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    Clinical Trial Results:
    A Phase 2B, randomized, blinded, dose-ranging, active-controlled, parallel-group, multi-center study to evaluate the dose response relationship of GSK1278863 over the first 4 weeks of treatment and evaluate the safety and efficacy of GSK1278863 over 24 weeks in hemodialysis-dependent subjects with anemia associated with chronic kidney disease who switch from recombinant human erythropoietin.

    Summary
    EudraCT number
    2013-002682-19
    Trial protocol
    ES   SE   CZ   GB   DK   HU   FR  
    Global end of trial date
    06 Feb 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    04 Jan 2017
    First version publication date
    03 Jun 2016
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Minor changes required.

    Trial information

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    Trial identification
    Sponsor protocol code
    PHI113633
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 May 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Characterize the dose-response relationship between GSK1278863 and Hgb at Week 4.
    Protection of trial subjects
    N/A
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Nov 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 46
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    Czech Republic: 10
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Japan: 24
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Norway: 4
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Russian Federation: 47
    Worldwide total number of subjects
    216
    EEA total number of subjects
    70
    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)
    140
    From 65 to 84 years
    70
    85 years and over
    6

    Subject disposition

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    Recruitment
    Recruitment details
    Eligible participants (par.) were hemodialysis-dependent with anemia associated with chronic kidney disease who were switched from a stable dose of recombinant human erythropoietin (rhEPO).

    Pre-assignment
    Screening details
    Study consisted of Screening Phase of at least 4 weeks (wk), 24-wk Treatment Phase and Follow-up visit approximately 4 wk after completion of treatment. A total of 216 par. with a stable hemoglobin (Hgb) between 9.0-11.5 grams (g)/deciliter (dL) (France sites only: 10.0-11.5 g/dL) were randomized and 210 par. entered into the 24-wk Treatment Phase.

    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
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Control
    Arm description
    Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching film coated tablets were administered orally for 4 weeks.

    Arm title
    GSK1278863 4 mg
    Arm description
    Participants received GSK1278863 4 milligrams (mg) once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1278863
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK1278863 film coated tablets were administered orally at a dosage of 4 milligrams (mg), 6 mg, 8 mg, 10 mg, or 12 mg per randomization schedule for 4 weeks and then dose adjusted if necessary for every 4 weeks to achieve hemoglobin (Hgb) within the range of 10.0-11.5 grams (g)/deciliter (dL) for the remaining 20 weeks.

    Arm title
    GSK1278863 6 mg
    Arm description
    Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1278863
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK1278863 film coated tablets were administered orally at a dosage of 4 milligrams (mg), 6 mg, 8 mg, 10 mg, or 12 mg per randomization schedule for 4 weeks and then dose adjusted if necessary for every 4 weeks to achieve hemoglobin (Hgb) within the range of 10.0-11.5 grams (g)/deciliter (dL) for the remaining 20 weeks.

    Arm title
    GSK1278863 8 mg
    Arm description
    Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1278863
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK1278863 film coated tablets were administered orally at a dosage of 4 milligrams (mg), 6 mg, 8 mg, 10 mg, or 12 mg per randomization schedule for 4 weeks and then dose adjusted if necessary for every 4 weeks to achieve hemoglobin (Hgb) within the range of 10.0-11.5 grams (g)/deciliter (dL) for the remaining 20 weeks.

    Arm title
    GSK1278863 10 mg
    Arm description
    Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1278863
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK1278863 film coated tablets were administered orally at a dosage of 4 milligrams (mg), 6 mg, 8 mg, 10 mg, or 12 mg per randomization schedule for 4 weeks and then dose adjusted if necessary for every 4 weeks to achieve hemoglobin (Hgb) within the range of 10.0-11.5 grams (g)/deciliter (dL) for the remaining 20 weeks.

    Arm title
    GSK1278863 12 mg
    Arm description
    Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1278863
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK1278863 film coated tablets were administered orally at a dosage of 4 milligrams (mg), 6 mg, 8 mg, 10 mg, or 12 mg per randomization schedule for 4 weeks and then dose adjusted if necessary for every 4 weeks to achieve hemoglobin (Hgb) within the range of 10.0-11.5 grams (g)/deciliter (dL) for the remaining 20 weeks.

    Number of subjects in period 1
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Started
    39
    39
    40
    39
    40
    19
    Completed
    36
    30
    35
    35
    37
    14
    Not completed
    3
    9
    5
    4
    3
    5
         Protocol deviation
    -
    -
    1
    -
    -
    -
         Protocol-defined Stopping Criteria
    -
    3
    2
    1
    -
    -
         Physician decision
    -
    1
    -
    -
    -
    -
         Adverse event, serious fatal
    -
    1
    1
    -
    2
    -
         Consent withdrawn by subject
    2
    4
    1
    3
    1
    5
         Lost to follow-up
    1
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Control
    Reporting group description
    Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 4 mg
    Reporting group description
    Participants received GSK1278863 4 milligrams (mg) once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 6 mg
    Reporting group description
    Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 8 mg
    Reporting group description
    Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 10 mg
    Reporting group description
    Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 12 mg
    Reporting group description
    Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg Total
    Number of subjects
    39 39 40 39 40 19 216
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    59.7 ± 18.74 58.7 ± 13.33 63.5 ± 14 60.1 ± 10.36 55.4 ± 15.5 59.9 ± 13.26 -
    Gender categorical
    Units: Subjects
        Female
    13 15 12 15 17 8 80
        Male
    26 24 28 24 23 11 136
    Race, Customized
    Units: Subjects
        African American/African Heritage
    7 4 5 3 4 4 27
        American Indian Or Alaskan Native
    1 0 0 0 0 0 1
        Asian - East Asian Heritage
    2 1 3 1 1 0 8
        Asian - Japanese Heritage
    5 4 4 5 4 2 24
        Asian - South East Asian Heritage
    0 1 0 1 0 1 3
        Native Hawaiian Or Other Pacific Islander
    1 0 0 1 0 0 2
        White - Arabic/North African Heritage
    0 0 2 0 0 0 2
        White - White/Caucasian/European Heritage
    23 28 26 28 31 12 148
        Mixed Race
    0 1 0 0 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Control
    Reporting group description
    Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 4 mg
    Reporting group description
    Participants received GSK1278863 4 milligrams (mg) once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 6 mg
    Reporting group description
    Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 8 mg
    Reporting group description
    Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 10 mg
    Reporting group description
    Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 12 mg
    Reporting group description
    Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Primary: Change from Baseline in hemoglobin (Hgb) at Week 4

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    End point title
    Change from Baseline in hemoglobin (Hgb) at Week 4
    End point description
    Baseline Hgb value was the average of three Hgb values taken during the screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing W4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.
    End point type
    Primary
    End point timeframe
    Baseline (Week -4, Week-2 and Day 1) and Week 4 Intent-to-Treat (ITT) population consisted of all randomized participants who received one dose of study, have a Baseline and at least one corresponding treatment assessment.
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    39 [1]
    38 [2]
    39 [3]
    38 [4]
    39 [5]
    17 [6]
    Units: grams (g)/deciliter (dL)
        arithmetic mean (standard deviation)
    -0.64 ± 0.829
    -0.24 ± 0.989
    0.08 ± 1.131
    0.42 ± 0.796
    0.64 ± 1.177
    0.61 ± 1.245
    Notes
    [1] - ITT Population. Only participants with data available at specific time point were analyzed.
    [2] - ITT Population. Only participants with data available at specific time point were analyzed.
    [3] - ITT Population. Only participants with data available at specific time point were analyzed.
    [4] - ITT Population. Only participants with data available at specific time point were analyzed.
    [5] - ITT Population. Only participants with data available at specific time point were analyzed.
    [6] - ITT Population. Only participants with data available at specific time point were analyzed.
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    E0 (g/dL)
    Point estimate
    -0.664
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.96
         upper limit
    -0.387
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    ED50 (milligrams[mg])
    Point estimate
    33.531
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.566
         upper limit
    48.948
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Emax (g/dL)
    Point estimate
    5.234
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.691
         upper limit
    7.94
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Gamma
    Point estimate
    1.145
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.748
         upper limit
    1.738
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Var
    Point estimate
    1.012
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    1.234
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Alpha
    Point estimate
    -0.206
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.397
         upper limit
    -0.014
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Minimally Effective Dose (MED) (mg)
    Point estimate
    0.418
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    2.342
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Dose that achieves a change of -0.25g/dL
    Point estimate
    2.423
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    4.15
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Target Dose (TD) (mg)
    Point estimate
    4.406
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.544
         upper limit
    5.995
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Dose that achieves a change of 0.25 g/dL
    Point estimate
    6.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.698
         upper limit
    8.01
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Dose that achieves a change of 0.5 g/dL
    Point estimate
    8.542
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.931
         upper limit
    10.523
    Statistical analysis title
    Statistical analysis 12
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 10 mg v GSK1278863 12 mg v GSK1278863 8 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Dose that achieves a change of 0.75 g/dL
    Point estimate
    10.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.024
         upper limit
    14.004
    Statistical analysis title
    Statistical analysis 13
    Statistical analysis description
    Posterior median and 95% credibility intervals were estimated using Bayesian methods.
    Comparison groups
    Control v GSK1278863 4 mg v GSK1278863 6 mg v GSK1278863 8 mg v GSK1278863 10 mg v GSK1278863 12 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Dose that achieves a change of 1 g/dL
    Point estimate
    13.248
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.891
         upper limit
    18.916

    Secondary: Hgb concentration at Week 24

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    End point title
    Hgb concentration at Week 24
    End point description
    Hgb values measured at Week 24 are presented.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    24 [7]
    18 [8]
    27 [9]
    26 [10]
    24 [11]
    11 [12]
    Units: g/dL
        arithmetic mean (standard deviation)
    10.56 ± 0.974
    10.29 ± 0.864
    10.54 ± 1.01
    10.63 ± 1.099
    10.28 ± 0.856
    10.7 ± 0.867
    Notes
    [7] - ITT Population. Only participants with data available at specific time point were analyzed.
    [8] - ITT Population. Only participants with data available at specific time point were analyzed.
    [9] - ITT Population. Only participants with data available at specific time point were analyzed.
    [10] - ITT Population. Only participants with data available at specific time point were analyzed.
    [11] - ITT Population. Only participants with data available at specific time point were analyzed.
    [12] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Percentage of time within, below, and above Hgb target range between Weeks 20 and 24

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    End point title
    Percentage of time within, below, and above Hgb target range between Weeks 20 and 24
    End point description
    The percentage of time in Hgb target range between Weeks 20 and 24 for a participant was calculated by dividing the total number of days that Hgb was within the target range (10.0 to 11.5 g/dL) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the participant remained on treatment during the defined period. Similarly, percentage of time above Hgb target range and percentage of time below Hgb target range were calculated.
    End point type
    Secondary
    End point timeframe
    Week 20 to Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    31 [13]
    22 [14]
    28 [15]
    27 [16]
    25 [17]
    14 [18]
    Units: Percentage of time
    arithmetic mean (standard deviation)
        Percentage of time within target range
    54.59 ± 42.044
    74.77 ± 38.797
    57.38 ± 40.505
    37.46 ± 41.775
    48.97 ± 42.49
    55.23 ± 40.35
        Percentage of time above target range
    24.65 ± 38.556
    6.89 ± 22.137
    17.18 ± 30.446
    33.15 ± 42.856
    18.27 ± 33.698
    26.88 ± 36.154
        Percentage of time below target range
    20.76 ± 36.587
    18.34 ± 35.778
    25.44 ± 40.12
    29.39 ± 42.67
    32.76 ± 43.78
    17.89 ± 36.836
    Notes
    [13] - ITT Population. Only participants with data available at specific time point were analyzed.
    [14] - ITT Population. Only participants with data available at specific time point were analyzed.
    [15] - ITT Population. Only participants with data available at specific time point were analyzed.
    [16] - ITT Population. Only participants with data available at specific time point were analyzed.
    [17] - ITT Population. Only participants with data available at specific time point were analyzed.
    [18] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with Hgb in the target range at Week 24

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    End point title
    Number of participants with Hgb in the target range at Week 24
    End point description
    The number of participants with Hgb in the target range of 10.0 to 11.5 g/dL at Week 24 was recorded for each arm.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    24 [19]
    18 [20]
    27 [21]
    26 [22]
    24 [23]
    11 [24]
    Units: Participants
    14
    13
    16
    10
    15
    8
    Notes
    [19] - ITT Population. Only participants with data available at specific time point were analyzed.
    [20] - ITT Population. Only participants with data available at specific time point were analyzed.
    [21] - ITT Population. Only participants with data available at specific time point were analyzed.
    [22] - ITT Population. Only participants with data available at specific time point were analyzed.
    [23] - ITT Population. Only participants with data available at specific time point were analyzed.
    [24] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants reaching pre-defined Hgb stopping criteria

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    End point title
    Number of participants reaching pre-defined Hgb stopping criteria
    End point description
    The number of participants who reached the Hgb stopping criteria of Hgb concentration <7.5 g/dL were presented.
    End point type
    Secondary
    End point timeframe
    Up to 24 weeks
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    39 [25]
    38 [26]
    39 [27]
    38 [28]
    39 [29]
    17 [30]
    Units: Participants
    0
    0
    0
    0
    0
    0
    Notes
    [25] - ITT Population
    [26] - ITT Population
    [27] - ITT Population
    [28] - ITT Population
    [29] - ITT Population
    [30] - ITT Population
    No statistical analyses for this end point

    Secondary: Maximum observed change from Baseline in Erythropoietin (EPO)

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    End point title
    Maximum observed change from Baseline in Erythropoietin (EPO)
    End point description
    Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (pre-dose) for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose), Week 4 (6-12 hours post-dose), Week 4 (7-13, 8-14, 9-15 hours post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 3 hour post-dose), Week 24 (pre-dose), and Week 28 (pre-dose) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-dose values minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    36 [31]
    37 [32]
    37 [33]
    37 [34]
    36 [35]
    16 [36]
    Units: international units(IU)/Liter (L)
        arithmetic mean (standard deviation)
    1946.45 ± 8456.313
    48.86 ± 117.05
    36.63 ± 35.485
    84.53 ± 225.768
    82 ± 99.66
    24.63 ± 235.82
    Notes
    [31] - ITT Population. Only participants with data available at specific time point were analyzed.
    [32] - ITT Population. Only participants with data available at specific time point were analyzed.
    [33] - ITT Population. Only participants with data available at specific time point were analyzed.
    [34] - ITT Population. Only participants with data available at specific time point were analyzed.
    [35] - ITT Population. Only participants with data available at specific time point were analyzed.
    [36] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

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    End point title
    Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)
    End point description
    Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (pre-dose) for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose), Week 4 (6-12 hours post-dose), Week 4 (7-13, 8-14, 9-15 hours post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 3 hour post-dose), Week 24 (pre-dose), and Week 28 (pre-dose) for VEGF measurement. The maximum observed percent change from Baseline in VEGF was recorded for each arm. Baseline value for VEGF is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    36 [37]
    37 [38]
    37 [39]
    37 [40]
    36 [41]
    16 [42]
    Units: Percent change
        geometric mean (confidence interval 95%)
    36.02 (16.45 to 58.87)
    36.92 (19.33 to 57.11)
    41.73 (22.65 to 63.77)
    54.91 (37.38 to 74.69)
    50.65 (31.88 to 72.1)
    50.97 (21.49 to 87.6)
    Notes
    [37] - ITT Population. Only participants with data available at specific time point were analyzed.
    [38] - ITT Population. Only participants with data available at specific time point were analyzed.
    [39] - ITT Population. Only participants with data available at specific time point were analyzed.
    [40] - ITT Population. Only participants with data available at specific time point were analyzed.
    [41] - ITT Population. Only participants with data available at specific time point were analyzed.
    [42] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Population plasma Pharmacokinetic (PK) parameters of GSK1278863 and metabolites

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    End point title
    Population plasma Pharmacokinetic (PK) parameters of GSK1278863 and metabolites [43]
    End point description
    Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2499166, GSK2531403, GSK2531400, GSK2531399, and GSK2531398) concentrations measurement on Day (D) 1 (pre-dose [PrD), at Week (W) 4 (6-12, 7-13, 8-14, and 9-15 hour [hr] post-dose [PoD), and at W20 (PrD, 1, 2, and 3 hour PoD). Pharmacokinetic population: All participants from whom a PK sample has been obtained and analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1, Week 4, and Week 20
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There is no statistical information to present.
    End point values
    GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    39 [44]
    40 [45]
    39 [46]
    40 [47]
    19 [48]
    Units: nanograms (ng)/milliliter (mL)
    arithmetic mean (standard deviation)
        GSK1278863, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK1278863, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    6.3 ± 10.04
    9.3 ± 19.06
    7.7 ± 18.46
    25.4 ± 53.37
    9 ± 18.8
        GSK1278863, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    10.6 ± 25.15
    16.3 ± 57.24
    8.7 ± 19.85
    19.9 ± 42.65
    8 ± 16.92
        GSK1278863, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    7.5 ± 16.8
    8.1 ± 23.76
    5.6 ± 11.75
    12.7 ± 28.6
    4.6 ± 6.87
        GSK1278863, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    6.8 ± 14.53
    4.6 ± 10.49
    4.4 ± 9.19
    11.3 ± 25.36
    11.2 ± 33.59
        GSK1278863, W20, PrD, n=23, 28, 27, 23, 14
    2.3 ± 6.44
    0.7 ± 2.55
    0.9 ± 2.82
    7.9 ± 30.99
    6.6 ± 20.22
        GSK1278863, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    25.9 ± 35.74
    37.6 ± 53.77
    88.2 ± 153.06
    58.5 ± 85.91
    65.2 ± 127.21
        GSK1278863, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    34.2 ± 31.76
    52.4 ± 53.32
    62.8 ± 85.37
    82.7 ± 117.97
    63.3 ± 102.15
        GSK1278863, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    43.6 ± 58.36
    39.2 ± 44.59
    44.1 ± 70.53
    71.2 ± 110.91
    65.8 ± 100.8
        GSK2391220, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK2391220, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    9.1 ± 6.68
    12.9 ± 8.32
    18.5 ± 13.72
    20.1 ± 12.32
    21.3 ± 17.34
        GSK2391220, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    5.1 ± 4.22
    6.7 ± 5.51
    10.3 ± 8.55
    10.9 ± 6.37
    13.1 ± 12.44
        GSK2391220, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    3.8 ± 3.66
    4.5 ± 4.16
    7.4 ± 6.44
    7.4 ± 4.51
    7.2 ± 6.97
        GSK2391220, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    3.3 ± 3.76
    3.3 ± 3.15
    5.3 ± 4.86
    5.4 ± 3.63
    6.6 ± 5.72
        GSK2391220, W20, PrD, n=23, 28, 27, 23, 14
    5 ± 7.72
    3.2 ± 4.97
    4.1 ± 5.84
    4.6 ± 9.29
    3.5 ± 6.69
        GSK2391220, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    3.9 ± 5.59
    2.7 ± 3.6
    4.3 ± 4.9
    5 ± 8.1
    2.6 ± 3.64
        GSK2391220, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    5.4 ± 5.58
    4.5 ± 4.96
    6.5 ± 6.93
    8.1 ± 10.33
    4.9 ± 4.08
        GSK2391220, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    5.3 ± 4.64
    5 ± 5.26
    7.3 ± 6.69
    8.2 ± 6.52
    6.1 ± 4.92
        GSK2487818, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK2487818, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    3.1 ± 2.82
    4.1 ± 4.47
    5.7 ± 6.31
    7.2 ± 6.57
    5.2 ± 4.66
        GSK2487818, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    1.8 ± 1.75
    2.6 ± 3.81
    3.5 ± 4.55
    4.1 ± 3.73
    3.7 ± 4.61
        GSK2487818, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    1.5 ± 1.67
    1.9 ± 3.21
    2.7 ± 3.58
    2.7 ± 2.44
    1.7 ± 1.68
        GSK2487818, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    1.4 ± 1.88
    1.5 ± 2.46
    1.9 ± 2.85
    1.9 ± 1.92
    1.9 ± 2.21
        GSK2487818, W20, PrD, n=23, 28, 27, 23, 14
    1.2 ± 3.38
    0.5 ± 1.05
    0.7 ± 1.28
    1.3 ± 4.09
    0.7 ± 1.84
        GSK2487818, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    2 ± 3.82
    1.3 ± 1.73
    2.7 ± 3.97
    3.4 ± 5.88
    1 ± 1.34
        GSK2487818, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    3.8 ± 4.58
    3.6 ± 4.36
    5 ± 5.82
    6.3 ± 8.04
    3.7 ± 3.28
        GSK2487818, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    3.9 ± 3.49
    4.3 ± 4.76
    5.7 ± 5.28
    6.5 ± 5.05
    5 ± 4.43
        GSK2506102, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK2506102, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    3.2 ± 1.98
    4.9 ± 2.68
    6.6 ± 4.16
    7.6 ± 4.3
    9 ± 6.19
        GSK2506102, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    1.8 ± 1.31
    2.5 ± 1.71
    3.7 ± 2.6
    4.1 ± 2.15
    5.4 ± 4.1
        GSK2506102, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    1.3 ± 1.07
    1.6 ± 1.16
    2.6 ± 1.94
    2.9 ± 1.68
    2.9 ± 2.24
        GSK2506102, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    1.1 ± 1.16
    1.2 ± 0.88
    1.9 ± 1.52
    2.1 ± 1.23
    2.7 ± 2.04
        GSK2506102, W20, PrD, n=23, 28, 27, 23, 14
    2.3 ± 1.99
    1.9 ± 2.05
    2.3 ± 2.09
    2.6 ± 2.87
    2.2 ± 2.87
        GSK2506102, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    1.4 ± 1.27
    1.1 ± 1.4
    1.4 ± 1.22
    1.8 ± 2.12
    1.4 ± 1.57
        GSK2506102, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    1.5 ± 1.25
    1.2 ± 1.24
    1.8 ± 1.72
    2.2 ± 2.53
    1.6 ± 1.37
        GSK2506102, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    1.4 ± 1.12
    1.3 ± 1.26
    1.9 ± 1.53
    2.1 ± 1.66
    1.7 ± 1.42
        GSK2531398, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK2531398, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    3.4 ± 2.46
    4.9 ± 3.11
    6.9 ± 4.52
    8 ± 4.87
    7.9 ± 5.75
        GSK2531398, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    2 ± 1.72
    2.7 ± 2.41
    4 ± 2.97
    4.5 ± 2.7
    4.9 ± 4.05
        GSK2531398, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    1.5 ± 1.46
    1.8 ± 1.86
    2.9 ± 2.3
    3.1 ± 1.95
    2.5 ± 1.78
        GSK2531398, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    1.4 ± 1.58
    1.4 ± 1.49
    2.1 ± 1.99
    2.2 ± 1.38
    2.3 ± 1.42
        GSK2531398, W20, PrD, n=23, 28, 27, 23, 14
    1.5 ± 2.31
    1.2 ± 2.03
    1.4 ± 1.93
    1.6 ± 3.8
    1.2 ± 2.67
        GSK2531398, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    1.3 ± 1.89
    1 ± 1.34
    1.6 ± 1.81
    2 ± 3.58
    1 ± 1.45
        GSK2531398, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    2.1 ± 2.24
    1.9 ± 2.09
    2.9 ± 3.28
    3.5 ± 4.69
    2.1 ± 1.79
        GSK2531398, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    2.3 ± 2.04
    2.2 ± 2.2
    3.3 ± 2.89
    3.8 ± 3.1
    2.8 ± 2.34
        GSK2531401, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0.02
        GSK2531401, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    9.9 ± 8
    14.7 ± 10.02
    22.2 ± 14.71
    24.5 ± 18.27
    29.1 ± 24.55
        GSK2531401, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    5.4 ± 4.49
    7.1 ± 5.53
    11.8 ± 8.49
    13.1 ± 9.5
    17.3 ± 16.03
        GSK2531401, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    4 ± 3.63
    4.5 ± 3.5
    8.1 ± 5.74
    9 ± 7.05
    10.1 ± 10.61
        GSK2531401, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    3.3 ± 3.36
    3.2 ± 2.35
    5.9 ± 4.66
    6.3 ± 4.9
    8.7 ± 8.72
        GSK2531401, W20, PrD, n=23, 28, 27, 23, 14
    7.7 ± 7.71
    7.3 ± 7.34
    7.9 ± 7.37
    9.3 ± 10.95
    7.2 ± 10.04
        GSK2531401, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    4.2 ± 4.52
    4 ± 6.77
    4.7 ± 4.18
    5.6 ± 7.48
    4.5 ± 5.44
        GSK2531401, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    4.2 ± 4.44
    3.6 ± 4.5
    4.8 ± 4.08
    6.1 ± 8.21
    4.4 ± 4.41
        GSK2531401, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    4.1 ± 4.07
    3.6 ± 4.55
    5 ± 4.64
    5.5 ± 5.38
    4.5 ± 4.28
        GSK2531403, D1, PrD, n=39, 40, 39, 40, 18
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
        GSK2531403, W4, 6-12 hr PoD, n=36, 37, 37, 35, 15
    11.4 ± 7.47
    17 ± 9.89
    23.1 ± 15.22
    25.4 ± 14.25
    28.8 ± 21.46
        GSK2531403, W4, 7-13 hr PoD, n=36, 37, 35, 35, 15
    6.3 ± 4.84
    8.6 ± 6.43
    13.1 ± 9.73
    13.9 ± 7.66
    17.4 ± 14.72
        GSK2531403, W4, 8-14 hr PoD, n=35, 37, 36, 35, 15
    4.7 ± 4.23
    5.7 ± 4.63
    9.3 ± 7.37
    9.6 ± 5.5
    9.9 ± 9.05
        GSK2531403, W4, 9-15 hr PoD, n=35, 36, 36, 35, 15
    4.1 ± 4.6
    4.1 ± 3.41
    6.7 ± 5.5
    6.9 ± 4.25
    8.9 ± 7.79
        GSK2531403, W20, PrD, n=23, 28, 27, 23, 14
    7.8 ± 8.53
    6 ± 8.08
    6.7 ± 6.74
    7.8 ± 11.14
    6.2 ± 8.78
        GSK2531403, W20, 1 hr PoD, n=23, 27, 27, 24, 13
    4.9 ± 5.56
    3.8 ± 4.88
    5 ± 4.71
    6.2 ± 8.65
    4 ± 4.8
        GSK2531403, W20, 2 hr PoD, n=23, 27, 27, 24, 13
    5.7 ± 5.43
    4.7 ± 4.91
    6.8 ± 6.54
    8.5 ± 10.83
    5.5 ± 4.58
        GSK2531403, W20, 3 hr PoD, n=23, 27, 27, 24, 14
    5.5 ± 4.52
    5.1 ± 5.18
    7.4 ± 6.43
    8.4 ± 6.86
    6.5 ± 5.14
    Notes
    [44] - PK Population. Only participants with data available at specific time point were analyzed.
    [45] - PK Population. Only participants with data available at specific time point were analyzed.
    [46] - PK Population. Only participants with data available at specific time point were analyzed.
    [47] - PK Population. Only participants with data available at specific time point were analyzed.
    [48] - PK Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Percent change from Baseline in hepcidin at Week 24

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    End point title
    Percent change from Baseline in hepcidin at Week 24
    End point description
    Hepcidin is a regulator of iron metabolism. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    32 [49]
    20 [50]
    29 [51]
    26 [52]
    25 [53]
    14 [54]
    Units: Percent change
        geometric mean (confidence interval 95%)
    3.63 (-20.39 to 34.89)
    -17.39 (-42.36 to 18.4)
    -11.85 (-26.47 to 5.67)
    -30.28 (-48.08 to -6.37)
    -6.91 (-28.69 to 21.52)
    -42.13 (-62.82 to -9.95)
    Notes
    [49] - ITT Population. Only participants with data available at specific time point were analyzed.
    [50] - ITT Population. Only participants with data available at specific time point were analyzed.
    [51] - ITT Population. Only participants with data available at specific time point were analyzed.
    [52] - ITT Population. Only participants with data available at specific time point were analyzed.
    [53] - ITT Population. Only participants with data available at specific time point were analyzed.
    [54] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in ferritin at Week 24

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    End point title
    Change from Baseline in ferritin at Week 24
    End point description
    Baseline value for ferritin is the pre-dose value on Day 1. Change from Baseline in ferritin was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    33 [55]
    20 [56]
    29 [57]
    27 [58]
    25 [59]
    14 [60]
    Units: Micrograms/Liter
        arithmetic mean (standard deviation)
    56.8 ± 214.27
    -29.4 ± 357.1
    -50.4 ± 408.99
    -95.6 ± 304.61
    -20.2 ± 227.34
    -125.2 ± 354.64
    Notes
    [55] - ITT Population. Only participants with data available at specific time point were analyzed.
    [56] - ITT Population. Only participants with data available at specific time point were analyzed.
    [57] - ITT Population. Only participants with data available at specific time point were analyzed.
    [58] - ITT Population. Only participants with data available at specific time point were analyzed.
    [59] - ITT Population. Only participants with data available at specific time point were analyzed.
    [60] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in transferrin at Week 24

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    End point title
    Change from Baseline in transferrin at Week 24
    End point description
    Baseline value for transferrin is the pre-dose value on Day 1. Change from Baseline in transferrin was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    33 [61]
    20 [62]
    29 [63]
    27 [64]
    25 [65]
    14 [66]
    Units: grams (g)/Liter (L)
        arithmetic mean (standard deviation)
    -0.133 ± 0.2903
    0.238 ± 0.3709
    0.198 ± 0.2891
    0.226 ± 0.2706
    0.249 ± 0.3213
    0.393 ± 0.3165
    Notes
    [61] - ITT Population. Only participants with data available at specific time point were analyzed.
    [62] - ITT Population. Only participants with data available at specific time point were analyzed.
    [63] - ITT Population. Only participants with data available at specific time point were analyzed.
    [64] - ITT Population. Only participants with data available at specific time point were analyzed.
    [65] - ITT Population. Only participants with data available at specific time point were analyzed.
    [66] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Percent change from Baseline in transferrin saturation at Week 24

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    End point title
    Percent change from Baseline in transferrin saturation at Week 24
    End point description
    Transferrin saturation is measured as a percentage, it is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline =: 100*(exp[Mean change log scale]-1).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    32 [67]
    20 [68]
    29 [69]
    27 [70]
    25 [71]
    14 [72]
    Units: Percent change
        geometric mean (confidence interval 95%)
    -9 (-27.3 to 13.9)
    -3.7 (-22.9 to 20.4)
    -12.1 (-23.4 to 0.9)
    -8.3 (-22.9 to 9)
    8.2 (-7.7 to 26.8)
    -2.5 (-16 to 13.2)
    Notes
    [67] - ITT Population. Only participants with data available at specific time point were analyzed.
    [68] - ITT Population. Only participants with data available at specific time point were analyzed.
    [69] - ITT Population. Only participants with data available at specific time point were analyzed.
    [70] - ITT Population. Only participants with data available at specific time point were analyzed.
    [71] - ITT Population. Only participants with data available at specific time point were analyzed.
    [72] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in total iron at Week 24

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    End point title
    Change from Baseline in total iron at Week 24
    End point description
    Baseline value for total iron is the pre-dose value on Day 1. Change from Baseline in total iron was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    33 [73]
    20 [74]
    29 [75]
    27 [76]
    25 [77]
    14 [78]
    Units: Micromoles/Liter
        arithmetic mean (standard deviation)
    -0.8 ± 7.64
    0.9 ± 9.75
    0.3 ± 5.2
    0.2 ± 6.51
    2 ± 3.96
    1.6 ± 3.18
    Notes
    [73] - ITT Population. Only participants with data available at specific time point were analyzed.
    [74] - ITT Population. Only participants with data available at specific time point were analyzed.
    [75] - ITT Population. Only participants with data available at specific time point were analyzed.
    [76] - ITT Population. Only participants with data available at specific time point were analyzed.
    [77] - ITT Population. Only participants with data available at specific time point were analyzed.
    [78] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in total iron binding capacity at Week 24

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    End point title
    Change from Baseline in total iron binding capacity at Week 24
    End point description
    Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline value for total iron binding capacity is the pre-dose value on Day 1. Change from Baseline in total iron binding capacity was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    32 [79]
    20 [80]
    29 [81]
    27 [82]
    25 [83]
    14 [84]
    Units: Micromoles/Liter
        arithmetic mean (standard deviation)
    -2 ± 4.48
    6 ± 7.93
    4.2 ± 6.79
    6.6 ± 5.75
    4.8 ± 6.25
    6.2 ± 6.44
    Notes
    [79] - ITT Population. Only participants with data available at specific time point were analyzed.
    [80] - ITT Population. Only participants with data available at specific time point were analyzed.
    [81] - ITT Population. Only participants with data available at specific time point were analyzed.
    [82] - ITT Population. Only participants with data available at specific time point were analyzed.
    [83] - ITT Population. Only participants with data available at specific time point were analyzed.
    [84] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in reticulocyte hemoglobin at Week 24

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    End point title
    Change from Baseline in reticulocyte hemoglobin at Week 24
    End point description
    Baseline value for reticulocyte hemoglobin is the pre-dose value on Day 1. Change from Baseline in reticulocyte hemoglobin was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    30 [85]
    20 [86]
    29 [87]
    26 [88]
    24 [89]
    12 [90]
    Units: Picogram
        arithmetic mean (standard deviation)
    -0.19 ± 1.61
    -0.28 ± 1.948
    -0.62 ± 2.046
    -0.42 ± 1.458
    -0.51 ± 1.377
    -0.63 ± 1.119
    Notes
    [85] - ITT Population. Only participants with data available at specific time point were analyzed.
    [86] - ITT Population. Only participants with data available at specific time point were analyzed.
    [87] - ITT Population. Only participants with data available at specific time point were analyzed.
    [88] - ITT Population. Only participants with data available at specific time point were analyzed.
    [89] - ITT Population. Only participants with data available at specific time point were analyzed.
    [90] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematocrit at Week 24

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    End point title
    Change from Baseline in hematocrit at Week 24
    End point description
    Hematocrit is the ratio of the volume of red blood cells to the total volume of blood. Baseline value for hematocrit is the pre-dose value on Day 1. Change from Baseline in hematocrit was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    30 [91]
    20 [92]
    29 [93]
    28 [94]
    26 [95]
    13 [96]
    Units: Fraction of 1
        arithmetic mean (standard deviation)
    -0.0028 ± 0.04358
    -0.0096 ± 0.04073
    0.002 ± 0.03579
    0.0043 ± 0.04254
    -0.0021 ± 0.02678
    0.0108 ± 0.03557
    Notes
    [91] - ITT Population. Only participants with data available at specific time point were analyzed.
    [92] - ITT Population. Only participants with data available at specific time point were analyzed.
    [93] - ITT Population. Only participants with data available at specific time point were analyzed.
    [94] - ITT Population. Only participants with data available at specific time point were analyzed.
    [95] - ITT Population. Only participants with data available at specific time point were analyzed.
    [96] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in red blood cells at Week 24

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    End point title
    Change from Baseline in red blood cells at Week 24
    End point description
    Baseline value for red blood cells is the pre-dose value on Day 1. Change from Baseline in red blood cells was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    30 [97]
    20 [98]
    29 [99]
    28 [100]
    26 [101]
    13 [102]
    Units: 10^12 cells/Liter
        arithmetic mean (standard deviation)
    0.01 ± 0.46
    -0.06 ± 0.396
    0.04 ± 0.374
    0.07 ± 0.399
    0.03 ± 0.3
    0.17 ± 0.366
    Notes
    [97] - ITT Population. Only participants with data available at specific time point were analyzed.
    [98] - ITT Population. Only participants with data available at specific time point were analyzed.
    [99] - ITT Population. Only participants with data available at specific time point were analyzed.
    [100] - ITT Population. Only participants with data available at specific time point were analyzed.
    [101] - ITT Population. Only participants with data available at specific time point were analyzed.
    [102] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in reticulocyte count at Week 24

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    End point title
    Change from Baseline in reticulocyte count at Week 24
    End point description
    A reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline value for reticulocyte count is the pre-dose value on Day 1. Change from Baseline in reticulocyte count was calculated as the Week 24 value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    End point values
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Number of subjects analysed
    31 [103]
    20 [104]
    30 [105]
    28 [106]
    26 [107]
    12 [108]
    Units: Percentage of reticulocytes in blood
        arithmetic mean (standard deviation)
    0.4 ± 0.663
    0.16 ± 1.162
    0.18 ± 0.571
    0.03 ± 0.684
    -0.15 ± 0.838
    0.1 ± 0.527
    Notes
    [103] - ITT Population. Only participants with data available at specific time point were analyzed.
    [104] - ITT Population. Only participants with data available at specific time point were analyzed.
    [105] - ITT Population. Only participants with data available at specific time point were analyzed.
    [106] - ITT Population. Only participants with data available at specific time point were analyzed.
    [107] - ITT Population. Only participants with data available at specific time point were analyzed.
    [108] - ITT Population. Only participants with data available at specific time point were analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to 28 weeks).
    Adverse event reporting additional description
    Post baseline SAEs and non-serious AEs were reported for the Safety population which consisted of all participants who received at least one dose of study drug.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Control
    Reporting group description
    Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 4 mg
    Reporting group description
    Participants received GSK1278863 4 milligrams (mg) once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 6 mg
    Reporting group description
    Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 8 mg
    Reporting group description
    Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 10 mg
    Reporting group description
    Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Reporting group title
    GSK1278863 12 mg
    Reporting group description
    Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

    Serious adverse events
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 39 (28.21%)
    10 / 39 (25.64%)
    8 / 40 (20.00%)
    8 / 39 (20.51%)
    11 / 40 (27.50%)
    1 / 19 (5.26%)
         number of deaths (all causes)
    0
    2
    1
    0
    2
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Steal syndrome
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superior vena cava stenosis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural mesothelioma
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Amyloidosis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Oligomenorrhoea
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine inflammation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dialysis related complication
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft thrombosis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt stenosis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Troponin I increased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Fluid overload
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Control GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 10 mg GSK1278863 12 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 39 (43.59%)
    28 / 39 (71.79%)
    17 / 40 (42.50%)
    25 / 39 (64.10%)
    21 / 40 (52.50%)
    6 / 19 (31.58%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    Hypertension
         subjects affected / exposed
    1 / 39 (2.56%)
    6 / 39 (15.38%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    4 / 40 (10.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    6
    0
    2
    6
    0
    Hypotension
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    2
    2
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    3 / 40 (7.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    3
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    1
    1
    0
    1
    0
    1
    Face oedema
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    2
    3
    1
    0
    Pain
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    Dialysis related complication
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    1
    3
    0
    Procedural site reaction
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    3 / 40 (7.50%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    3
    2
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    1
    0
    1
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    3
    3
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    1
    2
    2
    0
    Dyspnoea
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    Headache
         subjects affected / exposed
    2 / 39 (5.13%)
    4 / 39 (10.26%)
    1 / 40 (2.50%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    6
    1
    2
    8
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    2
    1
    1
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Retinal artery embolism
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 39 (0.00%)
    4 / 39 (10.26%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    6
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    2 / 39 (5.13%)
    5 / 39 (12.82%)
    2 / 40 (5.00%)
    7 / 39 (17.95%)
    2 / 40 (5.00%)
    1 / 19 (5.26%)
         occurrences all number
    2
    7
    2
    10
    2
    1
    Dyspepsia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 39 (0.00%)
    6 / 39 (15.38%)
    3 / 40 (7.50%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    1 / 19 (5.26%)
         occurrences all number
    0
    7
    4
    2
    5
    1
    Toothache
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    0
    Vomiting
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 39 (7.69%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    3
    2
    1
    2
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 39 (7.69%)
    0 / 40 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    3
    0
    1
    2
    0
    Pruritus generalised
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    4
    2
    2
    0
    Back pain
         subjects affected / exposed
    4 / 39 (10.26%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    4 / 40 (10.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    0
    2
    1
    6
    0
    Muscle spasms
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    10
    1
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    3
    1
    1
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    Pain in extremity
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    3 / 39 (7.69%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    2
    1
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
    4 / 39 (10.26%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    1
    4
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    3
    1
    1
    0
    Device related infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    5 / 39 (12.82%)
    5 / 39 (12.82%)
    6 / 40 (15.00%)
    3 / 39 (7.69%)
    4 / 40 (10.00%)
    1 / 19 (5.26%)
         occurrences all number
    8
    10
    9
    4
    5
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    0
    3
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Sep 2013
    To revise the GSK1278863 Dose Adjustment Algorithm as requested by the United States Food and Drug Administration (FDA) and to clarify and correct language throughout.
    04 Oct 2013
    This amendment was for Japan only. To revise the Time and Events Table to add a HemoCue at Week 2 as requested by the Pharmaceuticals and Medical Device Agency (Japan) (PMDA).
    06 Jan 2014
    This amendment is for France only. To revise the lower threshold for the hemoglobin inclusion criterion to 10.0 g/dL for sites in France as requested by the National Agency for the Safety of Medicine and Health Products in France.
    23 Jan 2014
    To revise lipid and biomarker assessments, to add reconfirmation of the corrected QT (QTc) inclusion criterion at Day 1, to remove requirement for male contraception, to allow an interim cut of data to be taken to facilitate dose modelling, and to make minor clarifications throughout.

    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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