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    Clinical Trial Results:
    An Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2586881 in Participants with Pulmonary Arterial Hypertension

    Summary
    EudraCT number
    		 2017-000212-41
    Trial protocol
    		 ES   DE  
    Global end of trial date
    07 May 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Apr 2020
    First version publication date
    23 Apr 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    206246
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Aug 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate changes in the pulmonary hemodynamics after single IV doses of GSK2586881 administered to participants with PAH receiving background PAH therapy
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Feb 2018
    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
    Germany: 11
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United States: 7
    Worldwide total number of subjects
    23
    EEA total number of subjects
    16
    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)
    19
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This phase 2a, open-label, dose-escalation study comprised of 4 cohorts. Participants received GSK2586881 by single intravenous (IV) infusion at following doses: 0.1 milligram per kilogram (mg/kg) or 0.2 mg/kg or 0.4 mg/kg or 0.8 mg/kg.

    Pre-assignment
    Screening details
    		 A total of 31 participants were screened and of them 7 participants were screen failures and one withdrew consent before dosing. Hence, a total of 23 participants received study treatment. This study was conducted at 4 centers in Germany, 2 centers in Spain, and 2 centers in the United States.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK2586881 0.1 mg/kg
    Arm description
    		 Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586881
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2586881 is a clear colorless liquid for IV infusion. Participants received a single IV dose of 0.1 mg/kg GSK2586881.

    Arm title
    		 GSK2586881 0.2 mg/kg
    Arm description
    		 Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586881
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2586881 is a clear colorless liquid for IV infusion. Participants received a single IV dose of 0.2 mg/kg GSK2586881.

    Arm title
    		 GSK2586881 0.4 mg/kg
    Arm description
    		 Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586881
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2586881 is a clear colorless liquid for IV infusion. Participants received a single IV dose of 0.4 mg/kg GSK2586881.

    Arm title
    		 GSK2586881 0.8 mg/kg
    Arm description
    		 Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2586881
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2586881 is a clear colorless liquid for IV infusion. Participants received a single IV dose of 0.8 mg/kg GSK2586881.

    Number of subjects in period 1
    		GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Started
    4
    5
    6
    8
    Completed
    4
    5
    6
    8

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK2586881 0.1 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.2 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.4 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.8 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg Total
    Number of subjects
    		 4 5 6 8 23
    Age categorical
    Units: Subjects
        Total participants
    		 4 5 6 8 23
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 32.0 ± 4.97 55.4 ± 14.96 52.5 ± 8.67 50.3 ± 13.35 -
    Sex: Female, Male
    Units: Participants
        Female
    		 3 3 4 5 15
        Male
    		 1 2 2 3 8
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 0 1 1 1 3
        White - White/Caucasian/European Heritage
    		 4 4 5 7 20

    End points

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    End points reporting groups
    Reporting group title
    GSK2586881 0.1 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.2 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.4 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.8 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Primary: Change from Baseline in pulmonary vascular resistance (PVR)

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    End point title
    		 Change from Baseline in pulmonary vascular resistance (PVR) [1]
    End point description
    PVR is the resistance generated by pulmonary circulation. Pulmonary arterial catheters were placed in participants and PVR values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Evaluable Population comprised of all participants who were in the safety population, who completed all Day 1 assessments (including up to 24 hours post dose) and were not deemed to have had major protocol deviations. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [2]
    5 [3]
    5 [4]
    8 [5]
    Units: Ratio
    geometric mean (confidence interval 95%)
        1 hour post-dose (Day 1)
    0.936 (0.725 to 1.208)
    0.885 (0.686 to 1.141)
    0.813 (0.561 to 1.178)
    1.017 (0.862 to 1.198)
        2 hours post-dose (Day 1)
    0.926 (0.671 to 1.279)
    1.043 (0.910 to 1.195)
    0.945 (0.788 to 1.134)
    0.974 (0.823 to 1.153)
        4 hours post-dose (Day 1)
    0.907 (0.552 to 1.490)
    0.895 (0.668 to 1.199)
    0.924 (0.589 to 1.448)
    1.116 (1.050 to 1.186)
    Notes
    [2] - Evaluable Population
    [3] - Evaluable Population
    [4] - Evaluable Population
    [5] - Evaluable Population
    No statistical analyses for this end point

    Primary: Change from Baseline in cardiac output (CO)

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    End point title
    		 Change from Baseline in cardiac output (CO) [6]
    End point description
    CO is the amount of blood pumped by the heart per minute. Pulmonary arterial catheters were placed in participants and CO values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [7]
    5 [8]
    5 [9]
    8 [10]
    Units: Ratio
    geometric mean (confidence interval 95%)
        1 hour post-dose (Day 1)
    1.046 (0.881 to 1.240)
    1.079 (0.966 to 1.206)
    1.076 (0.758 to 1.528)
    0.990 (0.948 to 1.033)
        2 hours post-dose (Day 1)
    1.025 (0.829 to 1.269)
    1.029 (0.950 to 1.116)
    0.929 (0.712 to 1.210)
    1.012 (0.944 to 1.085)
        4 hours post-dose (Day 1)
    1.114 (0.804 to 1.545)
    1.138 (0.949 to 1.365)
    0.882 (0.734 to 1.060)
    1.002 (0.935 to 1.075)
    Notes
    [7] - Evaluable Population
    [8] - Evaluable Population
    [9] - Evaluable Population
    [10] - Evaluable Population
    No statistical analyses for this end point

    Primary: Change from Baseline in mean pulmonary artery pressure (mPAP)

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    End point title
    		 Change from Baseline in mean pulmonary artery pressure (mPAP) [11]
    End point description
    The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Pulmonary arterial catheters were placed in participants and mPAP values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
    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 no statistical data to report.
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [12]
    5 [13]
    5 [14]
    8 [15]
    Units: Ratio
    geometric mean (confidence interval 95%)
        1 hour post-dose (Day 1)
    0.950 (0.781 to 1.154)
    0.995 (0.960 to 1.032)
    0.939 (0.799 to 1.104)
    0.989 (0.879 to 1.114)
        2 hours post-dose (Day 1)
    0.937 (0.781 to 1.126)
    0.994 (0.924 to 1.070)
    0.910 (0.766 to 1.081)
    0.996 (0.867 to 1.144)
        4 hours post-dose (Day 1)
    0.991 (0.812 to 1.211)
    1.029 (0.881 to 1.202)
    0.973 (0.897 to 1.054)
    1.062 (0.958 to 1.177)
    Notes
    [12] - Evaluable Population
    [13] - Evaluable Population
    [14] - Evaluable Population
    [15] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Number of participants with non-serious adverse events (AEs)

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    End point title
    		 Number of participants with non-serious adverse events (AEs)
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Safety Population comprised of all participants who took at least 1 dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Day 28
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [16]
    5 [17]
    6 [18]
    8 [19]
    Units: Participants
    1
    3
    5
    2
    Notes
    [16] - Safety Population
    [17] - Safety Population
    [18] - Safety Population
    [19] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with serious adverse events (SAEs)

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    End point title
    		 Number of participants with serious adverse events (SAEs)
    End point description
    Any untoward event resulting in death, life threatening, requiring 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 were categorized as SAE.
    End point type
    Secondary
    End point timeframe
    Up to Day 28
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [20]
    5 [21]
    6 [22]
    8 [23]
    Units: Participants
    0
    0
    0
    0
    Notes
    [20] - Safety Population
    [21] - Safety Population
    [22] - Safety Population
    [23] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameters: alkaline phosphatase, alanine amino transferase and aspartate amino transferase

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    End point title
    		 Change from Baseline in clinical chemistry parameters: alkaline phosphatase, alanine amino transferase and aspartate amino transferase
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters: alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [24]
    5 [25]
    6 [26]
    8 [27]
    Units: International units per liter
    arithmetic mean (standard deviation)
        Alkaline phosphatase, 24 hours post-dose (Day 1)
    4.8 ± 8.42
    -1.4 ± 7.44
    5.3 ± 3.08
    3.1 ± 3.48
        Alkaline phosphatase, Day 7 to Day 14
    6.5 ± 5.00
    3.2 ± 4.21
    3.0 ± 3.52
    2.6 ± 4.31
        ALT, 24 hours post-dose (Day 1)
    -2.0 ± 2.16
    0.0 ± 1.58
    -1.8 ± 3.76
    -0.1 ± 2.17
        ALT, Day 7 to Day 14
    1.3 ± 0.96
    1.8 ± 3.27
    -4.3 ± 12.94
    0.9 ± 4.85
        AST, 24 hours post-dose (Day 1)
    0.0 ± 1.63
    -0.4 ± 0.55
    0.5 ± 1.76
    -1.8 ± 3.77
        AST, Day 7 to Day 14
    2.8 ± 2.50
    1.4 ± 1.67
    -0.3 ± 3.67
    -0.9 ± 6.71
    Notes
    [24] - Safety Population
    [25] - Safety Population
    [26] - Safety Population
    [27] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine

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    End point title
    		 Change from Baseline in clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [28]
    5 [29]
    6 [30]
    8 [31]
    Units: Micromoles per liter
    arithmetic mean (standard deviation)
        Direct bilirubin, 24 hours post-dose (Day 1)
    2.0 ± 1.63
    0.4 ± 0.89
    0.3 ± 1.97
    1.0 ± 2.14
        Direct bilirubin, Day 7 to Day 14
    1.0 ± 1.15
    0.0 ± 0.00
    0.0 ± 1.26
    0.5 ± 2.56
        Total bilirubin, 24 hours post-dose (Day 1)
    3.0 ± 4.16
    0.8 ± 1.79
    0.7 ± 4.84
    4.8 ± 6.76
        Total bilirubin, Day 7 to Day 14
    1.5 ± 3.42
    0.4 ± 2.61
    -1.7 ± 3.44
    0.0 ± 4.14
        Creatinine, 24 hours post-dose (Day 1)
    5.08 ± 4.102
    10.80 ± 6.110
    12.22 ± 20.214
    1.76 ± 2.759
        Creatinine, Day 7 to Day 14
    -1.12 ± 6.530
    8.68 ± 13.353
    4.57 ± 9.638
    3.20 ± 4.885
    Notes
    [28] - Safety Population
    [29] - Safety Population
    [30] - Safety Population
    [31] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameters: calcium, glucose, potassium, sodium and blood urea nitrogen (BUN)

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    End point title
    		 Change from Baseline in clinical chemistry parameters: calcium, glucose, potassium, sodium and blood urea nitrogen (BUN)
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters: calcium, glucose, potassium, sodium and BUN. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [32]
    5 [33]
    6 [34]
    8 [35]
    Units: Millimoles per liter
    arithmetic mean (standard deviation)
        Calcium, 24 hours post-dose (Day 1)
    0.035 ± 0.1427
    0.012 ± 0.0867
    0.047 ± 0.1033
    0.060 ± 0.0466
        Calcium, Day 7 to Day 14
    0.025 ± 0.1399
    0.064 ± 0.0888
    0.047 ± 0.1250
    0.115 ± 0.0583
        Glucose, 24 hours post-dose (Day 1)
    0.85 ± 0.957
    1.10 ± 1.398
    0.50 ± 1.752
    0.89 ± 2.039
        Glucose, Day 7 to Day 14
    0.95 ± 1.760
    -0.32 ± 0.646
    -0.57 ± 0.635
    -0.20 ± 1.995
        Potassium, 24 hours post-dose (Day 1)
    0.28 ± 0.377
    0.18 ± 0.179
    0.08 ± 0.306
    -0.05 ± 0.239
        Potassium, Day 7 to Day 14
    0.10 ± 0.356
    0.22 ± 0.148
    0.25 ± 0.207
    0.18 ± 0.301
        Sodium, 24 hours post-dose (Day 1)
    -1.3 ± 1.26
    -0.6 ± 2.30
    -0.2 ± 1.47
    -1.0 ± 1.85
        Sodium, Day 7 to Day 14
    -0.3 ± 4.19
    0.0 ± 1.87
    0.5 ± 1.64
    0.0 ± 1.60
        BUN, 24 hours post-dose (Day 1)
    0.00 ± 1.080
    -0.20 ± 0.758
    0.83 ± 1.033
    -0.25 ± 0.463
        BUN, Day 7 to Day 14
    -0.25 ± 1.258
    1.50 ± 1.541
    0.00 ± 1.000
    0.31 ± 1.067
    Notes
    [32] - Safety Population
    [33] - Safety Population
    [34] - Safety Population
    [35] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameter: total protein

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    End point title
    		 Change from Baseline in clinical chemistry parameter: total protein
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter, total protein. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [36]
    5 [37]
    6 [38]
    8 [39]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1)
    1.3 ± 6.13
    0.6 ± 3.78
    1.8 ± 2.93
    2.6 ± 3.66
        Day 7 to Day 14
    1.5 ± 2.38
    6.2 ± 4.55
    2.0 ± 4.73
    4.9 ± 3.31
    Notes
    [36] - Safety Population
    [37] - Safety Population
    [38] - Safety Population
    [39] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell (WBC) count

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    End point title
    		 Change from Baseline in hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell (WBC) count
    End point description
    Blood samples were collected for the assessment of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils (T.neutrophils), platelet count and WBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [40]
    5 [41]
    6 [42]
    8 [43]
    Units: Giga cells per liter
    arithmetic mean (standard deviation)
        Basophils, 24 hours post-dose (Day 1), n=4,4,6,3
    -0.008 ± 0.0359
    0.013 ± 0.0206
    -0.005 ± 0.0302
    0.003 ± 0.0115
        Basophils, Day 7 to Day 14, n=4,5,6,8
    0.000 ± 0.0327
    0.002 ± 0.0192
    0.008 ± 0.0306
    0.003 ± 0.0238
        Eosinophils, 24 hours post-dose (Day 1), n=4,4,6,3
    0.007 ± 0.0695
    0.018 ± 0.0222
    0.012 ± 0.0662
    -0.007 ± 0.0503
        Eosinophils, Day 7 to Day 14, n=4,5,6,8
    -0.035 ± 0.0835
    0.004 ± 0.0230
    -0.025 ± 0.0807
    0.023 ± 0.1004
        Lymphocytes, 24 hours post-dose (Day 1), n=4,4,6,3
    0.000 ± 0.5509
    -0.070 ± 0.1612
    -0.157 ± 0.1558
    0.190 ± 0.4553
        Lymphocytes, Day 7 to Day 14, n=4,5,6,8
    -0.025 ± 0.4277
    -0.054 ± 0.1422
    -0.250 ± 0.2001
    0.130 ± 0.4032
        Monocytes, 24 hours post-dose (Day 1), n=4,4,6,3
    0.050 ± 0.0673
    -0.028 ± 0.0914
    0.098 ± 0.1125
    0.140 ± 0.0700
        Monocytes, Day 7 to Day 14, n=4,5,6,8
    0.038 ± 0.1066
    0.038 ± 0.0998
    0.047 ± 0.1263
    0.091 ± 0.1654
        T.neutrophils, 24 hours post-dose(Day1),n=4,4,6,3
    0.643 ± 1.0052
    0.415 ± 0.3924
    0.738 ± 0.5615
    0.727 ± 0.7298
        T.neutrophils, Day 7 to Day 14, n=4,5,6,8
    0.185 ± 0.9008
    0.504 ± 0.4884
    0.397 ± 1.3173
    0.366 ± 0.7204
        Platelets, 24 hours post-dose (Day 1), n=4,4,6,5
    11.8 ± 36.28
    -33.0 ± 73.51
    7.8 ± 16.65
    12.6 ± 27.74
        Platelets, Day 7 to Day 14, n=4,5,6,8
    35.3 ± 17.40
    19.8 ± 45.03
    14.3 ± 52.89
    23.4 ± 24.44
        WBC count, 24 hours post-dose (Day 1), n=4,4,6,5
    0.35 ± 1.330
    0.30 ± 0.183
    0.68 ± 0.542
    2.16 ± 2.492
        WBC count, Day 7 to Day 14, n=4,5,6,8
    -0.20 ± 1.334
    0.46 ± 0.498
    0.20 ± 1.355
    0.64 ± 0.588
    Notes
    [40] - Safety Population
    [41] - Safety Population
    [42] - Safety Population
    [43] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: hemoglobin

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    End point title
    		 Change from Baseline in hematology parameter: hemoglobin
    End point description
    Blood samples were collected for the assessment of hematology parameter, hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [44]
    5 [45]
    6 [46]
    8 [47]
    Units: Grams per liter
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    1.8 ± 11.09
    2.0 ± 5.72
    5.0 ± 4.77
    3.0 ± 5.61
        Day 7 to Day 14, n=4,5,6,8
    -4.3 ± 6.55
    3.4 ± 5.98
    -1.5 ± 7.09
    4.0 ± 5.15
    Notes
    [44] - Safety Population
    [45] - Safety Population
    [46] - Safety Population
    [47] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: hematocrit

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    End point title
    		 Change from Baseline in hematology parameter: hematocrit
    End point description
    Blood samples were collected for the assessment of hematology parameter, hematocrit. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [48]
    5 [49]
    6 [50]
    8 [51]
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    0.0030 ± 0.02858
    0.0053 ± 0.02156
    0.0098 ± 0.01546
    0.0140 ± 0.02448
        Day 7 to Day 14, n=4,5,6,8
    -0.0225 ± 0.00929
    0.0104 ± 0.02173
    0.0030 ± 0.02391
    0.0135 ± 0.01891
    Notes
    [48] - Safety Population
    [49] - Safety Population
    [50] - Safety Population
    [51] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: Mean corpuscle hemoglobin

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    End point title
    		 Change from Baseline in hematology parameter: Mean corpuscle hemoglobin
    End point description
    Blood samples were collected for the assessment of hematology parameter, mean corpuscle hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [52]
    5 [53]
    6 [54]
    8 [55]
    Units: Picograms
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    -0.08 ± 0.150
    0.05 ± 0.507
    0.25 ± 0.302
    -0.10 ± 0.235
        Day 7 to Day 14, n=4,5,6,8
    0.10 ± 0.483
    0.04 ± 0.182
    -0.33 ± 0.314
    0.15 ± 0.177
    Notes
    [52] - Safety Population
    [53] - Safety Population
    [54] - Safety Population
    [55] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: Mean corpuscle volume

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    End point title
    		 Change from Baseline in hematology parameter: Mean corpuscle volume
    End point description
    Blood samples were collected for the assessment of hematology parameter, mean corpuscle volume. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [56]
    5 [57]
    6 [58]
    8 [59]
    Units: Femtoliters
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    -0.5 ± 2.52
    0.0 ± 0.82
    -0.5 ± 0.84
    0.6 ± 1.95
        Day 7 to Day 14, n=4,5,6,8
    -1.5 ± 2.08
    -0.2 ± 0.84
    0.7 ± 1.03
    0.8 ± 1.04
    Notes
    [56] - Safety Population
    [57] - Safety Population
    [58] - Safety Population
    [59] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: Red blood cell (RBC) count

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    End point title
    		 Change from Baseline in hematology parameter: Red blood cell (RBC) count
    End point description
    Blood samples were collected for the assessment of hematology parameter: RBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [60]
    5 [61]
    6 [62]
    8 [63]
    Units: Trillion cells per liter
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    0.03 ± 0.435
    0.03 ± 0.287
    0.13 ± 0.163
    0.12 ± 0.192
        Day 7 to Day 14, n=4,5,6,8
    -0.20 ± 0.183
    0.14 ± 0.261
    0.00 ± 0.310
    0.11 ± 0.203
    Notes
    [60] - Safety Population
    [61] - Safety Population
    [62] - Safety Population
    [63] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter: Reticulocytes

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    End point title
    		 Change from Baseline in hematology parameter: Reticulocytes
    End point description
    Blood samples were collected for the assessment of hematology parameter: reticulocytes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [64]
    5 [65]
    6 [66]
    8 [67]
    Units: Percentage of reticulocytes in blood
    arithmetic mean (standard deviation)
        24 hours post-dose (Day 1), n=4,4,6,5
    0.0012 ± 0.00330
    0.0017 ± 0.00310
    0.0017 ± 0.00216
    0.0000 ± 0.00100
        Day 7 to Day 14, n=4,5,6,8
    0.0058 ± 0.00411
    0.0014 ± 0.00358
    0.0025 ± 0.00333
    0.0040 ± 0.00325
    Notes
    [64] - Safety Population
    [65] - Safety Population
    [66] - Safety Population
    [67] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of Participants With Urinalysis Results by Dipstick Method

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    End point title
    		 Number of Participants With Urinalysis Results by Dipstick Method
    End point description
    Urine samples were collected to assess urine bilirubin, urine occult blood, urine glucose, urine ketones, and urine protein by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones and urine protein can be read as negative, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample.
    End point type
    Secondary
    End point timeframe
    24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [68]
    5 [69]
    6 [70]
    8 [71]
    Units: Participants
        Bilirubin, 24 hours post-dose (Day 1), negative
    4
    5
    6
    8
        Bilirubin, 24 hours post-dose (Day 1), trace
    0
    0
    0
    0
        Bilirubin, 24 hours post-dose (Day 1), 1+
    0
    0
    0
    0
        Bilirubin, 24 hours post-dose (Day 1), 2+
    0
    0
    0
    0
        Bilirubin, 24 hours post-dose (Day 1), 3+
    0
    0
    0
    0
        Occult Blood, 24 hours post-dose (Day 1), negative
    2
    5
    4
    7
        Occult Blood, 24 hours post-dose (Day 1), trace
    0
    0
    2
    1
        Occult Blood, 24 hours post-dose (Day 1), 1+
    1
    0
    0
    0
        Occult Blood, 24 hours post-dose (Day 1), 2+
    1
    0
    0
    0
        Occult Blood, 24 hours post-dose (Day 1), 3+
    0
    0
    0
    0
        Glucose, 24 hours post-dose (Day 1), negative
    4
    5
    5
    8
        Glucose, 24 hours post-dose (Day 1), trace
    0
    0
    0
    0
        Glucose, 24 hours post-dose (Day 1), 1+
    0
    0
    0
    0
        Glucose, 24 hours post-dose (Day 1), 2+
    0
    0
    0
    0
        Glucose, 24 hours post-dose (Day 1), 3+
    0
    0
    1
    0
        Ketones, 24 hours post-dose (Day 1), negative
    4
    4
    3
    8
        Ketones, 24 hours post-dose (Day 1), trace
    0
    1
    3
    0
        Ketones, 24 hours post-dose (Day 1), 1+
    0
    0
    0
    0
        Ketones, 24 hours post-dose (Day 1), 2+
    0
    0
    0
    0
        Ketones, 24 hours post-dose (Day 1), 3+
    0
    0
    0
    0
        Protein, 24 hours post-dose (Day 1), negative
    4
    4
    6
    8
        Protein, 24 hours post-dose (Day 1), trace
    0
    1
    0
    0
        Protein, 24 hours post-dose (Day 1), 1+
    0
    0
    0
    0
        Protein, 24 hours post-dose (Day 1), 2+
    0
    0
    0
    0
        Protein, 24 hours post-dose (Day 1), 3+
    0
    0
    0
    0
    Notes
    [68] - Safety Population
    [69] - Safety Population
    [70] - Safety Population
    [71] - Safety Population
    No statistical analyses for this end point

    Secondary: Change From Baseline in pulse rate

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    End point title
    		 Change From Baseline in pulse rate
    End point description
    Pulse rate was measured in supine position after at least a 5-minute rest. Change from Baseline in pulse rate was evaluated. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [72]
    5 [73]
    6 [74]
    8 [75]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        0.5 hour post-dose (Day 1), n=4,5,6,8
    -1.3 ± 5.85
    -0.8 ± 3.42
    3.5 ± 8.64
    3.6 ± 6.00
        1 hour post-dose (Day 1), n=4,5,6,8
    -3.0 ± 6.98
    0.8 ± 6.69
    -0.7 ± 3.67
    -1.0 ± 3.93
        2 hours post-dose (Day 1), n=4,5,6,8
    -5.0 ± 7.62
    -0.4 ± 1.95
    -1.8 ± 6.65
    1.0 ± 5.93
        4 hours post-dose (Day 1), n=4,5,6,8
    -1.8 ± 6.80
    11.6 ± 13.67
    -1.2 ± 6.40
    -0.8 ± 7.42
        8 hours post-dose (Day 1), n=4,4,6,8
    2.8 ± 6.90
    1.8 ± 5.19
    5.7 ± 5.85
    8.6 ± 9.83
        24 hours post-dose (Day 1), n=4,5,6,8
    4.3 ± 11.27
    3.6 ± 6.50
    7.5 ± 7.12
    13.0 ± 9.20
        Day 7 to Day 14, n=4,5,6,8
    10.0 ± 14.31
    4.4 ± 5.86
    5.3 ± 6.25
    9.8 ± 8.36
    Notes
    [72] - Safety Population
    [73] - Safety Population
    [74] - Safety Population
    [75] - Safety Population
    No statistical analyses for this end point

    Secondary: Change From Baseline in respiratory rate

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    End point title
    		 Change From Baseline in respiratory rate
    End point description
    Respiratory rate was measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [76]
    5 [77]
    6 [78]
    8 [79]
    Units: Breaths per minute
    arithmetic mean (standard deviation)
        0.5 hour post-dose (Day 1), n=4,5,6,8
    -2.5 ± 3.11
    -3.4 ± 4.39
    -2.2 ± 4.92
    0.1 ± 1.13
        1 hour post-dose (Day 1), n=4,5,6,8
    -2.8 ± 1.71
    -3.2 ± 5.67
    1.8 ± 9.22
    0.0 ± 0.76
        2 hours post-dose (Day 1), n=4,5,6,8
    -2.0 ± 2.16
    -2.6 ± 2.97
    -3.0 ± 4.52
    -1.0 ± 4.50
        4 hours post-dose (Day 1), n=4,5,6,8
    -2.5 ± 2.08
    -2.2 ± 5.63
    -2.2 ± 3.54
    0.1 ± 0.64
        8 hours post-dose (Day 1), n=4,4,6,8
    -2.0 ± 1.63
    -0.3 ± 3.50
    0.2 ± 2.56
    1.1 ± 2.59
        24 hours post-dose (Day 1), n=4,5,6,8
    -1.8 ± 0.96
    0.8 ± 2.28
    0.3 ± 2.58
    -0.1 ± 1.81
        Day 7 to Day 14, n=4,5,6,8
    -0.5 ± 1.73
    -0.4 ± 3.58
    2.0 ± 2.28
    0.3 ± 1.16
    Notes
    [76] - Safety Population
    [77] - Safety Population
    [78] - Safety Population
    [79] - Safety Population
    No statistical analyses for this end point

    Secondary: Change From Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP)

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    End point title
    		 Change From Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP)
    End point description
    DBP and SBP were measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [80]
    5 [81]
    6 [82]
    8 [83]
    Units: Millimeters of mercury
    arithmetic mean (standard deviation)
        DBP, 0.5 hour post-dose (Day 1), n=4,5,6,8
    -3.5 ± 8.58
    -1.0 ± 10.42
    -5.0 ± 14.67
    -3.3 ± 4.53
        DBP, 1 hour post-dose (Day 1), n=4,5,6,8
    -2.0 ± 6.22
    0.6 ± 8.56
    -4.3 ± 9.73
    -2.3 ± 3.73
        DBP, 2 hours post-dose (Day 1), n=4,5,6,8
    0.5 ± 12.40
    1.2 ± 10.55
    -5.8 ± 8.80
    3.3 ± 5.87
        DBP, 4 hours post-dose (Day 1), n=4,5,6,8
    -1.5 ± 2.65
    3.0 ± 8.37
    -2.7 ± 13.22
    1.6 ± 6.07
        DBP, 8 hours post-dose (Day 1), n=4,4,6,8
    -12.3 ± 6.65
    -6.3 ± 8.66
    -10.2 ± 9.15
    -1.0 ± 9.32
        DBP, 24 hours post-dose (Day 1), n=4,5,6,8
    -7.5 ± 7.94
    -8.6 ± 9.61
    -2.8 ± 10.61
    -3.1 ± 8.46
        DBP, Day 7 to Day 14, n=4,5,6,8
    -4.5 ± 7.19
    -2.2 ± 6.91
    -2.5 ± 11.78
    2.8 ± 12.83
        SBP, 0.5 hour post-dose (Day 1), n=4,5,6,8
    -2.3 ± 12.28
    -0.2 ± 12.60
    -5.2 ± 6.11
    -0.1 ± 5.03
        SBP, 1 hour post-dose (Day 1), n=4,5,6,8
    -1.8 ± 9.91
    3.4 ± 12.68
    -2.7 ± 9.37
    3.0 ± 8.07
        SBP, 2 hours post-dose (Day 1), n=4,5,6,8
    1.0 ± 15.12
    2.0 ± 10.20
    -0.7 ± 18.84
    2.0 ± 11.80
        SBP, 4 hours post-dose (Day 1), n=4,5,6,8
    5.5 ± 19.69
    4.2 ± 9.34
    6.3 ± 13.03
    6.1 ± 13.53
        SBP, 8 hours post-dose (Day 1), n=4,4,6,8
    -4.5 ± 10.38
    3.0 ± 16.57
    -5.2 ± 7.63
    -4.8 ± 9.65
        SBP, 24 hours post-dose (Day 1), n=4,5,6,8
    -2.5 ± 4.51
    -0.2 ± 14.72
    -4.7 ± 11.41
    -3.8 ± 14.85
        SBP, Day 7 to Day 14, n=4,5,6,8
    2.0 ± 21.37
    6.0 ± 6.78
    -5.8 ± 15.07
    -2.1 ± 9.63
    Notes
    [80] - Safety Population
    [81] - Safety Population
    [82] - Safety Population
    [83] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with abnormal electrocardiogram (ECG) findings

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    End point title
    		 Number of participants with abnormal electrocardiogram (ECG) findings
    End point description
    12-lead ECGs were obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    4 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [84]
    5 [85]
    6 [86]
    8 [87]
    Units: Participants
        Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8
    1
    3
    3
    7
        Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8
    0
    0
    0
    0
        Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8
    1
    3
    4
    5
        Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8
    0
    0
    0
    0
        Abnormal NCS, Day 7 to Day 14, n=4,5,6,8
    1
    3
    3
    3
        Abnormal CS, Day 7 to Day 14, n=4,5,6,8
    0
    0
    0
    0
    Notes
    [84] - Safety Population
    [85] - Safety Population
    [86] - Safety Population
    [87] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in pulse oximetry parameter: Percent oxygen in blood

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    End point title
    		 Change from Baseline in pulse oximetry parameter: Percent oxygen in blood
    End point description
    Percent oxygen in blood was measured using pulse oximetry after the participant had rested for at least 5 minutes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [88]
    5 [89]
    6 [90]
    8 [91]
    Units: Percentage of oxygen in blood
    arithmetic mean (standard deviation)
        0.5 hour post-dose (Day 1), n=4,5,6,8
    -1.0 ± 2.30
    -1.7 ± 2.77
    0.8 ± 2.31
    -0.5 ± 2.03
        1 hour post-dose (Day 1), n=4,5,6,8
    -0.7 ± 2.87
    -2.1 ± 2.79
    -0.3 ± 1.03
    -0.9 ± 2.48
        2 hours post-dose (Day 1), n=4,5,6,8
    -1.5 ± 1.91
    -0.7 ± 1.99
    0.6 ± 1.21
    0.9 ± 1.37
        4 hours post-dose (Day 1), n=4,5,6,8
    -0.7 ± 2.21
    -1.0 ± 1.87
    -0.3 ± 1.96
    0.5 ± 2.13
        8 hours post-dose (Day 1), n=4,4,6,8
    -0.7 ± 2.50
    -0.2 ± 3.58
    0.8 ± 2.31
    0.4 ± 2.98
        24 hours post-dose (Day 1), n=4,5,6,8
    -1.0 ± 2.00
    -2.3 ± 3.06
    2.1 ± 1.60
    1.0 ± 3.28
        Day 7 to Day 14, n=4,5,6,8
    -0.2 ± 0.95
    -2.9 ± 2.37
    0.5 ± 3.33
    0.8 ± 2.49
    Notes
    [88] - Safety Population
    [89] - Safety Population
    [90] - Safety Population
    [91] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with positive immunogenicity results

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    End point title
    		 Number of participants with positive immunogenicity results
    End point description
    Immunogenicity samples were collected into a serum-separating tube, mixed by gentle inversion 5 times and left to coagulate at room temperature for a minimum of 30 minutes and a maximum of 60 minutes. All samples were first tested for anti-angiotensin converting enzyme type 2 (ACE2) binding antibodies by screening and confirmation assay steps. If post-dose samples were found to be positive for anti-ACE2 binding antibodies, they would have been further characterized for anti-ACE2 neutralizing antibodies. Number of participants with positive immunogenicity results post-dosing are presented.
    End point type
    Secondary
    End point timeframe
    Up to Day 28
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [92]
    5 [93]
    6 [94]
    8 [95]
    Units: Participants
    0
    0
    0
    0
    Notes
    [92] - Safety Population
    [93] - Safety Population
    [94] - Safety Population
    [95] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in systemic Renin-Angiotensin System (RAS) peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

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    End point title
    		 Change from Baseline in systemic Renin-Angiotensin System (RAS) peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)
    End point description
    Blood samples were collected to evaluate systemic RAS peptides: Angiotensin (Ang) II, Ang (1-5) and Ang (1-7). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). 99999 indicates confidence interval could not be estimated as more than 75 percentage (%) of the values were below lower limit of quantification.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [96]
    5 [97]
    5 [98]
    8 [99]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Ang II, 0.08 hour post-dose (Day 1), n=4,5,5,8
    0.143 (0.028 to 0.723)
    0.185 (-99999 to 99999)
    1.020 (0.063 to 16.661)
    0.254 (0.078 to 0.831)
        Ang II, 0.5 hour post-dose (Day 1), n=4,5,5,8
    0.179 (0.040 to 0.792)
    0.210 (-99999 to 99999)
    0.500 (0.065 to 3.825)
    0.211 (-99999 to 99999)
        Ang II, 1 hour post-dose (Day 1), n=4,5,5,8
    0.238 (0.097 to 0.582)
    0.162 (-99999 to 99999)
    0.420 (0.086 to 2.062)
    0.235 (-99999 to 99999)
        Ang II, 2 hours post-dose (Day 1), n=4,5,5,8
    0.230 (0.041 to 1.280)
    0.166 (-99999 to 99999)
    0.393 (0.159 to 0.970)
    0.211 (-99999 to 99999)
        Ang II, 4 hours post-dose (Day 1), n=4,5,5,8
    0.372 (0.159 to 0.872)
    0.187 (-99999 to 99999)
    0.398 (0.161 to 0.980)
    0.387 (0.160 to 0.933)
        Ang II, 8 hours post-dose (Day 1), n=4,5,5,8
    0.889 (0.148 to 5.327)
    0.669 (0.249 to 1.798)
    0.503 (0.311 to 0.813)
    0.277 (0.080 to 0.963)
        Ang II, 24 hours post-dose (Day 1), n=4,5,5,8
    2.329 (0.692 to 7.836)
    1.372 (0.462 to 4.070)
    0.763 (0.267 to 2.184)
    0.939 (0.186 to 4.751)
        Ang II, Day 7 to Day 14, n=4,5,5,7
    1.625 (0.084 to 31.300)
    2.380 (0.703 to 8.063)
    0.616 (0.115 to 3.307)
    1.826 (0.399 to 8.354)
        Ang (1-5), 0.08 hour post-dose (Day 1), n=4,5,4,6
    1.884 (0.505 to 7.026)
    4.696 (1.303 to 16.923)
    2.222 (0.774 to 6.373)
    2.982 (1.360 to 6.535)
        Ang (1-5), 0.5 hour post-dose (Day 1), n=4,5,4,6
    2.342 (0.435 to 12.622)
    5.325 (1.427 to 19.873)
    2.895 (1.206 to 6.950)
    3.187 (1.303 to 7.797)
        Ang (1-5), 1 hour post-dose (Day 1), n=4,5,4,6
    2.427 (0.414 to 14.225)
    4.263 (1.463 to 12.418)
    2.572 (0.775 to 8.539)
    3.264 (1.134 to 9.396)
        Ang (1-5), 2 hours post-dose (Day 1), n=4,5,4,6
    2.269 (0.344 to 14.945)
    3.499 (1.377 to 8.890)
    3.423 (0.698 to 16.789)
    2.463 (0.982 to 6.174)
        Ang (1-5), 4 hours post-dose (Day 1), n=4,5,4,6
    2.442 (0.344 to 17.340)
    2.740 (1.245 to 6.033)
    3.513 (0.750 to 16.459)
    2.717 (1.033 to 7.146)
        Ang (1-5), 8 hours post-dose (Day 1), n=4,5,4,6
    4.365 (1.094 to 17.420)
    4.125 (0.716 to 23.775)
    6.691 (0.812 to 55.117)
    4.882 (1.581 to 15.072)
        Ang (1-5), 24 hours post-dose (Day 1), n=4,5,4,6
    2.397 (0.879 to 6.536)
    3.701 (1.413 to 9.690)
    2.573 (0.403 to 16.426)
    5.117 (1.910 to 13.712)
        Ang (1-5), Day 7 to Day 14, n=4,5,3,6
    1.469 (0.714 to 3.020)
    2.110 (0.775 to 5.744)
    0.548 (-99999 to 99999)
    1.642 (0.781 to 3.450)
        Ang (1-7), 0.08 hour post-dose (Day 1), n=4,5,5,7
    2.252 (0.366 to 13.855)
    4.392 (1.405 to 13.732)
    3.465 (1.025 to 11.719)
    1.817 (0.969 to 3.405)
        Ang (1-7), 0.5 hour post-dose (Day 1), n=4,5,5,7
    2.943 (0.335 to 25.843)
    4.935 (1.383 to 17.617)
    2.242 (0.639 to 7.865)
    2.205 (1.260 to 3.859)
        Ang (1-7), 1 hour post-dose (Day 1), n=4,5,5,7
    3.002 (0.318 to 28.319)
    3.494 (1.438 to 8.490)
    2.362 (0.542 to 10.291)
    1.780 (0.783 to 4.047)
        Ang (1-7), 2 hours post-dose (Day 1), n=4,5,5,7
    2.311 (0.161 to 33.222)
    4.025 (1.393 to 11.630)
    3.471 (0.651 to 18.500)
    1.949 (1.012 to 3.756)
        Ang (1-7), 4 hours post-dose (Day 1), n=4,5,5,7
    3.350 (0.230 to 48.748)
    3.115 (1.349 to 7.190)
    3.623 (0.679 to 19.331)
    1.818 (0.715 to 4.623)
        Ang (1-7), 8 hours post-dose (Day 1), n=4,5,5,7
    4.910 (0.654 to 36.845)
    3.517 (0.635 to 19.477)
    6.002 (0.762 to 47.289)
    4.229 (1.433 to 12.477)
        Ang (1-7), 24 hours post-dose (Day 1), n=4,5,5,7
    3.423 (0.618 to 18.944)
    4.096 (1.430 to 11.730)
    2.812 (0.503 to 15.732)
    7.095 (2.426 to 20.752)
        Ang (1-7), Day 7 to Day 14, n=4,5,5,6
    1.190 (0.684 to 2.073)
    1.904 (0.596 to 6.089)
    0.925 (-99999 to 99999)
    1.932 (1.111 to 3.362)
    Notes
    [96] - Evaluable Population
    [97] - Evaluable Population
    [98] - Evaluable Population
    [99] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in pulmonary wedge RAS peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

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    End point title
    		 Change from Baseline in pulmonary wedge RAS peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)
    End point description
    Blood samples were collected to evaluate pulmonary wedge RAS peptides: Ang II, Ang (1-7) and Ang (1-5). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). 99999 indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [100]
    4 [101]
    4 [102]
    8 [103]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Ang II, 1 hour post-dose (Day 1), n=4,4,4,8
    0.270 (0.059 to 1.244)
    0.190 (0.025 to 1.475)
    0.394 (0.046 to 3.414)
    0.369 (-99999 to 99999)
        Ang II, 2 hours post-dose (Day 1), n=4,4,4,8
    0.310 (0.068 to 1.419)
    0.193 (0.025 to 1.476)
    0.505 (0.147 to 1.738)
    0.369 (-99999 to 99999)
        Ang II, 4 hours post-dose (Day 1), n=4,4,3,8
    0.332 (0.089 to 1.240)
    0.191 (0.025 to 1.475)
    0.183 (0.038 to 0.879)
    0.420 (-99999 to 99999)
        Ang (1-5), 1 hour post-dose (Day 1), n=4,4,4,7
    2.985 (0.279 to 31.931)
    3.313 (0.892 to 12.310)
    2.709 (0.792 to 9.269)
    1.834 (0.743 to 4.528)
        Ang (1-5), 2 hours post-dose (Day 1), n=4,4,3,7
    3.443 (0.282 to 42.025)
    4.621 (0.803 to 26.600)
    5.246 (1.386 to 19.859)
    1.562 (0.566 to 4.312)
        Ang (1-5), 4 hours post-dose (Day 1), n=4,4,3,7
    2.373 (0.401 to 14.050)
    3.213 (0.757 to 13.646)
    5.239 (1.565 to 17.541)
    1.472 (0.575 to 3.768)
        Ang (1-7), 1 hour post-dose (Day 1), n=4,4,4,8
    2.840 (0.353 to 22.846)
    4.150 (0.912 to 18.880)
    2.993 (0.356 to 25.136)
    1.558 (0.969 to 2.504)
        Ang (1-7), 2 hours post-dose (Day 1), n=4,4,4,8
    3.376 (0.279 to 40.910)
    3.792 (0.878 to 16.368)
    4.476 (0.612 to 32.754)
    1.589 (0.830 to 3.043)
        Ang (1-7), 4 hours post-dose (Day 1), n=4,4,3,8
    2.857 (0.362 to 22.550)
    3.151 (0.849 to 11.693)
    8.521 (0.733 to 99.048)
    1.693 (0.818 to 3.504)
    Notes
    [100] - Evaluable Population
    [101] - Evaluable Population
    [102] - Evaluable Population
    [103] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Systemic RAS peptide: Angiotensin II/Angiotensin (1-7) ratio at indicated time points

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    End point title
    		 Systemic RAS peptide: Angiotensin II/Angiotensin (1-7) ratio at indicated time points
    End point description
    Blood samples were collected to assess systemic RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented. Assessment of follow up visit was conducted between any day of Days 7 to 14. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). 99999 indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
    End point type
    Secondary
    End point timeframe
    0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [104]
    5 [105]
    5 [106]
    8 [107]
    Units: Ratio
    geometric mean (confidence interval 95%)
        0.08 hour post-dose (Day 1), n=4,5,5,8
    0.752 (0.175 to 3.239)
    0.463 (-99999 to 99999)
    1.450 (0.313 to 6.711)
    0.843 (0.491 to 1.447)
        0.5 hour post-dose (Day 1), n=4,5,5,8
    0.718 (0.186 to 2.779)
    0.468 (-99999 to 99999)
    1.097 (-99999 to 99999)
    0.590 (-99999 to 99999)
        1 hour post-dose (Day 1), n=4,5,5,8
    0.937 (0.351 to 2.504)
    0.509 (-99999 to 99999)
    0.875 (-99999 to 99999)
    0.794 (-99999 to 99999)
        2 hours post-dose (Day 1), n=4,5,5,8
    1.174 (0.539 to 2.559)
    0.455 (-99999 to 99999)
    0.558 (0.150 to 2.077)
    0.657 (-99999 to 99999)
        4 hours post-dose (Day 1), n=4,5,5,8
    1.312 (0.571 to 3.011)
    0.659 (-99999 to 99999)
    0.540 (0.136 to 2.144)
    1.283 (0.530 to 3.102)
        8 hours post-dose (Day 1), n=4,5,5,8
    2.139 (0.623 to 7.339)
    2.093 (0.778 to 5.625)
    0.412 (0.083 to 2.055)
    0.439 (0.181 to 1.062)
        24 hours post-dose (Day 1), n=4,5,5,8
    8.041 (2.416 to 26.757)
    3.682 (1.929 to 7.030)
    1.335 (0.908 to 1.965)
    0.946 (0.435 to 2.054)
        Day 7 to Day 14, n=4,5,5,7
    16.132 (1.204 to 216.087)
    13.742 (3.829 to 49.326)
    3.278 (-99999 to 99999)
    6.156 (2.618 to 14.479)
    Notes
    [104] - Evaluable Population
    [105] - Evaluable Population
    [106] - Evaluable Population
    [107] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Pulmonary Wedge RAS peptide: Angiotensin II/Angiotensin (1-7) ratio at indicated time points

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    End point title
    		 Pulmonary Wedge RAS peptide: Angiotensin II/Angiotensin (1-7) ratio at indicated time points
    End point description
    Blood samples were collected to assess pulmonary wedge RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). 99999 indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
    End point type
    Secondary
    End point timeframe
    1 hour, 2 hours and 4 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [108]
    4 [109]
    4 [110]
    8 [111]
    Units: Ratio
    geometric mean (confidence interval 95%)
        1 hour post-dose (Day 1), n=4,4,4,8
    0.888 (0.275 to 2.866)
    0.443 (0.108 to 1.821)
    0.620 (0.058 to 6.650)
    0.789 (-99999 to 99999)
        2 hours post-dose (Day 1), n=4,4,4,8
    0.858 (0.253 to 2.908)
    0.493 (0.116 to 2.096)
    0.531 (0.117 to 2.403)
    0.774 (-99999 to 99999)
        4 hours post-dose (Day 1), n=4,4,3,8
    1.085 (0.478 to 2.462)
    0.587 (0.172 to 2.003)
    0.148 (0.012 to 1.759)
    0.826 (-99999 to 99999)
    Notes
    [108] - Evaluable Population
    [109] - Evaluable Population
    [110] - Evaluable Population
    [111] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in disease biomarkers: N-terminal pro B-type natriuretic peptide (NT pro-BNP)

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    End point title
    		 Change from Baseline in disease biomarkers: N-terminal pro B-type natriuretic peptide (NT pro-BNP)
    End point description
    Blood samples were collected at specific time points to evaluate NT pro-BNP, a biomarker of disease activity. NT-pro-BNP is a biomarker of cardiac stress or ventricular workload and decreases as a result of reduced force of contraction if pulmonary blood pressure is reduced. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [112]
    5 [113]
    4 [114]
    8 [115]
    Units: Ratio
    geometric mean (confidence interval 95%)
        2 hours post-dose (Day 1)
    1.034 (0.955 to 1.119)
    1.005 (0.842 to 1.199)
    0.923 (0.795 to 1.071)
    1.015 (0.841 to 1.224)
        4 hours post-dose (Day 1)
    1.025 (0.924 to 1.138)
    1.042 (0.852 to 1.276)
    0.944 (0.795 to 1.120)
    1.074 (0.840 to 1.373)
        24 hours post-dose (Day 1)
    0.606 (0.253 to 1.453)
    0.896 (0.481 to 1.670)
    0.703 (0.430 to 1.151)
    0.810 (0.539 to 1.217)
    Notes
    [112] - Evaluable Population
    [113] - Evaluable Population
    [114] - Evaluable Population
    [115] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in nitrite, nitrate and endogenous nitrite (biomarkers of nitric oxide [NO])

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    End point title
    		 Change from Baseline in nitrite, nitrate and endogenous nitrite (biomarkers of nitric oxide [NO])
    End point description
    Blood samples were collected at specific time points to evaluate levels of nitrite, nitrate and endogenous nitrite (En. nitrite) (biomarkers of NO). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [116]
    4 [117]
    5 [118]
    8 [119]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Nitrite, 2 hours post-dose (Day 1), n=4,4,5,8
    1.246 (0.440 to 3.533)
    1.029 (0.870 to 1.216)
    0.530 (0.145 to 1.931)
    0.858 (0.797 to 0.923)
        Nitrite, 4 hours post-dose (Day 1), n=4,4,5,8
    0.760 (0.635 to 0.910)
    0.992 (0.749 to 1.312)
    0.679 (0.420 to 1.096)
    0.770 (0.654 to 0.907)
        Nitrite, 24 hours post-dose (Day 1), n=4,4,4,7
    1.038 (0.898 to 1.199)
    1.146 (1.044 to 1.259)
    0.667 (0.245 to 1.814)
    0.914 (0.605 to 1.381)
        Nitrate, 2 hours post-dose (Day 1), n=4,4,5,8
    1.251 (0.432 to 3.623)
    1.025 (0.862 to 1.218)
    0.485 (0.108 to 2.177)
    0.836 (0.768 to 0.910)
        Nitrate, 4 hours post-dose (Day 1), n=4,4,5,8
    0.739 (0.595 to 0.917)
    0.977 (0.700 to 1.362)
    0.655 (0.395 to 1.086)
    0.762 (0.649 to 0.895)
        Nitrate, 24 hours post-dose (Day 1), n=4,4,4,7
    1.017 (0.853 to 1.212)
    1.149 (1.049 to 1.259)
    0.641 (0.222 to 1.854)
    0.911 (0.597 to 1.390)
        En. nitrite, 2 hours post-dose (Day 1), n=4,4,5,8
    1.099 (0.798 to 1.512)
    2.036 (0.309 to 13.411)
    1.171 (0.878 to 1.563)
    0.975 (0.647 to 1.469)
        En. nitrite, 4 hours post-dose (Day 1), n=4,4,5,8
    1.245 (0.665 to 2.330)
    2.819 (0.079 to 100.021)
    1.329 (0.643 to 2.747)
    0.820 (0.466 to 1.443)
        En. nitrite, 24 hours post-dose (Day 1), n=4,4,4,7
    1.290 (0.543 to 3.063)
    1.399 (0.503 to 3.894)
    1.289 (0.501 to 3.316)
    1.271 (0.614 to 2.634)
    Notes
    [116] - Evaluable Population
    [117] - Evaluable Population
    [118] - Evaluable Population
    [119] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in disease biomarker: cardiac troponin-I

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    End point title
    		 Change from Baseline in disease biomarker: cardiac troponin-I
    End point description
    Blood samples were collected at specific time points to assess cardiac troponin I. Cardiac troponin I is a biomarker of cardiac stress. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed. 99999 indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [120]
    5 [121]
    5 [122]
    8 [123]
    Units: Ratio
    geometric mean (confidence interval 95%)
        2 hours post-dose (Day 1)
    1.565 (0.660 to 3.714)
    1.320 (0.824 to 2.114)
    1.585 (0.657 to 3.822)
    1.414 (0.761 to 2.628)
        4 hours post-dose (Day 1)
    1.968 (0.543 to 7.131)
    1.149 (0.782 to 1.688)
    1.695 (0.592 to 4.856)
    2.030 (1.064 to 3.873)
        24 hours post-dose (Day 1)
    1.316 (0.549 to 3.154)
    1.000 (-99999 to 99999)
    1.000 (-99999 to 99999)
    1.000 (-99999 to 99999)
    Notes
    [120] - Evaluable Population
    [121] - Evaluable Population
    [122] - Evaluable Population
    [123] - Evaluable Population
    No statistical analyses for this end point

    Secondary: Maximum observed plasma concentration (Cmax) of GSK2586881

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    End point title
    		 Maximum observed plasma concentration (Cmax) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of Cmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic population comprised of participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [124]
    5 [125]
    6 [126]
    8 [127]
    Units: Micrograms per milliliter
        geometric mean (geometric coefficient of variation)
    1.5159 ± 37.0
    4.0229 ± 37.4
    8.9701 ± 26.1
    14.8042 ± 33.1
    Notes
    [124] - Pharmacokinetic Population
    [125] - Pharmacokinetic Population
    [126] - Pharmacokinetic Population
    [127] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Time to Cmax (tmax) of GSK2586881

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    End point title
    		 Time to Cmax (tmax) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of tmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [128]
    5 [129]
    6 [130]
    8 [131]
    Units: Hours
        median (full range (min-max))
    0.08333 (0.0833 to 0.1333)
    0.16667 (0.0667 to 0.5000)
    0.10000 (0.0667 to 0.5500)
    0.13333 (0.0833 to 0.6333)
    Notes
    [128] - Pharmacokinetic Population
    [129] - Pharmacokinetic Population
    [130] - Pharmacokinetic Population
    [131] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC[0-t]) of GSK2586881

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    End point title
    		 Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC[0-t]) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of AUC(0-t). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [132]
    5 [133]
    6 [134]
    8 [135]
    Units: Hours*micrograms per milliliter
        geometric mean (geometric coefficient of variation)
    3.941 ± 53.6
    17.874 ± 30.9
    46.789 ± 16.3
    68.042 ± 37.0
    Notes
    [132] - Pharmacokinetic Population
    [133] - Pharmacokinetic Population
    [134] - Pharmacokinetic Population
    [135] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) of GSK2586881

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    End point title
    		 Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of AUC(0-inf). Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed. 99999 indicates terminal elimination phase could not be identified from the concentration-time profile for any participants in the 0.1 mg/kg treatment group over the study period; hence, AUC(0-inf) could not be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [136]
    2 [137]
    6 [138]
    7 [139]
    Units: Hours*micrograms per milliliter
        geometric mean (geometric coefficient of variation)
    99999 ± 99999
    25.26 ± 7.7
    52.46 ± 20.0
    76.87 ± 42.1
    Notes
    [136] - Pharmacokinetic Population
    [137] - Pharmacokinetic Population
    [138] - Pharmacokinetic Population
    [139] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Last observed quantifiable concentration (Ct) of GSK2586881

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    End point title
    		 Last observed quantifiable concentration (Ct) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of Ct. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [140]
    5 [141]
    6 [142]
    8 [143]
    Units: Micrograms per milliliter
        geometric mean (geometric coefficient of variation)
    0.2563 ± 22.8
    0.3327 ± 54.4
    0.4800 ± 44.9
    0.6380 ± 54.9
    Notes
    [140] - Pharmacokinetic Population
    [141] - Pharmacokinetic Population
    [142] - Pharmacokinetic Population
    [143] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Time of the last quantifiable concentration (tlast) of GSK2586881

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    End point title
    		 Time of the last quantifiable concentration (tlast) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of tlast. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [144]
    5 [145]
    6 [146]
    8 [147]
    Units: Hours
        median (full range (min-max))
    8.000 (4.20 to 8.47)
    24.000 (8.18 to 24.25)
    24.017 (23.73 to 24.15)
    24.117 (23.97 to 24.28)
    Notes
    [144] - Pharmacokinetic Population
    [145] - Pharmacokinetic Population
    [146] - Pharmacokinetic Population
    [147] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Plasma clearance (CL) of GSK2586881

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    End point title
    		 Plasma clearance (CL) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of CL. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed. 99999 indicates terminal elimination phase could not be identified from the concentration-time profile for any participants in the 0.1 mg/kg treatment group over the study period; hence, CL could not be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [148]
    2 [149]
    6 [150]
    7 [151]
    Units: Liters per hour
        geometric mean (geometric coefficient of variation)
    99999 ± 99999
    0.5838 ± 10.1
    0.6207 ± 16.8
    0.8170 ± 30.8
    Notes
    [148] - Pharmacokinetic Population
    [149] - Pharmacokinetic Population
    [150] - Pharmacokinetic Population
    [151] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Apparent volume of distribution of GSK2586881

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    End point title
    		 Apparent volume of distribution of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed. 99999 indicates terminal elimination phase could not be identified from the concentration-time profile for any participants in the 0.1 mg/kg treatment group over the study period; hence, apparent volume of distribution could not be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [152]
    2 [153]
    6 [154]
    7 [155]
    Units: Liters
        geometric mean (geometric coefficient of variation)
    99999 ± 99999
    6.443 ± 2.4
    6.593 ± 20.5
    8.084 ± 20.6
    Notes
    [152] - Pharmacokinetic Population
    [153] - Pharmacokinetic Population
    [154] - Pharmacokinetic Population
    [155] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Apparent terminal phase half-life (t1/2) of GSK2586881

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    End point title
    		 Apparent terminal phase half-life (t1/2) of GSK2586881
    End point description
    Blood samples were collected at indicated time points for evaluation of t1/2. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed. 99999 indicates terminal elimination phase could not be identified from the concentration-time profile for any participants in the 0.1 mg/kg treatment group over the study period; hence, t1/2 could not be estimated.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [156]
    2 [157]
    6 [158]
    7 [159]
    Units: Hours
        geometric mean (geometric coefficient of variation)
    99999 ± 99999
    7.651 ± 7.7
    7.362 ± 23.2
    6.858 ± 19.6
    Notes
    [156] - Pharmacokinetic Population
    [157] - Pharmacokinetic Population
    [158] - Pharmacokinetic Population
    [159] - Pharmacokinetic Population
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in cardiac index (CI)

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    End point title
    		 Change from Baseline in cardiac index (CI)
    End point description
    Cardiac index (CI) was measured using thermodilution. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
    End point values
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Number of subjects analysed
    4 [160]
    5 [161]
    5 [162]
    8 [163]
    Units: Ratio
    geometric mean (confidence interval 95%)
        1 hour post-dose (Day 1)
    1.045 (0.874 to 1.248)
    1.076 (0.947 to 1.223)
    1.084 (0.766 to 1.533)
    0.990 (0.948 to 1.034)
        2 hours post-dose (Day 1)
    1.021 (0.816 to 1.278)
    1.029 (0.951 to 1.113)
    0.926 (0.719 to 1.193)
    1.020 (0.948 to 1.097)
        4 hours post-dose (Day 1)
    1.107 (0.801 to 1.530)
    1.128 (0.941 to 1.352)
    0.889 (0.740 to 1.068)
    1.000 (0.933 to 1.072)
    Notes
    [160] - Evaluable Population
    [161] - Evaluable Population
    [162] - Evaluable Population
    [163] - Evaluable Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-SAEs and SAEs were reported from start of study treatment and up to Day 28
    Adverse event reporting additional description
    Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    GSK2586881 0.1 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.2 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.4 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Reporting group title
    GSK2586881 0.8 mg/kg
    Reporting group description
    		 Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.

    Serious adverse events
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 8 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 5 (60.00%)
    5 / 6 (83.33%)
    2 / 8 (25.00%)
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    2 / 6 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 May 2017
    Amendment 1: Protocol was amended to include risk of exposure to ionizing radiating which was previously omitted as well as for updating information around participants re-screening numbers.
    07 Nov 2017
    Amendment 2: This was a non-substantial amendment to clarify the target population to be enrolled, the changes made to the inclusion and exclusion criteria. In addition, an upper limit for the six minute walk (6MW) was added, the evaluable population was changed, and the proposed linear regression analysis was expanded.
    01 Dec 2017
    Amendment 3: This was a substantial amendment to enable characterization of the response at a lower starting level of 0.1 mg/kg GSK2586881.
    10 Jul 2018
    Amendment 4: This was a substantial amendment with changes to the inclusion and exclusion criteria to more accurately reflect the participant population.

    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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