
    1.6 ( 2.15 )
    0.1 ( 1.96 )
    -1.1 ( 3.06 )
    0.6 ( 1.67 )
        Chloride; Week10; n=7,8,4,7,8
    0.9 ( 2.41 )
    0.9 ( 2.42 )
    0.3 ( 1.71 )
    -0.7 ( 1.25 )
    0.9 ( 2.1 )
        Chloride; Week12; n=7,7,7,8,7
    0.3 ( 2.14 )
    1.4 ( 2.76 )
    0.3 ( 1.98 )
    -0.5 ( 2.88 )
    0.6 ( 1.13 )
        Chloride; Week16; n=5,6,3,6,6
    -0.4 ( 2.19 )
    1.5 ( 2.35 )
    -0.7 ( 2.08 )
    -1.5 ( 2.66 )
    1.2 ( 1.33 )
        Carbon Dioxide; Week2; n=9,9,9,9,10
    0 ( 1.8 )
    -1 ( 1.32 )
    -0.4 ( 3 )
    -0.1 ( 1.62 )
    1.1 ( 2.38 )
        Carbon Dioxide; Week3; n=1,1,1,0,0
    -1 ( 99999 )
    3 ( 99999 )
    5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Carbon Dioxide; Week4; n=8,9,8,9,9
    -0.4 ( 2.77 )
    -1.3 ( 2.45 )
    0.4 ( 3.29 )
    0.2 ( 1.64 )
    0.9 ( 2.03 )
        Carbon Dioxide; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    7 ( 99999 )
    4 ( 99999 )
    4 ( 99999 )
        Carbon Dioxide; Week6; n=7,10,6,10,8
    -0.9 ( 2.19 )
    0.5 ( 2.17 )
    0.3 ( 1.51 )
    0.9 ( 2.69 )
    0.4 ( 1.6 )
        Carbon Dioxide; Week8; n=8,7,9,9,9
    0.3 ( 1.98 )
    -1 ( 2.45 )
    -1.1 ( 3.59 )
    -0.1 ( 2.71 )
    0.9 ( 2.26 )
        Carbon Dioxide; Week10; n=7,8,4,7,8
    -1.6 ( 2.88 )
    -0.1 ( 1.81 )
    0.3 ( 2.99 )
    0.6 ( 2.15 )
    0.5 ( 1.77 )
        Carbon Dioxide; Week12; n=7,7,7,8,7
    -2.1 ( 2.34 )
    -1.3 ( 1.38 )
    -0.6 ( 3.64 )
    0.1 ( 2.42 )
    1.7 ( 2.56 )
        Carbon Dioxide; Week16; n=5,6,3,6,6
    -0.2 ( 0.84 )
    -1.8 ( 1.83 )
    1.7 ( 1.53 )
    0.8 ( 2.23 )
    0 ( 3.69 )
        Glucose; Week2; n=9,9,9,9,10
    0.2 ( 0.304 )
    0.04 ( 0.384 )
    0.27 ( 1.302 )
    0.03 ( 0.779 )
    0.07 ( 0.368 )
        Glucose; Week3; n=1,1,1,0,0
    1.7 ( 99999 )
    -0.1 ( 99999 )
    -1.3 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Glucose; Week4; n=8,9,8,9,9
    0.11 ( 0.348 )
    0.11 ( 0.276 )
    -0.14 ( 0.403 )
    0.12 ( 0.851 )
    0.32 ( 0.338 )
        Glucose; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -0.5 ( 99999 )
    0.7 ( 99999 )
    0.4 ( 99999 )
        Glucose; Week6; n=7,10,6,10,8
    0.46 ( 0.506 )
    0.09 ( 0.428 )
    0.53 ( 1.813 )
    -0.08 ( 1.191 )
    0.69 ( 1.106 )
        Glucose; Week8; n=8,7,9,9,9
    0.06 ( 0.444 )
    -0.01 ( 0.186 )
    0.26 ( 0.646 )
    0.11 ( 0.796 )
    0 ( 0.403 )
        Glucose; Week10; n=7,8,4,7,8
    0.21 ( 0.334 )
    0.03 ( 0.271 )
    0 ( 0.356 )
    -0.2 ( 0.889 )
    0.05 ( 0.487 )
        Glucose; Week12; n=7,7,7,8,7
    0.16 ( 0.613 )
    0.16 ( 0.424 )
    -0.31 ( 0.414 )
    -0.19 ( 0.559 )
    -0.03 ( 0.386 )
        Glucose; Week16; n=5,6,3,6,6
    0.12 ( 0.383 )
    0.13 ( 0.207 )
    -0.07 ( 0.289 )
    1.48 ( 4.014 )
    -0.02 ( 0.271 )
        HDL Cholesterol, Fasted; Week2; n=0,1,0,0,1
    99999 ( 99999 )
    -0.3 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.25 ( 99999 )
        HDL Cholesterol, Fasted; Week3; n=1,1,0,0,0
    -0.18 ( 99999 )
    -0.27 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        HDL Cholesterol, Fasted; Week4; n=1,1,2,0,1
    0.66 ( 99999 )
    0.4 ( 99999 )
    0.225 ( 0.0354 )
    99999 ( 99999 )
    -0.09 ( 99999 )
        HDL Cholesterol, Fasted; Week6; n=0,1,0,1,0
    99999 ( 99999 )
    0.1 ( 99999 )
    99999 ( 99999 )
    0.08 ( 99999 )
    99999 ( 99999 )
        HDL Cholesterol, Fasted; Week8; n=0,0,3,01
    99999 ( 99999 )
    99999 ( 99999 )
    -0.013 ( 0.3664 )
    99999 ( 99999 )
    -0.08 ( 99999 )
        HDL Cholesterol, Fasted; Week10; n=2,1,0,0,0
    0.125 ( 0.0354 )
    -0.2 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.03 ( 99999 )
        HDL Cholesterol, Fasted; Week12; n=5,6,4,6,5
    0.06 ( 0.1925 )
    0.06 ( 0.1637 )
    0.098 ( 0.3063 )
    0.487 ( 0.3847 )
    -0.158 ( 0.177 )
        HDL Cholesterol, Not fasted; Week2; n=9,8,9,9,9
    -0.013 ( 0.1655 )
    0.145 ( 0.1305 )
    -0.24 ( 0.3226 )
    0.107 ( 0.4241 )
    0.046 ( 0.2051 )
        HDL Cholesterol, Not fasted; Week3; n=0,0,1,0,0
    99999 ( 99999 )
    99999 ( 99999 )
    -0.09 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        HDL Cholesterol, Not fasted; Week4; n=7,8,6,9,8
    -0.029 ( 0.1046 )
    0.16 ( 0.1336 )
    -0.145 ( 0.125 )
    0.294 ( 0.2932 )
    0.017 ( 0.1951 )
        HDL Cholesterol, Not fasted; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.05 ( 99999 )
    0.05 ( 99999 )
    0.06 ( 99999 )
        HDL Cholesterol, Not fasted; Week6; n=7,9,6,9,8
    -0.05 ( 0.1751 )
    0.159 ( 0.309 )
    0.073 ( 0.207 )
    0.322 ( 0.2712 )
    0.04 ( 0.3704 )
        HDL Cholesterol, Not fasted; Week8; n=8,7,6,8,8
    0.066 ( 0.0639 )
    0.11 ( 0.2728 )
    0.033 ( 0.2309 )
    0.543 ( 0.4174 )
    -0.05 ( 0.2594 )
        HDL Cholesterol, Not fasted; Week10; n=5,7,4,7,7
    -0.138 ( 0.1397 )
    0.136 ( 0.0969 )
    0.058 ( 0.2804 )
    0.464 ( 0.2531 )
    -0.151 ( 0.2769 )
        HDL Cholesterol, Not fasted; Week12; n=2,1,4,2,2
    -0.165 ( 0.1909 )
    -0.1 ( 99999 )
    0.12 ( 0.1581 )
    0.175 ( 0.0212 )
    0.045 ( 0.1344 )
        HDL Cholesterol, Not fasted; Week16; n=5,6,3,6,6
    -0.278 ( 0.2805 )
    -0.003 ( 0.2211 )
    -0.2 ( 0.2931 )
    0.137 ( 0.1875 )
    -0.103 ( 0.2808 )
        Potassium; Week2; n=9,9,9,9,10
    -0.18 ( 0.299 )
    0.01 ( 0.196 )
    -0.13 ( 0.312 )
    -0.18 ( 0.367 )
    0.1 ( 0.447 )
        Potassium; Week3; n=1,1,1,0,0
    0 ( 99999 )
    0.2 ( 99999 )
    0.2 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Potassium; Week4; n=8,9,8,9,9
    -0.06 ( 0.141 )
    0.07 ( 0.461 )
    -0.15 ( 0.421 )
    -0.16 ( 0.34 )
    0.13 ( 0.367 )
        Potassium; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -0.4 ( 99999 )
    0 ( 99999 )
    0.2 ( 99999 )
        Potassium; Week6; n=7,10,6,10,8
    0.03 ( 0.214 )
    0.15 ( 0.403 )
    0.03 ( 0.197 )
    -0.18 ( 0.371 )
    0.13 ( 0.392 )
        Potassium; Week8; n=8,7,9,9,9
    -0.06 ( 0.338 )
    0.03 ( 0.315 )
    0 ( 0.418 )
    -0.06 ( 0.283 )
    -0.08 ( 0.399 )
        Potassium; Week10; n=7,8,4,7,8
    -0.26 ( 0.223 )
    0.05 ( 0.382 )
    -0.03 ( 0.222 )
    -0.14 ( 0.42 )
    0.04 ( 0.207 )
        Potassium; Week12; n=7,7,7,8,7
    -0.06 ( 0.113 )
    -0.04 ( 0.369 )
    0.04 ( 0.341 )
    -0.11 ( 0.383 )
    -0.09 ( 0.334 )
        Potassium; Week16; n=5,6,3,6,6
    -0.2 ( 0.292 )
    -0.08 ( 0.371 )
    0.07 ( 0.321 )
    -0.12 ( 0.286 )
    0 ( 0.363 )
        LDL Cholesterol, Fasted; Week2; n=0,1,0,0,1
    99999 ( 99999 )
    -0.38 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.4 ( 99999 )
        LDL Cholesterol, Fasted; Week3; n=1,1,0,0,0
    -0.62 ( 99999 )
    -0.34 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        LDL Cholesterol, Fasted; Week4; n=1,1,2,0,1
    1.5 ( 99999 )
    1.3 ( 99999 )
    0.52 ( 1.3576 )
    99999 ( 99999 )
    0.07 ( 99999 )
        LDL Cholesterol, Fasted; Week6; n=0,1,0,1,0
    99999 ( 99999 )
    -0.21 ( 99999 )
    99999 ( 99999 )
    -1 ( 99999 )
    99999 ( 99999 )
        LDL Cholesterol, Fasted; Week8; n=0,0,3,01
    99999 ( 99999 )
    99999 ( 99999 )
    0.37 ( 0.2946 )
    99999 ( 99999 )
    -0.35 ( 99999 )
        LDL Cholesterol, Fasted; Week10; n=2,1,0,0,0
    0.01 ( 0.396 )
    0.14 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.18 ( 99999 )
        LDL Cholesterol, Fasted; Week12; n=4,5,4,6,5
    0.147 ( 0.287 )
    0 ( 0.3272 )
    0.105 ( 0.2464 )
    0.187 ( 0.283 )
    0.096 ( 0.3396 )
        LDL Cholesterol, Not fasted; Week2; n=9,7,9,9,9
    -0.271 ( 0.6127 )
    0.157 ( 0.5447 )
    -0.212 ( 0.3942 )
    0.144 ( 0.6862 )
    -0.016 ( 0.2168 )
        LDL Cholesterol, Not fasted; Week3; n=0,0,1,0,0
    99999 ( 99999 )
    99999 ( 99999 )
    0.19 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        LDL Cholesterol, Not fasted; Week4; n=7,7,6,9,8
    -0.104 ( 0.4535 )
    -0.089 ( 0.3488 )
    -0.03 ( 0.3504 )
    0.086 ( 0.6037 )
    -0.023 ( 0.5208 )
        LDL Cholesterol, Not fasted; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.1 ( 99999 )
    -0.62 ( 99999 )
    0.55 ( 99999 )
        LDL Cholesterol, Not fasted; Week6; n=7,8,6,9,8
    -0.301 ( 0.6443 )
    0.349 ( 0.578 )
    0.052 ( 0.5242 )
    0.25 ( 0.5119 )
    -0.101 ( 0.428 )
        LDL Cholesterol, Not fasted; Week8; n=8,6,6,8,8
    0.143 ( 0.635 )
    0.085 ( 0.6563 )
    0.102 ( 0.4613 )
    0.166 ( 0.663 )
    0.091 ( 0.3331 )
        LDL Cholesterol, Not fasted; Week10; n=5,6,4,7,7
    -0.492 ( 0.2993 )
    0.385 ( 0.6471 )
    -0.198 ( 0.3826 )
    0.121 ( 0.6339 )
    -0.424 ( 0.2717 )
        LDL Cholesterol, Not fasted; Week12; n=2,1,4,2,2
    -0.105 ( 0.8839 )
    0.43 ( 99999 )
    -0.253 ( 0.3269 )
    0.54 ( 0.3111 )
    0.105 ( 0.0919 )
        LDL Cholesterol, Not fasted; Week16; n=5,5,3,6,6
    -0.48 ( 0.6055 )
    0.294 ( 0.6993 )
    -0.267 ( 0.2479 )
    -0.055 ( 0.542 )
    -0.082 ( 0.3476 )
        Magnesium; Week2; n=9,9,9,9,10
    -0.02 ( 0.0548 )
    0.023 ( 0.0904 )
    0.011 ( 0.0766 )
    0.019 ( 0.0417 )
    -0.003 ( 0.046 )
        Magnesium; Week3; n=1,1,1,0,0
    0.07 ( 99999 )
    0.13 ( 99999 )
    0.14 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Magnesium; Week4; n=8,9,8,9,9
    0.015 ( 0.0207 )
    0.006 ( 0.0841 )
    0.025 ( 0.0573 )
    0.004 ( 0.0557 )
    -0.013 ( 0.0433 )
        Magnesium; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.08 ( 99999 )
    0 ( 99999 )
    0.05 ( 99999 )
        Magnesium; Week6; n=7,10,6,10,8
    -0.016 ( 0.0493 )
    0.009 ( 0.0745 )
    0.03 ( 0.0978 )
    0.007 ( 0.0675 )
    0.004 ( 0.0555 )
        Magnesium; Week8; n=8,7,9,9,9
    0.001 ( 0.0391 )
    0.013 ( 0.0909 )
    0.023 ( 0.063 )
    0 ( 0.0524 )
    -0.019 ( 0.0523 )
        Magnesium; Week10; n=7,8,4,7,8
    -0.021 ( 0.0641 )
    0.023 ( 0.1057 )
    -0.06 ( 0.0572 )
    -0.013 ( 0.0468 )
    -0.009 ( 0.0562 )
        Magnesium; Week12; n=7,7,7,8,7
    -0.007 ( 0.0509 )
    0.013 ( 0.0789 )
    -0.016 ( 0.0808 )
    -0.005 ( 0.0396 )
    -0.019 ( 0.0521 )
        Magnesium; Week16; n=5,6,3,6,6
    -0.024 ( 0.0152 )
    0.032 ( 0.1005 )
    -0.05 ( 0.11 )
    -0.023 ( 0.0509 )
    -0.018 ( 0.0571 )
        Phosphate; Week2; n=9,9,9,9,10
    -0.073 ( 0.1103 )
    -0.032 ( 0.2049 )
    -0.148 ( 0.1866 )
    -0.114 ( 0.2266 )
    0.009 ( 0.193 )
        Phosphate; Week3; n=1,1,1,0,0
    -0.03 ( 99999 )
    0.03 ( 99999 )
    0.1 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Phosphate; Week4; n=8,9,8,9,9
    -0.045 ( 0.1683 )
    -0.043 ( 0.114 )
    -0.134 ( 0.1987 )
    -0.197 ( 0.1091 )
    -0.074 ( 0.1664 )
        Phosphate; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.05 ( 99999 )
    -0.02 ( 99999 )
    0.22 ( 99999 )
        Phosphate; Week6; n=7,10,6,10,8
    0.004 ( 0.0704 )
    0.014 ( 0.1047 )
    0.095 ( 0.119 )
    -0.12 ( 0.1595 )
    -0.028 ( 0.2064 )
        Phosphate; Week8; n=8,7,9,9,9
    -0.032 ( 0.3227 )
    0.026 ( 0.136 )
    0.059 ( 0.1365 )
    -0.09 ( 0.1179 )
    -0.1 ( 0.2302 )
        Phosphate; Week10; n=7,8,4,7,8
    -0.051 ( 0.1788 )
    -0.054 ( 0.2326 )
    0.085 ( 0.2089 )
    -0.144 ( 0.1929 )
    -0.039 ( 0.1174 )
        Phosphate; Week12; n=7,7,7,8,7
    -0.116 ( 0.2435 )
    -0.131 ( 0.2291 )
    0.071 ( 0.1065 )
    -0.105 ( 0.1775 )
    0.026 ( 0.1439 )
        Phosphate; Week16; n=5,6,3,6,6
    0.008 ( 0.1232 )
    -0.118 ( 0.1614 )
    -0.01 ( 0.1473 )
    -0.133 ( 0.2058 )
    0.023 ( 0.0816 )
        Sodium; Week2; n=9,9,9,9,10
    -1.1 ( 1.83 )
    -0.9 ( 1.45 )
    -1.3 ( 2.74 )
    -1.4 ( 1.01 )
    0.1 ( 1.6 )
        Sodium; Week3; n=1,1,1,0,0
    -1 ( 99999 )
    -1 ( 99999 )
    -3 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Sodium; Week4; n=8,9,8,9,9
    -1.6 ( 2 )
    -1.6 ( 1.13 )
    -1 ( 2.39 )
    -1.2 ( 2.22 )
    0.7 ( 2.24 )
        Sodium; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -3 ( 99999 )
    -2 ( 99999 )
    -4 ( 99999 )
        Sodium; Week6; n=7,10,6,10,8
    -0.7 ( 1.25 )
    -1.4 ( 1.71 )
    -1.7 ( 1.63 )
    -0.7 ( 1.57 )
    0.5 ( 2.39 )
        Sodium; Week8; n=8,7,9,9,9
    -0.6 ( 2.26 )
    -0.4 ( 2.07 )
    -1.1 ( 2.76 )
    -1.6 ( 2.74 )
    0 ( 1.73 )
        Sodium; Week10; n=7,8,4,7,8
    -0.4 ( 2.44 )
    -0.5 ( 1.07 )
    -0.5 ( 3 )
    -0.1 ( 1.46 )
    0.4 ( 1.69 )
        Sodium; Week12; n=7,7,7,8,7
    -0.4 ( 1.13 )
    -0.9 ( 1.57 )
    -1.6 ( 2.99 )
    -0.6 ( 1.85 )
    0 ( 1.29 )
        Sodium; Week16; n=5,6,3,6,6
    -1 ( 2 )
    0.3 ( 1.86 )
    -1.3 ( 3.21 )
    -1.2 ( 1.72 )
    0.7 ( 1.51 )
        Triglycerides, Fasted; Week2; n=0,1,0,0,1
    99999 ( 99999 )
    2.68 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.06 ( 99999 )
        Triglycerides, Fasted; Week3; n=1,1,0,0,0
    0.51 ( 99999 )
    1.01 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Triglycerides, Fasted; Week4; n=1,1,2,0,1
    -1.25 ( 99999 )
    0.2 ( 99999 )
    0.55 ( 0.495 )
    99999 ( 99999 )
    0.46 ( 99999 )
        Triglycerides, Fasted; Week6; n=0,1,0,1,0
    99999 ( 99999 )
    0 ( 99999 )
    99999 ( 99999 )
    0.16 ( 99999 )
    99999 ( 99999 )
        Triglycerides, Fasted; Week8; n=0,0,3,01
    99999 ( 99999 )
    99999 ( 99999 )
    0.29 ( 0.27 )
    99999 ( 99999 )
    -0.45 ( 99999 )
        Triglycerides, Fasted; Week10; n=2,1,0,0,0
    0.44 ( 0.6788 )
    0.56 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.53 ( 99999 )
        Triglycerides, Fasted; Week12; n=5,6,4,6,5
    0.474 ( 1.4676 )
    -0.252 ( 0.6544 )
    -0.072 ( 0.4272 )
    -0.232 ( 0.5087 )
    -0.394 ( 0.4215 )
        Triglycerides, Not Fasted; Week2; n=9,8,9,9,9
    0.142 ( 0.6915 )
    -0.358 ( 0.783 )
    0.224 ( 0.6196 )
    -0.118 ( 0.397 )
    0.146 ( 0.3789 )
        Triglycerides, Not Fasted; Week3; n=0,0,1,0,0
    99999 ( 99999 )
    99999 ( 99999 )
    1.61 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Triglycerides, Not Fasted; Week4; n=7,8,6,9,8
    -0.116 ( 0.533 )
    -0.208 ( 0.7373 )
    0.218 ( 0.3916 )
    -0.388 ( 0.3914 )
    0.099 ( 0.3549 )
        Triglycerides, Not Fasted; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.36 ( 99999 )
    0.05 ( 99999 )
    -0.1 ( 99999 )
        Triglycerides, Not Fasted; Week6; n=7,9,6,9,8
    0.316 ( 0.9129 )
    -0.239 ( 0.4658 )
    0.145 ( 0.2891 )
    0.05 ( 0.7227 )
    0.105 ( 0.3932 )
        Triglycerides, Not Fasted; Week8; n=8,7,6,8,8
    -0.182 ( 0.7551 )
    -0.299 ( 0.737 )
    0.093 ( 0.2452 )
    -0.314 ( 0.3539 )
    -0.02 ( 0.2491 )
        Triglycerides, Not Fasted; Week10; n=5,7,4,7,7
    0.354 ( 0.441 )
    -0.38 ( 0.6995 )
    -0.03 ( 0.0622 )
    -0.259 ( 0.4313 )
    0.199 ( 0.4482 )
        Triglycerides, Not Fasted; Week12; n=2,1,4,2,2
    -0.065 ( 0.1344 )
    0.04 ( 99999 )
    -0.03 ( 0.1842 )
    -0.555 ( 0.7566 )
    -0.015 ( 0.3748 )
        Triglycerides, Not Fasted; Week16; n=5,6,3,6,6
    0.082 ( 0.7262 )
    -0.235 ( 0.8101 )
    0.257 ( 0.3683 )
    -0.107 ( 0.4525 )
    0.2 ( 0.2739 )
        Urea; Week2; n=9,9,9,9,10
    0.6 ( 1.017 )
    0.7 ( 1.595 )
    -0.28 ( 1.28 )
    -0.08 ( 0.736 )
    -0.1 ( 1.357 )
        Urea; Week3; n=1,1,1,0,0
    -0.4 ( 99999 )
    1.2 ( 99999 )
    2.4 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Urea; Week4; n=8,9,8,9,9
    0.56 ( 1.581 )
    -0.53 ( 0.957 )
    -0.33 ( 1.243 )
    0.21 ( 1.014 )
    0.08 ( 1.352 )
        Urea; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    1 ( 99999 )
    -1.6 ( 99999 )
    -0.1 ( 99999 )
        Urea; Week6; n=7,10,6,10,8
    0.09 ( 1.224 )
    -0.05 ( 1.178 )
    0.32 ( 0.9 )
    0.14 ( 1.372 )
    0.56 ( 0.877 )
        Urea; Week8; n=8,7,9,9,9
    -0.3 ( 1.331 )
    -1 ( 1.021 )
    0.09 ( 1.447 )
    0.37 ( 0.866 )
    0.16 ( 1.014 )
        Urea; Week10; n=7,8,4,7,8
    0 ( 1.954 )
    -0.93 ( 1.077 )
    1.03 ( 1.615 )
    0.39 ( 1.804 )
    -0.06 ( 1.158 )
        Urea; Week12; n=7,7,7,8,7
    -0.51 ( 1.548 )
    -0.47 ( 1.889 )
    -0.11 ( 1.199 )
    0.41 ( 1.988 )
    0.29 ( 0.501 )
        Urea; Week16; n=5,6,3,6,6
    -0.32 ( 1.069 )
    -0.68 ( 2.282 )
    -0.17 ( 0.666 )
    -0.03 ( 1.546 )
    -0.18 ( 1.085 )
        VLDL Cholesterol; Week2; n=9,8,9,9,10
    -0.014 ( 0.3899 )
    0.16 ( 0.4416 )
    0.081 ( 0.2732 )
    -0.008 ( 0.2493 )
    0.009 ( 0.0681 )
        VLDL Cholesterol; Week3; n=1,1,1,0,0
    0.24 ( 99999 )
    0.46 ( 99999 )
    0.75 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        VLDL Cholesterol; Week4; n=8,8,8,9,9
    -0.18 ( 0.2344 )
    0.065 ( 0.2066 )
    0.136 ( 0.1591 )
    -0.13 ( 0.1935 )
    0.01 ( 0.1916 )
        VLDL Cholesterol; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.17 ( 99999 )
    0.02 ( 99999 )
    0.12 ( 99999 )
        VLDL Cholesterol; Week6; n=7,9,6,10,8
    0.073 ( 0.4708 )
    -0.004 ( 0.0879 )
    0.007 ( 0.1586 )
    0.071 ( 0.3474 )
    -0.011 ( 0.176 )
        VLDL Cholesterol; Week8; n=8,6,9,9,9
    -0.151 ( 0.4333 )
    0.003 ( 0.1986 )
    0.024 ( 0.1483 )
    -0.126 ( 0.1764 )
    -0.104 ( 0.1613 )
        VLDL Cholesterol; Week10; n=7,7,4,7,8
    0.11 ( 0.2424 )
    0.01 ( 0.1751 )
    -0.098 ( 0.1531 )
    -0.064 ( 0.2046 )
    -0.014 ( 0.2629 )
        VLDL Cholesterol; Week12; n=6,6,7,8,7
    -0.075 ( 0.0914 )
    0.018 ( 0.1486 )
    0.031 ( 0.1247 )
    -0.138 ( 0.251 )
    -0.116 ( 0.2032 )
        VLDL Cholesterol; Week16; n=5,5,3,6,6
    -0.05 ( 0.2547 )
    0.038 ( 0.1659 )
    0.027 ( 0.2801 )
    0.012 ( 0.2164 )
    -0.012 ( 0.1447 )
    Notes
    [71] - ITT Population. “Not available (NA)” data is presented as “99999”
    [72] - ITT Population. “Not available (NA)” data is presented as “99999”
    [73] - ITT Population. “Not available (NA)” data is presented as “99999”
    [74] - ITT Population. “Not available (NA)” data is presented as “99999”
    [75] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in bilirubin, creatinine, iron binding capacity, iron and uric acid at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in bilirubin, creatinine, iron binding capacity, iron and uric acid at the indicated time points up to Week 16 [76]
    End point description
    Change from Baseline in the bilirubin, direct and indirect bilirubin, creatinine, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), iron and uric acid values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [76] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [77]
    10 [78]
    10 [79]
    10 [80]
    11 [81]
    Units: Micromoles per liter
    arithmetic mean (standard deviation)
        Direct Bilirubin; Week2; n=9,9,9,9,10
    -0.1 ( 1.17 )
    0.2 ( 0.83 )
    -0.1 ( 0.93 )
    -0.1 ( 0.33 )
    -0.1 ( 0.74 )
        Direct Bilirubin; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -1 ( 99999 )
    1 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Direct Bilirubin; Week4; n=8,9,8,9,9
    0.1 ( 0.99 )
    0.6 ( 0.88 )
    0.6 ( 1.19 )
    0.4 ( 0.53 )
    0.1 ( 0.33 )
        Direct Bilirubin; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    2 ( 99999 )
    1 ( 99999 )
    0 ( 99999 )
        Direct Bilirubin; Week6; n=7,10,6,10,8
    0.3 ( 0.95 )
    -0.1 ( 1.1 )
    0.8 ( 1.17 )
    0 ( 0.47 )
    -0.5 ( 0.93 )
        Direct Bilirubin; Week8; n=8,7,9,9,9
    0.3 ( 1.04 )
    0.6 ( 1.13 )
    0.2 ( 1.3 )
    0 ( 0.87 )
    0.1 ( 0.33 )
        Direct Bilirubin; Week10; n=7,8,4,7,8
    0.3 ( 0.76 )
    0.3 ( 0.71 )
    0.8 ( 0.96 )
    0.6 ( 0.53 )
    -0.4 ( 0.74 )
        Direct Bilirubin; Week12; n=7,7,7,8,7
    0.4 ( 0.79 )
    0.4 ( 0.79 )
    0.4 ( 0.98 )
    -0.1 ( 0.83 )
    0 ( 0 )
        Direct Bilirubin; Week16; n=5,6,3,6,6
    -0.4 ( 0.89 )
    0.3 ( 0.82 )
    1 ( 1.73 )
    0.2 ( 0.41 )
    0 ( 0.63 )
        Bilirubin; Week2; n=9,9,9,9,10
    0.8 ( 1.99 )
    0.8 ( 2.44 )
    -0.4 ( 1.42 )
    0.6 ( 1.94 )
    -1.1 ( 2.47 )
        Bilirubin; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -2 ( 99999 )
    6 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Bilirubin; Week4; n=8,9,8,9,9
    0.5 ( 2.27 )
    1.9 ( 2.52 )
    2.9 ( 4.16 )
    1.6 ( 1.33 )
    -1.6 ( 1.33 )
        Bilirubin; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    4.3 ( 2.52 )
    0 ( 99999 )
    0 ( 99999 )
        Bilirubin; Week6; n=7,10,7,10,8
    1.9 ( 3.02 )
    -0.2 ( 2.15 )
    2.9 ( 3.29 )
    0.3 ( 1.57 )
    -1.9 ( 2.8 )
        Bilirubin; Week8; n=8,7,9,9,9
    1.4 ( 2.01 )
    -0.7 ( 3.4 )
    0.9 ( 4.34 )
    0.4 ( 1.13 )
    -1.8 ( 1.72 )
        Bilirubin; Week10; n=7,8,4,7,8
    0.4 ( 2.7 )
    0 ( 3.02 )
    1.8 ( 4.57 )
    1.4 ( 1.99 )
    -2.4 ( 1.77 )
        Bilirubin; Week12; n=7,7,7,8,7
    0.3 ( 2.63 )
    0.6 ( 3.64 )
    2 ( 3.92 )
    0.1 ( 2.47 )
    -2.1 ( 1.77 )
        Bilirubin; Week16; n=5,6,3,6,6
    -0.4 ( 2.7 )
    0.2 ( 2.79 )
    4 ( 6.93 )
    1 ( 2.1 )
    -2.3 ( 2.07 )
        Indirect Bilirubin; Week2; n=9,9,9,9,10
    0.9 ( 1.83 )
    0.6 ( 2.24 )
    -0.3 ( 0.87 )
    0.7 ( 1.66 )
    -1.2 ( 2.2 )
        Indirect Bilirubin; Week3; n=1,1,1,0,0
    0 ( 99999 )
    -1 ( 99999 )
    5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Indirect Bilirubin; Week4; n=8,9,8,9,9
    0.4 ( 2.13 )
    1.3 ( 2.35 )
    2.3 ( 3.65 )
    1.1 ( 1.05 )
    -1.4 ( 1.42 )
        Indirect Bilirubin; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    5 ( 99999 )
    -1 ( 99999 )
    0 ( 99999 )
        Indirect Bilirubin; Week6; n=7,10,6,10,8
    1.6 ( 2.57 )
    -0.1 ( 2.18 )
    1.5 ( 2.59 )
    0.3 ( 1.34 )
    -1.4 ( 2.83 )
        Indirect Bilirubin; Week8; n=8,7,9,9,9
    1.4 ( 2.07 )
    -1.3 ( 3.04 )
    0.7 ( 3.57 )
    0.4 ( 0.73 )
    -1.9 ( 1.69 )
        Indirect Bilirubin; Week10; n=7,8,4,7,8
    0.1 ( 2.85 )
    -0.3 ( 3.11 )
    1 ( 3.92 )
    0.9 ( 1.57 )
    -2 ( 1.77 )
        Indirect Bilirubin; Week12; n=7,7,7,8,7
    -0.1 ( 2.48 )
    0.1 ( 3.34 )
    1.6 ( 3.41 )
    0.3 ( 1.83 )
    -2.1 ( 1.77 )
        Indirect Bilirubin; Week16; n=5,6,3,6,6
    0 ( 2.92 )
    -0.2 ( 2.93 )
    3 ( 5.2 )
    0.8 ( 1.72 )
    -2.3 ( 1.86 )
        Creatinine; Week2; n=9,9,9,9,10
    2.31 ( 9.124 )
    1.79 ( 3.958 )
    3.34 ( 5.611 )
    6.09 ( 6.748 )
    -0.53 ( 4.592 )
        Creatinine; Week3; n=1,1,1,0,0
    8.5 ( 99999 )
    -3.4 ( 99999 )
    3.5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Creatinine; Week4; n=8,9,8,9,9
    2.4 ( 5.475 )
    1.34 ( 6.522 )
    1.71 ( 5.713 )
    5.72 ( 5.253 )
    -2.76 ( 3.749 )
        Creatinine; Week5; n=0,0,3,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    9.8 ( 99999 )
    2.8 ( 99999 )
    3.1 ( 99999 )
        Creatinine; Week6; n=6,9,7,9,8
    0.67 ( 5.167 )
    1.22 ( 3.868 )
    2.17 ( 3.472 )
    5.87 ( 7.206 )
    -2.66 ( 2.67 )
        Creatinine; Week8; n=9,7,9,9,9
    4.66 ( 4.364 )
    6.19 ( 6.258 )
    3.49 ( 7.516 )
    8.14 ( 6.011 )
    -2.99 ( 4.281 )
        Creatinine; Week10; n=7,8,4,7,8
    2.3 ( 4.974 )
    3.03 ( 6.911 )
    5.3 ( 3.997 )
    10.19 ( 5.328 )
    -0.8 ( 4.798 )
        Creatinine; Week12; n=7,7,7,8,7
    -0.29 ( 3.402 )
    1.49 ( 6.839 )
    2.26 ( 7.047 )
    5.97 ( 6.331 )
    -3.3 ( 2.796 )
        Creatinine; Week16; n=5,6,3,6,6
    -0.26 ( 3.259 )
    0.5 ( 4.944 )
    1.33 ( 3.781 )
    -0.03 ( 5.32 )
    -4.62 ( 3.779 )
        TIBC; Week2; n=9,9,9,9,10
    -1.6 ( 4.33 )
    1.2 ( 2.99 )
    1 ( 4.5 )
    3.8 ( 4.74 )
    -1.8 ( 6 )
        TIBC; Week3; n=1,1,1,0,0
    5 ( 99999 )
    -8 ( 99999 )
    0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        TIBC; Week4; n=8,9,8,9,9
    1.1 ( 5.46 )
    2.7 ( 4.66 )
    4 ( 6.5 )
    3.4 ( 4.67 )
    -1 ( 4.66 )
        TIBC; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -4 ( 99999 )
    3 ( 99999 )
    3 ( 99999 )
        TIBC; Week6; n=7,10,6,10,8
    0.3 ( 2.21 )
    0.5 ( 5.66 )
    4 ( 2.76 )
    3.9 ( 8.2 )
    1 ( 4.81 )
        TIBC; Week8; n=8,7,9,9,8
    1.3 ( 6.8 )
    -0.7 ( 5.06 )
    2.9 ( 5.09 )
    4.2 ( 9.82 )
    -1.9 ( 8.89 )
        TIBC; Week10; n=7,8,4,7,8
    0.1 ( 4.06 )
    2 ( 4.14 )
    0.8 ( 5.68 )
    7 ( 8.94 )
    -2 ( 6.19 )
        TIBC; Week12; n=7,7,7,8,7
    1.1 ( 5.27 )
    3.4 ( 3.99 )
    2.3 ( 6.6 )
    7.1 ( 9.78 )
    -2.3 ( 3.9 )
        TIBC; Week16; n=5,6,3,6,6
    -1.2 ( 2.86 )
    3.7 ( 4.32 )
    0.3 ( 5.86 )
    3.7 ( 6.31 )
    -4.2 ( 6.97 )
        UIBC; Week2; n=9,9,9,9,10
    -3.2 ( 9.24 )
    -2.4 ( 11.39 )
    0.4 ( 9.46 )
    3 ( 9.8 )
    -1.2 ( 9.13 )
        UIBC; Week3; n=1,1,1,0,0
    5 ( 99999 )
    -13 ( 99999 )
    -31 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        UIBC; Week4; n=8,9,8,9,9
    3.8 ( 7.25 )
    -1.6 ( 10.09 )
    0.5 ( 10.98 )
    1.3 ( 6.4 )
    0.4 ( 7.23 )
        UIBC; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -4 ( 99999 )
    12 ( 99999 )
    12 ( 99999 )
        UIBC; Week6; n=7,10,6,10,8
    -3.1 ( 8.07 )
    -0.8 ( 5.31 )
    6 ( 8.15 )
    4.5 ( 11.31 )
    5.6 ( 8.05 )
        UIBC; Week8; n=8,7,9,9,9
    3.3 ( 8.21 )
    1.3 ( 8.85 )
    4.3 ( 5.96 )
    5.4 ( 9.96 )
    -0.4 ( 11.08 )
        UIBC; Week10; n=7,8,4,7,8
    0.7 ( 8.01 )
    4.8 ( 7.92 )
    -1.3 ( 9.74 )
    3.6 ( 10.18 )
    0.5 ( 9.1 )
        UIBC; Week12; n=7,7,7,8,7
    1 ( 6 )
    4.7 ( 6.78 )
    1.4 ( 10.81 )
    5.8 ( 7.65 )
    2.1 ( 5.01 )
        UIBC; Week16; n=5,6,3,6,6
    2 ( 6 )
    3.8 ( 7.19 )
    0 ( 7.55 )
    3.8 ( 10.03 )
    -2.2 ( 5.78 )
        Iron; Week2; n=9,9,9,9,10
    1.7 ( 6.32 )
    3.7 ( 11.43 )
    0.6 ( 9.03 )
    0.8 ( 9.02 )
    -0.6 ( 7.09 )
        Iron; Week3; n=1,1,1,0,0
    0 ( 99999 )
    5 ( 99999 )
    31 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Iron; Week4; n=8,9,8,9,9
    -2.6 ( 3.38 )
    4.2 ( 11.04 )
    3.5 ( 7.98 )
    2.1 ( 7.29 )
    -1.4 ( 4.13 )
        Iron; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0 ( 99999 )
    -9 ( 99999 )
    -9 ( 99999 )
        Iron; Week6; n=7,10,6,10,8
    3.4 ( 9.47 )
    1.3 ( 2.16 )
    -2 ( 6.45 )
    -0.6 ( 6.02 )
    -4.6 ( 6.8 )
        Iron; Week8; n=8,7,9,9,9
    -2 ( 7.45 )
    -2 ( 6.06 )
    -1.4 ( 4.8 )
    -1.2 ( 6.14 )
    -1.6 ( 3.91 )
        Iron; Week10; n=7,8,4,7,8
    -0.6 ( 4.96 )
    -2.8 ( 4.8 )
    2 ( 9.2 )
    3.4 ( 4.89 )
    -2.5 ( 5.13 )
        Iron; Week12; n=7,7,7,8,7
    0.1 ( 6.41 )
    -1.3 ( 6.18 )
    0.9 ( 9.99 )
    1.4 ( 11.15 )
    -4.4 ( 3.36 )
        Iron; Week16; n=5,6,3,6,6
    -3.2 ( 6.06 )
    -0.2 ( 5.34 )
    0.3 ( 4.16 )
    -0.2 ( 4.36 )
    -2 ( 2.9 )
        Uric acid; Week2; n=9,9,9,9,10
    -5.7 ( 34.67 )
    5.8 ( 50.46 )
    -14.4 ( 24.81 )
    -13.4 ( 14.48 )
    2.2 ( 35.59 )
        Uric acid; Week3; n=1,1,1,0,0
    -8 ( 99999 )
    37 ( 99999 )
    -73 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Uric acid; Week4; n=8,9,8,9,9
    -4.6 ( 49.4 )
    0.4 ( 57.21 )
    -16.8 ( 26.38 )
    -15.9 ( 32.94 )
    -7.2 ( 31.58 )
        Uric acid; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -14 ( 99999 )
    -45 ( 99999 )
    9 ( 99999 )
        Uric acid; Week6; n=7,10,6,10,8
    -11.3 ( 29.83 )
    1.7 ( 54.57 )
    -14.5 ( 16.84 )
    -15.8 ( 25.33 )
    -2.1 ( 30.02 )
        Uric acid; Week8; n=8,7,9,9,9
    2.4 ( 30.83 )
    -2 ( 62.41 )
    -16.2 ( 40.28 )
    -6.1 ( 46.93 )
    0.7 ( 35.19 )
        Uric acid; Week10; n=7,8,4,7,8
    -4.7 ( 35.92 )
    -5.1 ( 53.14 )
    -8.8 ( 33.18 )
    -14.9 ( 41.09 )
    -1.9 ( 29.46 )
        Uric acid; Week12; n=7,7,7,8,7
    -14.9 ( 19.07 )
    2.3 ( 75.78 )
    -23.3 ( 28.6 )
    -12.3 ( 36.1 )
    -7.1 ( 18.25 )
        Uric acid; Week16; n=5,6,3,6,6
    -13 ( 31.1 )
    -9.5 ( 60.18 )
    -13 ( 19.47 )
    -23.7 ( 28.89 )
    -4.7 ( 25.45 )
    Notes
    [77] - ITT Population. “Not available (NA)” data is presented as “99999”
    [78] - ITT Population. “Not available (NA)” data is presented as “99999”
    [79] - ITT Population. “Not available (NA)” data is presented as “99999”
    [80] - ITT Population. “Not available (NA)” data is presented as “99999”
    [81] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in albumin/globulin, BUN/creatinine and transferrin saturation at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in albumin/globulin, BUN/creatinine and transferrin saturation at the indicated time points up to Week 16 [82]
    End point description
    Change from baseline in the albumin/globulin, blood urea nitrogen (BUN)/creatinine and transferrin saturation values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [82] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [83]
    10 [84]
    10 [85]
    10 [86]
    11 [87]
    Units: Ratio
    arithmetic mean (standard deviation)
        Albumin/Globulin; Week2; n=9,9,9,9,10
    0.07 ( 0.173 )
    0.03 ( 0.122 )
    -0.04 ( 0.133 )
    0.09 ( 0.117 )
    -0.12 ( 0.132 )
        Albumin/Globulin; Week3; n=1,1,1,0,0
    -0.1 ( 99999 )
    -0.1 ( 99999 )
    0.4 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Albumin/Globulin; Week4; n=8,9,8,9,9
    0.13 ( 0.149 )
    0.07 ( 0.166 )
    0.05 ( 0.207 )
    0.17 ( 0.087 )
    -0.06 ( 0.194 )
        Albumin/Globulin; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.5 ( 99999 )
    0 ( 99999 )
    -0.1 ( 99999 )
        Albumin/Globulin; Week6; n=7,10,6,10,8
    0.01 ( 0.107 )
    0.03 ( 0.142 )
    0.15 ( 0.266 )
    0.21 ( 0.129 )
    -0.11 ( 0.196 )
        Albumin/Globulin; Week8; n=8,7,9,9,9
    0.09 ( 0.189 )
    0.11 ( 0.146 )
    0.12 ( 0.164 )
    0.18 ( 0.139 )
    -0.02 ( 0.139 )
        Albumin/Globulin; Week10; n=7,8,4,7,8
    0.11 ( 0.168 )
    0.05 ( 0.193 )
    0.03 ( 0.096 )
    0.21 ( 0.107 )
    -0.1 ( 0.131 )
        Albumin/Globulin; Week12; n=7,7,7,8,7
    0.03 ( 0.125 )
    0.09 ( 0.297 )
    0.03 ( 0.309 )
    0.1 ( 0.227 )
    -0.04 ( 0.151 )
        Albumin/Globulin; Week16; n=5,6,3,6,6
    -0.04 ( 0.055 )
    -0.05 ( 0.176 )
    -0.07 ( 0.153 )
    0.07 ( 0.25 )
    -0.13 ( 0.186 )
        BUN/Creatinine; Week2; n=9,9,9,9,10
    8.8 ( 18.91 )
    8.9 ( 27.81 )
    -9.1 ( 22.05 )
    -7.4 ( 15.45 )
    0.3 ( 21.19 )
        BUN/Creatinine; Week3; n=1,1,1,0,0
    -15 ( 99999 )
    21 ( 99999 )
    40 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        BUN/Creatinine; Week4; n=8,9,8,9,9
    4 ( 19.27 )
    -10.2 ( 22.94 )
    -7.3 ( 20.95 )
    -3.7 ( 15.7 )
    7.8 ( 23.2 )
        BUN/Creatinine; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    1 ( 99999 )
    -36 ( 99999 )
    -4 ( 99999 )
        BUN/Creatinine; Week6; n=6,9,6,9,8
    -0.7 ( 16.49 )
    -1 ( 17.48 )
    2 ( 15.05 )
    -5.8 ( 20.52 )
    15.4 ( 14.92 )
        BUN/Creatinine; Week8; n=8,7,9,9,9
    -11.8 ( 21.42 )
    -23.9 ( 21.14 )
    -4 ( 16.48 )
    -5.2 ( 12.78 )
    8.7 ( 19.92 )
        BUN/Creatinine; Week10; n=7,8,4,7,8
    -2.6 ( 29.07 )
    -17.8 ( 22.25 )
    9.8 ( 22.9 )
    -7.4 ( 34.32 )
    3 ( 20.73 )
        BUN/Creatinine; Week12; n=7,7,7,8,7
    -8.7 ( 23.14 )
    -9.3 ( 35.49 )
    -4.3 ( 16.2 )
    -1 ( 28.24 )
    10.9 ( 7.6 )
        BUN/Creatinine; Week16; n=5,6,3,6,6
    -5.2 ( 15.99 )
    -11.8 ( 43.73 )
    -5.7 ( 6.66 )
    0.2 ( 33.39 )
    6.8 ( 25.88 )
        Transferrin saturation; Week2; n=9,9,9,9,10
    0.036 ( 0.1093 )
    0.05 ( 0.1577 )
    0.002 ( 0.1242 )
    0.004 ( 0.1599 )
    0 ( 0.1036 )
        Transferrin saturation; Week3; n=1,1,1,0,0
    0 ( 99999 )
    0.13 ( 99999 )
    0.46 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Transferrin saturation; Week4; n=8,9,8,9,9
    -0.05 ( 0.0763 )
    0.04 ( 0.1459 )
    0.043 ( 0.1172 )
    0.018 ( 0.111 )
    -0.024 ( 0.0641 )
        Transferrin saturation; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    0.01 ( 99999 )
    -0.17 ( 99999 )
    -0.2 ( 99999 )
        Transferrin saturation; Week6; n=7,10,6,10,8
    0.049 ( 0.1297 )
    0.016 ( 0.0317 )
    -0.033 ( 0.0905 )
    -0.011 ( 0.1343 )
    -0.08 ( 0.1251 )
        Transferrin saturation; Week8; n=8,7,9,9,8
    -0.039 ( 0.1246 )
    -0.029 ( 0.0888 )
    -0.03 ( 0.0758 )
    -0.031 ( 0.1046 )
    -0.026 ( 0.0847 )
        Transferrin saturation; Week10; n=7,8,4,7,8
    -0.01 ( 0.0906 )
    -0.048 ( 0.0742 )
    0.045 ( 0.1392 )
    0.031 ( 0.084 )
    -0.036 ( 0.0868 )
        Transferrin saturation; Week12; n=7,7,7,8,7
    -0.007 ( 0.1013 )
    -0.024 ( 0.0856 )
    0.01 ( 0.1502 )
    -0.013 ( 0.1659 )
    -0.071 ( 0.0549 )
        Transferrin saturation; Week16; n=5,6,3,6,6
    -0.054 ( 0.1095 )
    -0.01 ( 0.078 )
    0.017 ( 0.0723 )
    -0.015 ( 0.0922 )
    -0.028 ( 0.044 )
    Notes
    [83] - ITT Population. “Not available (NA)” data is presented as “99999”
    [84] - ITT Population. “Not available (NA)” data is presented as “99999”
    [85] - ITT Population. “Not available (NA)” data is presented as “99999”
    [86] - ITT Population. “Not available (NA)” data is presented as “99999”
    [87] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in creatinine clearance at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in creatinine clearance at the indicated time points up to Week 16 [88]
    End point description
    Change from Baseline in the Creatinine Clearance values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [88] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [89]
    10 [90]
    10 [91]
    10 [92]
    11 [93]
    Units: Milliliter per minute (mL/min)
    arithmetic mean (standard deviation)
        Creatinine clearance; Week2; n=9,9,9,9,10
    -1.8 ( 27.86 )
    -5.6 ( 9.34 )
    -5.9 ( 11.89 )
    -13.2 ( 16.84 )
    1.7 ( 8.03 )
        Creatinine clearance; Week3; n=1,1,0,0,0
    -13 ( 99999 )
    4 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Creatinine clearance; Week4; n=8,9,8,9,9
    -7.1 ( 16.25 )
    -3.2 ( 11.2 )
    -6.8 ( 13.66 )
    -13.2 ( 13.55 )
    7.7 ( 10.78 )
        Creatinine clearance; Week5; n=0,0,1,1,1
    99999 ( 99999 )
    99999 ( 99999 )
    -36 ( 99999 )
    -13 ( 99999 )
    -5 ( 99999 )
        Creatinine clearance; Week6; n=0,3,1,2,0
    99999 ( 99999 )
    3.7 ( 1.53 )
    5 ( 99999 )
    -9.5 ( 99999 )
    99999 ( 99999 )
        Creatinine clearance; Week8; n=8,7,8,9,9
    -10.6 ( 11.19 )
    -12.1 ( 14.58 )
    -10.9 ( 17.21 )
    -18.3 ( 18.83 )
    10.1 ( 13.91 )
        Creatinine clearance; Week10; n=2,2,1,1,2
    -10 ( 14.14 )
    7.5 ( 4.95 )
    -6 ( 99999 )
    -29 ( 99999 )
    -10.5 ( 10.61 )
        Creatinine clearance; Week12; n=7,7,7,8,7
    -2.1 ( 17.03 )
    -3 ( 14.41 )
    -3 ( 23.79 )
    -14.6 ( 18.07 )
    9.6 ( 10.28 )
        Creatinine clearance; Week16; n=5,6,3,6,6
    -3.6 ( 17.81 )
    -1 ( 10.53 )
    -1 ( 3.46 )
    -1.7 ( 10.61 )
    14.8 ( 14.8 )
    Notes
    [89] - ITT Population. “Not available (NA)” data is presented as “99999”
    [90] - ITT Population. “Not available (NA)” data is presented as “99999”
    [91] - ITT Population. “Not available (NA)” data is presented as “99999”
    [92] - ITT Population. “Not available (NA)” data is presented as “99999”
    [93] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils SG, platelets and leukocytes at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils SG, platelets and leukocytes at the indicated time points up to Week 16 [94]
    End point description
    Change from Baseline in the basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils segmented (SG), platelets and leukocytes values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [94] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [95]
    10 [96]
    10 [97]
    10 [98]
    11 [99]
    Units: Billions per liter
    arithmetic mean (standard deviation)
        Basophils, Week1, n=9,10,9,10,11
    -0.002 ( 0.0335 )
    0.002 ( 0.0114 )
    -0.004 ( 0.0219 )
    0.004 ( 0.0178 )
    -0.003 ( 0.0195 )
        Basophils, Week2, n=9,9,10,9,9
    0.001 ( 0.0271 )
    -0.004 ( 0.0133 )
    -0.008 ( 0.014 )
    0.004 ( 0.0088 )
    -0.003 ( 0.0122 )
        Basophils, Week3, n=9,7,9,6,7
    -0.002 ( 0.0468 )
    0 ( 0.0141 )
    0.004 ( 0.03 )
    0.01 ( 0.0261 )
    0.001 ( 0.0135 )
        Basophils, Week4, n=6,9,9,9,9
    0 ( 0.0469 )
    0.002 ( 0.013 )
    -0.001 ( 0.0176 )
    0.002 ( 0.0164 )
    -0.007 ( 0.01 )
        Basophils, Week5, n=7,6,6,9,7
    -0.011 ( 0.0449 )
    0.012 ( 0.0147 )
    0.002 ( 0.0354 )
    0 ( 0.015 )
    -0.004 ( 0.019 )
        Basophils, Week6, n=7,10,6,10,7
    -0.023 ( 0.0399 )
    0.003 ( 0.0106 )
    -0.013 ( 0.0137 )
    0 ( 0.0082 )
    -0.006 ( 0.0127 )
        Basophils, Week8, n=8,7,9,9,9
    -0.011 ( 0.0458 )
    0.001 ( 0.0146 )
    0.019 ( 0.047 )
    0.003 ( 0.015 )
    -0.002 ( 0.0164 )
        Basophils, Week10, n=7,8,4,7,8
    -0.011 ( 0.0324 )
    0 ( 0.0076 )
    -0.018 ( 0.0096 )
    0.001 ( 0.0069 )
    0.001 ( 0.0083 )
        Basophils, Week12, n=7,7,7,8,7
    -0.014 ( 0.0264 )
    0.006 ( 0.0215 )
    -0.01 ( 0.0058 )
    -0.005 ( 0.0093 )
    -0.001 ( 0.0285 )
        Basophils, Week16, n=5,6,3,6,6
    -0.006 ( 0.0207 )
    -0.003 ( 0.0121 )
    -0.007 ( 0.0115 )
    0.008 ( 0.0214 )
    -0.005 ( 0.0105 )
        Eosinophils, Week1, n=9,10,9,10,11
    0.006 ( 0.0515 )
    -0.027 ( 0.0707 )
    -0.051 ( 0.1523 )
    0.035 ( 0.0665 )
    -0.003 ( 0.0631 )
        Eosinophils, Week2, n=9,9,10,9,9
    0.137 ( 0.2082 )
    -0.023 ( 0.1009 )
    0.003 ( 0.2005 )
    0.03 ( 0.0705 )
    -0.003 ( 0.0332 )
        Eosinophils, Week3, n=9,7,9,6,7
    0.072 ( 0.1225 )
    -0.02 ( 0.1071 )
    -0.05 ( 0.1396 )
    0.023 ( 0.0288 )
    0.064 ( 0.0981 )
        Eosinophils, Week4, n=6,9,9,9,9
    -0.002 ( 0.0523 )
    -0.044 ( 0.0879 )
    -0.027 ( 0.1622 )
    -0.027 ( 0.0534 )
    -0.009 ( 0.0267 )
        Eosinophils, Week5, n=7,6,6,9,7
    0.019 ( 0.0752 )
    -0.035 ( 0.1009 )
    0.008 ( 0.0449 )
    -0.017 ( 0.0585 )
    -0.014 ( 0.0162 )
        Eosinophils, Week6, n=7,10,6,10,7
    -0.017 ( 0.0499 )
    -0.05 ( 0.101 )
    -0.023 ( 0.0186 )
    -0.028 ( 0.0711 )
    -0.011 ( 0.0212 )
        Eosinophils, Week8, n=8,7,9,9,9
    0.016 ( 0.0437 )
    -0.04 ( 0.0935 )
    -0.029 ( 0.1039 )
    -0.017 ( 0.043 )
    0 ( 0.0265 )
        Eosinophils, Week10, n=7,8,4,7,8
    0.039 ( 0.0917 )
    0.001 ( 0.126 )
    -0.033 ( 0.0299 )
    -0.019 ( 0.1125 )
    0.008 ( 0.0459 )
        Eosinophils, Week12, n=7,7,7,8,7
    0.021 ( 0.0767 )
    -0.009 ( 0.126 )
    -0.014 ( 0.0351 )
    -0.008 ( 0.0504 )
    0.047 ( 0.0682 )
        Eosinophils, Week16, n=5,6,3,6,6
    0.002 ( 0.0295 )
    -0.048 ( 0.1034 )
    0.053 ( 0.1274 )
    -0.052 ( 0.0773 )
    0.032 ( 0.0504 )
        Lymphocytes, Week1, n=9,10,9,10,11
    0.763 ( 1.5656 )
    0.115 ( 0.701 )
    -0.127 ( 0.4761 )
    0.148 ( 0.5696 )
    -0.1 ( 0.41 )
        Lymphocytes, Week2, n=9,9,10,9,9
    0.407 ( 1.0582 )
    0.043 ( 0.2932 )
    -0.36 ( 0.3286 )
    -0.258 ( 0.7151 )
    -0.086 ( 0.3673 )
        Lymphocytes, Week3, n=9,7,9,6,7
    0.754 ( 1.2905 )
    0.151 ( 0.2727 )
    0.139 ( 0.6525 )
    0.173 ( 0.5052 )
    0.193 ( 0.6479 )
        Lymphocytes, Week4, n=6,9,9,9,9
    0.813 ( 1.4774 )
    0.033 ( 0.292 )
    0.308 ( 0.8582 )
    -0.151 ( 0.4103 )
    -0.02 ( 0.5295 )
        Lymphocytes, Week5, n=7,6,6,9,7
    0.286 ( 0.5651 )
    0.142 ( 0.1136 )
    0.332 ( 1.2818 )
    -0.017 ( 0.5348 )
    0.054 ( 0.5757 )
        Lymphocytes, Week6, n=7,10,6,10,7
    0.246 ( 0.4796 )
    -0.136 ( 0.2762 )
    0.297 ( 0.832 )
    -0.059 ( 0.5509 )
    -0.183 ( 0.4596 )
        Lymphocytes, Week8, n=8,7,9,9,9
    0.519 ( 1.2726 )
    0.131 ( 0.93 )
    0.227 ( 0.8526 )
    0 ( 0.6471 )
    -0.084 ( 0.3248 )
        Lymphocytes, Week10, n=7,8,4,7,8
    0.127 ( 0.3555 )
    0.128 ( 0.4077 )
    -0.19 ( 0.1206 )
    -0.161 ( 0.4008 )
    -0.011 ( 0.5503 )
        Lymphocytes, Week12, n=7,7,7,8,7
    -0.06 ( 0.3709 )
    -0.05 ( 0.0887 )
    0.221 ( 0.5321 )
    -0.328 ( 0.4631 )
    0.081 ( 0.6077 )
        Lymphocytes, Week16, n=5,6,3,6,6
    0.064 ( 0.4868 )
    0.163 ( 0.5223 )
    0.117 ( 0.0833 )
    0.01 ( 0.6658 )
    0.075 ( 0.4366 )
        Monocytes, Week1, n=9,10,9,10,11
    -0.066 ( 0.349 )
    -0.006 ( 0.1543 )
    0.056 ( 0.2089 )
    0.02 ( 0.1585 )
    -0.055 ( 0.1408 )
        Monocytes, Week2, n=9,9,10,9,9
    -0.149 ( 0.4253 )
    0.042 ( 0.1965 )
    -0.034 ( 0.1685 )
    -0.116 ( 0.1068 )
    -0.009 ( 0.1291 )
        Monocytes, Week3, n=9,7,9,6,7
    -0.153 ( 0.3728 )
    0.024 ( 0.139 )
    0.163 ( 0.2259 )
    -0.02 ( 0.1682 )
    -0.017 ( 0.0673 )
        Monocytes, Week4, n=6,9,9,9,9
    -0.165 ( 0.4373 )
    0.038 ( 0.1776 )
    0.167 ( 0.5101 )
    -0.043 ( 0.2149 )
    -0.038 ( 0.1102 )
        Monocytes, Week5, n=7,6,6,9,7
    0.006 ( 0.1131 )
    0.058 ( 0.1425 )
    0.062 ( 0.1843 )
    -0.02 ( 0.1912 )
    -0.001 ( 0.1272 )
        Monocytes, Week6, n=7,10,6,10,7
    -0.074 ( 0.1254 )
    -0.057 ( 0.1542 )
    0.038 ( 0.1209 )
    -0.117 ( 0.1517 )
    -0.076 ( 0.0783 )
        Monocytes, Week8, n=8,7,9,9,9
    -0.129 ( 0.3993 )
    0.041 ( 0.1325 )
    0.008 ( 0.1173 )
    -0.047 ( 0.0843 )
    -0.013 ( 0.091 )
        Monocytes, Week10, n=7,8,4,7,8
    0.01 ( 0.0995 )
    -0.006 ( 0.1413 )
    -0.015 ( 0.1234 )
    -0.08 ( 0.1743 )
    -0.054 ( 0.0803 )
        Monocytes, Week12, n=7,7,7,8,7
    -0.004 ( 0.119 )
    0.006 ( 0.1001 )
    0.094 ( 0.2385 )
    -0.049 ( 0.1195 )
    -0.036 ( 0.0675 )
        Monocytes, Week16, n=5,6,3,6,6
    -0.004 ( 0.0378 )
    -0.047 ( 0.1565 )
    -0.01 ( 0.0964 )
    -0.14 ( 0.1296 )
    0.043 ( 0.1293 )
        Neutrophils, Week1, n=9,10,9,10,11
    -0.192 ( 1.4294 )
    1.638 ( 3.9206 )
    1.422 ( 0.8979 )
    0.092 ( 2.6648 )
    0.439 ( 1.5593 )
        Neutrophils, Week2, n=9,9,10,9,9
    -1.231 ( 1.6188 )
    0.247 ( 1.7058 )
    0.14 ( 0.8193 )
    -1.291 ( 2.8048 )
    -0.023 ( 0.512 )
        Neutrophils, Week3, n=9,7,9,6,7
    0.069 ( 1.3707 )
    0.327 ( 2.4038 )
    0.912 ( 1.4991 )
    -2.055 ( 2.4167 )
    0.206 ( 1.6235 )
        Neutrophils, Week4, n=6,9,9,9,9
    -0.033 ( 1.6415 )
    0.052 ( 1.8589 )
    0.606 ( 0.6448 )
    -1.423 ( 2.1838 )
    -0.241 ( 0.8247 )
        Neutrophils, Week5, n=7,6,6,9,7
    -0.153 ( 1.3439 )
    0.09 ( 2.0247 )
    1.387 ( 2.6017 )
    -1.407 ( 3.1341 )
    0.893 ( 0.7082 )
        Neutrophils, Week6, n=7,9,6,10,7
    -0.054 ( 1.6672 )
    -0.031 ( 2.3978 )
    0.927 ( 2.0966 )
    -0.445 ( 2.4812 )
    0.151 ( 1.2003 )
        Neutrophils, Week8, n=8,7,9,9,9
    -0.629 ( 1.6773 )
    -0.216 ( 2.159 )
    0.46 ( 1.1872 )
    -1.619 ( 3.3418 )
    -0.177 ( 0.7237 )
        Neutrophils, Week10, n=7,8,4,7,8
    -1.124 ( 1.257 )
    0.189 ( 1.5403 )
    0.798 ( 0.9581 )
    -1.474 ( 4.2315 )
    -0.356 ( 1.144 )
        Neutrophils, Week12, n=7,7,7,8,7
    -0.087 ( 1.3356 )
    0.196 ( 0.8878 )
    0.164 ( 1.1213 )
    -1.576 ( 3.7465 )
    -0.563 ( 0.4907 )
        Neutrophils, Week16, n=5,6,3,6,6
    -1.25 ( 1.8168 )
    -0.693 ( 1.52 )
    0.233 ( 0.9611 )
    -0.938 ( 2.3948 )
    0.332 ( 0.4296 )
        Neutrophils SG, Week1, n=9,10,9,10,11
    -0.192 ( 1.4294 )
    1.638 ( 3.9206 )
    1.422 ( 0.8979 )
    0.092 ( 2.6648 )
    0.439 ( 1.5593 )
        Neutrophils SG, Week2, n=9,9,10,9,9
    -1.231 ( 1.6188 )
    0.247 ( 1.7058 )
    0.14 ( 0.8193 )
    -1.291 ( 2.8048 )
    -0.023 ( 0.512 )
        Neutrophils SG, Week3, n=9,7,9,6,7
    0.069 ( 1.3707 )
    0.327 ( 2.4038 )
    0.912 ( 1.4991 )
    -2.055 ( 2.4167 )
    0.206 ( 1.6235 )
        Neutrophils SG, Week4, n=6,9,9,9,9
    -0.033 ( 1.6415 )
    0.052 ( 1.8589 )
    0.606 ( 0.6448 )
    -1.423 ( 2.1838 )
    -0.241 ( 0.8247 )
        Neutrophils SG, Week5, n=7,6,6,9,7
    -0.153 ( 1.3439 )
    0.09 ( 2.0247 )
    1.387 ( 2.6017 )
    -1.407 ( 3.1341 )
    0.893 ( 0.7082 )
        Neutrophils SG, Week6, n=7,10,6,10,7
    -0.054 ( 1.6672 )
    0.119 ( 2.31 )
    0.927 ( 2.0966 )
    -0.445 ( 2.4812 )
    0.151 ( 1.2003 )
        Neutrophils SG, Week8, n=8,7,9,9,9
    -0.629 ( 1.6773 )
    -0.216 ( 2.159 )
    0.46 ( 1.1872 )
    -1.619 ( 3.3418 )
    -0.177 ( 0.7237 )
        Neutrophils SG, Week10, n=7,8,4,7,8
    -1.124 ( 1.257 )
    0.189 ( 1.5403 )
    0.798 ( 0.9581 )
    -1.474 ( 4.2315 )
    -0.356 ( 1.144 )
        Neutrophils SG, Week12, n=7,7,7,8,7
    -0.087 ( 1.3356 )
    0.196 ( 0.8878 )
    0.164 ( 1.1213 )
    -1.576 ( 3.7465 )
    -0.563 ( 0.4907 )
        Neutrophils SG, Week16, n=5,6,3,6,6
    -1.25 ( 1.8168 )
    -0.693 ( 1.52 )
    0.233 ( 0.9611 )
    -0.938 ( 2.3948 )
    0.332 ( 0.4296 )
        Platelets, Week1, n=9,10,9,10,11
    -2.3 ( 24.32 )
    -4.7 ( 30.15 )
    13.8 ( 41.28 )
    23.8 ( 26.09 )
    10.6 ( 21.81 )
        Platelets, Week2, n=9,9,10,9,9
    -31.3 ( 48.71 )
    -48.4 ( 50.31 )
    -45.2 ( 44.47 )
    -32.2 ( 33.25 )
    2.6 ( 17.08 )
        Platelets, Week3, n=9,7,9,6,7
    2.4 ( 25.74 )
    -36.7 ( 39.77 )
    0 ( 29.29 )
    -39.2 ( 58.51 )
    16.9 ( 29.04 )
        Platelets, Week4, n=6,9,9,9,9
    -10.8 ( 22.74 )
    -32.2 ( 45.34 )
    -0.1 ( 47.01 )
    -19.1 ( 17.52 )
    18.9 ( 30.53 )
        Platelets, Week5, n=7,6,7,9,7
    3.1 ( 30.99 )
    -35.7 ( 57.01 )
    12.1 ( 66.55 )
    -15.6 ( 38.46 )
    41.4 ( 35.64 )
        Platelets, Week6, n=7,10,5,10,8
    7.7 ( 38.77 )
    -18.9 ( 36.06 )
    -9.6 ( 20.48 )
    1.8 ( 43.42 )
    29 ( 36.18 )
        Platelets, Week8, n=8,7,9,9,9
    -11.3 ( 51.49 )
    -33 ( 29.68 )
    -6.9 ( 34.56 )
    -1.9 ( 65.75 )
    15.8 ( 28.31 )
        Platelets, Week10, n=7,8,4,7,8
    2.4 ( 25.1 )
    -19.5 ( 30.8 )
    -16.5 ( 23.95 )
    -12.4 ( 67.01 )
    24.4 ( 42.88 )
        Platelets, Week12, n=7,7,7,8,7
    13.6 ( 26.69 )
    -29.7 ( 57.09 )
    -3 ( 19.08 )
    -14.4 ( 43.84 )
    25.1 ( 34.12 )
        Platelets, Week16, n=5,6,3,6,6
    7.8 ( 31.88 )
    -35.2 ( 40.04 )
    9 ( 16.52 )
    10.8 ( 54.17 )
    16.5 ( 23.71 )
        Leukocytes, Week1, n=9,10,9,10,11
    0.53 ( 2.076 )
    1.73 ( 3.604 )
    1.3 ( 0.763 )
    0.3 ( 2.489 )
    0.29 ( 1.575 )
        Leukocytes, Week2, n=9,9,10,9,9
    -0.81 ( 1.548 )
    0.3 ( 1.938 )
    -0.27 ( 1.033 )
    -1.62 ( 2.984 )
    -0.12 ( 0.634 )
        Leukocytes, Week3, n=9,7,9,6,7
    0.77 ( 1.942 )
    0.47 ( 2.404 )
    1.16 ( 1.998 )
    -1.88 ( 2.283 )
    0.44 ( 1.212 )
        Leukocytes, Week4, n=6,9,9,9,9
    0.62 ( 1.321 )
    0.06 ( 1.902 )
    1.03 ( 1.464 )
    -1.62 ( 2.411 )
    -0.31 ( 1.029 )
        Leukocytes, Week5, n=7,6,6,9,7
    0.17 ( 0.75 )
    0.27 ( 2.201 )
    1.78 ( 3.843 )
    -1.46 ( 2.985 )
    0.93 ( 0.986 )
        Leukocytes, Week6, n=7,10,6,10,7
    0.1 ( 1.398 )
    -0.15 ( 2.314 )
    1.25 ( 1.712 )
    -0.65 ( 2.911 )
    -0.11 ( 1.295 )
        Leukocytes, Week8, n=8,7,9,9,9
    -0.2 ( 1.098 )
    -0.09 ( 2.126 )
    0.7 ( 1.795 )
    -1.68 ( 3.515 )
    -0.28 ( 1.003 )
        Leukocytes, Week10, n=7,8,4,7,8
    -0.94 ( 0.964 )
    0.31 ( 1.49 )
    0.53 ( 1.097 )
    -1.73 ( 4.375 )
    -0.41 ( 1.331 )
        Leukocytes, Week12, n=7,7,7,8,7
    -0.14 ( 1.33 )
    0.16 ( 0.913 )
    0.44 ( 1.533 )
    -1.95 ( 3.777 )
    -0.47 ( 0.73 )
        Leukocytes, Week16, n=5,6,3,6,6
    -1.2 ( 1.678 )
    -0.65 ( 1.15 )
    0.4 ( 1.153 )
    -1.1 ( 2.45 )
    0.5 ( 0.839 )
    Notes
    [95] - ITT Population
    [96] - ITT Population
    [97] - ITT Population
    [98] - ITT Population
    [99] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils SG/leukocytes and EDW at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils SG/leukocytes and EDW at the indicated time points up to Week 16 [100]
    End point description
    Change from Baseline in the basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils segmented (SG)/leukocytes and erythrocyte distribution width (EDW) values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (n=X,X,X,X,X). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [100] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [101]
    10 [102]
    10 [103]
    10 [104]
    11 [105]
    Units: Percentage
    arithmetic mean (standard deviation)
        Basophils/Leukocytes, Week1, n=9,10,9,10,11
    -0.02 ( 0.367 )
    -0.03 ( 0.149 )
    -0.08 ( 0.441 )
    -0.01 ( 0.242 )
    -0.09 ( 0.266 )
        Basophils/Leukocytes, Week2, n=9,9,10,9,9
    0.12 ( 0.373 )
    -0.09 ( 0.145 )
    -0.14 ( 0.272 )
    0.07 ( 0.173 )
    -0.12 ( 0.244 )
        Basophils/Leukocytes, Week3, n=9,7,9,6,7
    -0.04 ( 0.416 )
    -0.04 ( 0.251 )
    0.18 ( 0.595 )
    0.18 ( 0.431 )
    0.01 ( 0.277 )
        Basophils/Leukocytes, Week4, n=6,9,9,9,9
    0.02 ( 0.462 )
    -0.02 ( 0.244 )
    -0.07 ( 0.357 )
    0.03 ( 0.26 )
    -0.12 ( 0.179 )
        Basophils/Leukocytes, Week5, n=7,6,6,9,7
    -0.11 ( 0.449 )
    0.18 ( 0.248 )
    -0.13 ( 0.344 )
    -0.03 ( 0.229 )
    -0.14 ( 0.288 )
        Basophils/Leukocytes, Week6, n=7,10,6,10,7
    -0.24 ( 0.387 )
    0.05 ( 0.196 )
    -0.28 ( 0.299 )
    -0.03 ( 0.106 )
    -0.09 ( 0.234 )
        Basophils/Leukocytes, Week8, n=8,7,9,9,9
    -0.09 ( 0.455 )
    0.03 ( 0.214 )
    0.4 ( 0.941 )
    0.11 ( 0.203 )
    -0.07 ( 0.296 )
        Basophils/Leukocytes, Week10, n=7,8,4,7,8
    -0.07 ( 0.35 )
    -0.01 ( 0.21 )
    -0.35 ( 0.173 )
    0.06 ( 0.172 )
    0.03 ( 0.139 )
        Basophils/Leukocytes, Week12, n=7,7,7,8,7
    -0.17 ( 0.243 )
    0.03 ( 0.298 )
    -0.17 ( 0.138 )
    -0.05 ( 0.214 )
    -0.06 ( 0.369 )
        Basophils/Leukocytes, Week16, n=5,6,3,6,6
    0 ( 0.308 )
    -0.08 ( 0.172 )
    -0.1 ( 0.3 )
    0.12 ( 0.279 )
    -0.1 ( 0.228 )
        Eosinophils/Leukocytes, Week1, n=9,10,9,10,11
    0.11 ( 1.054 )
    -0.69 ( 1.501 )
    -2.21 ( 5.829 )
    0.49 ( 0.716 )
    0.1 ( 1.052 )
        Eosinophils/Leukocytes, Week2, n=9,9,10,9,9
    2.1 ( 2.264 )
    -0.39 ( 1.394 )
    -0.64 ( 7.039 )
    1.29 ( 2.389 )
    -0.07 ( 0.515 )
        Eosinophils/Leukocytes, Week3, n=9,7,9,6,7
    0.61 ( 1.114 )
    -0.73 ( 1.947 )
    -2.08 ( 5.652 )
    0.87 ( 0.437 )
    1.59 ( 2.26 )
        Eosinophils/Leukocytes, Week4, n=6,9,9,9,9
    -0.37 ( 0.958 )
    -0.89 ( 1.578 )
    -1.7 ( 5.803 )
    -0.04 ( 0.642 )
    -0.07 ( 0.57 )
        Eosinophils/Leukocytes, Week5, n=7,6,6,9,7
    0.2 ( 1.405 )
    -0.73 ( 1.188 )
    0.15 ( 0.997 )
    0.12 ( 0.574 )
    -0.24 ( 0.31 )
        Eosinophils/Leukocytes, Week6, n=7,10,6,10,7
    -0.43 ( 1.048 )
    -0.86 ( 1.581 )
    -0.58 ( 0.496 )
    -0.16 ( 0.662 )
    -0.04 ( 0.42 )
        Eosinophils/Leukocytes, Week8, n=8,7,9,9,9
    0.1 ( 0.678 )
    -0.74 ( 1.259 )
    -1.2 ( 3.844 )
    0.29 ( 0.695 )
    0.12 ( 0.67 )
        Eosinophils/Leukocytes, Week10, n=7,8,4,7,8
    0.87 ( 2.131 )
    -0.19 ( 2.307 )
    -0.8 ( 0.757 )
    0.51 ( 2.343 )
    0.46 ( 1.234 )
        Eosinophils/Leukocytes, Week12, n=7,7,7,8,7
    0.06 ( 1.212 )
    -0.34 ( 2.167 )
    -0.37 ( 0.848 )
    0.75 ( 1.449 )
    1.14 ( 1.408 )
        Eosinophils/Leukocytes, Week16, n=5,6,3,6,6
    0.24 ( 0.77 )
    -0.87 ( 1.742 )
    1.33 ( 2.829 )
    -0.55 ( 0.718 )
    0.53 ( 0.763 )
        Lymphocytes/Leukocytes, Week1, n=9,10,9,10,11
    7.37 ( 10.9 )
    -2.44 ( 11.9 )
    -7.27 ( 7.597 )
    -0.18 ( 8.646 )
    -1.85 ( 7.021 )
        Lymphocytes/Leukocytes, Week2, n=9,9,10,9,9
    5.57 ( 11.455 )
    -0.09 ( 5.623 )
    -6.49 ( 6.821 )
    1.56 ( 9.714 )
    -1.49 ( 6.214 )
        Lymphocytes/Leukocytes, Week3, n=9,7,9,6,7
    6.17 ( 12.256 )
    0.64 ( 8.374 )
    -2.63 ( 7.333 )
    9.45 ( 6.77 )
    3.99 ( 14.729 )
        Lymphocytes/Leukocytes, Week4, n=6,9,9,9,9
    8.02 ( 12.199 )
    0.27 ( 8.848 )
    -1.2 ( 5.79 )
    4.68 ( 8.387 )
    -0.31 ( 6.648 )
        Lymphocytes/Leukocytes, Week5, n=7,6,6,9,7
    1.93 ( 9.353 )
    1.87 ( 7.289 )
    -3.7 ( 8.298 )
    6.59 ( 10.764 )
    -2.39 ( 4.963 )
        Lymphocytes/Leukocytes, Week6, n=7,10,6,10,7
    4.07 ( 10.43 )
    -0.84 ( 7.714 )
    0.73 ( 15.625 )
    1.79 ( 5.275 )
    -2.81 ( 8.409 )
        Lymphocytes/Leukocytes, Week8, n=8,7,9,9,9
    6.49 ( 13.921 )
    0.89 ( 10.618 )
    -0.08 ( 11.076 )
    7.33 ( 12.026 )
    -0.62 ( 3.987 )
        Lymphocytes/Leukocytes, Week10, n=7,8,4,7,8
    4.69 ( 8.153 )
    0.04 ( 7.789 )
    -6.05 ( 4.08 )
    3.69 ( 10.497 )
    0.77 ( 7.583 )
        Lymphocytes/Leukocytes, Week12, n=7,7,7,8,7
    -0.41 ( 6.828 )
    -1.86 ( 3.134 )
    3.1 ( 9.892 )
    2.74 ( 11.547 )
    2.83 ( 9.272 )
        Lymphocytes/Leukocytes, Week16, n=5,6,3,6,6
    4.58 ( 10.518 )
    4.75 ( 11.131 )
    0.67 ( 5.311 )
    3.5 ( 10.198 )
    -1.2 ( 4.572 )
        Monocytes/Leukocytes, Week1, n=9,10,9,10,11
    -0.23 ( 4.618 )
    -1.44 ( 1.851 )
    -0.26 ( 4.954 )
    -0.1 ( 3.053 )
    -0.86 ( 2.037 )
        Monocytes/Leukocytes, Week2, n=9,9,10,9,9
    -0.78 ( 4.229 )
    -0.01 ( 2.606 )
    -0.66 ( 3.168 )
    -0.78 ( 2.485 )
    -0.12 ( 2.164 )
        Monocytes/Leukocytes, Week3, n=9,7,9,6,7
    -1.96 ( 4.246 )
    -0.19 ( 2.83 )
    1.66 ( 5.079 )
    0.63 ( 3.533 )
    -0.51 ( 1.142 )
        Monocytes/Leukocytes, Week4, n=6,9,9,9,9
    -2.05 ( 4.077 )
    0.12 ( 2.8 )
    0.34 ( 3.968 )
    0.8 ( 5.071 )
    -0.51 ( 1.722 )
        Monocytes/Leukocytes, Week5, n=7,6,6,9,7
    -0.27 ( 2.188 )
    0.72 ( 1.309 )
    0.37 ( 4.712 )
    0.68 ( 4.668 )
    -0.87 ( 1.863 )
        Monocytes/Leukocytes, Week6, n=7,10,6,10,7
    -1 ( 1.69 )
    -0.51 ( 2.682 )
    -0.97 ( 4.149 )
    -1.82 ( 2.439 )
    -1.13 ( 0.972 )
        Monocytes/Leukocytes, Week8, n=8,7,9,9,9
    -1.24 ( 2.856 )
    1.34 ( 4.065 )
    -0.17 ( 2.401 )
    0.69 ( 2.816 )
    0.29 ( 1.642 )
        Monocytes/Leukocytes, Week10, n=7,8,4,7,8
    0.59 ( 1.416 )
    -0.65 ( 2.519 )
    -0.98 ( 3.645 )
    0.03 ( 3.539 )
    -0.45 ( 1.448 )
        Monocytes/Leukocytes, Week12, n=7,7,7,8,7
    0.04 ( 2.326 )
    -0.2 ( 1.882 )
    1.34 ( 3.38 )
    0.95 ( 3.746 )
    -0.04 ( 0.986 )
        Monocytes/Leukocytes, Week16, n=5,6,3,6,6
    0.94 ( 1.358 )
    -0.43 ( 2.207 )
    -0.83 ( 0.569 )
    -1.62 ( 2.091 )
    0.3 ( 1.74 )
        Neutrophils/Leukocytes, Week1, n=8,10,9,10,11
    -6.89 ( 10.974 )
    4.6 ( 14.042 )
    9.81 ( 9.751 )
    -0.2 ( 11.49 )
    2.71 ( 8.625 )
        Neutrophils/Leukocytes, Week2, n=8,9,10,9,9
    -6.95 ( 10.766 )
    0.58 ( 7.422 )
    7.93 ( 8.472 )
    -2.13 ( 10.553 )
    1.8 ( 8.24 )
        Neutrophils/Leukocytes, Week3, n=8,7,9,6,7
    -4.61 ( 12.278 )
    0.31 ( 11.97 )
    2.88 ( 10.999 )
    -11.13 ( 8.861 )
    -5.07 ( 16.55 )
        Neutrophils/Leukocytes, Week4, n=5,9,9,9,9
    -6.88 ( 11.033 )
    0.52 ( 12.138 )
    2.62 ( 9.988 )
    -5.47 ( 9.665 )
    1.01 ( 7.743 )
        Neutrophils/Leukocytes, Week5, n=6,6,6,9,7
    -1.67 ( 11.661 )
    -2.03 ( 7.169 )
    3.32 ( 12.056 )
    -7.36 ( 13.85 )
    3.64 ( 5.422 )
        Neutrophils/Leukocytes, Week6, n=6,10,6,10,7
    -2.7 ( 13 )
    2.16 ( 9.334 )
    1.1 ( 16.691 )
    0.22 ( 5.022 )
    4.07 ( 8.798 )
        Neutrophils/Leukocytes, Week8, n=7,7,9,9,9
    -5.21 ( 13.064 )
    -1.51 ( 13.268 )
    1.04 ( 10.843 )
    -8.42 ( 13.702 )
    0.28 ( 5.261 )
        Neutrophils/Leukocytes, Week10, n=6,8,4,7,8
    -5.93 ( 11.454 )
    0.81 ( 11.653 )
    8.18 ( 5.705 )
    -4.29 ( 12.505 )
    -0.81 ( 8.921 )
        Neutrophils/Leukocytes, Week12, n=6,7,7,8,7
    0.68 ( 7.055 )
    2.37 ( 5.459 )
    -3.9 ( 10.99 )
    -4.39 ( 14.892 )
    -3.87 ( 8.832 )
        Neutrophils/Leukocytes, Week16, n=4,6,3,6,6
    -5.38 ( 13.405 )
    -3.37 ( 12.751 )
    -1.07 ( 4.007 )
    -1.45 ( 11.237 )
    0.47 ( 5.895 )
        Neutrophils SG/Leukocytes, Week1, n=9,10,9,10,11
    -7.22 ( 10.314 )
    4.6 ( 14.042 )
    9.81 ( 9.751 )
    -0.2 ( 11.49 )
    2.71 ( 8.625 )
        Neutrophils SG/Leukocytes, Week2, n=9,9,10,9,9
    -6.98 ( 10.071 )
    0.58 ( 7.422 )
    7.93 ( 8.472 )
    -2.13 ( 10.553 )
    1.8 ( 8.24 )
        Neutrophils SG/Leukocytes, Week3, n=9,7,9,6,7
    -4.78 ( 11.496 )
    0.31 ( 11.97 )
    2.88 ( 10.999 )
    -11.13 ( 8.861 )
    -5.07 ( 16.55 )
        Neutrophils SG/Leukocytes, Week4, n=6,9,9,9,9
    -5.62 ( 10.342 )
    0.52 ( 12.138 )
    2.62 ( 9.988 )
    -5.47 ( 9.665 )
    1.01 ( 7.743 )
        Neutrophils SG/Leukocytes, Week5, n=7,6,6,9,7
    -1.74 ( 10.647 )
    -2.03 ( 7.169 )
    3.32 ( 12.056 )
    -7.36 ( 13.85 )
    3.64 ( 5.422 )
        Neutrophils SG/Leukocytes, Week6, n=7,10,6,10,7
    -2.4 ( 11.894 )
    2.16 ( 9.334 )
    1.1 ( 16.691 )
    0.22 ( 5.022 )
    4.07 ( 8.798 )
        Neutrophils SG/Leukocytes, Week8, n=8,7,9,9,9
    -5.26 ( 12.096 )
    -1.51 ( 13.268 )
    1.04 ( 10.843 )
    -8.42 ( 13.702 )
    0.28 ( 5.261 )
        Neutrophils SG/Leukocytes, Week10, n=7,8,4,7,8
    -6.07 ( 10.462 )
    0.81 ( 11.653 )
    8.18 ( 5.705 )
    -4.29 ( 12.505 )
    -0.81 ( 8.921 )
        Neutrophils SG/Leukocytes, Week12, n=7,7,7,8,7
    0.49 ( 6.462 )
    2.37 ( 5.459 )
    -3.9 ( 10.99 )
    -4.39 ( 14.892 )
    -3.87 ( 8.832 )
        Neutrophils SG/Leukocytes, Week16, n=5,6,3,6,6
    -5.76 ( 11.641 )
    -3.37 ( 12.751 )
    -1.07 ( 4.007 )
    -1.45 ( 11.237 )
    0.47 ( 5.895 )
        EDW, Week1, n=9,10,9,10,11
    0.07 ( 0.447 )
    0.03 ( 0.523 )
    -0.26 ( 0.75 )
    -0.25 ( 0.472 )
    -0.17 ( 0.427 )
        EDW, Week2, n=9,9,10,9,9
    0.28 ( 0.387 )
    0.22 ( 0.545 )
    0.08 ( 0.594 )
    -0.33 ( 0.654 )
    0.08 ( 0.672 )
        EDW, Week3, n=9,7,9,7,7
    0.14 ( 0.691 )
    0.37 ( 0.206 )
    0.44 ( 0.918 )
    -0.2 ( 0.936 )
    0.1 ( 0.847 )
        EDW, Week4, n=6,9,9,9,9
    0.85 ( 0.864 )
    0.1 ( 0.51 )
    0.54 ( 0.644 )
    -0.08 ( 1.099 )
    0.31 ( 1.288 )
        EDW, Week5, n=7,6,6,9,7
    0.59 ( 0.96 )
    0.43 ( 0.833 )
    1.2 ( 1.131 )
    0.39 ( 1.237 )
    0.41 ( 1.489 )
        EDW, Week6, n=7,10,6,10,8
    0.43 ( 1.268 )
    0.06 ( 0.744 )
    0.55 ( 1.544 )
    0.46 ( 0.987 )
    -0.02 ( 1.635 )
        EDW, Week8, n=8,7,9,9,9
    0.31 ( 1.169 )
    0.01 ( 0.773 )
    1.02 ( 1.498 )
    0.77 ( 0.97 )
    0.37 ( 1.907 )
        EDW, Week10, n=7,8,4,7,8
    0.23 ( 0.945 )
    0.06 ( 1.187 )
    0.5 ( 1.538 )
    0.91 ( 1.129 )
    0.91 ( 2.906 )
        EDW, Week12, n=7,7,7,8,7
    0.51 ( 1.794 )
    0.11 ( 1.275 )
    0.51 ( 1.235 )
    0.94 ( 1.25 )
    1.57 ( 2.715 )
        EDW, Week16, n=5,6,3,6,6
    0.7 ( 1.377 )
    0.57 ( 1.341 )
    0.5 ( 0.265 )
    0.52 ( 1.16 )
    1.72 ( 3.98 )
    Notes
    [101] - ITT Population
    [102] - ITT Population
    [103] - ITT Population
    [104] - ITT Population
    [105] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in erythrocytes and reticulocytes at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in erythrocytes and reticulocytes at the indicated time points up to Week 16 [106]
    End point description
    Change from Baseline in the erythrocyte and reticulocyte values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [106] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [107]
    10 [108]
    10 [109]
    10 [110]
    11 [111]
    Units: Trillion per liter
    arithmetic mean (standard deviation)
        Erythrocytes, Week1, n=9,10,9,10,11
    -0.07 ( 0.187 )
    -0.08 ( 0.162 )
    0.01 ( 0.226 )
    -0.06 ( 0.178 )
    -0.13 ( 0.127 )
        Erythrocytes, Week2, n=9,9,10,9,9
    -0.1 ( 0.166 )
    0.02 ( 0.277 )
    0.07 ( 0.226 )
    -0.07 ( 0.2 )
    -0.14 ( 0.088 )
        Erythrocytes, Week3, n=9,7,9,7,7
    -0.12 ( 0.172 )
    0.03 ( 0.263 )
    0.04 ( 0.201 )
    -0.04 ( 0.27 )
    -0.13 ( 0.221 )
        Erythrocytes, Week4, n=6,9,9,9,9
    -0.05 ( 0.207 )
    -0.07 ( 0.2 )
    0.04 ( 0.151 )
    -0.13 ( 0.283 )
    -0.09 ( 0.22 )
        Erythrocytes, Week5, n=7,6,7,9,7
    -0.27 ( 0.17 )
    0 ( 0.29 )
    0 ( 0.141 )
    -0.19 ( 0.176 )
    -0.07 ( 0.198 )
        Erythrocytes, Week6, n=7,10,6,10,8
    -0.17 ( 0.25 )
    0.08 ( 0.377 )
    0.08 ( 0.279 )
    -0.08 ( 0.204 )
    0.05 ( 0.12 )
        Erythrocytes, Week8, n=8,7,9,9,9
    0.04 ( 0.302 )
    -0.06 ( 0.151 )
    -0.06 ( 0.207 )
    -0.09 ( 0.341 )
    -0.04 ( 0.219 )
        Erythrocytes, Week10, n=7,8,4,7,8
    -0.13 ( 0.214 )
    -0.03 ( 0.296 )
    -0.05 ( 0.129 )
    -0.21 ( 0.146 )
    0.04 ( 0.256 )
        Erythrocytes, Week12, n=7,7,7,8,7
    -0.11 ( 0.227 )
    -0.01 ( 0.204 )
    0.01 ( 0.107 )
    -0.04 ( 0.311 )
    -0.04 ( 0.331 )
        Erythrocytes, Week16, n=5,6,3,6,6
    -0.02 ( 0.327 )
    -0.1 ( 0.21 )
    -0.17 ( 0.058 )
    -0.03 ( 0.32 )
    0.03 ( 0.28 )
        Reticulocytes, Week1, n=9,10,9,10,11
    0.01023 ( 0.013577 )
    -0.00241 ( 0.016591 )
    0.00822 ( 0.014942 )
    0.00233 ( 0.01305 )
    -0.00318 ( 0.015587 )
        Reticulocytes, Week2, n=9,9,10,9,9
    0.01356 ( 0.014036 )
    -0.00686 ( 0.020924 )
    -0.0008 ( 0.014329 )
    -0.0026 ( 0.017417 )
    -0.00031 ( 0.024158 )
        Reticulocytes, Week3, n=9,7,9,7,7
    0.02272 ( 0.022383 )
    0.00693 ( 0.032031 )
    0.01006 ( 0.011791 )
    0.00519 ( 0.022769 )
    -0.00409 ( 0.022753 )
        Reticulocytes, Week4, n=6,9,9,9,9
    0.01822 ( 0.008272 )
    0.00904 ( 0.039946 )
    0.00202 ( 0.018841 )
    0.00278 ( 0.020853 )
    0.00083 ( 0.025744 )
        Reticulocytes, Week5, n=7,6,7,9,7
    0.01267 ( 0.015672 )
    0.00122 ( 0.015623 )
    0.01227 ( 0.019674 )
    0.00874 ( 0.022087 )
    0.00009 ( 0.031287 )
        Reticulocytes, Week6, n=7,10,6,10,8
    0.00827 ( 0.018538 )
    0.00131 ( 0.020422 )
    -0.00193 ( 0.01615 )
    0.00872 ( 0.019709 )
    -0.00243 ( 0.023781 )
        Reticulocytes, Week8, n=8,7,9,9,9
    0.00609 ( 0.01307 )
    0.00561 ( 0.02537 )
    0.01772 ( 0.026266 )
    0.01912 ( 0.046264 )
    0.00214 ( 0.025027 )
        Reticulocytes, Week10, n=7,8,4,7,8
    0.01343 ( 0.005743 )
    -0.00155 ( 0.024259 )
    -0.00227 ( 0.010259 )
    0.01686 ( 0.027415 )
    0.00125 ( 0.035393 )
        Reticulocytes, Week12, n=7,7,7,8,7
    0.00839 ( 0.01347 )
    0.00454 ( 0.019287 )
    0.00017 ( 0.011061 )
    0.00011 ( 0.025521 )
    0.00859 ( 0.009494 )
        Reticulocytes, Week16, n=5,6,3,6,6
    0.00778 ( 0.01031 )
    -0.00515 ( 0.012694 )
    0.00853 ( 0.013776 )
    0.00412 ( 0.023629 )
    0.00195 ( 0.008808 )
    Notes
    [107] - ITT Population
    [108] - ITT Population
    [109] - ITT Population
    [110] - ITT Population
    [111] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in hemoglobin and EMCHC at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in hemoglobin and EMCHC at the indicated time points up to Week 16 [112]
    End point description
    Change from Baseline in the hemoglobin and erythrocyte mean corpuscular hemoglobin concentration (EMCHC) values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [112] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [113]
    10 [114]
    10 [115]
    10 [116]
    11 [117]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        Hemoglobin, Week1, n=9,10,9,10,11
    -2.4 ( 5.61 )
    -2.5 ( 4.14 )
    0.2 ( 6.46 )
    -0.7 ( 6.07 )
    -4.3 ( 4.47 )
        Hemoglobin, Week2, n=9,9,10,9,9
    -2.6 ( 4.42 )
    -0.3 ( 7.48 )
    1.6 ( 6.47 )
    -1 ( 6.52 )
    -5.2 ( 3.38 )
        Hemoglobin, Week3, n=9,7,9,7,7
    -3.6 ( 4.75 )
    0.9 ( 5.46 )
    1 ( 5.63 )
    -0.9 ( 6.67 )
    -5.1 ( 6.15 )
        Hemoglobin, Week4, n=6,9,9,9,9
    -1.8 ( 7.14 )
    -1.6 ( 6.56 )
    1.8 ( 4.74 )
    -3.1 ( 8.91 )
    -4.7 ( 7.16 )
        Hemoglobin, Week5, n=7,6,7,9,7
    -8.6 ( 3.99 )
    -0.5 ( 7.97 )
    2.1 ( 4.45 )
    -3.9 ( 7.15 )
    -5.1 ( 7.22 )
        Hemoglobin, Week6, n=7,10,6,10,8
    -6.3 ( 5.68 )
    2.4 ( 11.46 )
    3.8 ( 7 )
    -1.7 ( 6.85 )
    -2.4 ( 6.72 )
        Hemoglobin, Week8, n=8,7,9,9,9
    0.3 ( 8.94 )
    -3.1 ( 5.24 )
    -0.1 ( 5.82 )
    -3.3 ( 9.33 )
    -5.9 ( 7.54 )
        Hemoglobin, Week10, n=7,8,4,7,8
    -4.9 ( 5.21 )
    -2.1 ( 9 )
    1.5 ( 3.7 )
    -3.6 ( 7.37 )
    -4.1 ( 7.74 )
        Hemoglobin, Week12, n=7,7,7,8,7
    -6 ( 6.58 )
    -3.7 ( 5.35 )
    1.4 ( 1.72 )
    -2.1 ( 8.72 )
    -7.7 ( 5.22 )
        Hemoglobin, Week16, n=5,6,3,6,6
    -6.6 ( 7.67 )
    -6.2 ( 6.11 )
    -3 ( 1.73 )
    -4.2 ( 4.31 )
    -4.7 ( 8.12 )
        EMCHC, Week1, n=9,10,9,10,11
    -4.6 ( 6.52 )
    -3.9 ( 5.7 )
    2.4 ( 4.93 )
    1.4 ( 6.79 )
    -0.5 ( 6.33 )
        EMCHC, Week2, n=9,9,10,9,9
    -2.8 ( 7.28 )
    -3.3 ( 5.57 )
    3.8 ( 3.99 )
    4 ( 5.59 )
    0.1 ( 5.13 )
        EMCHC, Week3, n=9,7,9,7,7
    1.3 ( 4.64 )
    -2.4 ( 5.91 )
    2.3 ( 6.52 )
    2.9 ( 11.63 )
    -2.9 ( 4.63 )
        EMCHC, Week4, n=6,9,9,9,9
    -1.7 ( 5.89 )
    1.8 ( 7.53 )
    2.1 ( 6.39 )
    6.4 ( 7.99 )
    -0.4 ( 5.32 )
        EMCHC, Week5, n=7,6,7,9,7
    -3.1 ( 7.9 )
    -3.3 ( 5.85 )
    1.4 ( 3.41 )
    3.9 ( 7.99 )
    -3.1 ( 9.23 )
        EMCHC, Week6, n=7,10,6,10,8
    -4.1 ( 9.82 )
    -0.8 ( 6.66 )
    3 ( 4.24 )
    1.8 ( 10.21 )
    -3.1 ( 10.72 )
        EMCHC, Week8, n=8,7,9,9,9
    0.4 ( 5.63 )
    -1.9 ( 6.04 )
    2.3 ( 6.2 )
    1.7 ( 10.69 )
    -1.6 ( 9.74 )
        EMCHC, Week10, n=7,8,4,7,8
    0.6 ( 6.8 )
    1.4 ( 5.26 )
    2.3 ( 4.19 )
    4.3 ( 8.56 )
    -2.9 ( 7.75 )
        EMCHC, Week12, n=7,7,7,8,7
    -3.7 ( 11.79 )
    -0.9 ( 4.22 )
    3.1 ( 7.88 )
    3.4 ( 7.42 )
    -6 ( 8.33 )
        EMCHC, Week16, n=5,6,3,6,6
    -6.6 ( 9.96 )
    0.3 ( 7.26 )
    5 ( 5.57 )
    -3.2 ( 13.35 )
    1.8 ( 15.66 )
    Notes
    [113] - ITT Population
    [114] - ITT Population
    [115] - ITT Population
    [116] - ITT Population
    [117] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in EMCH at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in EMCH at the indicated time points up to Week 16 [118]
    End point description
    Change from Baseline in the hemoglobin and erythrocyte mean corpuscular hemoglobin (EMCH) values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [118] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [119]
    10 [120]
    10 [121]
    10 [122]
    11 [123]
    Units: Picograms
    arithmetic mean (standard deviation)
        EMCH, Week1, n=9,10,9,10,11
    -0.17 ( 0.45 )
    -0.22 ( 0.563 )
    0.13 ( 0.316 )
    0.25 ( 0.517 )
    -0.13 ( 0.529 )
        EMCH, Week2, n=9,9,10,9,9
    0.01 ( 0.22 )
    -0.38 ( 0.58 )
    0.09 ( 0.348 )
    0.1 ( 0.532 )
    -0.18 ( 0.62 )
        EMCH, Week3, n=9,7,9,7,7
    0.16 ( 0.553 )
    -0.11 ( 0.626 )
    -0.04 ( 0.43 )
    -0.03 ( 1.029 )
    -0.66 ( 0.75 )
        EMCH, Week4, n=6,9,9,9,9
    0.03 ( 0.869 )
    0 ( 0.458 )
    0.1 ( 0.65 )
    0.14 ( 0.609 )
    -0.49 ( 1.177 )
        EMCH, Week5, n=7,6,7,9,7
    -0.16 ( 0.447 )
    -0.1 ( 0.4 )
    0.5 ( 0.216 )
    0.49 ( 0.747 )
    -0.79 ( 1.442 )
        EMCH, Week6, n=7,10,6,10,8
    -0.23 ( 0.655 )
    -0.34 ( 0.847 )
    0.23 ( 0.367 )
    0.15 ( 0.72 )
    -1 ( 1.504 )
        EMCH, Week8, n=8,7,9,9,9
    -0.12 ( 0.907 )
    -0.46 ( 0.791 )
    0.28 ( 0.455 )
    -0.17 ( 1.428 )
    -1.19 ( 1.691 )
        EMCH, Week10, n=7,8,4,7,8
    -0.33 ( 0.668 )
    -0.35 ( 0.548 )
    0.52 ( 0.126 )
    0.54 ( 1.229 )
    -1.37 ( 1.972 )
        EMCH, Week12, n=7,7,7,8,7
    -0.56 ( 0.774 )
    -0.84 ( 0.914 )
    0.26 ( 0.675 )
    -0.15 ( 1.323 )
    -1.79 ( 2.323 )
        EMCH, Week16, n=5,6,3,6,6
    -1.18 ( 1.178 )
    -0.9 ( 0.957 )
    0.3 ( 0.5 )
    -0.88 ( 1.731 )
    -1.43 ( 2.868 )
    Notes
    [119] - ITT Population.
    [120] - ITT Population.
    [121] - ITT Population.
    [122] - ITT Population.
    [123] - ITT Population.
    No statistical analyses for this end point

    Primary: Change from Baseline in EMCV and MPV at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in EMCV and MPV at the indicated time points up to Week 16 [124]
    End point description
    Change from Baseline in the erythrocyte mean corpuscular volume (EMCV) and mean platelet volume (MPV) values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [124] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [125]
    10 [126]
    10 [127]
    10 [128]
    11 [129]
    Units: Femtoliters
    arithmetic mean (standard deviation)
        EMCV, Week1, n=9,10,9,10,11
    0.4 ( 1.42 )
    0.6 ( 1.9 )
    -0.6 ( 1.13 )
    0.2 ( 1.32 )
    -0.3 ( 1.68 )
        EMCV, Week2, n=9,9,10,9,9
    0.6 ( 1.74 )
    -0.3 ( 1.66 )
    -0.7 ( 0.95 )
    -1 ( 1.41 )
    -0.4 ( 2.7 )
        EMCV, Week3, n=9,7,9,7,7
    -0.1 ( 1.69 )
    0.7 ( 1.7 )
    -0.7 ( 1.66 )
    -0.9 ( 1.21 )
    -1 ( 2.24 )
        EMCV, Week4, n=6,9,9,9,9
    0.3 ( 2.8 )
    -0.3 ( 2.45 )
    -0.3 ( 1.73 )
    -1.7 ( 1.41 )
    -1.1 ( 2.98 )
        EMCV, Week5, n=7,6,7,9,7
    0 ( 1 )
    0.8 ( 2.64 )
    1.1 ( 0.9 )
    0.1 ( 1.96 )
    -1.6 ( 3.41 )
        EMCV, Week6, n=7,10,6,10,8
    0.3 ( 1.98 )
    -0.8 ( 2.25 )
    0.2 ( 2.14 )
    -0.1 ( 2.08 )
    -2.1 ( 4.22 )
        EMCV, Week8, n=8,7,9,9,9
    -0.6 ( 2.83 )
    -1 ( 2.52 )
    0.2 ( 2.28 )
    -1.2 ( 1.99 )
    -3.1 ( 4.01 )
        EMCV, Week10, n=7,8,4,7,8
    -1.6 ( 2.44 )
    -1.5 ( 1.85 )
    1 ( 0.82 )
    0.4 ( 2.3 )
    -3.5 ( 5.15 )
        EMCV, Week12, n=7,7,7,8,7
    -0.9 ( 4.45 )
    -2.4 ( 2.15 )
    -0.3 ( 1.7 )
    -1.6 ( 2.39 )
    -3.7 ( 6.34 )
        EMCV, Week16, n=5,6,3,6,6
    -2.2 ( 5.45 )
    -3 ( 2.83 )
    0 ( 0 )
    -1.7 ( 2.16 )
    -5.3 ( 6.28 )
        MPV, Week1, n=9,10,9,10,11
    0.12 ( 0.273 )
    -0.04 ( 0.45 )
    0.06 ( 0.317 )
    -0.37 ( 0.696 )
    -0.16 ( 0.32 )
        MPV, Week2, n=9,9,10,9,9
    0.1 ( 0.24 )
    -0.02 ( 0.556 )
    0.31 ( 0.626 )
    -0.22 ( 0.821 )
    -0.08 ( 0.509 )
        MPV, Week3, n=9,7,9,7,7
    -0.09 ( 0.352 )
    -0.01 ( 0.631 )
    -0.17 ( 0.76 )
    -0.45 ( 0.829 )
    -0.17 ( 0.335 )
        MPV, Week4, n=6,9,9,9,9
    -0.08 ( 0.248 )
    -0.02 ( 0.572 )
    -0.24 ( 0.675 )
    -0.24 ( 0.805 )
    -0.02 ( 0.421 )
        MPV, Week5, n=7,6,7,9,7
    -0.1 ( 0.416 )
    0.12 ( 0.595 )
    -0.1 ( 0.258 )
    -0.49 ( 0.772 )
    -0.07 ( 0.616 )
        MPV, Week6, n=7,10,6,10,8
    0.2 ( 0.648 )
    -0.14 ( 0.731 )
    -0.17 ( 0.388 )
    -0.56 ( 0.76 )
    -0.09 ( 0.569 )
        MPV, Week8, n=8,7,9,9,9
    -0.17 ( 0.396 )
    -0.06 ( 0.704 )
    -0.13 ( 0.557 )
    -0.39 ( 1.029 )
    -0.12 ( 0.663 )
        MPV, Week10, n=7,8,4,7,8
    -0.16 ( 0.447 )
    -0.1 ( 0.374 )
    0.05 ( 0.48 )
    -0.46 ( 0.832 )
    0.01 ( 0.579 )
        MPV, Week12, n=7,7,7,8,7
    -0.07 ( 0.736 )
    0.2 ( 0.569 )
    0.01 ( 0.689 )
    -0.24 ( 0.778 )
    -0.03 ( 0.789 )
        MPV, Week16, n=5,6,3,6,6
    0.1 ( 0.566 )
    -0.08 ( 0.631 )
    -0.7 ( 0.52 )
    -0.38 ( 1.003 )
    0 ( 0.559 )
    Notes
    [125] - ITT Population
    [126] - ITT Population
    [127] - ITT Population
    [128] - ITT Population
    [129] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in hematocrit and reticulocytes/erythrocytes at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in hematocrit and reticulocytes/erythrocytes at the indicated time points up to Week 16 [130]
    End point description
    Change from Baseline in the hematocrit and reticulocytes/erythrocytes values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [130] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [131]
    10 [132]
    10 [133]
    10 [134]
    11 [135]
    Units: Fraction of 1
    arithmetic mean (standard deviation)
        Hematocrit, Week1, n=9,10,9,10,11
    -0.0023 ( 0.01869 )
    -0.0029 ( 0.01554 )
    -0.0028 ( 0.02198 )
    -0.0037 ( 0.01824 )
    -0.0128 ( 0.01308 )
        Hematocrit, Week2, n=9,9,10,9,9
    -0.0059 ( 0.01841 )
    0.0036 ( 0.02677 )
    -0.0001 ( 0.01959 )
    -0.0086 ( 0.0199 )
    -0.0154 ( 0.01507 )
        Hematocrit, Week3, n=9,7,9,7,7
    -0.0127 ( 0.01796 )
    0.0067 ( 0.02298 )
    -0.0003 ( 0.01761 )
    -0.0061 ( 0.02975 )
    -0.0124 ( 0.02204 )
        Hematocrit, Week4, n=6,9,9,9,9
    -0.0037 ( 0.01691 )
    -0.0067 ( 0.02438 )
    0.0027 ( 0.01525 )
    -0.0172 ( 0.02486 )
    -0.0136 ( 0.02166 )
        Hematocrit, Week5, n=7,6,7,9,7
    -0.0241 ( 0.01661 )
    0.0038 ( 0.0312 )
    0.0037 ( 0.0151 )
    -0.0168 ( 0.02156 )
    -0.0127 ( 0.01685 )
        Hematocrit, Week6, n=7,10,6,10,8
    -0.0147 ( 0.02043 )
    0.0069 ( 0.03471 )
    0.0082 ( 0.01863 )
    -0.0088 ( 0.01862 )
    -0.0038 ( 0.01552 )
        Hematocrit, Week8, n=8,7,9,9,9
    -0.0008 ( 0.0306 )
    -0.0074 ( 0.01758 )
    -0.0034 ( 0.01955 )
    -0.0124 ( 0.03152 )
    -0.0168 ( 0.02049 )
        Hematocrit, Week10, n=7,8,4,7,8
    -0.0173 ( 0.01505 )
    -0.008 ( 0.03033 )
    0.0015 ( 0.005 )
    -0.016 ( 0.01893 )
    -0.0106 ( 0.01983 )
        Hematocrit, Week12, n=7,7,7,8,7
    -0.0151 ( 0.02123 )
    -0.0099 ( 0.01541 )
    -0.0007 ( 0.01132 )
    -0.011 ( 0.02818 )
    -0.0181 ( 0.02038 )
        Hematocrit, Week16, n=5,6,3,6,6
    -0.0126 ( 0.0167 )
    -0.0195 ( 0.0195 )
    -0.0163 ( 0.00379 )
    -0.0087 ( 0.02391 )
    -0.019 ( 0.01455 )
        Reticulocytes/Erythrocytes, Week1, n=9,10,9,10,11
    0.0026 ( 0.00305 )
    -0.0004 ( 0.0042 )
    0.002 ( 0.00339 )
    0.0009 ( 0.00311 )
    -0.0004 ( 0.0037 )
        Reticulocytes/Erythrocytes, Week2, n=9,9,10,9,9
    0.0036 ( 0.00357 )
    -0.0018 ( 0.00502 )
    -0.0002 ( 0.00346 )
    -0.0001 ( 0.00392 )
    0.0002 ( 0.0054 )
        Reticulocytes/Erythrocytes, Week3, n=9,7,9,7,7
    0.0059 ( 0.00629 )
    0.002 ( 0.00777 )
    0.0023 ( 0.0025 )
    0.0016 ( 0.0055 )
    -0.0003 ( 0.00559 )
        Reticulocytes/Erythrocytes, Week4, n=6,9,9,9,9
    0.0045 ( 0.00243 )
    0.0024 ( 0.00961 )
    0.0002 ( 0.00471 )
    0.0014 ( 0.00654 )
    0.0007 ( 0.0061 )
        Reticulocytes/Erythrocytes, Week5, n=7,6,7,9,7
    0.0037 ( 0.00407 )
    0.0003 ( 0.00446 )
    0.0027 ( 0.00461 )
    0.0031 ( 0.00613 )
    0.0006 ( 0.00728 )
        Reticulocytes/Erythrocytes, Week6, n=7,10,6,10,8
    0.0021 ( 0.00418 )
    -0.0001 ( 0.00461 )
    -0.0007 ( 0.00413 )
    0.0025 ( 0.00495 )
    -0.0006 ( 0.00545 )
        Reticulocytes/Erythrocytes, Week8, n=8,7,9,9,9
    0.0013 ( 0.00337 )
    0.0017 ( 0.00556 )
    0.0042 ( 0.00608 )
    0.0049 ( 0.00957 )
    0.0008 ( 0.00533 )
        Reticulocytes/Erythrocytes, Week10, n=7,8,4,7,8
    0.0036 ( 0.00151 )
    -0.0002 ( 0.00557 )
    -0.0005 ( 0.00238 )
    0.0047 ( 0.00582 )
    0.0004 ( 0.00821 )
        Reticulocytes/Erythrocytes, Week12, n=7,7,7,8,7
    0.0023 ( 0.00304 )
    0.0009 ( 0.00418 )
    -0.0001 ( 0.00219 )
    0.0004 ( 0.0059 )
    0.002 ( 0.00294 )
        Reticulocytes/Erythrocytes, Week16, n=5,6,3,6,6
    0.002 ( 0.00173 )
    -0.0007 ( 0.00258 )
    0.0023 ( 0.00306 )
    0.0013 ( 0.0048 )
    0.0003 ( 0.00197 )
    Notes
    [131] - ITT Population
    [132] - ITT Population
    [133] - ITT Population
    [134] - ITT Population
    [135] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with urinalysis data at the indicated time points up to Week 16

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    End point title
    		 Number of participants with urinalysis data at the indicated time points up to Week 16 [136]
    End point description
    Number of participants with negative and positives (trace, +, ++ and +++) data for urine glucose (UGLU), urine ketones (UKET) and urine occult blood (UOB) are summarised for each post-Baseline assesment until Week 16. Urinalysis was performed by dipstick method. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). A value of 99999 indicates no participants were analyzed therefore there is no data for this time point.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [136] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [137]
    10 [138]
    10 [139]
    10 [140]
    11 [141]
    Units: Participants
        UGLU, Negative, Baseline, n=9,10,10,10,11
    9
    10
    10
    10
    11
        UGLU, Positive, Baseline, n=9,10,10,10,11
    0
    0
    0
    0
    0
        UGLU, Negative, Week2, n=9,9,9,9,10
    9
    9
    9
    9
    10
        UGLU, Positive, Week2, n=9,9,9,9,10
    0
    0
    0
    0
    0
        UGLU, Negative, Week3, n=1,1,0,0,0
    1
    1
    99999
    99999
    99999
        UGLU, Positive, Week3, n=1,1,0,0,0
    0
    0
    99999
    99999
    99999
        UGLU, Negative, Week4, n=8,9,8,8,9
    8
    9
    8
    8
    9
        UGLU, Positive, Week4, n=8,9,8,8,9
    0
    0
    0
    0
    0
        UGLU, Negative, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    2
        UGLU, Positive, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    0
        UGLU, Negative, Week6, n=7,10,6,9,8
    7
    10
    6
    9
    8
        UGLU, Positive, Week6, n=7,10,6,9,8
    0
    0
    0
    0
    0
        UGLU, Negative, Week8, n=8,7,9,9,9
    8
    7
    9
    9
    9
        UGLU, Positive, Week8, n=8,7,9,9,9
    0
    0
    0
    0
    0
        UGLU, Negative, Week10, n=7,8,4,7,8
    7
    8
    4
    7
    8
        UGLU, Positive, Week10, n=7,8,4,7,8
    0
    0
    0
    0
    0
        UGLU, Negative, Week12, n=7,7,7,8,7
    7
    7
    7
    8
    7
        UGLU, Positive, Week12, n=7,7,7,8,7
    0
    0
    0
    0
    0
        UGLU, Negative, Week16, n=5,6,3,6,6
    5
    6
    3
    5
    6
        UGLU, Positive, Week16, n=5,6,3,6,6
    0
    0
    0
    1
    0
        UKET, Negative, Baseline, n=9,10,10,10,11
    9
    10
    10
    10
    11
        UKET, Positive, Baseline, n=9,10,10,10,11
    0
    0
    0
    0
    0
        UKET, Negative, Week2, n=9,9,9,9,10
    9
    9
    6
    7
    10
        UKET, Positive, Week2, n=9,9,9,9,10
    0
    0
    3
    2
    0
        UKET, Negative, Week3, n=1,1,0,0,0
    0
    1
    99999
    99999
    99999
        UKET, Positive, Week3, n=1,1,0,0,0
    1
    0
    99999
    99999
    99999
        UKET, Negative, Week4, n=8,9,8,8,9
    8
    9
    6
    7
    9
        UKET, Positive, Week4, n=8,9,8,8,9
    0
    0
    2
    1
    0
        UKET, Negative, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    2
        UKET, Positive, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    0
        UKET, Negative, Week6, n=7,10,6,9,8
    6
    9
    5
    6
    8
        UKET, Positive, Week6, n=7,10,6,9,8
    1
    1
    1
    3
    0
        UKET, Negative, Week8, n=8,7,9,9,9
    8
    7
    8
    9
    9
        UKET, Positive, Week8, n=8,7,9,9,9
    0
    0
    1
    0
    0
        UKET, Negative, Week10, n=7,8,4,7,8
    7
    8
    3
    7
    8
        UKET, Positive, Week10, n=7,8,4,7,8
    0
    0
    1
    0
    0
        UKET, Negative, Week12, n=7,7,7,8,7
    6
    7
    6
    8
    7
        UKET, Positive, Week12, n=7,7,7,8,7
    1
    0
    1
    0
    0
        UKET, Negative, Week16, n=5,6,3,6,6
    5
    6
    3
    6
    6
        UKET, Positive, Week16, n=5,6,3,6,6
    0
    0
    0
    0
    0
        UOB, Negative, Baseline, n=9,10,10,10,11
    7
    10
    8
    9
    9
        UOB, Positive, Baseline, n=9,10,10,10,11
    2
    0
    2
    1
    2
        UOB, Negative, Week2, n=9,9,9,9,10
    7
    7
    6
    7
    4
        UOB, Positive, Week2, n=9,9,9,9,10
    2
    2
    3
    2
    6
        UOB, Negative, Week3, n=1,1,0,0,0
    1
    1
    99999
    99999
    99999
        UOB, Positive, Week3, n=1,1,0,0,0
    0
    0
    99999
    99999
    99999
        UOB, Negative, Week4, n=8,9,8,8,9
    5
    7
    6
    6
    7
        UOB, Positive, Week4, n=8,9,8,8,9
    3
    2
    2
    2
    2
        UOB, Negative, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    2
        UOB, Positive, Week5, n=0,0,0,0,2
    99999
    99999
    99999
    99999
    0
        UOB, Negative, Week6, n=7,10,6,9,8
    6
    10
    4
    7
    4
        UOB, Positive, Week6, n=7,10,6,9,8
    1
    0
    2
    2
    4
        UOB, Negative, Week8, n=8,7,9,9,9
    6
    5
    6
    6
    7
        UOB, Positive, Week8, n=8,7,9,9,9
    2
    2
    3
    3
    2
        UOB, Negative, Week10, n=7,8,4,7,8
    4
    7
    3
    6
    3
        UOB, Positive, Week10, n=7,8,4,7,8
    3
    1
    1
    1
    5
        UOB, Negative, Week12, n=7,7,7,8,7
    6
    5
    4
    8
    4
        UOB, Positive, Week12, n=7,7,7,8,7
    1
    2
    3
    0
    3
        UOB, Negative, Week16, n=5,6,3,6,6
    4
    4
    2
    5
    3
        UOB, Positive, Week16, n=5,6,3,6,6
    1
    2
    1
    1
    3
    Notes
    [137] - ITT Population. “Not available (NA)” data is presented as “99999”
    [138] - ITT Population. “Not available (NA)” data is presented as “99999”
    [139] - ITT Population. “Not available (NA)” data is presented as “99999”
    [140] - ITT Population. “Not available (NA)” data is presented as “99999”
    [141] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in urine protein at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in urine protein at the indicated time points up to Week 16 [142]
    End point description
    Change from Baseline in the urine protein values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [142] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [143]
    10 [144]
    10 [145]
    10 [146]
    11 [147]
    Units: Milligrams per liter
    arithmetic mean (standard deviation)
        Protein, Week2, n=9,9,9,9,10
    28.3 ( 74.16 )
    107 ( 273.2 )
    171.2 ( 368.95 )
    32.1 ( 79.19 )
    -26.2 ( 129.76 )
        Protein, Week3, n=1,1,0,0,0
    328 ( 99999 )
    -48 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Protein, Week4, n=8,9,8,8,9
    -19.8 ( 61.6 )
    8.3 ( 110.52 )
    40 ( 155.5 )
    15.9 ( 47.72 )
    -56.6 ( 140.52 )
        Protein, Week5, n=0,0,0,0,1
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -70 ( 99999 )
        Protein, Week6, n=7,10,6,9,8
    -32.1 ( 46.48 )
    -26.9 ( 50.61 )
    16.3 ( 102.91 )
    32.7 ( 79.87 )
    -27.6 ( 65.98 )
        Protein, Week8, n=8,7,9,9,9
    6.3 ( 42.81 )
    -19.3 ( 45.15 )
    -4.9 ( 74.08 )
    -2.7 ( 43.87 )
    -14.9 ( 156.33 )
        Protein, Week10, n=7,8,4,6,8
    -32 ( 64.44 )
    11.1 ( 63.62 )
    2.5 ( 43.81 )
    15.8 ( 48.02 )
    46.9 ( 123.75 )
        Protein, Week12, n=7,7,7,8,7
    -1.7 ( 39.77 )
    6.6 ( 96.54 )
    -33.7 ( 72.29 )
    25.1 ( 55.58 )
    33.9 ( 146.43 )
        Protein, Week16, n=5,6,3,5,6
    2.4 ( 9.61 )
    62.2 ( 153.9 )
    -31 ( 19 )
    33.6 ( 44.18 )
    -37.3 ( 52.7 )
    Notes
    [143] - ITT Population. “Not available (NA)” data is presented as “99999”
    [144] - ITT Population. “Not available (NA)” data is presented as “99999”
    [145] - ITT Population. “Not available (NA)” data is presented as “99999”
    [146] - ITT Population. “Not available (NA)” data is presented as “99999”
    [147] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Change from Baseline in urine protein/creatinine at the indicated time points up to Week 16

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    End point title
    		 Change from Baseline in urine protein/creatinine at the indicated time points up to Week 16 [148]
    End point description
    Change from Baseline in the urine protein/creatinine values are summarised for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Primary
    End point timeframe
    Baseline, Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16
    Notes
    [148] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [149]
    10 [150]
    10 [151]
    10 [152]
    11 [153]
    Units: Milligrams per millimole of creatinine
    arithmetic mean (standard deviation)
        Protein/Creatinine, Week2, n=9,9,9,9,10
    0.728996 ( 6.069632 )
    29.8511 ( 94.14456 )
    9.816302 ( 13.05664 )
    1.973316 ( 3.402596 )
    -5.92749 ( 15.42145 )
        Protein/Creatinine, Week3, n=1,1,0,0,0
    1.80992 ( 99999 )
    -1.6968 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Protein/Creatinine, Week4, n=8,9,8,8,9
    0.53732 ( 7.831058 )
    4.235716 ( 12.84549 )
    4.75104 ( 8.108199 )
    2.60176 ( 3.212062 )
    -9.99227 ( 15.35153 )
        Protein/Creatinine, Week5, n=0,0,0,0,1
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.28048 ( 99999 )
        Protein/Creatinine, Week6, n=7,10,6,9,8
    -0.95344 ( 3.146321 )
    -0.83709 ( 7.142045 )
    3.1108 ( 4.608165 )
    2.224693 ( 1.939604 )
    -3.33704 ( 16.14217 )
        Protein/Creatinine, Week8, n=8,7,9,9,9
    -4.76518 ( 5.17726 )
    -1.30896 ( 3.115669 )
    -0.55303 ( 3.480368 )
    2.564053 ( 3.167865 )
    -5.54288 ( 13.05642 )
        Protein/Creatinine, Week10, n=7,8,4,6,8
    -0.30704 ( 5.187394 )
    -2.13514 ( 4.764656 )
    -3.33704 ( 7.572284 )
    1.036933 ( 1.839954 )
    -4.75104 ( 10.35333 )
        Protein/Creatinine, Week12, n=7,7,7,8,7
    -3.68448 ( 8.260047 )
    -0.58176 ( 7.232438 )
    -1.84224 ( 5.912875 )
    1.6968 ( 3.279087 )
    -1.616 ( 16.75879 )
        Protein/Creatinine, Week16, n=5,6,3,5,6
    -3.25786 ( 3.336944 )
    4.92072 ( 6.728025 )
    -1.92304 ( 6.565834 )
    2.760128 ( 5.543226 )
    -8.50285 ( 16.47525 )
    Notes
    [149] - ITT Population. “Not available (NA)” data is presented as “99999”
    [150] - ITT Population. “Not available (NA)” data is presented as “99999”
    [151] - ITT Population. “Not available (NA)” data is presented as “99999”
    [152] - ITT Population. “Not available (NA)” data is presented as “99999”
    [153] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Primary: Number of participants with any adverse events (AEs) and any serious adverse events (SAEs) up to Week 16

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    End point title
    		 Number of participants with any adverse events (AEs) and any serious adverse events (SAEs) up to Week 16 [154]
    End point description
    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.
    End point type
    Primary
    End point timeframe
    Up to Week 16
    Notes
    [154] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [155]
    10 [156]
    10 [157]
    10 [158]
    11 [159]
    Units: Participants
        Any AE
    8
    7
    7
    6
    7
        Any SAE
    1
    2
    4
    1
    0
    Notes
    [155] - ITT Population
    [156] - ITT Population
    [157] - ITT Population
    [158] - ITT Population
    [159] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with severity Grade 1, 2, 3, 4 and 5 adverse events (AEs)

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    End point title
    		 Number of participants with severity Grade 1, 2, 3, 4 and 5 adverse events (AEs) [160]
    End point description
    The Common Terminology Criteria for Adverse Events (CTCAE, Version 4) has categorised AEs in five grades. Grade refers to the severity of the AE. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    End point type
    Primary
    End point timeframe
    Up to 16 Weeks
    Notes
    [160] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [161]
    10 [162]
    10 [163]
    10 [164]
    11 [165]
    Units: Participants
        Grade 1
    3
    3
    0
    3
    3
        Grade 2
    3
    4
    4
    2
    4
        Grade 3
    2
    0
    2
    0
    0
        Grade 4
    0
    0
    1
    1
    0
        Grade 5
    0
    0
    0
    0
    0
    Notes
    [161] - ITT Population
    [162] - ITT Population
    [163] - ITT Population
    [164] - ITT Population
    [165] - ITT Population
    No statistical analyses for this end point

    Secondary: SRI Response Rate at Week 4, 8, 12 and 16

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    End point title
    		 SRI Response Rate at Week 4, 8, 12 and 16
    End point description
    The relationship between dose of GSK2586184 and clinical response was assessed by the SLE Responder Index (SRI). The percentage of participants achieving a response on the composite endpoint are summarised. Response is defined as:>= 4 point reduction from the Baseline in the SELENA SLEDAI score and no worsening (increase of <0.30 points from the Baseline) in Physicians Global Assessment (PGA),and no new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with the Baseline. Baseline value is defined as the last Pre-treatment value observed.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 12 and 16
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [166]
    10 [167]
    10 [168]
    10 [169]
    11 [170]
    Units: Percentage
        Week4
    29
    13
    29
    50
    50
        Week8
    67
    14
    99999
    99999
    14
        Week12
    25
    20
    25
    40
    99999
        Week16
    99999
    99999
    11
    25
    40
    Notes
    [166] - ITT Population. “Not available (NA)” data is presented as “99999”
    [167] - ITT Population. “Not available (NA)” data is presented as “99999”
    [168] - ITT Population. “Not available (NA)” data is presented as “99999”
    [169] - ITT Population. “Not available (NA)” data is presented as “99999”
    [170] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Secondary: Change from baseline in SLEDAI-2K score and the S2K RI-50 score over time (up to Week 12).

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    End point title
    		 Change from baseline in SLEDAI-2K score and the S2K RI-50 score over time (up to Week 12).
    End point description
    The relationship between dose of GSK2586184 and clinical response was assessed by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and SLEDAI-2K Responder Index 50 (S2K RI-50) scores. SLEDAI-2K is a revised version of the SLEDAI in which the persistent active disease in the items rash, alopecia, mucosal ulcers and proteinuria would be scored as opposed to new occurrences as are measured in the SLEDAI. S2K RI-50 detects a minimum 50% improvement in disease manifestations among lupus participants. It covers 9 organ systems, utilising the same 24 descriptors and reflects disease activity over the previous 30 days. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Due to early termination of the study, data for this endpoint was not summarized.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    0 [171]
    0 [172]
    0 [173]
    0 [174]
    0 [175]
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [171] - ITT Population
    [172] - ITT Population
    [173] - ITT Population
    [174] - ITT Population
    [175] - ITT Population
    No statistical analyses for this end point

    Secondary: Mean GSK2586184 plasma concentrations on Weeks 2, 4, 6, 8, 10 and 12

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    End point title
    		 Mean GSK2586184 plasma concentrations on Weeks 2, 4, 6, 8, 10 and 12 [176]
    End point description
    Plasma pharmacokinetic (PK) pre-dose (PRD) samples were collected for all participants at Weeks 2, 4, 8, 10 and 12 prior to the morning dose. At Week 2, additional blood sample were collected at 1hour (hr) and 4 hr post-dose (POD) and at Week 6, additional blood sample were collected, from 6 hr to 10 hr POD. PK Population comprised of all participants randomised to treatment, who have taken at least one dose. Only participants for whom plasma PK samples were obtained were assessed (represented by n=X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the Pharmacokinetic(PK) Population.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 10 and 12
    Notes
    [176] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID
    Number of subjects analysed
    9 [177]
    10 [178]
    10 [179]
    10 [180]
    Units: Nanograms per milliliter
    arithmetic mean (standard deviation)
        Week2, PRD, n=8,8,9,9
    6.51 ( 9.581 )
    30.89 ( 41.553 )
    17.57 ( 17.588 )
    281.96 ( 406.519 )
        Week2, 1 hr POD, n=7,8,8,8
    128.53 ( 99.475 )
    217.44 ( 318.654 )
    500.29 ( 732.243 )
    1012.64 ( 679.64 )
        Week2, 4 hr POD, n=8,8,8,9
    55.84 ( 27.093 )
    309.73 ( 192.275 )
    614.71 ( 322.065 )
    1109.96 ( 791.706 )
        Week4, PRD, n=6,8,7,8
    16.78 ( 13.92 )
    58.28 ( 122.699 )
    4.61 ( 7.881 )
    196.74 ( 358.94 )
        Week6, PRD, n=0,0,0,1
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    70.4 ( 99999 )
        Week6, 6-10 hr POD, n=7,7,6,7
    59.44 ( 43.154 )
    176.26 ( 101.379 )
    89.4 ( 90.543 )
    442.16 ( 310.46 )
        Week8, PRD, n=6,7,4,7
    9.25 ( 7.317 )
    34.71 ( 51.246 )
    32.25 ( 28.339 )
    296.21 ( 421.816 )
        Week10, PRD, n=4,6,4,6
    11.73 ( 9.132 )
    31.05 ( 28.26 )
    27.65 ( 3.387 )
    159.02 ( 156.092 )
        Week12, PRD, n=4,5,4,5
    31.88 ( 38.916 )
    13.18 ( 13.492 )
    15.53 ( 15.274 )
    180.36 ( 118.498 )
    Notes
    [177] - PK Population. “Not available (NA)” data is presented as “99999”
    [178] - PK Population. “Not available (NA)” data is presented as “99999”
    [179] - PK Population. “Not available (NA)” data is presented as “99999”
    [180] - PK Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Secondary: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) up to Week 12

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    End point title
    		 Area under the concentration-time curve over the dosing interval (AUC[0-tau]) up to Week 12 [181]
    End point description
    Plasma PK PRD samples were collected for all participants at Weeks 2, 4, 8, 10 and 12 prior to the morning dose. At Week 2, additional blood sample were collected at 1hr and 4 hr POD and at Week 6, additional blood sample were collected, from 6 hr to 10 hr POD. AUC(0-tau).is calculated from a population pharmacokinetic model using Non Linear Mixed Effect Model (NONMEM) after log-transformation of PK data. Only participants for whom plasma PK samples were obtained and assessed.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 10 and 12
    Notes
    [181] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID
    Number of subjects analysed
    8 [182]
    8 [183]
    8 [184]
    9 [185]
    Units: Nanogram per milliliter*hour (ng/mL*h)
        geometric mean (geometric coefficient of variation)
    932.4138 ( 25.6 )
    1815.871 ( 30.4 )
    3375.907 ( 18 )
    7656.32 ( 20.1 )
    Notes
    [182] - PK Population
    [183] - PK Population
    [184] - PK Population
    [185] - PK Population
    No statistical analyses for this end point

    Secondary: Apparent clearance (CL/F) up to Week 12

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    End point title
    		 Apparent clearance (CL/F) up to Week 12 [186]
    End point description
    Plasma PK PRD samples were collected for all participants at Weeks 2, 4, 8, 10 and 12 prior to the morning dose. At Week 2, additional blood sample were collected at 1hr and 4 hr POD and at Week 6, additional blood sample were collected, from 6 hr to 10 hr POD. CL/F is calculated, as dose divided by AUC(0-tau), from a population pharmacokinetic model using Non Linear Mixed Effect Model (NONMEM) after log-transformation of PK data. Only participants for whom plasma PK samples were obtained and assessed.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 10 and 12
    Notes
    [186] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID
    Number of subjects analysed
    8 [187]
    8 [188]
    8 [189]
    9 [190]
    Units: Liter per hour (L/h)
        geometric mean (geometric coefficient of variation)
    53.62426 ( 25.6 )
    55.06999 ( 30.4 )
    59.24334 ( 18 )
    52.24442 ( 20.1 )
    Notes
    [187] - PK Population
    [188] - PK Population
    [189] - PK Population
    [190] - PK Population
    No statistical analyses for this end point

    Secondary: Volume of distribution (Vss) up to Week 12

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    End point title
    		 Volume of distribution (Vss) up to Week 12 [191]
    End point description
    Plasma PK PRD samples were collected for all participants at Weeks 2, 4, 8, 10 and 12 prior to the morning dose. At Week 2, additional blood sample were collected at 1hr and 4 hr POD and at Week 6, additional blood sample were collected, from 6 hr to 10 hr POD. Apparent volume of distribution is calculated as dose divided by (AUC[0-tau] lambda z) where lambda z is the terminal phase rate constant. Vss is calculated from a population pharmacokinetic model using Non Linear Mixed Effect Model (NONMEM) after log-transformation of PK data. Only participants for whom plasma PK samples were obtained and assessed.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 10 and 12
    Notes
    [191] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no statistics for this endpoint.
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID
    Number of subjects analysed
    8 [192]
    8 [193]
    8 [194]
    9 [195]
    Units: Liter (L)
        geometric mean (geometric coefficient of variation)
    226.0024 ( 20.3 )
    174.2176 ( 24.1 )
    178.1342 ( 22.4 )
    188.2714 ( 30.2 )
    Notes
    [192] - PK Population
    [193] - PK Population
    [194] - PK Population
    [195] - PK Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in the SF-36 Domain Scores up to Week 16

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    End point title
    		 Mean change from Baseline in the SF-36 Domain Scores up to Week 16
    End point description
    The Short Form (36) Health Survey (SF-36v2 ) is a participant-reported survey of participant health and measures general health-related quality of life. There are 36 items grouped into nine health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health, Reported health transition (RHT). SF-36v2 gives a score for each of these domains based on the questions as assessed by participants. The lower the score the more disability and the higher the score the less disability. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed ( n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 12 and 16
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [196]
    10 [197]
    10 [198]
    10 [199]
    11 [200]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Physical Functioning, Week12, n=7,7,7,8,7
    5.71 ( 8.215 )
    4.21 ( 13.584 )
    2.41 ( 7.82 )
    10.11 ( 11.019 )
    -0.3 ( 10.829 )
        Physical Functioning, Week16, n=5,6,3,8,6
    5.47 ( 8.096 )
    12.98 ( 8.87 )
    -0.47 ( 5.358 )
    10.71 ( 16.17 )
    -1.91 ( 15.312 )
        Role Physical, Week12, n=7,7,7,8,7
    5.95 ( 7.328 )
    5.6 ( 6.739 )
    5.95 ( 4.659 )
    6.12 ( 8.484 )
    2.45 ( 9.898 )
        Role Physical, Week16, n=5,6,3,5,6
    8.33 ( 5.638 )
    6.53 ( 5.059 )
    -0.82 ( 9.272 )
    2.94 ( 11.142 )
    3.27 ( 9.506 )
        Bodily Pain, Week12, n=7,7,7,8,7
    4.77 ( 10.497 )
    6.1 ( 12.968 )
    8.21 ( 9.106 )
    8.93 ( 15.33 )
    0.54 ( 13.516 )
        Bodily Pain, Week16, n=5,6,3,5,6
    1.61 ( 7.068 )
    7.82 ( 7.814 )
    8.31 ( 14.396 )
    2.54 ( 11.578 )
    0.56 ( 16.192 )
        General Health, Week12, n=7,7,6,8,7
    2.32 ( 7.131 )
    2.79 ( 4.674 )
    7.55 ( 6.145 )
    3.93 ( 9.358 )
    2.59 ( 11.34 )
        General Health, Week16, n=5,6,3,5,6
    3.91 ( 6.702 )
    3.26 ( 5.38 )
    6.2 ( 8.828 )
    -0.1 ( 4.413 )
    -0.56 ( 8.417 )
        Vitality, Week12, n=7,7,6,8,7
    10.26 ( 16.294 )
    7.14 ( 9.14 )
    6.76 ( 9.138 )
    9.5 ( 11.487 )
    4.01 ( 9.316 )
        Vitality, Week16, n=5,6,3,5,6
    13.11 ( 14.375 )
    7.28 ( 4.265 )
    -1.04 ( 4.769 )
    4.37 ( 9.261 )
    7.28 ( 11.956 )
        Social Functioning, Week12, n=7,7,7,8,7
    10.91 ( 13.725 )
    5.45 ( 7.713 )
    9.35 ( 5.188 )
    6.14 ( 11.454 )
    2.34 ( 5.323 )
        Social Functioning, Week16, n=5,6,3,5,6
    10.91 ( 6.68 )
    6.36 ( 4.106 )
    0 ( 10.908 )
    4.36 ( 10.491 )
    0 ( 6.899 )
        Role Emotional, Week12, n=7,7,7,8,7
    2.22 ( 13.439 )
    12.22 ( 9.097 )
    8.89 ( 8.609 )
    5.83 ( 10.995 )
    12.22 ( 17.59 )
        Role Emotional, Week16, n=5,6,3,5,6
    3.11 ( 9.281 )
    9.72 ( 6.387 )
    -1.3 ( 14.717 )
    7 ( 12.715 )
    12.31 ( 18.629 )
        Mental Health, Week12, n=7,7,6,8,7
    12.07 ( 11.578 )
    7.84 ( 8.75 )
    12.67 ( 9.037 )
    1.06 ( 5.619 )
    7.24 ( 14.619 )
        Mental Health, Week16, n=5,6,3,5,6
    7.88 ( 11.679 )
    6.57 ( 4.24 )
    2.5 ( 15.433 )
    0 ( 7.45 )
    7.51 ( 15.695 )
        RHT, Week12, n=7,7,7,8,7
    -1 ( 1.155 )
    -0.71 ( 1.704 )
    0 ( 0.577 )
    -1 ( 1.604 )
    -0.86 ( 1.215 )
        RHT, Week16, n=5,6,3,5,6
    -0.6 ( 0.894 )
    -1.33 ( 1.506 )
    0.33 ( 0.577 )
    -1 ( 1.225 )
    -0.83 ( 1.169 )
        Mental Component Score, Week12, n=7,7,7,8,7
    9.63 ( 11.024 )
    9.96 ( 10.001 )
    10.36 ( 8.828 )
    2.92 ( 7.755 )
    10.07 ( 12.215 )
        Mental Component Score, Week16, n=5,6,3,5,6
    8.7 ( 11.33 )
    6.23 ( 2.984 )
    -0.29 ( 14.48 )
    2.17 ( 7.842 )
    10.7 ( 11.68 )
        Physical Component Score, Week12, n=7,7,7,8,7
    3.73 ( 5.825 )
    2.47 ( 9.909 )
    3.56 ( 5.166 )
    9.13 ( 10.534 )
    -2.3 ( 11.504 )
        Physical Component Score, Week16, n=5,6,3,5,6
    4.69 ( 4.649 )
    7.94 ( 5.192 )
    3.37 ( 4.772 )
    5.1 ( 10.742 )
    -3.43 ( 12.23 )
    Notes
    [196] - ITT Population
    [197] - ITT Population
    [198] - ITT Population
    [199] - ITT Population
    [200] - ITT Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in the Brief Fatigue Inventory (BFI) Domain Score up to Week 16

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    End point title
    		 Mean change from Baseline in the Brief Fatigue Inventory (BFI) Domain Score up to Week 16
    End point description
    The BFI was developed to quickly measure severity of fatigue in participants as well as its impact on their ability to function over the previous 24 hrs. It consists of nine items that look at fatigue in the past that are rated on a 0 -10 numeric rating scale where 0 is no fatigue or does not interfere and 10 is bad fatigue or completely interferes with activity. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [201]
    10 [202]
    10 [203]
    10 [204]
    11 [205]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        BFI Domain Score, Week2, n=9,10,9,8,10
    -1.3827 ( 1.63121 )
    0.6333 ( 1.27124 )
    -1.2469 ( 2.74187 )
    -0.75 ( 3.05606 )
    -1.1889 ( 1.90951 )
        BFI Domain Score, Week4, n=8,8,8,8,10
    -1.625 ( 2.05732 )
    0.2639 ( 0.74875 )
    -2.0833 ( 2.14283 )
    -2.375 ( 3.30033 )
    -1.2778 ( 2.3624 )
        BFI Domain Score, Week6, n=7,10,6,9,8
    -1.7778 ( 2.19521 )
    -0.8556 ( 1.3789 )
    -2.2593 ( 2.87232 )
    -1.5926 ( 3.33148 )
    -0.9861 ( 3.02747 )
        BFI Domain Score, Week8, n=8,7,9,8,9
    -2.0972 ( 2.30897 )
    -1.0794 ( 2.36113 )
    -2.4198 ( 2.60388 )
    -2.3889 ( 2.54761 )
    -1.0741 ( 1.84759 )
        BFI Domain Score, Week10, n=7,8,4,6,8
    -2 ( 1.05604 )
    -1.1944 ( 2.77857 )
    -1.7778 ( 2.91865 )
    -2.3333 ( 2.9523 )
    -0.75 ( 2.26448 )
        BFI Domain Score, Week12, n=7,7,7,8,7
    -2.1111 ( 1.41712 )
    -1.6508 ( 3.00988 )
    -2.7302 ( 2.23133 )
    -2 ( 4.02155 )
    -0.4603 ( 2.08209 )
        BFI Domain Score, Week16, n=5,6,3,5,6
    -2.2667 ( 0.73535 )
    -1.1667 ( 2.09025 )
    -1.037 ( 2.31563 )
    -0.8667 ( 4.33291 )
    -2 ( 3.47336 )
    Notes
    [201] - ITT Population
    [202] - ITT Population
    [203] - ITT Population
    [204] - ITT Population
    [205] - ITT Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in the Brief Pain Inventory (BPI) Domain Score up to Week 16

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    End point title
    		 Mean change from Baseline in the Brief Pain Inventory (BPI) Domain Score up to Week 16
    End point description
    The BPI is a questionnaire used to assess the severity of pain and the impact of pain on daily functioning in the following areas: general activity, mood, walking ability, normal work, including outside the home and housework, relations with other people, enjoyment of life and sleep. Two sub scores are derived from questionnaire: the worst pain score and the interference score. To derive a valid worst pain score, a minimum of 3 (out of 6) non missing values were required versus 4 (out of 7) for the interference score. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. Only those participants available at the specified time points were analysed (represented by n=X,X,X,X,X in category titles). Different participants may have been analysed at different time points, so the overall number of participants analysed reflects everyone in the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 10, 12 and 16
    End point values
    		 GSK2586184 50 mg BID GSK2586184 100 mg BID GSK2586184 200 mg BID GSK2586184 400 mg BID Placebo
    Number of subjects analysed
    9 [206]
    10 [207]
    10 [208]
    10 [209]
    11 [210]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Worst Pain Score, Week2, n=9,10,9,8,10
    -1.3333 ( 1.69558 )
    -0.375 ( 1.43008 )
    -0.25 ( 2.48433 )
    -2.2813 ( 2.43647 )
    -0.45 ( 0.71492 )
        Worst Pain Score, Week4, n=8,8,8,8,10
    -1.125 ( 2.29518 )
    -0.3125 ( 1.51628 )
    -0.125 ( 2.63561 )
    -2.1563 ( 2.75466 )
    -0.725 ( 1.88727 )
        Worst Pain Score, Week6, n=7,10,6,9,8
    -1.6071 ( 2.68816 )
    -1.4 ( 1.60814 )
    -0.5417 ( 1.13376 )
    -1.9688 ( 2.91069 )
    -1.0625 ( 2.90858 )
        Worst Pain Score, Week8, n=8,7,9,8,9
    -1.7188 ( 1.86336 )
    -1.7143 ( 2.29777 )
    -0.6111 ( 1.13376 )
    -2.2188 ( 2.76275 )
    -0.5833 ( 1.48429 )
        Worst Pain Score, Week10, n=7,8,4,6,8
    -1.1429 ( 0.85217 )
    -1.4063 ( 2.6184 )
    -1 ( 0.79057 )
    -1.9167 ( 3.1846 )
    -1.1563 ( 3.31646 )
        Worst Pain Score, Week12, n=7,7,7,8,7
    -1.1786 ( 1.25594 )
    -2.1429 ( 3.08172 )
    -1.4643 ( 1.20268 )
    -2.0313 ( 2.95936 )
    -0.0714 ( 2.46523 )
        Worst Pain Score, Week16, n=5,6,3,5,6
    -0.75 ( 1.23744 )
    -3.0417 ( 2.69452 )
    0.1667 ( 1.75594 )
    -0.55 ( 3.62888 )
    -0.875 ( 2.41221 )
        Interference Score, Week2, n=9,10,9,8,10
    -1.7619 ( 2.76088 )
    -0.2857 ( 1.34687 )
    -0.4286 ( 2.75533 )
    -1.8929 ( 2.27004 )
    -1.1 ( 1.13499 )
        Interference Score, Week4, n=8,8,8,8,10
    -1.5179 ( 3.45562 )
    -0.6607 ( 0.97172 )
    -0.9643 ( 1.97469 )
    -2.2679 ( 1.85233 )
    -1.2571 ( 2.12938 )
        Interference Score, Week6, n=7,10,6,9,8
    -2.4898 ( 3.61578 )
    -1.8714 ( 2.43784 )
    -1.7381 ( 1.43261 )
    -2.127 ( 2.44995 )
    -1.375 ( 3.27811 )
        Interference Score, Week8, n=8,7,9,8,9
    -1.7321 ( 3.03088 )
    -1.1224 ( 2.52932 )
    -1.6349 ( 2.58144 )
    -2.125 ( 1.96238 )
    -1.3333 ( 1.58275 )
        Interference Score, Week10, n=7,8,4,6,8
    -2.1224 ( 1.79839 )
    -0.5714 ( 3.16872 )
    -1.75 ( 2.25085 )
    -1.4762 ( 1.87283 )
    -1.6845 ( 3.05462 )
        Interference Score, Week12, n=7,7,7,8,7
    -2.5102 ( 2.17884 )
    -1.4898 ( 3.7169 )
    -2.3878 ( 1.9927 )
    -1.4464 ( 2.86269 )
    -0.7143 ( 2.25877 )
        Interference Score, Week16, n=5,6,3,5,6
    -1.5143 ( 1.19352 )
    -2.881 ( 2.27572 )
    -1.381 ( 1.51411 )
    -0.6286 ( 3.07823 )
    -1.9048 ( 2.40011 )
    Notes
    [206] - ITT Population. “Not available (NA)” data is presented as “99999”
    [207] - ITT Population. “Not available (NA)” data is presented as “99999”
    [208] - ITT Population. “Not available (NA)” data is presented as “99999”
    [209] - ITT Population. “Not available (NA)” data is presented as “99999”
    [210] - ITT Population. “Not available (NA)” data is presented as “99999”
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug until the follow-up contact (up to Week 16).
    Adverse event reporting additional description
    SAEs and non-serious AEs were reported for members of the ITT population, comprised of all participants who were randomised to treatment, who received at least one dose of study medication and who have at least one valid post dose assessment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    GSK2586184 100 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 100 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 50 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 50 milligram (mg) of GSK2586184, twice daily (BID) with food for 12 weeks.

    Reporting group title
    GSK2586184 400 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 400 mg of GSK2586184, BID with food for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a combination of 2 film coated tablets of GSK2586184 matching placebo, BID with food for 12 weeks.

    Reporting group title
    GSK2586184 200 mg BID
    Reporting group description
    		 Participants received a combination of 2 film coated tablets, so that each participant received a total of 200 mg of GSK2586184, BID with food for 12 weeks.

    Serious adverse events
    		 GSK2586184 100 mg BID GSK2586184 50 mg BID GSK2586184 400 mg BID Placebo GSK2586184 200 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    4 / 10 (40.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Blighted ovum
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK2586184 100 mg BID GSK2586184 50 mg BID GSK2586184 400 mg BID Placebo GSK2586184 200 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 10 (60.00%)
    8 / 9 (88.89%)
    6 / 10 (60.00%)
    7 / 11 (63.64%)
    5 / 10 (50.00%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    1
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Local swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Cough
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cystatin C increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Migraine
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Tension headache
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tremor
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    3 / 10 (30.00%)
         occurrences all number
    0
    0
    0
    0
    6
    Leukopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    3
    Anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Microcytic anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    2
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    1
    Gastrointestinal disorders
    Aphthous stomatitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dermatitis contact
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Fibromyalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    1
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Osteochondritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Periostitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
    3 / 11 (27.27%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    2
    3
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    1
    0
    2
    0
    2
    Pharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    Vaginal infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    2
    Vulvovaginitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Herpes simplex
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Oral fungal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Viral pharyngitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Jul 2013
    Generated to include revisions made in country specific amendments 01, 02, and 03 as well as clarification of assessments, inclusion of a statement regarding a potential temporary pause to recruitment and correction of typographical errors. A detailed list of changes was provided in Appendix 16.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Mar 2014
    Early Termination
    -

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

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