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    Clinical Trial Results:
    A phase I/II, open-label, 2 arm study to investigate the safety, clinical activity, pharmacokinetics and pharmacodynamics of GSK2879552 administered alone or in combination with azacitidine, in adult subjects with IPSS-R high and very high risk myelodysplastic syndromes (MDS) previously treated with hypomethylating agents (HMA)

    Summary
    EudraCT number
    		 2016-002294-35
    Trial protocol
    		 ES  
    Global end of trial date
    18 Dec 2018

    Results information
    Results version number
    		 v1
    This version publication date
    01 Mar 2019
    First version publication date
    01 Mar 2019
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    205744
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Oct 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Dec 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Part I. To determine the recommended phase 2 dose (RP2D) of GSK2879552 administered alone and in combination with azacitidine in adult subjects with HR MDS previously treated with HMA. Part II. To evaluate clinical activity after treatment with GSK2879552, alone or in combination with azacitidine, in adult subjects with HR MDS previously treated with HMA
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    5
    EEA total number of subjects
    2
    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)
    0
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in adult participants with myelodysplastic syndromes (MDS). The study was conducted in 3 centers among 2 countries.

    Pre-assignment
    Screening details
    		 Total 5 participants were included into Part 1 and received GSK2879552. The study was terminated during Part 1 and hence Part 2 was not conducted as the risk benefit in earlier studies do not favor continuation of this study.

    Period 1
    Period 1 title
    Part 1: Dose Confirmation (Upto 2 years) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Part 1: GSK2879552
    Arm description
    		 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2879552
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2879552 was administered orally once a day as continuous daily dosing in each cycle (of 28 days) until disease progression.

    Number of subjects in period 1
    		Part 1: GSK2879552
    Started
    5
    Completed
    0
    Not completed
    5
         Adverse event, serious fatal
    2
         Study terminated by sponsor
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1: GSK2879552
    Reporting group description
    		 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.

    Reporting group values
    		 Part 1: GSK2879552 Total
    Number of subjects
    		 5 5
    Age categorical
    Part 1 data is presented as study was terminated during Part 1 and hence Part 2 was not initiated.
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 5 5
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age Continuous
    99 indicates data was not available as study was terminated during Part 1 and hence Part 2 was not initiated. Only Part 1 data is presented.
    Units: years
        arithmetic mean (standard deviation)
    		 77.2 ± 5.07 -
    Sex: Female, Male
    Part 1 data is presented as study was terminated during Part 1 and hence Part 2 was not initiated.
    Units: Subjects
        Female
    		 3 3
        Male
    		 2 2
    Race, Customized
    Part 1 data is presented as study was terminated during Part 1 and hence Part 2 was not initiated.
    Units: Subjects
        White - White/Caucasian/European Heritage
    		 5 5

    End points

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    End points reporting groups
    Reporting group title
    Part 1: GSK2879552
    Reporting group description
    		 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.

    Subject analysis set title
    Part 2: GSK2879552
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.

    Subject analysis set title
    Part 2: GSK2879552+Azacitidine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).

    Subject analysis set title
    Part 1: GSK2879552+Azacitidine
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study. Participants were also received azacitidine on days 1 to 7 of 28 days cycle via IV or SC administration.

    Primary: Part 1: Number of participants with any non-serious adverse event (non-SAE), serious AE (SAE), dose limiting toxicities (DLT), dose reductions or delays and withdrawals due to toxicities

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    End point title
    		 Part 1: Number of participants with any non-serious adverse event (non-SAE), serious AE (SAE), dose limiting toxicities (DLT), dose reductions or delays and withdrawals due to toxicities [1]
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.
    End point type
    Primary
    End point timeframe
    Up to 2 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [2]
    Units: Participants
        Non-SAEs
    5
        SAEs
    1
        DLT
    0
        Dose reductions or delays
    0
        Withdrawals due to toxicities
    0
    Notes
    [2] - All Treated Subjects Population: All participants who received at least one dose of study treatment.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points [3]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [4]
    Units: 10^9 cells per liter
    arithmetic mean (standard deviation)
        Platelets, Cycle 1, Day 1, n=5
    -13.826 ± 16.2868
        Platelets, Cycle 1, Day 7, n=5
    -17.984 ± 15.7398
        Platelets, Cycle 1, Day 15, n=4
    -19.250 ± 8.2614
        Platelets, Cycle 1, Day 22, n=3
    -20.667 ± 14.3643
        Platelets, Cycle 2, Day 1, n=3
    -16.000 ± 18.7350
        Platelets, Cycle 2, Day 7, n=3
    -21.333 ± 28.3784
        Platelets, Cycle 2, Day 15, n=3
    -24.333 ± 15.3731
        Platelets, Cycle 2, Day 22, n=3
    -24.667 ± 19.3477
        Platelets, Cycle 3, Day 1, n=3
    -17.000 ± 14.1067
        Platelets, Cycle 4, Day 1, n=2
    -13.000 ± 4.2426
        Platelets, Cycle 5, Day 1, n=1
    -11.000 ± 99999
        Neutrophils, Cycle 1, Day 1, n=5
    -0.019 ± 0.1298
        Neutrophils, Cycle 1, Day 7, n=5
    0.035 ± 0.2058
        Neutrophils, Cycle 1, Day 15, n=4
    0.060 ± 0.3282
        Neutrophils, Cycle 1, Day 22, n=3
    0.100 ± 0.1732
        Neutrophils, Cycle 2, Day 1, n=3
    0.200 ± 0.3000
        Neutrophils, Cycle 2, Day 7, n=3
    0.300 ± 0.3606
        Neutrophils, Cycle 2, Day 15, n=3
    0.333 ± 0.3055
        Neutrophils, Cycle 2, Day 22, n=3
    0.267 ± 0.4041
        Neutrophils, Cycle 3, Day 1, n=3
    0.267 ± 0.3215
        Neutrophils, Cycle 4, Day 1, n=2
    0.650 ± 0.2121
        Neutrophils, Cycle 5, Day 1, n=1
    0.800 ± 99999
        Monocytes, Cycle 1, Day 1, n=5
    0.017 ± 0.1359
        Monocytes, Cycle 1, Day 7, n=5
    0.059 ± 0.0853
        Monocytes, Cycle 1, Day 15, n=4
    0.100 ± 0.0816
        Monocytes, Cycle 1, Day 22, n=3
    12.633 ± 21.7086
        Monocytes, Cycle 2, Day 1, n=3
    0.267 ± 0.2517
        Monocytes, Cycle 2, Day 7, n=3
    0.400 ± 0.6083
        Monocytes, Cycle 2, Day 15, n=3
    0.633 ± 0.7095
        Monocytes, Cycle 2, Day 22, n=3
    0.267 ± 0.2517
        Monocytes, Cycle 3, Day 1, n=3
    0.300 ± 0.1732
        Monocytes, Cycle 4, Day 1, n=2
    1.000 ± 0.1414
        Monocytes, Cycle 5, Day 1, n=1
    1.600 ± 99999
        Lymphocytes, Cycle 1, Day 1, n=5
    -0.036 ± 0.0924
        Lymphocytes, Cycle 1, Day 7, n=5
    0.008 ± 0.1761
        Lymphocytes, Cycle 1, Day 15, n=4
    -0.073 ± 0.0486
        Lymphocytes, Cycle 1, Day 22, n=3
    -0.033 ± 0.0577
        Lymphocytes, Cycle 2, Day 1, n=3
    -0.067 ± 0.1528
        Lymphocytes, Cycle 2, Day 7, n=3
    -0.033 ± 0.3055
        Lymphocytes, Cycle 2, Day 15, n=3
    0.033 ± 0.3786
        Lymphocytes, Cycle 2, Day 22, n=3
    0.033 ± 0.2082
        Lymphocytes, Cycle 3, Day 1, n=3
    -0.067 ± 0.3055
        Lymphocytes, Cycle 4, Day 1, n=2
    0.200 ± 0.0000
        Lymphocytes, Cycle 5, Day 1, n=1
    0.400 ± 99999
        Leucocytes, Cycle 1, Day 1, n=5
    -0.054 ± 0.1720
        Leucocytes, Cycle 1, Day 7, n=5
    0.154 ± 0.3257
        Leucocytes, Cycle 1, Day 15, n=4
    0.032 ± 0.3208
        Leucocytes, Cycle 1, Day 22, n=3
    0.267 ± 0.5132
        Leucocytes, Cycle 2, Day 1, n=3
    0.433 ± 0.7234
        Leucocytes, Cycle 2, Day 7, n=3
    0.700 ± 1.3748
        Leucocytes, Cycle 2, Day 15, n=3
    1.033 ± 1.4572
        Leucocytes, Cycle 2, Day 22, n=3
    0.633 ± 0.9292
        Leucocytes, Cycle 3, Day 1, n=3
    0.633 ± 0.9074
        Leucocytes, Cycle 4, Day 1, n=2
    2.000 ± 0.0000
        Leucocytes, Cycle 5, Day 1, n=1
    2.900 ± 99999
        Eosinophils, Cycle 1, Day 1, n=5
    -0.000 ± 0.0009
        Eosinophils, Cycle 1, Day 7, n=5
    0.016 ± 0.0252
        Eosinophils, Cycle 1, Day 15, n=4
    -0.008 ± 0.0150
        Eosinophils, Cycle 1, Day 22, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 2, Day 1, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 2, Day 7, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 2, Day 15, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 2, Day 22, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 3, Day 1, n=3
    0.000 ± 0.0000
        Eosinophils, Cycle 4, Day 1, n=2
    0.050 ± 0.0707
        Eosinophils, Cycle 5, Day 1, n=1
    0.100 ± 99999
        Basophils, Cycle 1, Day 1, n=5
    0.004 ± 0.0080
        Basophils, Cycle 1, Day 7, n=5
    0.017 ± 0.0323
        Basophils, Cycle 1, Day 15, n=4
    0.003 ± 0.0050
        Basophils, Cycle 1, Day 22, n=3
    0.000 ± 0.0000
        Basophils, Cycle 2, Day 1, n=3
    0.000 ± 0.0000
        Basophils, Cycle 2, Day 7, n=3
    0.000 ± 0.0000
        Basophils, Cycle 2, Day 15, n=3
    0.000 ± 0.0000
        Basophils, Cycle 2, Day 22, n=3
    0.000 ± 0.0000
        Basophils, Cycle 3, Day 1, n=3
    0.000 ± 0.0000
        Basophils, Cycle 4, Day 1, n=2
    0.050 ± 0.0707
        Basophils, Cycle 5, Day 1, n=1
    0.000 ± 99999
    Notes
    [4] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Mean corpuscular volume (MCV) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Mean corpuscular volume (MCV) at indicated time-points [5]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available due to standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [6]
    Units: Femtoliter
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, n=5
    -0.280 ± 1.5450
        Cycle 1, Day 7, n=4
    -0.400 ± 1.9442
        Cycle 1, Day 15, n=3
    -0.267 ± 3.6679
        Cycle 1, Day 22, n=3
    0.400 ± 5.1730
        Cycle 2, Day 1, n=3
    1.667 ± 6.0003
        Cycle 2, Day 7, n=3
    3.500 ± 6.3592
        Cycle 2, Day 15, n=3
    2.933 ± 7.3528
        Cycle 2, Day 22, n=3
    2.900 ± 9.0000
        Cycle 3, Day 1, n=3
    2.700 ± 9.7370
        Cycle 4, Day 1, n=2
    6.750 ± 6.2933
        Cycle 5, Day 1, n=1
    8.500 ± 99999
    Notes
    [6] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Mean corpuscular hemoglobin (MCH) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Mean corpuscular hemoglobin (MCH) at indicated time-points [7]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [8]
    Units: Picogram
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, n=5
    -1.100 ± 2.8679
        Cycle 1, Day 7, n=4
    -1.350 ± 3.3000
        Cycle 1, Day 15, n=3
    -0.100 ± 1.1358
        Cycle 1, Day 22, n=3
    0.067 ± 1.5308
        Cycle 2, Day 1, n=3
    0.833 ± 1.5177
        Cycle 2, Day 7, n=3
    1.067 ± 1.3796
        Cycle 2, Day 15, n=3
    0.900 ± 1.9672
        Cycle 2, Day 22, n=3
    0.767 ± 2.3798
        Cycle 3, Day 1, n=3
    0.933 ± 3.0665
        Cycle 4, Day 1, n=2
    1.950 ± 1.3435
        Cycle 5, Day 1, n=1
    2.200 ± 99999
    Notes
    [8] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Mean corpuscular hemoglobin concentration (MCHC) and Hemoglobin (Hb) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Mean corpuscular hemoglobin concentration (MCHC) and Hemoglobin (Hb) at indicated time-points [9]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [10]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        MCHC, Cycle 1, Day 1, n=5
    -10.400 ± 29.3053
        MCHC, Cycle 1, Day 7, n=4
    -12.500 ± 35.8190
        MCHC, Cycle 1, Day 15, n=3
    0.333 ± 2.0817
        MCHC, Cycle 1, Day 22, n=3
    0.000 ± 8.1854
        MCHC, Cycle 2, Day 1, n=3
    3.667 ± 6.6583
        MCHC, Cycle 2, Day 7, n=3
    -1.000 ± 12.4900
        MCHC, Cycle 2, Day 15, n=3
    0.000 ± 7.8102
        MCHC, Cycle 2, Day 22, n=3
    -2.000 ± 8.6603
        MCHC, Cycle 3, Day 1, n=3
    1.333 ± 6.0277
        MCHC, Cycle 4, Day 1, n=2
    -3.500 ± 9.1924
        MCHC, Cycle 5, Day 1, n=1
    -8.000 ± 99999
        Hb, Cycle 1, Day 1, n=5
    -2.000 ± 7.0000
        Hb, Cycle 1, Day 7, n=5
    -4.200 ± 11.3666
        Hb, Cycle 1, Day 15, n=4
    -5.000 ± 11.8040
        Hb, Cycle 1, Day 22, n=3
    2.000 ± 2.6458
        Hb, Cycle 2, Day 1, n=3
    -3.667 ± 12.5831
        Hb, Cycle 2, Day 7, n=3
    2.000 ± 13.4536
        Hb, Cycle 2, Day 15, n=3
    0.333 ± 16.5630
        Hb, Cycle 2, Day 22, n=3
    -3.000 ± 5.2915
        Hb, Cycle 3, Day 1, n=3
    -2.333 ± 7.2342
        Hb, Cycle 4, Day 1, n=2
    7.000 ± 4.2426
        Hb, Cycle 5, Day 1, n=1
    6.000 ± 99999
    Notes
    [10] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Hematocrit at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Hematocrit at indicated time-points [11]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [12]
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, n=5
    0.001 ± 0.0334
        Cycle 1, Day 7, n=5
    -0.008 ± 0.0525
        Cycle 1, Day 15, n=4
    -0.018 ± 0.0401
        Cycle 1, Day 22, n=3
    0.007 ± 0.0100
        Cycle 2, Day 1, n=3
    -0.014 ± 0.0396
        Cycle 2, Day 7, n=3
    0.007 ± 0.0448
        Cycle 2, Day 15, n=3
    0.002 ± 0.0520
        Cycle 2, Day 22, n=3
    -0.009 ± 0.0206
        Cycle 3, Day 1, n=3
    -0.008 ± 0.0244
        Cycle 4, Day 1, n=2
    0.024 ± 0.0191
        Cycle 5, Day 1, n=1
    0.023 ± 99999
    Notes
    [12] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in erythrocytes at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in erythrocytes at indicated time-points [13]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [14]
    Units: 10^12 cells per Liter
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, n=5
    0.030 ± 0.3489
        Cycle 1, Day 7, n=5
    -0.058 ± 0.5363
        Cycle 1, Day 15, n=4
    -0.138 ± 0.3216
        Cycle 1, Day 22, n=3
    0.077 ± 0.0643
        Cycle 2, Day 1, n=3
    -0.193 ± 0.2558
        Cycle 2, Day 7, n=3
    -0.017 ± 0.2996
        Cycle 2, Day 15, n=3
    -0.063 ± 0.3402
        Cycle 2, Day 22, n=3
    -0.173 ± 0.1901
        Cycle 3, Day 1, n=3
    -0.160 ± 0.2425
        Cycle 4, Day 1, n=2
    0.060 ± 0.0141
        Cycle 5, Day 1, n=1
    0.000 ± 99999
    Notes
    [14] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in percent reticulocytes at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in percent reticulocytes at indicated time-points [15]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    1 [16]
    Units: Percentage of reticulocytes
    arithmetic mean (standard deviation)
        Cycle 1, Day 7
    0.000 ± 99999
        Cycle 1, Day 22
    -0.100 ± 99999
        Cycle 2, Day 1
    -0.100 ± 99999
        Cycle 2, Day 7
    0.000 ± 99999
        Cycle 2, Day 15
    0.000 ± 99999
        Cycle 3, Day 1
    -0.100 ± 99999
        Cycle 4, Day 1
    -0.100 ± 99999
    Notes
    [16] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in blast/leukocytes at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in blast/leukocytes at indicated time-points [17]
    End point description
    Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants.
    End point type
    Primary
    End point timeframe
    Baseline and Day 1 of Cycle 1 (Cycle of 28 days)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    1 [18]
    Units: Ratio of blasts to leukocytes
        arithmetic mean (standard deviation)
    0.000 ± 99999
    Notes
    [18] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Alanine Aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Alanine Aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at indicated time-points [19]
    End point description
    Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [20]
    Units: International unit per liter (IU/L)
    arithmetic mean (standard deviation)
        ALT, Cycle 1, Day 1, n=4
    -10.000 ± 18.1292
        ALT Cycle 1, Day 7, n=5
    -3.000 ± 13.5093
        ALT Cycle 1, Day 15, n=4
    -6.250 ± 15.5000
        ALT Cycle 1, Day 22, n=3
    1.333 ± 15.1767
        ALT Cycle 2, Day 1, n=3
    3.000 ± 39.5095
        ALT Cycle 3, Day 1, n=3
    3.333 ± 42.0040
        ALT Cycle 4, Day 1, n=2
    33.000 ± 1.4142
        ALT Cycle 5, Day 1, n=1
    3.000 ± 99999
        ALP, Cycle 1, Day 1, n=4
    -4.750 ± 3.2016
        ALP Cycle 1, Day 7, n=5
    -6.800 ± 10.3053
        ALP Cycle 1, Day 15, n=4
    -4.250 ± 22.3961
        ALP Cycle 1, Day 22, n=3
    8.000 ± 21.6564
        ALP Cycle 2, Day 1, n=3
    23.667 ± 62.5007
        ALP Cycle 3, Day 1, n=3
    15.667 ± 31.3422
        ALP Cycle 4, Day 1, n=2
    18.500 ± 60.1041
        ALP Cycle 5, Day 1, n=1
    21.000 ± 99999
        AST, Cycle 1, Day 1, n=4
    -6.750 ± 14.8633
        AST Cycle 1, Day 7, n=5
    -3.200 ± 9.3381
        AST Cycle 1, Day 15, n=4
    -3.250 ± 17.6517
        AST Cycle 1, Day 22, n=3
    3.000 ± 27.5136
        AST Cycle 2, Day 1, n=3
    -0.333 ± 30.9246
        AST Cycle 3, Day 1, n=3
    -3.667 ± 38.5530
        AST Cycle 4, Day 1, n=2
    22.000 ± 21.2132
        AST Cycle 5, Day 1, n=1
    16.000 ± 99999
        LDH, Cycle 1, Day 1, n=4
    4.000 ± 90.9395
        LDH Cycle 1, Day 7, n=5
    -31.200 ± 47.2515
        LDH Cycle 1, Day 15, n=3
    4.000 ± 22.6053
        LDH Cycle 1, Day 22, n=3
    -12.000 ± 47.5710
        LDH Cycle 2, Day 1, n=3
    -18.333 ± 55.4106
        LDH Cycle 3, Day 1, n=3
    -20.667 ± 62.7402
        LDH Cycle 4, Day 1, n=2
    12.500 ± 3.5355
        LDH Cycle 5, Day 1, n=1
    11.000 ± 99999
        GGT, Cycle 1, Day 1, n=1
    -17.000 ± 99999
        GGT Cycle 1, Day 7, n=2
    -7.500 ± 9.1924
        GGT Cycle 1, Day 22, n=1
    0.000 ± 99999
        GGT Cycle 2, Day 1, n=1
    3.000 ± 99999
        GGT Cycle 3, Day 1, n=1
    8.000 ± 99999
        GGT Cycle 4, Day 1, n=1
    5.000 ± 99999
    Notes
    [20] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points [21]
    End point description
    Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [22]
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        Calcium, Cycle 1, Day 1, n=3
    -0.008 ± 0.0520
        Calcium Cycle 1, Day 7, n=4
    -0.075 ± 0.0535
        Calcium Cycle 1, Day 15, n=3
    -0.066 ± 0.0758
        Calcium Cycle 1, Day 22, n=3
    -0.033 ± 0.0624
        Calcium Cycle 2, Day 1, n=3
    -0.067 ± 0.0144
        Calcium Cycle 3, Day 1, n=3
    -0.183 ± 0.1523
        Calcium Cycle 4, Day 1, n=2
    -0.050 ± 0.0700
        Calcium, Cycle 5, Day 1, n=1
    -0.050 ± 99999
        Chloride, Cycle 1, Day 1, n=4
    -0.750 ± 0.5000
        Chloride Cycle 1, Day 7, n=5
    0.600 ± 4.3932
        Chloride Cycle 1, Day 15, n=4
    0.250 ± 2.5000
        Chloride Cycle 1, Day 22, n=3
    0.333 ± 1.1547
        Chloride Cycle 2, Day 1, n=3
    0.333 ± 1.5275
        Chloride Cycle 3, Day 1, n=3
    -0.333 ± 1.5275
        Chloride Cycle 4, Day 1, n=2
    0.000 ± 2.8284
        Chloride, Cycle 5, Day 1, n=1
    0.000 ± 99999
        Glucose, Cycle 1, Day 1, n=4
    0.527 ± 1.9147
        Glucose Cycle 1, Day 7, n=5
    -0.333 ± 1.5357
        Glucose Cycle 1, Day 15, n=4
    0.014 ± 0.7971
        Glucose Cycle 1, Day 22, n=3
    0.870 ± 0.9309
        Glucose Cycle 2, Day 1, n=3
    1.924 ± 2.1037
        Glucose Cycle 3, Day 1, n=3
    1.628 ± 2.8543
        Glucose Cycle 4, Day 1, n=2
    1.027 ± 1.2954
        Glucose, Cycle 5, Day 1, n=1
    1.110 ± 99999
        Potassium, Cycle 1, Day 1, n=4
    0.325 ± 0.5315
        Potassium Cycle 1, Day 7, n=5
    0.000 ± 0.4528
        Potassium Cycle 1, Day 15, n=4
    -0.025 ± 0.4272
        Potassium Cycle 1, Day 22, n=3
    0.067 ± 0.2887
        Potassium Cycle 2, Day 1, n=3
    0.067 ± 0.1528
        Potassium Cycle 3, Day 1, n=3
    -0.367 ± 0.3786
        Potassium Cycle 4, Day 1, n=2
    0.050 ± 0.0707
        Potassium, Cycle 5, Day 1, n=1
    0.500 ± 99999
        Sodium, Cycle 1, Day 1, n=4
    -1.750 ± 1.2583
        Sodium Cycle 1, Day 7, n=5
    -1.000 ± 2.2361
        Sodium Cycle 1, Day 15, n=4
    -2.000 ± 2.4495
        Sodium Cycle 1, Day 22, n=3
    -0.667 ± 2.0817
        Sodium Cycle 2, Day 1, n=3
    0.333 ± 0.5774
        Sodium Cycle 3, Day 1, n=3
    -1.000 ± 5.0000
        Sodium Cycle 4, Day 1, n=2
    -0.500 ± 2.1213
        Sodium, Cycle 5, Day 1, n=1
    0.000 ± 99999
        Urea nitrogen, Cycle 1, Day 1, n=3
    2.701 ± 2.3181
        Urea nitrogen Cycle 1, Day 7, n=4
    1.214 ± 3.4779
        Urea nitrogen Cycle 1, Day 15, n=3
    1.547 ± 3.3171
        Urea nitrogen Cycle 1, Day 22, n=3
    1.309 ± 3.8173
        Urea nitrogen Cycle 2, Day 1, n=3
    0.238 ± 2.1519
        Urea nitrogen Cycle 3, Day 1, n=3
    -1.190 ± 1.7610
        Urea nitrogen Cycle 4, Day 1, n=2
    -0.535 ± 1.2622
        Urea nitrogen, Cycle 5, Day 1, n=1
    -1.428 ± 99999
        Phosphate, Cycle 1, Day 1, n=1
    0.194 ± 99999
        Phosphate Cycle 1, Day 7, n=2
    -0.081 ± 0.1598
        Phosphate Cycle 1, Day 22, n=1
    -0.032 ± 99999
        Phosphate Cycle 2, Day 1, n=1
    0.194 ± 99999
        Phosphate Cycle 3, Day 1, n=1
    0.000 ± 99999
        Phosphate Cycle 4, Day 1, n=1
    0.032 ± 99999
    Notes
    [22] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Albumin and Protein at indicated time points

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    End point title
    		 Part 1: Change from Baseline in Albumin and Protein at indicated time points [23]
    End point description
    Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [24]
    Units: G/L
    arithmetic mean (standard deviation)
        Albumin, Cycle 1, Day 1, n=4
    -1.250 ± 2.2174
        Albumin Cycle 1, Day 7, n=4
    -1.250 ± 2.5000
        Albumin Cycle 1, Day 15, n=3
    -1.667 ± 1.5275
        Albumin Cycle 1, Day 22, n=3
    -1.333 ± 0.5774
        Albumin Cycle 2, Day 1, n=3
    -1.667 ± 2.0817
        Albumin Cycle 3, Day 1, n=3
    -6.000 ± 6.2450
        Albumin Cycle 4, Day 1, n=2
    0.000 ± 1.4142
        Albumin Cycle 5, Day 1, n=1
    1.000 ± 99999
        Protein, Cycle 1, Day 1, n=4
    -3.250 ± 3.8622
        Protein Cycle 1, Day 7, n=5
    -3.200 ± 4.3243
        Protein Cycle 1, Day 15, n=4
    -1.500 ± 4.4347
        Protein Cycle 1, Day 22, n=3
    -1.667 ± 1.1547
        Protein Cycle 2, Day 1, n=3
    -3.333 ± 5.8595
        Protein Cycle 3, Day 1, n=3
    -7.333 ± 6.8069
        Protein Cycle 4, Day 1, n=2
    -2.000 ± 2.8284
        Protein Cycle 5, Day 1, n=1
    0.000 ± 99999
    Notes
    [24] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Partial Pressure Carbon Dioxide (pCO2) at indicated time points

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    End point title
    		 Part 1: Change from Baseline in Partial Pressure Carbon Dioxide (pCO2) at indicated time points [25]
    End point description
    Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline and Day 1 of Cycle 1 (cycle of 28 days)
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    1 [26]
    Units: Kilopascal
        arithmetic mean (standard deviation)
    0.173 ± 99999
    Notes
    [26] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time-points [27]
    End point description
    Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [28]
    Units: Millimeters of mercury
    arithmetic mean (standard deviation)
        SBP, Cycle 1, Day 7, n=5
    -10.2 ± 4.76
        SBP, Cycle 1, Day 15, n=4
    -13.5 ± 3.87
        SBP, Cycle 2, Day 1, n=3
    -4.7 ± 3.79
        SBP, Cycle 3, Day 1, n=3
    -3.7 ± 8.39
        SBP, Cycle 4, Day 1, n=2
    -5.0 ± 2.83
        SBP, Cycle 5, Day 1, n=1
    -6.0 ± 99999
        DBP, Cycle 1, Day 7, n=5
    -2.6 ± 8.62
        DBP, Cycle 1, Day 15, n=4
    -3.5 ± 4.04
        DBP, Cycle 2, Day 1, n=3
    -7.3 ± 10.02
        DBP, Cycle 3, Day 1, n=3
    2.7 ± 4.73
        DBP, Cycle 4, Day 1, n=2
    3.0 ± 7.07
        DBP, Cycle 5, Day 1, n=1
    -4.0 ± 99999
    Notes
    [28] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in heart rate at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in heart rate at indicated time-points [29]
    End point description
    Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [30]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Cycle 1, Day 7, n=5
    4.8 ± 6.69
        Cycle 1, Day 15, n=4
    -2.5 ± 7.42
        Cycle 2, Day 1, n=3
    -6.3 ± 2.89
        Cycle 3, Day 1, n=3
    -1.0 ± 9.00
        Cycle 4, Day 1, n=2
    -2.0 ± 8.49
        Cycle 5, Day 1, n=1
    -1.0 ± 99999
    Notes
    [30] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in respiratory rate at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in respiratory rate at indicated time-points [31]
    End point description
    Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [32]
    Units: Breaths per minute
    arithmetic mean (standard deviation)
        Cycle 1, Day 7, n=5
    -0.4 ± 1.14
        Cycle 1, Day 15, n=4
    -0.5 ± 1.00
        Cycle 2, Day 1, n=3
    -1.0 ± 1.00
        Cycle 3, Day 1, n=3
    -0.3 ± 1.53
        Cycle 4, Day 1, n=2
    -0.5 ± 0.71
        Cycle 5, Day 1, n=1
    -1.0 ± 99999
    Notes
    [32] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in body temperature at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in body temperature at indicated time-points [33]
    End point description
    Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [34]
    Units: Celsius
    arithmetic mean (standard deviation)
        Cycle 1, Day 7, n=5
    0.14 ± 0.279
        Cycle 1, Day 15, n=4
    0.10 ± 0.216
        Cycle 2, Day 1, n=3
    0.27 ± 0.231
        Cycle 3, Day 1, n=3
    0.20 ± 0.300
        Cycle 4, Day 1, n=2
    0.10 ± 0.283
        Cycle 5, Day 1, n=1
    -0.20 ± 99999
    Notes
    [34] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in electrocardiogram (ECG) mean heart rate at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in electrocardiogram (ECG) mean heart rate at indicated time-points [35]
    End point description
    Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [36]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, n=2
    2.0 ± 2.83
        Cycle 1, Day 7, n=5
    -1.0 ± 11.94
        Cycle 2, Day 1, n=3
    -5.3 ± 5.51
        Cycle 3, Day 1, n=3
    2.3 ± 10.02
        Cycle 4, Day 1, n=2
    -3.0 ± 9.90
        Cycle 5, Day 1, n=1
    -7.0 ± 99999
    Notes
    [36] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF) at indicated time-points

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    End point title
    		 Part 1: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF) at indicated time-points [37]
    End point description
    Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [38]
    Units: Milliseconds
    arithmetic mean (standard deviation)
        PR interval, Cycle 1, Day 1, n=2
    0.0 ± 0.00
        PR interval, Cycle 1, Day 7, n=5
    39.8 ± 88.34
        PR interval, Cycle 2, Day 1, n=3
    6.0 ± 9.17
        PR interval, Cycle 3, Day 1, n=3
    0.7 ± 8.08
        PR interval, Cycle 4, Day 1, n=2
    6.0 ± 14.14
        PR interval, Cycle 5, Day 1, n=1
    12.0 ± 99999
        QRS duration, Cycle 1, Day 1, n=2
    -1.0 ± 4.24
        QRS duration, Cycle 1, Day 7, n=5
    -17.2 ± 39.61
        QRS duration, Cycle 2, Day 1, n=3
    2.0 ± 2.00
        QRS duration, Cycle 3, Day 1, n=3
    3.3 ± 1.15
        QRS duration, Cycle 4, Day 1, n=2
    -1.0 ± 1.41
        QRS duration, Cycle 5, Day 1, n=1
    -8.0 ± 99999
        QT interval, Cycle 1, Day 1, n=2
    0.0 ± 0.00
        QT interval, Cycle 1, Day 7, n=5
    -5.6 ± 29.37
        QT interval, Cycle 2, Day 1, n=3
    24.7 ± 18.58
        QT interval, Cycle 3, Day 1, n=3
    2.0 ± 18.00
        QT interval, Cycle 4, Day 1, n=1
    -4.0 ± 99999
        QT interval, Cycle 5, Day 1, n=1
    14.0 ± 99999
        QTcB interval, Cycle 1, Day 1, n=2
    7.0 ± 9.90
        QTcB interval, Cycle 1, Day 7, n=2
    -35.5 ± 82.73
        QTcF interval, Cycle 1, Day 1, n=2
    4.5 ± 6.36
        QTcF interval, Cycle 1, Day 7, n=5
    -9.4 ± 38.12
        QTcF interval, Cycle 2, Day 1, n=3
    8.0 ± 5.57
        QTcF interval, Cycle 3, Day 1, n=3
    13.0 ± 18.52
        QTcF interval, Cycle 4, Day 1, n=2
    -6.0 ± 19.80
        QTcF interval, Cycle 5, Day 1, n=1
    -8.0 ± 99999
    Notes
    [38] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Number of participants with abnormal findings during physical examination

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    End point title
    		 Part 1: Number of participants with abnormal findings during physical examination [39]
    End point description
    A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). All abnormal physical examination findings were reported as AEs within the AE specific case report form (CRF) page. Hence, data was not captured separately for this outcome as number of participants with abnormal findings with respect to physical examinations. 99999 indicates data was not available as all abnormal physical examination findings were reported as AEs.
    End point type
    Primary
    End point timeframe
    Up to 2 years
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [40]
    Units: Participants
    99999
    Notes
    [40] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 2: Percentage of participants with investigator-assessed best response assessed by Clinical Benefit Rate (CBR)

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    End point title
    		 Part 2: Percentage of participants with investigator-assessed best response assessed by Clinical Benefit Rate (CBR) [41]
    End point description
    CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 2: GSK2879552+Azacitidine Part 1: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [42]
    0 [43]
    Units: Percentage of Participants
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [42] - All Treated Subjects Population.
    [43] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 2: Percentage of participants with investigator-assessed best response assessed by Objective Response Rate (ORR)

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    End point title
    		 Part 2: Percentage of participants with investigator-assessed best response assessed by Objective Response Rate (ORR) [44]
    End point description
    Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [45]
    0 [46]
    Units: Percentage of Participants
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [45] - All Treated Subjects Population.
    [46] - All Treated Subjects Population.
    No statistical analyses for this end point

    Primary: Part 1: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points

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    End point title
    		 Part 1: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points [47]
    End point description
    Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)
    Notes
    [47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are not statistical data to report.
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [48]
    Units: Micromoles per liter (umol/L)
    arithmetic mean (standard deviation)
        Total Bilirubin, Cycle 1, Day 1, n=4
    -3.420 ± 5.4075
        Total Bilirubin Cycle 1, Day 7, n=5
    -1.094 ± 5.6580
        Total Bilirubin Cycle 1, Day 15, n=4
    0.128 ± 6.6278
        Total Bilirubin Cycle 1, Day 22, n=3
    -1.710 ± 2.9618
        Total Bilirubin Cycle 2, Day 1, n=3
    -2.850 ± 3.5596
        Total Bilirubin Cycle 3, Day 1, n=3
    0.000 ± 3.4200
        Total Bilirubin Cycle 4, Day 1, n=2
    -0.855 ± 3.6275
        Total Bilirubin, Cycle 5, Day 1, n=1
    -3.420 ± 99999
        Direct Bilirubin, Cycle 1, Day 1, n=1
    1.368 ± 99999
        Creatinine, Cycle 1, Day 1, n=4
    16.133 ± 25.5329
        Creatinine Cycle 1, Day 7, n=5
    4.066 ± 11.2271
        Creatinine Cycle 1, Day 15, n=4
    17.238 ± 17.4800
        Creatinine Cycle 1, Day 22, n=3
    23.279 ± 18.5500
        Creatinine Cycle 2, Day 1, n=3
    16.501 ± 16.6402
        Creatinine Cycle 3, Day 1, n=3
    15.912 ± 20.5613
        Creatinine Cycle 4, Day 1, n=2
    32.708 ± 8.7512
        Creatinine, Cycle 5, Day 1, n=1
    4.420 ± 99999
        Urate, Cycle 1, Day 1, n=1
    41.636 ± 99999
        Urate Cycle 1, Day 7, n=2
    5.948 ± 0.0000
        Urate Cycle 1, Day 22, n=1
    35.688 ± 99999
        Urate Cycle 2, Day 1, n=1
    65.428 ± 99999
        Urate Cycle 3, Day 1, n=1
    89.220 ± 99999
        Urate Cycle 4, Day 1, n=1
    59.480 ± 99999
    Notes
    [48] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants with investigator-assessed best response assessed by CBR

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    End point title
    		 Part 1: Percentage of participants with investigator-assessed best response assessed by CBR
    End point description
    CBR was defined as the percentage of participants achieving a confirmed CR or PR or mCR or confirmed HI or SD prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. IWG criteria, 2006 was used to evaluate response.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [49]
    Units: Percentage of Participants
        number (confidence interval 95%)
    40 (5.3 to 85.3)
    Notes
    [49] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 1: Percentage of participants with investigator-assessed best response assessed by ORR

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    End point title
    		 Part 1: Percentage of participants with investigator-assessed best response assessed by ORR
    End point description
    ORR was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. IWG criteria, 2006 was used to evaluate response.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [50]
    Units: Percentage of Participants
        number (confidence interval 95%)
    20 (0.5 to 71.6)
    Notes
    [50] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 1: Plasma concentration of GSK2879552

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    End point title
    		 Part 1: Plasma concentration of GSK2879552
    End point description
    Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood samples for pharmacokinetics were obtained and analyzed. 99999 indicates data was not available as standard deviation could not be calculated due to insufficient number of participants or measure value was 0 for all participants at that time frame. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [51]
    Units: Nanograms per milliliter
    arithmetic mean (standard deviation)
        Cycle 1, Day 1, pre-dose, n=5
    0.00 ± 99999
        Cycle 1, Day 1, 0.5 hour, n=4
    11.79 ± 9.270
        Cycle 1, Day 1, 1 hour, n=5
    8.18 ± 4.830
        Cycle 1, Day 1, 3 hour, n=5
    6.40 ± 1.990
        Cycle 1, Day 2, pre-dose, n=5
    1.03 ± 0.409
        Cycle 1, Day 4, pre-dose, n=5
    1.87 ± 0.716
        Cycle 1, Day 7, pre-dose, n=5
    1.97 ± 0.553
        Cycle 1, Day 7, 0.5 hour, n=5
    9.58 ± 8.395
        Cycle 1, Day 7, 1 hour, n=5
    9.17 ± 4.4777
        Cycle 1, Day 7, 3 hour, n=5
    8.58 ± 3.595
        Cycle 1, Day 15, pre-dose, n=3
    2.00 ± 0.798
        Cycle 1, Day 15, 0.5-1 hour, n=3
    13.39 ± 0.798
        Cycle 1, Day 22, pre-dose, n=3
    1.89 ± 0.723
        Cycle 2, Day 1, pre-dose, n=3
    2.16 ± 0.843
        Cycle 2, Day 7, pre-dose, n=3
    1.81 ± 0.585
        Cycle 2, Day 15, pre-dose, n=3
    2.33 ± 1.135
        Cycle 2, Day 22, pre-dose, n=3
    2.11 ± 0.709
        Cycle 3, Day 1, pre-dose, n=3
    1.99 ± 0.802
        Cycle 4, Day 1, pre-dose, n=2
    1.63 ± 0.085
        Cycle 5, Day 1, pre-dose, n=1
    1.97 ± 99999
    Notes
    [51] - PK Concentration Population.
    No statistical analyses for this end point

    Secondary: Part 1: Plasma concentration of Azacitidine

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    End point title
    		 Part 1: Plasma concentration of Azacitidine
    End point description
    Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine. Data was not collected due to blood samples were not collected as participants were not enrolled in GSK2879552 + Azacitidine arm due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)
    End point values
    		 Part 1: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [52]
    Units: Nanograms per milliliter
        arithmetic mean (standard deviation)
    ±
    Notes
    [52] - PK Population
    No statistical analyses for this end point

    Secondary: Part 1: Duration of Response

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    End point title
    		 Part 1: Duration of Response
    End point description
    Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment. Data was not collected for this endpoint as DOR could not be calculated because of the early termination of the study did not allow for this endpoint to be observed.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    0 [53]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    Notes
    [53] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 1: Progression-free Survival

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    End point title
    		 Part 1: Progression-free Survival
    End point description
    Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [54]
    Units: Weeks
        median (confidence interval 95%)
    22.4 (4.3 to 22.4)
    Notes
    [54] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 1: Overall Survival

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    End point title
    		 Part 1: Overall Survival
    End point description
    Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), the last date of known contact was used for those participants who had not died at the time of analysis; such participants were considered censored. 99999 indicates data was not available as the data and very small number of subjects do not allow meaningful calculation of the upper limit of 95% CI.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [55]
    Units: Weeks
        median (confidence interval 95%)
    22.4 (16.4 to 99999)
    Notes
    [55] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 1: Proportion of participants with disease progression to Acute Myeloblastic Leukemia (AML)

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    End point title
    		 Part 1: Proportion of participants with disease progression to Acute Myeloblastic Leukemia (AML)
    End point description
    The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [56]
    Units: Percentage of Participants
    40
    Notes
    [56] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 1: Time to AML progression

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    End point title
    		 Part 1: Time to AML progression
    End point description
    Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [57]
    Units: Weeks
        median (confidence interval 95%)
    22.4 (4.3 to 22.4)
    Notes
    [57] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 1: Number of participants with documented platelet and red blood cell (RBC) transfusions per month

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    End point title
    		 Part 1: Number of participants with documented platelet and red blood cell (RBC) transfusions per month
    End point description
    Number of participants with documented platelet and RBC transfusions have been presented.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Part 1: GSK2879552
    Number of subjects analysed
    5 [58]
    Units: Participants
        Platelets transfusion
    5
        RBC transfusion
    4
        RBC concentrated transfusion
    1
    Notes
    [58] - All Treated Subjects Population
    No statistical analyses for this end point

    Secondary: Part 2: Number of participants with any AEs and SAEs

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    End point title
    		 Part 2: Number of participants with any AEs and SAEs
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. All Treated Subject Population was defined as all participants who received at least one dose of study treatment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [59]
    0 [60]
    Units: Participants
    Notes
    [59] - All Treated Subjects Population.
    [60] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in Platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [61]
    0 [62]
    Units: 10^9 cells per liter
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [61] - All Treated Subjects Population.
    [62] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in MCV at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in MCV at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [63]
    0 [64]
    Units: Femtoliter
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [63] - All Treated Subjects Population.
    [64] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in MCH at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in MCH at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [65]
    0 [66]
    Units: Picogram
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [65] - All Treated Subjects Population.
    [66] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in MCHC and Hb at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in MCHC and Hb at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [67]
    0 [68]
    Units: Grams per liter
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [67] - All Treated Subjects Population.
    [68] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in Hematocrit at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in Hematocrit at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [69]
    0 [70]
    Units: Proportion of red blood cells in blood
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [69] - All Treated Subjects Population.
    [70] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in erythrocytes at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in erythrocytes at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [71]
    0 [72]
    Units: 10^12 cells per Liter
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [71] - All Treated Subjects Population.
    [72] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in percent reticulocytes at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in percent reticulocytes at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [73]
    0 [74]
    Units: Percentage of reticulocytes
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [73] - All Treated Subjects Population.
    [74] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in blast/leukocytes at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in blast/leukocytes at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [75]
    0 [76]
    Units: Ratio of blasts to leukocytes
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [75] - All Treated Subjects Population.
    [76] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in ALT, ALP, AST, LDH and GGT at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in ALT, ALP, AST, LDH and GGT at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [77]
    0 [78]
    Units: IU/L
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [77] - All Treated Subjects Population.
    [78] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen at indicated time-points
    End point description
    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [79]
    0 [80]
    Units: mmol/L
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [79] - All Treated Subjects Population.
    [80] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points

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    End point title
    		 Part 2: Change from Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and urate at indicated time points
    End point description
    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [81]
    0 [82]
    Units: umol/L
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [81] - All Treated Subjects Population.
    [82] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in Albumin and Protein at indicated time points

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    End point title
    		 Part 2: Change from Baseline in Albumin and Protein at indicated time points
    End point description
    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [83]
    0 [84]
    Units: G/L
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [83] - All Treated Subjects Population.
    [84] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in pCO2 at indicated time points

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    End point title
    		 Part 2: Change from Baseline in pCO2 at indicated time points
    End point description
    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [85]
    0 [86]
    Units: Kilopascal
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [85] - All Treated Subjects Population.
    [86] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in SBP and DBP at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in SBP and DBP at indicated time-points
    End point description
    Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [87]
    0 [88]
    Units: Millimeters of mercury
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [87] - All Treated Subjects Population.
    [88] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in heart rate at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in heart rate at indicated time-points
    End point description
    Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [89]
    0 [90]
    Units: Beats per minute
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [89] - All Treated Subjects Population.
    [90] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in respiratory rate at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in respiratory rate at indicated time-points
    End point description
    Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [91]
    0 [92]
    Units: Breaths per minute
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [91] - All Treated Subjects Population.
    [92] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in body temperature at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in body temperature at indicated time-points
    End point description
    Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [93]
    0 [94]
    Units: Celsius
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [93] - All Treated Subjects Population.
    [94] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in ECG mean heart rate at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in ECG mean heart rate at indicated time-points
    End point description
    Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [95]
    0 [96]
    Units: Beats per minute
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [95] - All Treated Subjects Population.
    [96] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time-points

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    End point title
    		 Part 2: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time-points
    End point description
    Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Baseline and up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [97]
    0 [98]
    Units: Milliseconds
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [97] - All Treated Subjects Population.
    [98] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Number of participants with abnormal findings during physical examination

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    End point title
    		 Part 2: Number of participants with abnormal findings during physical examination
    End point description
    A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [99]
    0 [100]
    Units: Participants
    Notes
    [99] - All Treated Subjects Population.
    [100] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Plasma clearance (CL/F) of GSK2879552

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    End point title
    		 Part 2: Plasma clearance (CL/F) of GSK2879552
    End point description
    Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [101]
    0 [102]
    Units: Liters per hour
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [101] - PK Concentration Population.
    [102] - PK Concentration Population.
    No statistical analyses for this end point

    Secondary: Part 2: Duration of Response

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    End point title
    		 Part 2: Duration of Response
    End point description
    Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [103]
    0 [104]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [103] - All Treated Subjects Population.
    [104] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Progression-free Survival

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    End point title
    		 Part 2: Progression-free Survival
    End point description
    Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [105]
    0 [106]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [105] - All Treated Subjects Population.
    [106] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Overall Survival

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    End point title
    		 Part 2: Overall Survival
    End point description
    Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [107]
    0 [108]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [107] - All Treated Subjects Population.
    [108] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Percentage of participants with disease progression to AML

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    End point title
    		 Part 2: Percentage of participants with disease progression to AML
    End point description
    The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [109]
    0 [110]
    Units: Percentage of Participants
    Notes
    [109] - All Treated Subjects Population.
    [110] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Time to AML progression

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    End point title
    		 Part 2: Time to AML progression
    End point description
    Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [111]
    0 [112]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [111] - All Treated Subjects Population.
    [112] - All Treated Subjects Population.
    No statistical analyses for this end point

    Secondary: Part 2: Number of participants with documented platelet and red blood cell (RBC) transfusions per month

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    End point title
    		 Part 2: Number of participants with documented platelet and red blood cell (RBC) transfusions per month
    End point description
    Number of participants with documented platelet and RBC transfusions were to be presented. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.
    End point type
    Secondary
    End point timeframe
    Up to 2.5 years
    End point values
    		 Part 2: GSK2879552 Part 2: GSK2879552+Azacitidine
    Number of subjects analysed
    0 [113]
    0 [114]
    Units: Participants
    Notes
    [113] - All Treated Subjects Population.
    [114] - All Treated Subjects Population.
    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 (Non-SAEs) were collected from the start of the study treatment up to Cycle 5 (each cycle of 28 days) in Part 1.
    Adverse event reporting additional description
    SAEs and Non-SAEs were reported by treatment for the All Treated Subjects Population which comprised of all participants who received at least one dose of study treatment. Data is presented for Part 1 only as data was not collected in Part 2 due to the study was terminated during Part 1 only, and Part 2 was not initiated.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Part 1: GSK2879552
    Reporting group description
    		 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.

    Serious adverse events
    		 Part 1: GSK2879552
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 5 (20.00%)
         number of deaths (all causes)
    2
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Sinusitis
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1: GSK2879552
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 5 (60.00%)
         occurrences all number
    3
    Oedema
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Insomnia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Investigations
    Weight decreased
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    White blood cell count decreased
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    2
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Dizziness
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Parosmia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Syncope
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Increased tendency to bruise
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Leukopenia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Dyspepsia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Gingival bleeding
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 5 (40.00%)
         occurrences all number
    2
    Blood blister
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Eczema
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Back pain
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Infections and infestations
    Staphylococcal infection
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Fungal infection
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Fluid overload
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2017
    Amendment No. 1: Addition of language to include a stopping rule that halts enrollment upon the occurrence of any encephalopathy, unless clearly attributable to central nervous system disease involvement or intercurrent illness. Minor clarifications, correction of typographical errors, reformatting of tables, administrative and grammatical changes to text and Time and Events tables/footnotes.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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