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Trial record 2 of 3 for:    GSK2586881
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A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03177603
Recruitment Status : Completed
First Posted : June 6, 2017
Results First Posted : April 21, 2020
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension, Pulmonary
Intervention Drug: GSK2586881
Enrollment 23
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 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.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Period Title: Cohort 1: Dose Level 0.1 mg/kg (28 Days)
Started 4 0 0 0
Completed 4 0 0 0
Not Completed 0 0 0 0
Period Title: Cohort 2: Dose Level 0.2 mg/kg (28 Days)
Started 0 5 0 0
Completed 0 5 0 0
Not Completed 0 0 0 0
Period Title: Cohort 3: Dose Level 0.4 mg/kg (28 Days)
Started 0 0 6 0
Completed 0 0 6 0
Not Completed 0 0 0 0
Period Title: Cohort 4: Dose Level 0.8 mg/kg (28 Days)
Started 0 0 0 8
Completed 0 0 0 8
Not Completed 0 0 0 0
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg Total
Hide Arm/Group Description Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose. Total of all reporting groups
Overall Number of Baseline Participants 4 5 6 8 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 5 participants 6 participants 8 participants 23 participants
32.0  (4.97) 55.4  (14.96) 52.5  (8.67) 50.3  (13.35) 48.8  (13.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 6 participants 8 participants 23 participants
Female
3
  75.0%
3
  60.0%
4
  66.7%
5
  62.5%
15
  65.2%
Male
1
  25.0%
2
  40.0%
2
  33.3%
3
  37.5%
8
  34.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 6 participants 8 participants 23 participants
Black or African American
0
   0.0%
1
  20.0%
1
  16.7%
1
  12.5%
3
  13.0%
White - White/Caucasian/European Heritage
4
 100.0%
4
  80.0%
5
  83.3%
7
  87.5%
20
  87.0%
1.Primary Outcome
Title Change From Baseline in Pulmonary Vascular Resistance (PVR)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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)
2.Primary Outcome
Title Change From Baseline in Cardiac Output (CO)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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)
3.Primary Outcome
Title Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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)
4.Secondary Outcome
Title Number of Participants With Non-serious Adverse Events (AEs)
Hide 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.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprised of all participants who took at least 1 dose of study treatment.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Measure Type: Count of Participants
Unit of Measure: Participants
1
  25.0%
3
  60.0%
5
  83.3%
2
  25.0%
5.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs)
Hide 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.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: International units per liter
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)
7.Secondary Outcome
Title Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter
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)
8.Secondary Outcome
Title Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Millimoles per liter
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)
9.Secondary Outcome
Title Change From Baseline in Clinical Chemistry Parameter: Total Protein
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Grams per liter
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)
10.Secondary Outcome
Title Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Giga cells per liter
Basophils, 24 hours post-dose (Day 1), n=4,4,6,3 Number Analyzed 4 participants 4 participants 6 participants 3 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 4 participants 6 participants 3 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 3 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 3 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 4 participants 6 participants 3 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-0.20  (1.334) 0.46  (0.498) 0.20  (1.355) 0.64  (0.588)
11.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Hemoglobin
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Grams per liter
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-4.3  (6.55) 3.4  (5.98) -1.5  (7.09) 4.0  (5.15)
12.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Hematocrit
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Proportion of red blood cells in blood
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-0.0225  (0.00929) 0.0104  (0.02173) 0.0030  (0.02391) 0.0135  (0.01891)
13.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Picograms
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
0.10  (0.483) 0.04  (0.182) -0.33  (0.314) 0.15  (0.177)
14.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Femtoliters
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-1.5  (2.08) -0.2  (0.84) 0.7  (1.03) 0.8  (1.04)
15.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Trillion cells per liter
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-0.20  (0.183) 0.14  (0.261) 0.00  (0.310) 0.11  (0.203)
16.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Reticulocytes
Hide 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.
Time Frame Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Percentage of reticulocytes in blood
24 hours post-dose (Day 1), n=4,4,6,5 Number Analyzed 4 participants 4 participants 6 participants 5 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
0.0058  (0.00411) 0.0014  (0.00358) 0.0025  (0.00333) 0.0040  (0.00325)
17.Secondary Outcome
Title Number of Participants With Urinalysis Results by Dipstick Method
Hide 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.
Time Frame 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Measure Type: Count of Participants
Unit of Measure: Participants
Bilirubin, 24 hours post-dose (Day 1), negative
4
 100.0%
5
 100.0%
6
 100.0%
8
 100.0%
Bilirubin, 24 hours post-dose (Day 1), trace
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bilirubin, 24 hours post-dose (Day 1), 1+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bilirubin, 24 hours post-dose (Day 1), 2+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bilirubin, 24 hours post-dose (Day 1), 3+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Occult Blood, 24 hours post-dose (Day 1), negative
2
  50.0%
5
 100.0%
4
  66.7%
7
  87.5%
Occult Blood, 24 hours post-dose (Day 1), trace
0
   0.0%
0
   0.0%
2
  33.3%
1
  12.5%
Occult Blood, 24 hours post-dose (Day 1), 1+
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
Occult Blood, 24 hours post-dose (Day 1), 2+
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
Occult Blood, 24 hours post-dose (Day 1), 3+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose, 24 hours post-dose (Day 1), negative
4
 100.0%
5
 100.0%
5
  83.3%
8
 100.0%
Glucose, 24 hours post-dose (Day 1), trace
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose, 24 hours post-dose (Day 1), 1+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose, 24 hours post-dose (Day 1), 2+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose, 24 hours post-dose (Day 1), 3+
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Ketones, 24 hours post-dose (Day 1), negative
4
 100.0%
4
  80.0%
3
  50.0%
8
 100.0%
Ketones, 24 hours post-dose (Day 1), trace
0
   0.0%
1
  20.0%
3
  50.0%
0
   0.0%
Ketones, 24 hours post-dose (Day 1), 1+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ketones, 24 hours post-dose (Day 1), 2+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ketones, 24 hours post-dose (Day 1), 3+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Protein, 24 hours post-dose (Day 1), negative
4
 100.0%
4
  80.0%
6
 100.0%
8
 100.0%
Protein, 24 hours post-dose (Day 1), trace
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
Protein, 24 hours post-dose (Day 1), 1+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Protein, 24 hours post-dose (Day 1), 2+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Protein, 24 hours post-dose (Day 1), 3+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18.Secondary Outcome
Title Change From Baseline in Pulse Rate
Hide 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Beats per minute
0.5 hour post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 8 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
10.0  (14.31) 4.4  (5.86) 5.3  (6.25) 9.8  (8.36)
19.Secondary Outcome
Title Change From Baseline in Respiratory Rate
Hide 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Breaths per minute
0.5 hour post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-0.5  (1.73) -0.4  (3.58) 2.0  (2.28) 0.3  (1.16)
20.Secondary Outcome
Title Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Hide 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
DBP, 0.5 hour post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
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 Number Analyzed 4 participants 4 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
2.0  (21.37) 6.0  (6.78) -5.8  (15.07) -2.1  (9.63)
21.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide 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.
Time Frame 4 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Measure Type: Count of Participants
Unit of Measure: Participants
Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
1
  25.0%
3
  60.0%
3
  50.0%
7
  87.5%
Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8 Number Analyzed 3 participants 5 participants 6 participants 8 participants
1
  33.3%
3
  60.0%
4
  66.7%
5
  62.5%
Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8 Number Analyzed 3 participants 5 participants 6 participants 8 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal NCS, Day 7 to Day 14, n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
1
  25.0%
3
  60.0%
3
  50.0%
3
  37.5%
Abnormal CS, Day 7 to Day 14, n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
22.Secondary Outcome
Title Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood
Hide 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Mean (Standard Deviation)
Unit of Measure: Percentage of oxygen in blood
0.5 hour post-dose (Day 1), n=4,5,6,8 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 4 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-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 Number Analyzed 4 participants 5 participants 6 participants 8 participants
-0.2  (0.95) -2.9  (2.37) 0.5  (3.33) 0.8  (2.49)
23.Secondary Outcome
Title Number of Participants With Positive Immunogenicity Results
Hide 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.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
24.Secondary Outcome
Title Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)
Hide Description Blood samples were collected to evaluate systemic RAS peptides: Angiotensin (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. Assessment of follow up visit was conducted between any day of Days 7 to 14.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Ang II, 0.08 hour post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.143
(0.028 to 0.723)
0.185 [1] 
(NA to NA)
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.179
(0.040 to 0.792)
0.210 [2] 
(NA to NA)
0.500
(0.065 to 3.825)
0.211 [2] 
(NA to NA)
Ang II, 1 hour post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.238
(0.097 to 0.582)
0.162 [2] 
(NA to NA)
0.420
(0.086 to 2.062)
0.235 [2] 
(NA to NA)
Ang II, 2 hours post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.230
(0.041 to 1.280)
0.166 [2] 
(NA to NA)
0.393
(0.159 to 0.970)
0.211 [2] 
(NA to NA)
Ang II, 4 hours post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.372
(0.159 to 0.872)
0.187 [2] 
(NA to NA)
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 4 participants 6 participants
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 Number Analyzed 4 participants 5 participants 3 participants 6 participants
1.469
(0.714 to 3.020)
2.110
(0.775 to 5.744)
0.548 [2] 
(NA to NA)
1.642
(0.781 to 3.450)
Ang (1-7), 0.08 hour post-dose (Day 1), n=4,5,5,7 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
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 Number Analyzed 4 participants 5 participants 5 participants 6 participants
1.190
(0.684 to 2.073)
1.904
(0.596 to 6.089)
0.925 [2] 
(NA to NA)
1.932
(1.111 to 3.362)
[1]
NA indicates confidence interval could not be estimated as more than 75 percentage (%) of the values were below lower limit of quantification.
[2]
NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
25.Secondary Outcome
Title Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)
Hide Description Blood samples were collected to evaluate pulmonary wedge RAS peptides: 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.
Time Frame Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 4 4 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Ang II, 1 hour post-dose (Day 1), n=4,4,4,8 Number Analyzed 4 participants 4 participants 4 participants 8 participants
0.270
(0.059 to 1.244)
0.190
(0.025 to 1.475)
0.394
(0.046 to 3.414)
0.369 [1] 
(NA to NA)
Ang II, 2 hours post-dose (Day 1), n=4,4,4,8 Number Analyzed 4 participants 4 participants 4 participants 8 participants
0.310
(0.068 to 1.419)
0.193
(0.025 to 1.476)
0.505
(0.147 to 1.738)
0.369 [1] 
(NA to NA)
Ang II, 4 hours post-dose (Day 1), n=4,4,3,8 Number Analyzed 4 participants 4 participants 3 participants 8 participants
0.332
(0.089 to 1.240)
0.191
(0.025 to 1.475)
0.183
(0.038 to 0.879)
0.420 [1] 
(NA to NA)
Ang (1-5), 1 hour post-dose (Day 1), n=4,4,4,7 Number Analyzed 4 participants 4 participants 4 participants 7 participants
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 Number Analyzed 4 participants 4 participants 3 participants 7 participants
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 Number Analyzed 4 participants 4 participants 3 participants 7 participants
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 Number Analyzed 4 participants 4 participants 4 participants 8 participants
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 Number Analyzed 4 participants 4 participants 4 participants 8 participants
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 Number Analyzed 4 participants 4 participants 3 participants 8 participants
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)
[1]
NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
26.Secondary Outcome
Title Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points
Hide 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
0.08 hour post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.752
(0.175 to 3.239)
0.463 [1] 
(NA to NA)
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.718
(0.186 to 2.779)
0.468 [1] 
(NA to NA)
1.097 [1] 
(NA to NA)
0.590 [1] 
(NA to NA)
1 hour post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
0.937
(0.351 to 2.504)
0.509 [1] 
(NA to NA)
0.875 [1] 
(NA to NA)
0.794 [1] 
(NA to NA)
2 hours post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
1.174
(0.539 to 2.559)
0.455 [1] 
(NA to NA)
0.558
(0.150 to 2.077)
0.657 [1] 
(NA to NA)
4 hours post-dose (Day 1), n=4,5,5,8 Number Analyzed 4 participants 5 participants 5 participants 8 participants
1.312
(0.571 to 3.011)
0.659 [1] 
(NA to NA)
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
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 Number Analyzed 4 participants 5 participants 5 participants 8 participants
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 Number Analyzed 4 participants 5 participants 5 participants 7 participants
16.132
(1.204 to 216.087)
13.742
(3.829 to 49.326)
3.278 [1] 
(NA to NA)
6.156
(2.618 to 14.479)
[1]
NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
27.Secondary Outcome
Title Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points
Hide 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.
Time Frame 1 hour, 2 hours and 4 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 4 4 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1 hour post-dose (Day 1), n=4,4,4,8 Number Analyzed 4 participants 4 participants 4 participants 8 participants
0.888
(0.275 to 2.866)
0.443
(0.108 to 1.821)
0.620
(0.058 to 6.650)
0.789 [1] 
(NA to NA)
2 hours post-dose (Day 1), n=4,4,4,8 Number Analyzed 4 participants 4 participants 4 participants 8 participants
0.858
(0.253 to 2.908)
0.493
(0.116 to 2.096)
0.531
(0.117 to 2.403)
0.774 [1] 
(NA to NA)
4 hours post-dose (Day 1), n=4,4,3,8 Number Analyzed 4 participants 4 participants 3 participants 8 participants
1.085
(0.478 to 2.462)
0.587
(0.172 to 2.003)
0.148
(0.012 to 1.759)
0.826 [1] 
(NA to NA)
[1]
NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
28.Secondary Outcome
Title Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 4 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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)
29.Secondary Outcome
Title Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO])
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 4 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Nitrite, 2 hours post-dose (Day 1), n=4,4,5,8 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 4 participants 7 participants
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 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 4 participants 7 participants
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 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 5 participants 8 participants
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 Number Analyzed 4 participants 4 participants 4 participants 7 participants
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)
30.Secondary Outcome
Title Change From Baseline in Disease Biomarker: Cardiac Troponin-I
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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 [1] 
(NA to NA)
1.000 [1] 
(NA to NA)
1.000 [1] 
(NA to NA)
[1]
NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
31.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of Cmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population comprised of participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per milliliter
1.5159
(37.0%)
4.0229
(37.4%)
8.9701
(26.1%)
14.8042
(33.1%)
32.Secondary Outcome
Title Time to Cmax (Tmax) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of tmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Median (Full Range)
Unit of Measure: Hours
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)
33.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of AUC(0-t). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*micrograms per milliliter
3.941
(53.6%)
17.874
(30.9%)
46.789
(16.3%)
68.042
(37.0%)
34.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of AUC(0-inf). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 2 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*micrograms per milliliter
NA [1] 
(NA%)
25.26
(7.7%)
52.46
(20.0%)
76.87
(42.1%)
[1]
The 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.
35.Secondary Outcome
Title Last Observed Quantifiable Concentration (Ct) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of Ct. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per milliliter
0.2563
(22.8%)
0.3327
(54.4%)
0.4800
(44.9%)
0.6380
(54.9%)
36.Secondary Outcome
Title Time of the Last Quantifiable Concentration (Tlast) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of tlast. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 6 8
Median (Full Range)
Unit of Measure: Hours
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)
37.Secondary Outcome
Title Plasma Clearance (CL) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of CL. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 2 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters per hour
NA [1] 
(NA%)
0.5838
(10.1%)
0.6207
(16.8%)
0.8170
(30.8%)
[1]
The 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, plasma clearance could not be estimated.
38.Secondary Outcome
Title Apparent Volume of Distribution of GSK2586881
Hide 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.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 2 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
NA [1] 
(NA%)
6.443
(2.4%)
6.593
(20.5%)
8.084
(20.6%)
[1]
The 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.
39.Secondary Outcome
Title Apparent Terminal Phase Half-life (t1/2) of GSK2586881
Hide Description Blood samples were collected at indicated time points for evaluation of t1/2. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 2 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
NA [1] 
(NA%)
7.651
(7.7%)
7.362
(23.2%)
6.858
(19.6%)
[1]
The 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.
40.Other Pre-specified Outcome
Title Change From Baseline in Cardiac Index (CI)
Hide 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.
Time Frame Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)
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Hide Analysis Population Description
Evaluable Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description:
Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Overall Number of Participants Analyzed 4 5 5 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
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)
Time Frame Non-SAEs and SAEs were reported from start of study treatment and up to Day 28
Adverse Event Reporting Description Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
 
Arm/Group Title GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Hide Arm/Group Description Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose. Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
All-Cause Mortality
GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)      0/5 (0.00%)      0/6 (0.00%)      0/8 (0.00%)    
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GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      0/5 (0.00%)      0/6 (0.00%)      0/8 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
GSK2586881 0.1 mg/kg GSK2586881 0.2 mg/kg GSK2586881 0.4 mg/kg GSK2586881 0.8 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/4 (25.00%)      3/5 (60.00%)      5/6 (83.33%)      2/8 (25.00%)    
Cardiac disorders         
Bradycardia † 1  0/4 (0.00%)  0 0/5 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1
Infections and infestations         
Pneumonia † 1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0
Upper respiratory tract infection † 1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0
Viral upper respiratory tract infection † 1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain † 1  1/4 (25.00%)  1 0/5 (0.00%)  0 2/6 (33.33%)  2 0/8 (0.00%)  0
Pain in extremity † 1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/6 (16.67%)  1 0/8 (0.00%)  0
Nervous system disorders         
Headache † 1  0/4 (0.00%)  0 0/5 (0.00%)  0 0/6 (0.00%)  0 1/8 (12.50%)  1
Respiratory, thoracic and mediastinal disorders         
Cough † 1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders         
Erythema † 1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03177603    
Other Study ID Numbers: 206246
2017-000212-41 ( EudraCT Number )
First Submitted: May 23, 2017
First Posted: June 6, 2017
Results First Submitted: April 6, 2020
Results First Posted: April 21, 2020
Last Update Posted: April 21, 2020