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    Clinical Trial Results:
    A multi-centre, randomized, double-blind (sponsor open), placebo controlled, repeat-dose, proof of mechanism study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and explore efficacy of GSK2330811 in participants with diffuse cutaneous systemic sclerosis

    Summary
    EudraCT number
    		 2016-003417-95
    Trial protocol
    		 GB   NL  
    Global end of trial date
    07 Jul 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 May 2021
    First version publication date
    15 May 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    201247
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Sep 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of repeat subcutaneous doses of GSK2330811 in participants with diffuse cutaneous systemic sclerosis (dcSSc)
    Protection of trial subjects
    Specific eligibility, monitoring and individual participant/study stopping rules were implemented in the study protocol to mitigate potential risks. Periodic review of safety and PK data by an internal GlaxoSmithKline (GSK) study-specific Data Review Committee, including at dose escalation. The protocol was amended to ensure safety monitoring during the corona virus disease-19 (COVID-19) pandemic, including the option for study assessments to be conducted remotely during the off-treatment follow up period and local safety laboratory tests to be performed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    United Kingdom: 14
    Country: Number of subjects enrolled
    United States: 13
    Worldwide total number of subjects
    35
    EEA total number of subjects
    4
    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)
    27
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a randomized, double-blind (sponsor open), proof of mechanism study of GSK2330811 in participants with diffuse cutaneous systemic sclerosis. This study was conducted in Canada, Netherlands, United Kingdom and United States.

    Pre-assignment
    Screening details
    		 A total of 35 participants were enrolled in this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo contains normal Saline (0.9 percent [%] weight per volume [w/v] Sodium Chloride)

    Arm title
    		 GSK2330811 100 mg
    Arm description
    		 Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2330811
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK2330811 was provided in vials each filled with 1 milliliter (mL) extractable volume at 100 milligram (mg) per mL

    Arm title
    		 GSK2330811 300 mg
    Arm description
    		 Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2330811
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK2330811 was provided in vials each filled with 1 milliliter (mL) extractable volume at 100 milligram (mg) per mL

    Number of subjects in period 1
    		Placebo GSK2330811 100 mg GSK2330811 300 mg
    Started
    8
    3
    24
    Completed
    7
    3
    22
    Not completed
    1
    0
    2
         Consent withdrawn by subject
    -
    -
    1
         Adverse event, non-fatal
    -
    -
    1
         Lost to follow-up
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 100 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 300 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg Total
    Number of subjects
    		 8 3 24 35
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 6 1 20 27
        From 65-84 years
    		 2 2 4 8
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 50.8 ( 15.42 ) 66.7 ( 4.73 ) 52.6 ( 12.59 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 6 1 19 26
        Male
    		 2 2 5 9
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    		 0 0 1 1
        Asian - East Asian Heritage
    		 1 0 0 1
        Black or African American
    		 0 0 3 3
        White - White/Caucasian/European Heritage
    		 7 3 20 30

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 100 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 300 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Subject analysis set title
    GSK2330811 100 mg and GSK2330811 300 mg - Overall
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received subcutaneous injection of GSK2330811 100 mg and 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Primary: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician. SAEs were collected up to Day 197, but the protocol also allowed investigators to report SAEs occurring after participants had completed the study. This outcome measure includes two SAEs reported after participants had completed the study, occurring on Day 306 and Day 603 following first dose. Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to Day 197, but protocol allowed for additional events to be collected; up to Day 603 post first dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [2]
    3 [3]
    24 [4]
    Units: Participants
        Non-SAEs
    8
    3
    24
        SAEs
    1
    0
    2
    Notes
    [2] - Safety Population.
    [3] - Safety Population.
    [4] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) count

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    End point title
    		 Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) count [5]
    End point description
    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [5] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [6]
    3 [7]
    23 [8]
    Units: Giga cells per liter
    arithmetic mean (standard deviation)
        Day 15: Basophils, n=8,3,23
    -0.006 ( 0.0262 )
    0.013 ( 0.0252 )
    0.007 ( 0.0325 )
        Day 29: Basophils, n=8,3,23
    -0.005 ( 0.0288 )
    -0.003 ( 0.0252 )
    0.003 ( 0.0350 )
        Day 43: Basophils, n=8,3,22
    -0.005 ( 0.0169 )
    0.027 ( 0.0635 )
    -0.005 ( 0.0323 )
        Day 57: Basophils, n=6,3,22
    -0.010 ( 0.0167 )
    0.013 ( 0.0404 )
    -0.004 ( 0.0333 )
        Day 71: Basophils, n=8,3,20
    -0.010 ( 0.0267 )
    -0.003 ( 0.0208 )
    -0.008 ( 0.0341 )
        Day 85: Basophils, n=7,2,22
    -0.020 ( 0.0294 )
    0.045 ( 0.0636 )
    0.000 ( 0.0344 )
        Day 113: Basophils, n=7,3,21
    -0.006 ( 0.0237 )
    0.040 ( 0.0693 )
    -0.002 ( 0.0390 )
        Day 155: Basophils, n=7,3,20
    0.004 ( 0.0270 )
    0.060 ( 0.0721 )
    0.000 ( 0.0400 )
        Day 197: Basophils, n=7,3,18
    -0.006 ( 0.0399 )
    0.033 ( 0.0208 )
    0.015 ( 0.0517 )
        Day 15: Eosinophils, n=8,3,23
    0.016 ( 0.0616 )
    0.070 ( 0.0700 )
    0.084 ( 0.2934 )
        Day 29: Eosinophils, n=8,3,23
    0.036 ( 0.0901 )
    0.060 ( 0.2007 )
    0.001 ( 0.1633 )
        Day 43: Eosinophils, n=8,3,22
    0.019 ( 0.0500 )
    0.103 ( 0.1026 )
    -0.015 ( 0.1954 )
        Day 57: Eosinophils, n=6,3,22
    0.010 ( 0.0473 )
    0.113 ( 0.1795 )
    -0.034 ( 0.1797 )
        Day 71: Eosinophils, n=8,3,20
    0.018 ( 0.0440 )
    0.137 ( 0.2344 )
    0.012 ( 0.1241 )
        Day 85: Eosinophils, n=7,2,22
    0.001 ( 0.0406 )
    0.130 ( 0.3111 )
    -0.035 ( 0.1773 )
        Day 113: Eosinophils, n=7,3,21
    0.056 ( 0.1005 )
    0.070 ( 0.0872 )
    0.087 ( 0.2873 )
        Day 155: Eosinophils, n=7,3,20
    0.003 ( 0.0403 )
    0.080 ( 0.0300 )
    0.005 ( 0.1695 )
        Day 197: Eosinophils, n=7,3,18
    0.069 ( 0.1426 )
    0.170 ( 0.1323 )
    0.056 ( 0.1302 )
        Day 15: Lymphocytes, n=8,3,23
    -0.116 ( 0.3926 )
    0.103 ( 0.3955 )
    -0.125 ( 0.4110 )
        Day 29: Lymphocytes, n=8,3,23
    -0.064 ( 0.2539 )
    0.477 ( 0.4177 )
    -0.102 ( 0.6071 )
        Day 43: Lymphocytes, n=8,3,22
    0.020 ( 0.2891 )
    0.530 ( 0.3270 )
    -0.078 ( 0.6156 )
        Day 57: Lymphocytes, n=6,3,22
    -0.043 ( 0.3732 )
    0.563 ( 0.3798 )
    0.105 ( 0.5853 )
        Day 71: Lymphocytes, n=8,3,20
    -0.060 ( 0.2384 )
    0.430 ( 0.3601 )
    0.155 ( 0.5169 )
        Day 85: Lymphocytes, n=7,2,22
    -0.109 ( 0.2202 )
    0.580 ( 0.4667 )
    0.313 ( 0.5521 )
        Day 113: Lymphocytes, n=7,3,21
    -0.297 ( 0.5087 )
    0.383 ( 0.3907 )
    0.287 ( 0.6783 )
        Day 155: Lymphocytes, n=7,3,20
    -0.046 ( 0.2327 )
    0.160 ( 0.2600 )
    0.202 ( 0.4504 )
        Day 197: Lymphocytes, n=7,3,18
    -0.066 ( 0.4108 )
    -0.010 ( 0.4419 )
    0.039 ( 0.7780 )
        Day 15: Monocytes, n=8,3,23
    0.096 ( 0.1507 )
    -0.017 ( 0.1102 )
    -0.051 ( 0.1659 )
        Day 29: Monocytes, n=8,3,23
    0.006 ( 0.0578 )
    -0.030 ( 0.3959 )
    -0.120 ( 0.2175 )
        Day 43: Monocytes, n=8,3,22
    0.103 ( 0.2093 )
    0.047 ( 0.1069 )
    -0.106 ( 0.2045 )
        Day 57: Monocytes, n=6,3,22
    -0.037 ( 0.0698 )
    -0.120 ( 0.1600 )
    -0.130 ( 0.2216 )
        Day 71: Monocytes, n=8,3,20
    0.050 ( 0.1414 )
    -0.003 ( 0.0404 )
    -0.070 ( 0.1838 )
        Day 85: Monocytes, n=7,2,22
    -0.007 ( 0.0652 )
    0.140 ( 0.1697 )
    -0.127 ( 0.2495 )
        Day 113: Monocytes, n=7,3,21
    0.070 ( 0.1494 )
    0.030 ( 0.1735 )
    -0.028 ( 0.2246 )
        Day 155: Monocytes, n=7,3,20
    0.064 ( 0.1229 )
    0.167 ( 0.1250 )
    -0.022 ( 0.1414 )
        Day 197: Monocytes, n=7,3,18
    0.051 ( 0.2242 )
    -0.043 ( 0.1266 )
    -0.053 ( 0.2234 )
        Day 15: Total neutrophils, n=8,3,23
    0.228 ( 1.3240 )
    1.060 ( 3.0143 )
    -0.917 ( 1.4114 )
        Day 29: Total neutrophils, n=8,3,23
    0.318 ( 1.4309 )
    0.323 ( 1.8591 )
    -1.104 ( 1.4251 )
        Day 43: Total neutrophils, n=8,3,22
    0.315 ( 1.3403 )
    -0.350 ( 1.4731 )
    -1.406 ( 1.4631 )
        Day 57: Total neutrophils, n=6,3,22
    0.538 ( 0.9156 )
    -0.517 ( 1.9998 )
    -1.387 ( 1.4428 )
        Day 71: Total neutrophils, n=8,3,20
    0.789 ( 2.1739 )
    -0.223 ( 1.8928 )
    -1.369 ( 1.6361 )
        Day 85: Total neutrophils, n=7,2,22
    -0.139 ( 1.1995 )
    -0.990 ( 2.9698 )
    -1.424 ( 2.3949 )
        Day 113: Total neutrophils, n=7,3,20
    0.680 ( 1.2472 )
    -0.263 ( 1.0384 )
    -1.002 ( 1.5195 )
        Day 155: Total neutrophils, n=7,3,20
    0.027 ( 1.2229 )
    -0.673 ( 2.1324 )
    -0.183 ( 1.2208 )
        Day 197: Total neutrophils, n=7,3,18
    0.317 ( 1.3578 )
    -1.603 ( 4.0868 )
    -0.001 ( 1.4937 )
        Day 15: Platelet count, n=8,3,23
    -1.5 ( 24.02 )
    -42.0 ( 32.70 )
    -124.6 ( 87.57 )
        Day 29: Platelet count, n=7,3,23
    -5.9 ( 20.38 )
    -39.7 ( 29.28 )
    -145.7 ( 94.01 )
        Day 43: Platelet count, n=8,3,23
    -16.1 ( 14.56 )
    -49.0 ( 22.27 )
    -150.2 ( 90.41 )
        Day 57: Platelet count, n=6,3,22
    -4.2 ( 20.40 )
    -66.0 ( 42.04 )
    -148.6 ( 90.99 )
        Day 71: Platelet count, n=7,3,20
    -12.3 ( 17.67 )
    -41.7 ( 45.21 )
    -129.4 ( 90.54 )
        Day 85: Platelet count, n=7,3,22
    -18.0 ( 25.89 )
    -48.0 ( 29.10 )
    -97.4 ( 73.99 )
        Day 113: Platelet count, n=7,3,20
    -14.4 ( 25.53 )
    -20.3 ( 42.52 )
    -61.2 ( 96.89 )
        Day 155: Platelet count, n=6,3,20
    -26.7 ( 19.62 )
    15.0 ( 31.24 )
    -6.9 ( 60.00 )
        Day 197: Platelet count, n=7,3,19
    -10.1 ( 30.30 )
    -20.7 ( 71.53 )
    -10.3 ( 42.86 )
        Day 15: WBC count, n=8,3,23
    0.20 ( 1.546 )
    1.20 ( 2.685 )
    -1.00 ( 1.487 )
        Day 29: WBC count, n=8,3,23
    0.28 ( 1.400 )
    0.80 ( 1.212 )
    -1.33 ( 1.927 )
        Day 43: WBC count, n=8,3,22
    0.46 ( 1.418 )
    0.33 ( 0.950 )
    -1.60 ( 2.039 )
        Day 57: WBC count, n=6,3,22
    0.43 ( 0.774 )
    0.03 ( 1.617 )
    -1.46 ( 1.947 )
        Day 71: WBC count, n=8,3,20
    0.76 ( 2.191 )
    0.33 ( 1.258 )
    -1.29 ( 1.953 )
        Day 85: WBC count, n=7,3,22
    -0.29 ( 1.182 )
    -0.10 ( 1.400 )
    -1.27 ( 2.509 )
        Day 113: WBC count, n=7,3,21
    0.47 ( 1.138 )
    0.27 ( 0.473 )
    -0.61 ( 1.913 )
        Day 155: WBC count, n=7,3,20
    0.07 ( 1.228 )
    -0.20 ( 1.778 )
    0.01 ( 1.571 )
        Day 197: WBC count, n=7,3,19
    0.31 ( 1.469 )
    -1.50 ( 4.444 )
    -0.01 ( 1.948 )
    Notes
    [6] - Safety Population.
    [7] - Safety Population.
    [8] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)

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    End point title
    		 Change From Baseline in Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) [9]
    End point description
    Blood samples were collected to analyze the hematology parameters: hemoglobin and MCHC. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [10]
    3 [11]
    23 [12]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        Day 15: Hemoglobin, n=8,3,23
    -2.8 ( 8.89 )
    2.0 ( 7.00 )
    -0.2 ( 5.31 )
        Day 29: Hemoglobin, n=8,3,23
    -2.5 ( 6.55 )
    -0.7 ( 11.06 )
    -3.7 ( 7.45 )
        Day 43: Hemoglobin, n=8,3,23
    -2.5 ( 6.39 )
    -1.7 ( 8.50 )
    -7.7 ( 9.06 )
        Day 57: Hemoglobin, n=6,3,22
    -3.8 ( 8.47 )
    -2.7 ( 11.15 )
    -13.7 ( 12.32 )
        Day 71: Hemoglobin, n=8,3,20
    -4.1 ( 10.38 )
    -6.3 ( 4.73 )
    -21.2 ( 11.61 )
        Day 85: Hemoglobin, n=7,3,22
    -3.9 ( 7.58 )
    -10.7 ( 6.11 )
    -22.0 ( 10.05 )
        Day 113: Hemoglobin, n=7,3,21
    -5.0 ( 8.43 )
    -9.0 ( 7.55 )
    -21.3 ( 10.49 )
        Day 155: Hemoglobin, n=7,3,20
    -6.3 ( 9.41 )
    -7.3 ( 6.03 )
    -14.3 ( 8.62 )
        Day 197: Hemoglobin, n=7,3,19
    -4.1 ( 8.88 )
    -6.7 ( 2.08 )
    -5.8 ( 6.58 )
        Day 15: MCHC, n=8,3,23
    0.9 ( 8.53 )
    -5.0 ( 3.00 )
    2.4 ( 7.83 )
        Day 29: MCHC, n=8,3,23
    -3.6 ( 6.39 )
    2.0 ( 13.11 )
    2.0 ( 8.30 )
        Day 43: MCHC, n=8,3,22
    -1.3 ( 9.27 )
    1.0 ( 7.55 )
    2.5 ( 4.86 )
        Day 57: MCHC, n=6,3,22
    -1.2 ( 10.11 )
    3.7 ( 4.93 )
    2.8 ( 8.42 )
        Day 71: MCHC, n=8,3,20
    2.3 ( 12.87 )
    2.7 ( 6.81 )
    0.5 ( 8.62 )
        Day 85: MCHC, n=7,3,22
    3.3 ( 10.53 )
    -1.7 ( 9.50 )
    2.8 ( 6.68 )
        Day 113: MCHC, n=7,3,20
    -0.4 ( 7.18 )
    5.0 ( 8.19 )
    -3.3 ( 8.16 )
        Day 155: MCHC, n=7,3,17
    -1.4 ( 5.26 )
    3.7 ( 4.16 )
    -4.2 ( 9.35 )
        Day 197: MCHC, n=7,3,15
    -0.4 ( 8.58 )
    -0.3 ( 7.02 )
    -3.5 ( 8.18 )
    Notes
    [10] - Safety Population.
    [11] - Safety Population.
    [12] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameter: Hematocrit

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    End point title
    		 Change From Baseline in Hematology Parameter: Hematocrit [13]
    End point description
    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [13] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [14]
    3 [15]
    23 [16]
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    -0.0089 ( 0.02744 )
    0.0127 ( 0.02203 )
    -0.0035 ( 0.01771 )
        Day 29: n=8,3,23
    -0.0023 ( 0.01955 )
    -0.0027 ( 0.04234 )
    -0.0141 ( 0.02486 )
        Day 43: n=8,3,22
    -0.0049 ( 0.01788 )
    -0.0057 ( 0.03564 )
    -0.0271 ( 0.03187 )
        Day 57: n=6,3,22
    -0.0092 ( 0.02500 )
    -0.0120 ( 0.03274 )
    -0.0444 ( 0.04224 )
        Day 71: n=8,3,20
    -0.0146 ( 0.02870 )
    -0.0217 ( 0.02329 )
    -0.0637 ( 0.03983 )
        Day 85: n=7,3,22
    -0.0151 ( 0.02591 )
    -0.0300 ( 0.01803 )
    -0.0688 ( 0.03265 )
        Day 113: n=7,3,20
    -0.0141 ( 0.03007 )
    -0.0323 ( 0.02822 )
    -0.0602 ( 0.02839 )
        Day 155: n=7,3,17
    -0.0164 ( 0.03169 )
    -0.0263 ( 0.01626 )
    -0.0349 ( 0.02482 )
        Day 197: n=7,3,15
    -0.0111 ( 0.02634 )
    -0.0193 ( 0.00981 )
    -0.0125 ( 0.02252 )
    Notes
    [14] - Safety Population.
    [15] - Safety Population.
    [16] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH)

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    End point title
    		 Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin (MCH) [17]
    End point description
    Blood samples were collected to analyze the hematology parameter: MCH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [17] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [18]
    3 [19]
    23 [20]
    Units: Picogram
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    -0.08 ( 0.711 )
    0.03 ( 0.493 )
    0.04 ( 0.503 )
        Day 29: n=8,3,23
    -0.24 ( 0.616 )
    0.37 ( 0.709 )
    -0.23 ( 0.437 )
        Day 43: n=8,3,22
    -0.23 ( 0.807 )
    -0.10 ( 0.173 )
    -0.41 ( 0.450 )
        Day 57: n=6,3,22
    -0.25 ( 0.750 )
    0.10 ( 0.361 )
    -0.39 ( 0.493 )
        Day 71: n=8,3,20
    0.18 ( 0.945 )
    0.17 ( 0.379 )
    -0.50 ( 0.503 )
        Day 85: n=7,3,22
    0.07 ( 1.034 )
    -0.30 ( 0.755 )
    -0.45 ( 0.709 )
        Day 113: n=7,3,20
    -0.06 ( 0.808 )
    0.87 ( 0.513 )
    -0.27 ( 0.873 )
        Day 155: n=7,3,17
    -0.16 ( 0.637 )
    0.90 ( 0.200 )
    0.04 ( 1.180 )
        Day 197: n=7,3,15
    -0.44 ( 1.015 )
    0.33 ( 0.208 )
    -0.23 ( 1.285 )
    Notes
    [18] - Safety Population.
    [19] - Safety Population.
    [20] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV)

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    End point title
    		 Change From Baseline in Hematology Parameters: Mean Corpuscle Volume (MCV), Mean Platelet Volume (MPV) [21]
    End point description
    Blood samples were collected to analyze the hematology parameters: MCV and MPV. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [22]
    3 [23]
    23 [24]
    Units: Femtoliter
    arithmetic mean (standard deviation)
        Day 15: MCV, n=8,3,23
    -0.63 ( 1.188 )
    1.33 ( 1.528 )
    -0.39 ( 1.725 )
        Day 29: MCV, n=8,3,23
    0.38 ( 1.188 )
    0.33 ( 1.155 )
    -1.17 ( 2.188 )
        Day 43: MCV, n=8,3,22
    -0.38 ( 2.326 )
    -0.67 ( 1.528 )
    -1.86 ( 1.583 )
        Day 57: MCV, n=6,3,22
    -0.17 ( 2.787 )
    -1.00 ( 0.000 )
    -1.77 ( 2.308 )
        Day 71: MCV, n=8,3,20
    -0.13 ( 3.441 )
    -0.67 ( 1.528 )
    -1.60 ( 2.722 )
        Day 85: MCV, n=7,3,22
    -0.71 ( 1.113 )
    -0.67 ( 0.577 )
    -2.05 ( 2.478 )
        Day 113: MCV, n=7,3,21
    -0.29 ( 2.563 )
    1.00 ( 1.732 )
    0.00 ( 3.225 )
        Day 155: MCV, n=7,3,20
    -0.14 ( 1.215 )
    1.67 ( 0.577 )
    1.26 ( 4.584 )
        Day 197: MCV, n=7,3,18
    -1.29 ( 1.799 )
    0.67 ( 2.082 )
    -0.02 ( 3.575 )
        Day 15: MPV, n=8,3,23
    0.04 ( 0.256 )
    0.20 ( 0.361 )
    0.45 ( 0.460 )
        Day 29: MPV, n=8,3,23
    -0.04 ( 0.378 )
    0.47 ( 0.764 )
    0.29 ( 0.630 )
        Day 43: MPV, n=7,3,22
    -0.14 ( 0.276 )
    0.23 ( 0.737 )
    0.07 ( 0.594 )
        Day 57: MPV, n=6,3,21
    0.23 ( 0.446 )
    0.47 ( 0.416 )
    0.12 ( 0.599 )
        Day 71: MPV, n=7,3,20
    -0.21 ( 0.393 )
    0.23 ( 0.231 )
    -0.15 ( 0.516 )
        Day 85: MPV, n=7,3,22
    0.00 ( 0.356 )
    0.43 ( 0.808 )
    -0.11 ( 0.462 )
        Day 113: MPV, n=7,3,19
    -0.04 ( 0.443 )
    0.30 ( 0.781 )
    0.03 ( 0.622 )
        Day 155: MPV, n=6,3,17
    0.17 ( 0.565 )
    0.10 ( 0.872 )
    0.01 ( 0.448 )
        Day 197: MPV, n=7,3,15
    -0.11 ( 0.385 )
    0.10 ( 0.781 )
    0.07 ( 0.580 )
    Notes
    [22] - Safety Population.
    [23] - Safety Population.
    [24] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) count, Reticulocyte count

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    End point title
    		 Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) count, Reticulocyte count [25]
    End point description
    Blood samples were collected to analyze the hematology parameters: RBC count and reticulocyte count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [25] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [26]
    3 [27]
    23 [28]
    Units: Tera cells per liter
    arithmetic mean (standard deviation)
        Day 15: RBC count, n=8,3,23
    -0.05 ( 0.321 )
    0.07 ( 0.208 )
    -0.01 ( 0.205 )
        Day 29: RBC count, n=8,3,23
    -0.03 ( 0.225 )
    -0.07 ( 0.404 )
    -0.11 ( 0.275 )
        Day 43: RBC count, n=8,3,22
    -0.03 ( 0.238 )
    -0.07 ( 0.321 )
    -0.22 ( 0.331 )
        Day 57: RBC count, n=6,3,22
    -0.07 ( 0.288 )
    -0.10 ( 0.361 )
    -0.42 ( 0.464 )
        Day 71: RBC count, n=8,3,20
    -0.13 ( 0.396 )
    -0.23 ( 0.208 )
    -0.66 ( 0.406 )
        Day 85: RBC count, n=7,3,22
    -0.10 ( 0.311 )
    -0.33 ( 0.208 )
    -0.68 ( 0.343 )
        Day 113: RBC count, n=7,3,20
    -0.13 ( 0.350 )
    -0.40 ( 0.265 )
    -0.68 ( 0.361 )
        Day 155: RBC count, n=7,3,17
    -0.17 ( 0.330 )
    -0.37 ( 0.252 )
    -0.47 ( 0.264 )
        Day 197: RBC count, n=7,3,15
    -0.04 ( 0.282 )
    -0.23 ( 0.058 )
    -0.15 ( 0.160 )
        Day 15: Reticulocyte count, n=8,3,23
    0.0109 ( 0.02401 )
    -0.0207 ( 0.02463 )
    -0.0160 ( 0.00964 )
        Day 29: Reticulocyte count, n=8,3,23
    -0.0001 ( 0.00543 )
    -0.0169 ( 0.00911 )
    -0.0132 ( 0.01784 )
        Day 43: Reticulocyte count, n=8,3,22
    -0.0032 ( 0.00554 )
    -0.0228 ( 0.02303 )
    -0.0109 ( 0.01699 )
        Day 57: Reticulocyte count, n=6,3,22
    -0.0058 ( 0.00638 )
    -0.0091 ( 0.02177 )
    -0.0031 ( 0.01656 )
        Day 71: Reticulocyte count, n=8,3,19
    0.0026 ( 0.01261 )
    -0.0125 ( 0.01878 )
    0.0065 ( 0.01934 )
        Day 85: Reticulocyte count, n=7,3,22
    -0.0044 ( 0.00539 )
    -0.0209 ( 0.02471 )
    0.0152 ( 0.02006 )
        Day 113: Reticulocyte count, n=7,3,20
    -0.0064 ( 0.01030 )
    0.0012 ( 0.02944 )
    0.0356 ( 0.02009 )
        Day 155: Reticulocyte count, n=7,3,17
    0.0006 ( 0.00623 )
    -0.0157 ( 0.02263 )
    0.0158 ( 0.01340 )
        Day 197: Reticulocyte count, n=7,3,16
    0.0003 ( 0.00550 )
    -0.0285 ( 0.03458 )
    0.0017 ( 0.01003 )
    Notes
    [26] - Safety Population.
    [27] - Safety Population.
    [28] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW)

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    End point title
    		 Change From Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) [29]
    End point description
    Blood samples were collected to analyze the hematology parameter: RDW. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [30]
    3 [31]
    23 [32]
    Units: Percentage of width
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    0.04 ( 0.711 )
    -0.27 ( 1.050 )
    -0.26 ( 0.667 )
        Day 29: n=8,3,23
    0.24 ( 0.417 )
    -0.53 ( 1.704 )
    -0.47 ( 1.036 )
        Day 43: n=8,3,22
    0.25 ( 0.583 )
    -0.97 ( 1.650 )
    -0.47 ( 1.049 )
        Day 57: n=6,3,22
    -0.02 ( 0.578 )
    -0.83 ( 2.248 )
    0.15 ( 1.331 )
        Day 71: n=8,3,20
    0.04 ( 0.725 )
    -0.23 ( 2.570 )
    0.96 ( 2.040 )
        Day 85: n=7,3,22
    -0.04 ( 0.663 )
    -0.20 ( 2.307 )
    1.67 ( 1.792 )
        Day 113: n=7,3,20
    0.26 ( 0.748 )
    0.73 ( 1.950 )
    4.24 ( 2.737 )
        Day 155: n=7,3,17
    -0.09 ( 0.771 )
    0.10 ( 1.916 )
    2.86 ( 1.636 )
        Day 197: n=7,3,15
    -0.16 ( 1.286 )
    -0.57 ( 1.872 )
    1.06 ( 1.375 )
    Notes
    [30] - Safety Population.
    [31] - Safety Population.
    [32] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Reticulocyte Production Index

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    End point title
    		 Change From Baseline in Reticulocyte Production Index [33]
    End point description
    Blood samples were collected to analyze the hematology parameter: Reticulocyte Production Index. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Reticulocyte Production Index (RPI) was calculated as 'Reticulocyte Production Index = Reticulocyte Count (percent [%]) multiply by (x) (hematocrit [%] divided by [/] 45) x 1/ reticulocyte maturation time'. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [33] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [34]
    3 [35]
    23 [36]
    Units: Unitless
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    0.2009 ( 0.49644 )
    -0.1787 ( 0.53867 )
    -0.2757 ( 0.20191 )
        Day 29: n=8,3,23
    0.0391 ( 0.09687 )
    -0.2397 ( 0.51850 )
    -0.2460 ( 0.35460 )
        Day 43: n=8,3,22
    -0.0691 ( 0.11447 )
    -0.3437 ( 0.55192 )
    -0.2342 ( 0.34389 )
        Day 57: n=6,3,22
    -0.0763 ( 0.13476 )
    -0.2877 ( 0.48015 )
    -0.1933 ( 0.32326 )
        Day 71: n=8,3,19
    0.0154 ( 0.24560 )
    -0.4643 ( 0.13444 )
    -0.1344 ( 0.29111 )
        Day 85: n=7,3,22
    -0.0831 ( 0.14906 )
    -0.4530 ( 0.48914 )
    -0.0112 ( 0.32736 )
        Day 113: n=7,3,20
    -0.1006 ( 0.21168 )
    -0.2633 ( 0.29016 )
    0.2826 ( 0.33003 )
        Day 155: n=7,3,17
    -0.0033 ( 0.24087 )
    -0.4720 ( 0.24857 )
    0.1105 ( 0.28718 )
        Day 197: n=7,3,15
    -0.0296 ( 0.11222 )
    -0.5693 ( 0.43160 )
    0.0087 ( 0.16995 )
    Notes
    [34] - Safety Population.
    [35] - Safety Population.
    [36] - Safety Population.
    No statistical analyses for this end point

    Primary: Change from Baseline Hematology Parameter: Reticulocytes

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    End point title
    		 Change from Baseline Hematology Parameter: Reticulocytes [37]
    End point description
    Blood samples were collected to analyze the hematology parameter: reticulocytes. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [37] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [38]
    3 [39]
    23 [40]
    Units: Percentage of reticulocytes
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    0.0026 ( 0.00534 )
    -0.0053 ( 0.00551 )
    -0.0037 ( 0.00236 )
        Day 29: n=8,3,23
    0.0001 ( 0.00155 )
    -0.0040 ( 0.00265 )
    -0.0030 ( 0.00423 )
        Day 43: n=8,3,22
    -0.0008 ( 0.00128 )
    -0.0057 ( 0.00611 )
    -0.0021 ( 0.00389 )
        Day 57: n=6,3,22
    -0.0012 ( 0.00214 )
    -0.0023 ( 0.00551 )
    0.0004 ( 0.00422 )
        Day 71: n=8,3,19
    0.0014 ( 0.00325 )
    -0.0027 ( 0.00551 )
    0.0037 ( 0.00625 )
        Day 85: n=7,3,22
    -0.0007 ( 0.00138 )
    -0.0043 ( 0.00651 )
    0.0065 ( 0.00647 )
        Day 113: n=7,3,20
    -0.0011 ( 0.00219 )
    0.0013 ( 0.00702 )
    0.0121 ( 0.00704 )
        Day 155: n=7,3,17
    0.0006 ( 0.00162 )
    -0.0027 ( 0.00603 )
    0.0054 ( 0.00405 )
        Day 197: n=7,3,15
    0.0001 ( 0.00157 )
    -0.0063 ( 0.00924 )
    0.0005 ( 0.00233 )
    Notes
    [38] - Safety Population.
    [39] - Safety Population.
    [40] - Safety Population.
    No statistical analyses for this end point

    Primary: Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

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    End point title
    		 Number of Participants With Worst-Case Chemistry Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline [41]
    End point description
    Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were low: <30 grams per liter (g/L) (albumin), high: >44.2 micromoles per liter (µmol/L) increase from Baseline (creatinine), low: <3 or high: >9 mmol/L (glucose), low: <3 or high: >5.5 mmol/L (potassium), and low: <130 or high: >150 mmol/L (sodium). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add up to 100%. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Up to Day 197
    Notes
    [41] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [42]
    3 [43]
    23 [44]
    Units: Participants
        Albumin: To Low
    0
    0
    0
        Albumin: To within Range or No Change
    8
    3
    23
        Albumin: To High
    0
    0
    0
        Creatinine: To Low
    0
    0
    0
        Creatinine: To within Range or No Change
    8
    3
    23
        Creatinine: To High
    0
    0
    0
        Glucose: To Low
    0
    0
    1
        Glucose: To within Range or No Change
    8
    2
    19
        Glucose: To High
    0
    1
    3
        Potassium: To Low
    0
    0
    0
        Potassium: To within Range or No Change
    7
    3
    22
        Potassium: To High
    1
    0
    1
        Sodium: To Low
    0
    0
    0
        Sodium: To within Range or No Change
    8
    3
    23
        Sodium: To High
    0
    0
    0
    Notes
    [42] - Safety Population.
    [43] - Safety Population.
    [44] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameter: Total Protein

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    End point title
    		 Change From Baseline in Chemistry Parameter: Total Protein [45]
    End point description
    Blood samples were collected to analyze chemistry parameter: total protein. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [45] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [46]
    3 [47]
    23 [48]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        Day 15: n=7,2,23
    1.0 ( 3.06 )
    0.5 ( 4.95 )
    0.4 ( 3.56 )
        Day 29: n=8,2,23
    -0.1 ( 3.14 )
    -1.0 ( 5.66 )
    0.7 ( 2.86 )
        Day 43: n=8,3,22
    -0.1 ( 2.36 )
    -0.3 ( 2.08 )
    -0.5 ( 3.52 )
        Day 57: n=7,3,22
    1.3 ( 2.29 )
    1.3 ( 2.08 )
    -0.5 ( 3.65 )
        Day 71: n=8,3,21
    -0.1 ( 3.56 )
    0.7 ( 1.15 )
    -1.1 ( 4.44 )
        Day 85: n=8,3,22
    0.3 ( 1.39 )
    0.0 ( 2.00 )
    0.3 ( 3.71 )
        Day 113: n=7,3,20
    -0.9 ( 2.61 )
    1.7 ( 0.58 )
    0.2 ( 4.06 )
        Day 155: n=7,3,18
    -1.3 ( 1.25 )
    3.0 ( 7.21 )
    -0.1 ( 4.59 )
        Day 197: n=7,3,19
    2.3 ( 3.90 )
    2.3 ( 3.51 )
    1.5 ( 5.00 )
    Notes
    [46] - Safety Population.
    [47] - Safety Population.
    [48] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH)

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    End point title
    		 Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) [49]
    End point description
    Blood samples were collected to analyze chemistry parameters: ALP, ALT, AST and LDH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [49] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [50]
    3 [51]
    23 [52]
    Units: International units per liter
    arithmetic mean (standard deviation)
        Day 15: ALP, n=7,2,23
    -1.3 ( 10.53 )
    -1.0 ( 4.24 )
    0.6 ( 5.67 )
        Day 29: ALP, n=8,2,23
    -2.3 ( 7.89 )
    4.5 ( 6.36 )
    -1.1 ( 10.94 )
        Day 43: ALP, n=8,3,22
    -4.4 ( 12.36 )
    0.7 ( 7.51 )
    -1.1 ( 9.00 )
        Day 57: ALP, n=7,3,22
    -5.0 ( 13.23 )
    3.3 ( 9.07 )
    1.0 ( 7.55 )
        Day 71: ALP, n=8,3,21
    -3.5 ( 10.94 )
    1.3 ( 1.53 )
    -3.0 ( 11.52 )
        Day 85: ALP, n=8,3,22
    -2.4 ( 11.96 )
    -2.3 ( 4.93 )
    -3.0 ( 11.65 )
        Day 113: ALP, n=7,3,20
    -1.3 ( 4.99 )
    -2.3 ( 4.93 )
    -6.3 ( 8.15 )
        Day 155: ALP, n=7,3,19
    -8.4 ( 15.88 )
    -3.3 ( 5.69 )
    -5.4 ( 9.84 )
        Day 197: ALP, n=7,3,19
    -3.6 ( 12.16 )
    -4.0 ( 6.93 )
    -2.1 ( 11.03 )
        Day 15: ALT, n=7,2,23
    -0.4 ( 2.70 )
    0.0 ( 1.41 )
    1.6 ( 3.85 )
        Day 29: ALT, n=8,2,23
    0.6 ( 1.85 )
    -2.0 ( 2.83 )
    3.3 ( 9.58 )
        Day 43: ALT, n=8,3,22
    1.3 ( 3.15 )
    4.0 ( 6.08 )
    3.1 ( 10.70 )
        Day 57: ALT, n=7,3,22
    -1.6 ( 1.27 )
    2.0 ( 4.58 )
    3.7 ( 10.03 )
        Day 71: ALT, n=8,3,21
    0.3 ( 2.82 )
    3.0 ( 6.24 )
    0.0 ( 2.67 )
        Day 85: ALT, n=8,3,22
    -1.5 ( 3.89 )
    -0.3 ( 2.52 )
    0.4 ( 4.27 )
        Day 113: ALT, n=7,3,20
    -1.4 ( 5.13 )
    4.7 ( 8.14 )
    0.2 ( 3.18 )
        Day 155: ALT, n=7,3,18
    -2.6 ( 6.65 )
    1.0 ( 1.00 )
    0.9 ( 3.95 )
        Day 197: ALT, n=7,3,21
    3.6 ( 3.87 )
    -0.3 ( 2.52 )
    2.4 ( 4.69 )
        Day 15: AST, n=7,2,23
    -0.1 ( 1.77 )
    0.5 ( 0.71 )
    1.7 ( 5.11 )
        Day 29: AST, n=8,2,23
    1.8 ( 7.11 )
    1.0 ( 1.41 )
    2.0 ( 5.42 )
        Day 43: AST, n=8,3,22
    1.6 ( 6.74 )
    2.0 ( 3.61 )
    0.9 ( 4.14 )
        Day 57: AST, n=7,3,22
    -0.6 ( 2.82 )
    2.3 ( 3.06 )
    2.0 ( 5.34 )
        Day 71: AST, n=8,3,21
    1.9 ( 5.00 )
    3.3 ( 4.93 )
    -0.3 ( 1.98 )
        Day 85: AST, n=8,3,22
    -0.8 ( 4.37 )
    0.3 ( 2.31 )
    -0.2 ( 2.20 )
        Day 113: AST, n=7,3,20
    -2.7 ( 4.39 )
    1.3 ( 4.04 )
    -0.9 ( 2.50 )
        Day 155: AST, n=7,3,18
    -5.0 ( 7.70 )
    2.3 ( 0.58 )
    -0.6 ( 2.66 )
        Day 197: AST, n=7,3,19
    0.1 ( 4.91 )
    2.7 ( 0.58 )
    1.2 ( 3.32 )
        Day 15: LDH, n=7,2,23
    4.1 ( 28.54 )
    -3.5 ( 51.62 )
    18.4 ( 32.34 )
        Day 29: LDH, n=8,2,23
    -7.0 ( 14.95 )
    11.0 ( 0.00 )
    20.9 ( 22.90 )
        Day 43: LDH, n=8,3,22
    12.1 ( 11.54 )
    2.7 ( 30.62 )
    27.2 ( 34.69 )
        Day 57: LDH, n=7,3,22
    -5.1 ( 19.36 )
    15.3 ( 31.02 )
    22.4 ( 23.71 )
        Day 71: LDH, n=8,3,21
    10.5 ( 29.62 )
    13.3 ( 26.95 )
    32.7 ( 29.90 )
        Day 85: LDH, n=8,3,22
    -2.5 ( 26.26 )
    3.0 ( 11.53 )
    24.9 ( 28.66 )
        Day 113: LDH, n=7,3,20
    -17.6 ( 17.89 )
    6.3 ( 25.50 )
    14.2 ( 26.43 )
        Day 155: LDH, n=7,3,17
    -20.4 ( 32.67 )
    1.0 ( 16.00 )
    13.4 ( 12.63 )
        Day 197: LDH, n=7,3,19
    -10.9 ( 27.97 )
    0.3 ( 20.60 )
    16.1 ( 21.91 )
    Notes
    [50] - Safety Population.
    [51] - Safety Population.
    [52] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin

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    End point title
    		 Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin [53]
    End point description
    Blood samples were collected to analyze chemistry parameters: total bilirubin and direct bilirubin. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [53] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [54]
    3 [55]
    23 [56]
    Units: Micromoles per liter
    arithmetic mean (standard deviation)
        Day 15: Total bilirubin, n=7,2,23
    0.571 ( 2.2254 )
    2.000 ( 2.8284 )
    -0.957 ( 1.8944 )
        Day 29: Total bilirubin, n=8,2,23
    -1.000 ( 2.8284 )
    -3.000 ( 1.4142 )
    -0.087 ( 1.8565 )
        Day 43: Total bilirubin, n=8,3,22
    -1.500 ( 1.4142 )
    -2.000 ( 2.0000 )
    -0.364 ( 1.4653 )
        Day 57: Total bilirubin, n=7,3,22
    -0.286 ( 1.3801 )
    -2.000 ( 0.0000 )
    -0.636 ( 2.0827 )
        Day 71: Total bilirubin, n=8,3,21
    0.250 ( 1.9821 )
    -1.333 ( 1.1547 )
    -0.095 ( 2.1425 )
        Day 85: Total bilirubin, n=8,3,22
    0.250 ( 2.7124 )
    -2.000 ( 0.0000 )
    -0.364 ( 1.8138 )
        Day 113: Total bilirubin, n=7,3,20
    0.000 ( 3.2660 )
    -1.333 ( 1.1547 )
    0.100 ( 1.5183 )
        Day 155: Total bilirubin, n=7,3,18
    -1.143 ( 3.0237 )
    -3.333 ( 1.1547 )
    -1.604 ( 2.4901 )
        Day 197: Total bilirubin, n=7,3,20
    0.571 ( 2.7603 )
    -4.000 ( 0.0000 )
    -1.416 ( 1.6976 )
        Day 15: Direct bilirubin, n=7,2,23
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -0.4 ( 1.59 )
        Day 29: Direct bilirubin, n=8,2,23
    -0.3 ( 0.71 )
    0.0 ( 0.00 )
    0.0 ( 1.21 )
        Day 43: Direct bilirubin, n=8,3,22
    -0.3 ( 0.71 )
    0.0 ( 0.00 )
    -0.2 ( 1.05 )
        Day 57: Direct bilirubin, n=7,3,22
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -0.4 ( 1.18 )
        Day 71: Direct bilirubin, n=8,3,21
    -0.3 ( 0.71 )
    0.0 ( 0.00 )
    -0.1 ( 1.18 )
        Day 85: Direct bilirubin, n=8,3,22
    -0.3 ( 0.71 )
    0.0 ( 0.00 )
    -0.2 ( 1.05 )
        Day 113: Direct bilirubin, n=7,3,20
    0.0 ( 1.15 )
    -0.7 ( 1.15 )
    -0.3 ( 0.98 )
        Day 155: Direct bilirubin, n=7,3,17
    -0.3 ( 0.76 )
    0.0 ( 0.00 )
    -0.2 ( 0.97 )
        Day 197: Direct bilirubin, n=7,3,17
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -0.1 ( 1.11 )
    Notes
    [54] - Safety Population.
    [55] - Safety Population.
    [56] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides

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    End point title
    		 Change From Baseline in Chemistry Parameters: Cholesterol, Direct High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides [57]
    End point description
    Blood samples were collected to analyze chemistry parameters: cholesterol, direct HDL cholesterol, LDL cholesterol and triglycerides. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose) and Day 85
    Notes
    [57] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [58]
    3 [59]
    22 [60]
    Units: Millimoles per liter
    arithmetic mean (standard deviation)
        Cholesterol: n=8,3,22
    -0.125 ( 0.7474 )
    0.067 ( 0.1258 )
    0.450 ( 0.5780 )
        Direct HDL Cholesterol: n=7,3,22
    -0.093 ( 0.1718 )
    -0.033 ( 0.0289 )
    -0.036 ( 0.2989 )
        LDL Cholesterol: n=7,3,21
    -0.091 ( 0.7376 )
    0.110 ( 0.1200 )
    0.274 ( 0.5011 )
        Triglycerides: n=8,3,22
    0.025 ( 0.3427 )
    -0.020 ( 0.0800 )
    0.535 ( 0.8036 )
    Notes
    [58] - Safety Population.
    [59] - Safety Population.
    [60] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea

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    End point title
    		 Change From Baseline in Chemistry Parameter: Corrected Calcium, Urea [61]
    End point description
    Blood samples were collected to analyze chemistry parameters: corrected calcium and urea. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [61] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [62]
    3 [63]
    23 [64]
    Units: Millimoles per liter
    arithmetic mean (standard deviation)
        Day 15: Corrected calcium, n=7,2,23
    0.011 ( 0.0540 )
    -0.020 ( 0.0566 )
    -0.013 ( 0.0725 )
        Day 29: Corrected calcium, n=8,2,23
    -0.035 ( 0.0563 )
    -0.070 ( 0.0424 )
    -0.036 ( 0.0809 )
        Day 43: Corrected calcium, n=8,3,22
    -0.003 ( 0.0483 )
    -0.060 ( 0.0200 )
    -0.061 ( 0.0737 )
        Day 57: Corrected calcium, n=7,3,22
    -0.003 ( 0.0509 )
    -0.060 ( 0.0721 )
    -0.069 ( 0.0827 )
        Day 71: Corrected calcium, n=8,3,21
    -0.023 ( 0.0362 )
    -0.020 ( 0.0000 )
    -0.066 ( 0.0705 )
        Day 85: Corrected calcium, n=8,3,22
    -0.043 ( 0.0599 )
    -0.027 ( 0.0808 )
    -0.049 ( 0.0689 )
        Day 113: Corrected calcium, n=7,3,20
    -0.026 ( 0.0746 )
    0.000 ( 0.0346 )
    -0.035 ( 0.0550 )
        Day 155: Corrected calcium, n=7,3,18
    -0.037 ( 0.0678 )
    0.000 ( 0.0346 )
    -0.034 ( 0.0508 )
        Day 197: Corrected calcium, n=7,3,19
    0.014 ( 0.0862 )
    -0.020 ( 0.0600 )
    -0.020 ( 0.0629 )
        Day 15: Urea, n=7,2,23
    0.0714 ( 1.13389 )
    -2.0000 ( 0.00000 )
    0.3043 ( 1.56481 )
        Day 29: Urea, n=8,2,23
    0.0000 ( 1.13389 )
    -0.7500 ( 0.35355 )
    0.3043 ( 1.67698 )
        Day 43: Urea, n=8,3,22
    0.4375 ( 1.08356 )
    -0.8333 ( 0.28868 )
    0.3182 ( 1.34116 )
        Day 57: Urea, n=7,3,22
    -0.1429 ( 1.14434 )
    -0.8333 ( 0.76376 )
    0.5682 ( 1.30289 )
        Day 71: Urea, n=8,3,21
    -0.1875 ( 1.30760 )
    -0.5000 ( 0.50000 )
    0.0952 ( 1.50515 )
        Day 85: Urea, n=8,3,22
    -0.1875 ( 1.25178 )
    -0.1667 ( 0.76376 )
    0.4091 ( 1.40269 )
        Day 113: Urea, n=7,3,20
    0.2857 ( 1.70434 )
    -0.8333 ( 0.28868 )
    0.4000 ( 1.47434 )
        Day 155: Urea, n=7,3,18
    0.2857 ( 1.75255 )
    -0.8333 ( 1.15470 )
    0.0912 ( 1.52540 )
        Day 197: Urea, n=7,3,19
    -0.0714 ( 2.11007 )
    -1.0000 ( 0.50000 )
    0.1510 ( 1.76450 )
    Notes
    [62] - Safety Population.
    [63] - Safety Population.
    [64] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Chemistry Parameter: estimated Glomerular Filtration Rate

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    End point title
    		 Change From Baseline in Chemistry Parameter: estimated Glomerular Filtration Rate [65]
    End point description
    Blood samples were collected to analyze chemistry parameter: estimated glomerular filtration rate. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [65] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [66]
    3 [67]
    23 [68]
    Units: Milliliter/minute/1.73 square meter
    arithmetic mean (standard deviation)
        Day 15: n=7,2,23
    -6.4180 ( 10.28099 )
    1.7630 ( 1.28693 )
    -0.7528 ( 9.25789 )
        Day 29: n=8,2,23
    -4.3085 ( 8.34077 )
    -2.7765 ( 9.78424 )
    -1.5543 ( 9.55847 )
        Day 43: n=8,3,22
    -0.4780 ( 9.34592 )
    -4.3223 ( 3.88914 )
    -3.4266 ( 6.99189 )
        Day 57: n=7,3,22
    1.3446 ( 7.12100 )
    2.6893 ( 5.61068 )
    -5.1256 ( 7.41957 )
        Day 71: n=8,3,21
    -0.4405 ( 12.50899 )
    -0.9993 ( 5.98467 )
    -2.5432 ( 7.12712 )
        Day 85: n=8,3,22
    -1.0010 ( 8.15284 )
    -7.1513 ( 6.77426 )
    -5.1038 ( 8.90164 )
        Day 113: n=7,3,20
    -2.7351 ( 12.23546 )
    -0.2900 ( 6.19990 )
    -8.5267 ( 7.71222 )
        Day 155: n=7,3,20
    -0.9239 ( 13.25672 )
    -3.9510 ( 5.74000 )
    -4.2795 ( 9.19612 )
        Day 197: n=7,3,21
    -4.2733 ( 15.36640 )
    -7.7100 ( 8.47159 )
    -2.7185 ( 8.91665 )
    Notes
    [66] - Safety Population.
    [67] - Safety Population.
    [68] - Safety Population.
    No statistical analyses for this end point

    Primary: Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick

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    End point title
    		 Number of Participants With Emergent Worst Case Urinalysis Results by Dipstick [69]
    End point description
    Urine samples were collected for the assessment of potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters: potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with emergent worst case any increase from Baseline values are presented. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Up to Day 197
    Notes
    [69] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [70]
    3 [71]
    23 [72]
    Units: Participants
        Potential of hydrogen, Any increase
    0
    0
    0
        Specific gravity, Any increase
    0
    0
    3
        Glucose, Any increase
    0
    0
    0
        Ketones, Any increase
    1
    0
    4
        Occult blood, Any increase
    2
    0
    3
        Protein, Any increase
    1
    0
    4
    Notes
    [70] - Safety Population.
    [71] - Safety Population.
    [72] - Safety Population.
    No statistical analyses for this end point

    Primary: Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria

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    End point title
    		 Number of Participants With Vital Signs Relative to Change From Baseline by Potential Clinical Importance (PCI) Criteria [73]
    End point description
    Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) were measured in a seated or semi-supine position after 5 minutes of rest using a completely automated device. PCI ranges were: SBP (increase or decrease from Baseline of >=40 millimeter of mercury [mmHg]), DBP (increase or decrease from Baseline of >=20 mmHg), and HR (increase or decrease from Baseline of >=30 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose) and up to Day 197
    Notes
    [73] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [74]
    3 [75]
    23 [76]
    Units: Participants
        DBP: Decrease >=20
    2
    0
    2
        DBP: Increase >=20
    0
    0
    1
        SBP: Decrease >=40
    0
    0
    0
        SBP: Increase >=40
    0
    0
    2
        HR: Decrease >=30
    0
    0
    0
        HR: Increase >=30
    1
    0
    2
    Notes
    [74] - Safety Population.
    [75] - Safety Population.
    [76] - Safety Population.
    No statistical analyses for this end point

    Primary: Change From Baseline in Body Temperature

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    End point title
    		 Change From Baseline in Body Temperature [77]
    End point description
    Body temperature was measured in a seated or semi-supine position after 5 minutes of rest. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1: Pre-dose), Days 15, 29, 43, 57, 71, 85, 113, 155 and 197
    Notes
    [77] - 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 are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [78]
    3 [79]
    23 [80]
    Units: Degrees Celsius
    arithmetic mean (standard deviation)
        Day 15: n=8,3,23
    0.037 ( 0.4689 )
    0.400 ( 0.4359 )
    0.117 ( 0.3833 )
        Day 29: n=8,3,23
    0.037 ( 0.3889 )
    0.467 ( 0.6807 )
    0.130 ( 0.3470 )
        Day 43: n=8,3,23
    0.012 ( 0.4121 )
    0.033 ( 0.4163 )
    0.039 ( 0.4197 )
        Day 57: n=7,3,22
    0.100 ( 0.2449 )
    0.133 ( 0.3215 )
    0.177 ( 0.4253 )
        Day 71: n=8,3,21
    -0.112 ( 0.5303 )
    0.267 ( 0.5132 )
    0.186 ( 0.4328 )
        Day 85: n=8,3,22
    0.012 ( 0.3563 )
    0.467 ( 0.5859 )
    -0.023 ( 0.3854 )
        Day 113: n=7,3,20
    -0.257 ( 0.3505 )
    0.400 ( 0.6245 )
    0.100 ( 0.4952 )
        Day 155: n=7,3,17
    -0.257 ( 0.3409 )
    0.167 ( 0.5033 )
    0.118 ( 0.6054 )
        Day 197: n=7,3,17
    -0.143 ( 0.4860 )
    0.267 ( 0.4933 )
    0.212 ( 0.5122 )
    Notes
    [78] - Safety Population.
    [79] - Safety Population.
    [80] - Safety Population.
    No statistical analyses for this end point

    Primary: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings

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    End point title
    		 Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings [81]
    End point description
    Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Up to Day 57
    Notes
    [81] - 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 are no statistical data to report.There are no statistical data to report.
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    7 [82]
    3 [83]
    23 [84]
    Units: Participants
        Abnormal- not clinically significant
    3
    2
    10
        Abnormal- clinically significant
    0
    0
    1
    Notes
    [82] - Safety Population.
    [83] - Safety Population.
    [84] - Safety Population.
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of GSK2330811

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    End point title
    		 Plasma Concentrations of GSK2330811 [85]
    End point description
    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK2330811. Pharmacokinetic (PK) Population was defined as participants in the ‘Safety’ population who received an active dose and for whom a PK sample was obtained and analyzed. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates, mean and standard deviation could not be calculated due to high proportion of non-quantifiable (NQ) values (more than [>] 30 percent [%] of values were imputed).
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    Notes
    [85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.
    End point values
    		 GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    3 [86]
    24 [87]
    Units: Nanogram per milliliter
    arithmetic mean (standard deviation)
        Day 1: n=3,24
    99999 ( 99999 )
    0.0 ( 99999 )
        Day 15: n=3,23
    5510.7 ( 2455.19 )
    16197.9 ( 6354.54 )
        Day 29: n=3,23
    7782.3 ( 1563.04 )
    23407.0 ( 8830.49 )
        Day 57: n=3,22
    9868.7 ( 818.51 )
    32645.7 ( 15225.01 )
        Day 85: n=3,22
    10993.0 ( 717.89 )
    29254.4 ( 16911.55 )
        Day 113: n=3,20
    4123.0 ( 420.29 )
    11087.1 ( 7661.76 )
        Day 155: n=3,16
    580.0 ( 408.47 )
    2892.9 ( 4093.61 )
        Day 197: n=3,17
    114.0 ( 99999 )
    729.2 ( 841.17 )
    Notes
    [86] - PK Population.
    [87] - PK Population.
    No statistical analyses for this end point

    Secondary: Concentration at the end of the dosing interval (Ctrough) of GSK2330811

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    End point title
    		 Concentration at the end of the dosing interval (Ctrough) of GSK2330811 [88]
    End point description
    Blood samples were collected at the indicated time points for PK analysis of GSK2330811. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    Notes
    [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.
    End point values
    		 GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    3 [89]
    22 [90]
    Units: Nanogram per milliliter
        arithmetic mean (standard deviation)
    10993.0 ( 717.89 )
    29254.4 ( 16911.55 )
    Notes
    [89] - PK Population.
    [90] - PK Population.
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL/F) of GSK2330811

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    End point title
    		 Apparent Clearance (CL/F) of GSK2330811
    End point description
    Blood samples were collected at the indicated time points for PK analysis of GSK2330811. Data was analyzed by population pharmacokinetic methods using a non-linear mixed-effects modelling approach. Only those participants with data available at the specified time points were analyzed. CL/F was estimated based on population PK modelling on the combination of data of participants dosed with GSK2330811, as it was more appropriate due to limited dose range (100 mg and 300 mg).
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    End point values
    		 GSK2330811 100 mg and GSK2330811 300 mg - Overall
    Number of subjects analysed
    26 [91]
    Units: Liter per hour
        geometric mean (confidence interval 95%)
    0.0147 (0.0132 to 0.0163)
    Notes
    [91] - PK Population.
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vss/F) of GSK2330811

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    End point title
    		 Apparent Volume of Distribution (Vss/F) of GSK2330811
    End point description
    Blood samples were collected at the indicated time points for PK analysis of GSK2330811. Data was analyzed by population pharmacokinetic methods using a non-linear mixed-effects modelling approach. Only those participants with data available at the specified time points were analyzed. 99999 indicates, PK parameters were calculated by fitting a population PK model using the combined data of participants dosed with 100 mg and 300 mg of GSK2330811. Since a minimal model was utilized, the Vss/F value was fixed to a plasma physiological value obtained from the literature. Hence, a confidence interval cannot be provided for this parameter.
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    End point values
    		 GSK2330811 100 mg and GSK2330811 300 mg - Overall
    Number of subjects analysed
    26 [92]
    Units: Liter
        geometric mean (confidence interval 95%)
    3.25 (-99999 to 99999)
    Notes
    [92] - PK Population.
    No statistical analyses for this end point

    Secondary: Serum Level of Total Oncostatin M (OSM)

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    End point title
    		 Serum Level of Total Oncostatin M (OSM)
    End point description
    Blood samples were collected at indicated timepoints for analysis of total OSM levels in serum. Per Protocol Population comprised of participants in the ‘Safety’ population who complied with the protocol. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [93]
    3 [94]
    23 [95]
    Units: Picogram per milliliter
    median (full range (min-max))
        Day 1: n=8,3,22
    22.110 (13.08 to 57.40)
    30.590 (6.19 to 38.71)
    27.455 (16.93 to 81.71)
        Day 15: n=8,3,23
    28.175 (18.07 to 57.48)
    576.850 (417.28 to 696.18)
    721.020 (496.63 to 1482.91)
        Day 29: n=8,3,23
    26.210 (12.84 to 48.82)
    499.540 (487.14 to 635.94)
    974.220 (398.94 to 2500.01)
        Day 57: n=7,3,22
    34.700 (13.40 to 43.94)
    651.710 (554.93 to 971.25)
    1211.570 (636.83 to 2350.65)
        Day 85: n=8,3,22
    17.275 (14.38 to 66.28)
    613.290 (555.09 to 1229.71)
    1357.645 (542.85 to 2500.01)
        Day 113: n=7,3,20
    23.350 (8.42 to 81.11)
    687.810 (419.04 to 935.76)
    1044.650 (186.06 to 2378.21)
        Day 155: n=7,3,17
    23.850 (13.13 to 43.07)
    206.900 (143.55 to 363.62)
    359.340 (58.13 to 1097.70)
        Day 197: n=7,3,17
    28.800 (19.58 to 36.13)
    54.290 (40.96 to 137.88)
    142.830 (28.82 to 607.09)
    Notes
    [93] - Per Protocol Population.
    [94] - Per Protocol Population.
    [95] - Per Protocol Population.
    No statistical analyses for this end point

    Secondary: Serum Level of Free OSM

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    End point title
    		 Serum Level of Free OSM
    End point description
    Blood samples were collected at indicated timepoints for analysis of free OSM levels in serum. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 29, 57, 85, 113, 155 and 197
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [96]
    3 [97]
    23 [98]
    Units: Picogram per milliliter
    median (full range (min-max))
        Day 1: n=8,3,22
    19.72 (8.3 to 45.3)
    28.93 (4.5 to 36.8)
    20.74 (8.8 to 56.0)
        Day 15: n=8,3,23
    23.85 (11.7 to 40.7)
    0.73 (0.73 to 0.73)
    0.73 (0.73 to 0.73)
        Day 29: n=8,3,23
    19.35 (4.5 to 37.1)
    0.73 (0.73 to 0.73)
    0.73 (0.73 to 0.73)
        Day 57: n=7,3,22
    27.62 (6.1 to 35.9)
    0.73 (0.73 to 0.73)
    0.73 (0.73 to 0.73)
        Day 85: n=8,3,22
    12.37 (5.9 to 47.6)
    0.73 (0.73 to 0.73)
    0.73 (0.73 to 0.73)
        Day 113: n=7,3,20
    16.78 (5.7 to 58.5)
    0.73 (0.73 to 0.73)
    0.73 (0.73 to 0.73)
        Day 155: n=7,3,17
    14.54 (7.3 to 32.7)
    0.73 (0.73 to 0.73)
    0.73 (0.7 to 1.7)
        Day 197: n=7,3,17
    18.43 (12.2 to 23.5)
    0.73 (0.73 to 0.73)
    0.73 (0.7 to 2.7)
    Notes
    [96] - Per Protocol Population.
    [97] - Per Protocol Population.
    [98] - Per Protocol Population.
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-GSK2330811 Antibodies

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    End point title
    		 Number of Participants With Positive Anti-GSK2330811 Antibodies
    End point description
    Serum samples were collected for the determination of anti-GSK2330811 antibodies (ADA) using a binding antibody detection assay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that were confirmed positive in the confirmation assay were reported as 'positive'. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Days 1, 15, 57, 85 and 197
    End point values
    		 Placebo GSK2330811 100 mg GSK2330811 300 mg
    Number of subjects analysed
    8 [99]
    3 [100]
    23 [101]
    Units: Participants
        Day 1: n=8,3,23
    0
    0
    3
        Day 15: n=8,3,23
    0
    0
    1
        Day 57: n=7,3,22
    0
    0
    2
        Day 85: n=8,3,22
    0
    0
    1
        Day 197: n=7,3,17
    0
    0
    0
    Notes
    [99] - Safety Population.
    [100] - Safety Population.
    [101] - Safety Population.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality, SAEs and non-SAEs were collected up to Day 197. The protocol allowed for additional SAEs to be collected after Day 197; collected up to Day 603 post first dose
    Adverse event reporting additional description
    Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received subcutaneous injection of placebo on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 300 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 300 mg on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Reporting group title
    GSK2330811 100 mg
    Reporting group description
    		 Participants received subcutaneous injection of GSK2330811 100 milligrams (mg) on Day 1 and then every other week until the final dose on Day 71 (Week 10).

    Serious adverse events
    		 Placebo GSK2330811 300 mg GSK2330811 100 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal cell carcinoma
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infected skin ulcer
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo GSK2330811 300 mg GSK2330811 100 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 8 (100.00%)
    24 / 24 (100.00%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Injection site erythema
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    6
    0
    Nodule
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 8 (25.00%)
    3 / 24 (12.50%)
    1 / 3 (33.33%)
         occurrences all number
    2
    4
    1
    Dyspnoea
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Cardiac murmur
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Electrocardiogram PR prolongation
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Haematocrit decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    6 / 24 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    6
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    3 / 24 (12.50%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    Red blood cell count decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Reticulocyte count increased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Reticulocyte percentage increased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Ligament sprain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 8 (0.00%)
    4 / 24 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Headache
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Paraesthesia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 8 (0.00%)
    4 / 24 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Neutropenia
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 8 (0.00%)
    3 / 24 (12.50%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    Ear and labyrinth disorders
    Ear pruritus
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Angular cheilitis
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 8 (12.50%)
    4 / 24 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    1
    5
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 8 (0.00%)
    3 / 24 (12.50%)
    1 / 3 (33.33%)
         occurrences all number
    0
    4
    1
    Nausea
         subjects affected / exposed
    1 / 8 (12.50%)
    3 / 24 (12.50%)
    0 / 3 (0.00%)
         occurrences all number
    1
    5
    0
    Vomiting
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Actinic elastosis
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Alopecia
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    Blister
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    2
    Hyperkeratosis
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    2
    Lentigo
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Lipoatrophy
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Night sweats
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Rash
         subjects affected / exposed
    1 / 8 (12.50%)
    3 / 24 (12.50%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Skin mass
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Skin ulcer
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 24 (4.17%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    1 / 3 (33.33%)
         occurrences all number
    0
    3
    1
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1
    Folliculitis
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Gastrointestinal bacterial overgrowth
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Paronychia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 24 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 24 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Skin bacterial infection
         subjects affected / exposed
    0 / 8 (0.00%)
    0 / 24 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
    4 / 24 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    1
    5
    4
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 24 (4.17%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Nov 2016
    Amendment 1: This amendment was executed in response to the Food and Drug Administration (FDA) request that the participant eligibility criteria be modified to include two forms of contraception for males and females of childbearing potential.
    12 Dec 2016
    Amendment 2: This amendment was primarily executed in response to an FDA recommendation for a 30 minute observation period after each dose is administered.
    20 Jul 2017
    Amendment 3: This amendment was primarily executed to add the additional exploratory endpoints of change in the Composite Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) and change in Patient Global Assessment.
    12 Nov 2018
    Amendment 4: This amendment was executed to provide clarification on the points detailed below: 1. Schedule of Activities, Exclusion Criteria and Clinical Laboratory Tests were updated to reflect use of QuantiFERON-TB Gold PLUS test at central laboratory. 2. Wording clarified in Inclusion Criteria and Permitted medications and Non-Drug Therapies to reflect intent that mycophenolate sodium dose allowed should be equivalent to mycophenolate mofetil dose. 3. Updated text from ‘will’ to ‘may’ in Sample Size Determination and Interim Analyses to indicate that it may not be feasible to conduct all interim analyses. 4. Wording updated to clarify circumstances when local laboratory results are acceptable in Clinical Laboratory Tests.
    01 Apr 2020
    Amendment 5: This amendment was executed in response to the COVID-19 pandemic to provide clarification on the points detailed below: 1. Schedule of Activities and Study Assessments and Procedures were updated to allow a virtual or telephone visit at Day 113, Day 155, Day 197 and Early Withdrawal (if required) to perform any study assessments that can be conducted remotely in circumstances in which an onsite visit is not possible due to the COVID-19 pandemic. 2. Schedule of Activities updated to extend the visit window on Day 113 to +/- 5 days, and on Day 155 and Day 197 to +/- 10. 3. Schedule of Activities and Clinical Laboratory Tests were updated to allow safety (hematology and chemistry) labs and pregnancy tests to be run locally at the clinical site or within the community at the discretion of the Investigator for the Day 113, Day 155, Day 197 and Early Withdrawal (if required) visits; and updated to allow urine pregnancy test to be performed for the Day 197 and Early Withdrawal (if required) visits if a serum pregnancy test cannot be performed.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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