Trial Outcomes & Findings for A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH) (NCT NCT03177603)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Results posted on

2020-04-21

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	GSK2586881 0.1 mg/kg Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Cohort 1: Dose Level 0.1 mg/kg (28 Days) STARTED	4	0	0	0
Cohort 1: Dose Level 0.1 mg/kg (28 Days) COMPLETED	4	0	0	0
Cohort 1: Dose Level 0.1 mg/kg (28 Days) NOT COMPLETED	0	0	0	0
Cohort 2: Dose Level 0.2 mg/kg (28 Days) STARTED	0	5	0	0
Cohort 2: Dose Level 0.2 mg/kg (28 Days) COMPLETED	0	5	0	0
Cohort 2: Dose Level 0.2 mg/kg (28 Days) NOT COMPLETED	0	0	0	0
Cohort 3: Dose Level 0.4 mg/kg (28 Days) STARTED	0	0	6	0
Cohort 3: Dose Level 0.4 mg/kg (28 Days) COMPLETED	0	0	6	0
Cohort 3: Dose Level 0.4 mg/kg (28 Days) NOT COMPLETED	0	0	0	0
Cohort 4: Dose Level 0.8 mg/kg (28 Days) STARTED	0	0	0	8
Cohort 4: Dose Level 0.8 mg/kg (28 Days) COMPLETED	0	0	0	8
Cohort 4: Dose Level 0.8 mg/kg (28 Days) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.	Total n=23 Participants Total of all reporting groups
Age, Continuous	32.0 Years STANDARD_DEVIATION 4.97 • n=5 Participants	55.4 Years STANDARD_DEVIATION 14.96 • n=7 Participants	52.5 Years STANDARD_DEVIATION 8.67 • n=5 Participants	50.3 Years STANDARD_DEVIATION 13.35 • n=4 Participants	48.8 Years STANDARD_DEVIATION 13.55 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	20 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Pulmonary Vascular Resistance (PVR) 1 hour post-dose (Day 1)	0.936 Ratio Interval 0.725 to 1.208	0.885 Ratio Interval 0.686 to 1.141	0.813 Ratio Interval 0.561 to 1.178	1.017 Ratio Interval 0.862 to 1.198
Change From Baseline in Pulmonary Vascular Resistance (PVR) 2 hours post-dose (Day 1)	0.926 Ratio Interval 0.671 to 1.279	1.043 Ratio Interval 0.91 to 1.195	0.945 Ratio Interval 0.788 to 1.134	0.974 Ratio Interval 0.823 to 1.153
Change From Baseline in Pulmonary Vascular Resistance (PVR) 4 hours post-dose (Day 1)	0.907 Ratio Interval 0.552 to 1.49	0.895 Ratio Interval 0.668 to 1.199	0.924 Ratio Interval 0.589 to 1.448	1.116 Ratio Interval 1.05 to 1.186

PRIMARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Cardiac Output (CO) 2 hours post-dose (Day 1)	1.025 Ratio Interval 0.829 to 1.269	1.029 Ratio Interval 0.95 to 1.116	0.929 Ratio Interval 0.712 to 1.21	1.012 Ratio Interval 0.944 to 1.085
Change From Baseline in Cardiac Output (CO) 4 hours post-dose (Day 1)	1.114 Ratio Interval 0.804 to 1.545	1.138 Ratio Interval 0.949 to 1.365	0.882 Ratio Interval 0.734 to 1.06	1.002 Ratio Interval 0.935 to 1.075
Change From Baseline in Cardiac Output (CO) 1 hour post-dose (Day 1)	1.046 Ratio Interval 0.881 to 1.24	1.079 Ratio Interval 0.966 to 1.206	1.076 Ratio Interval 0.758 to 1.528	0.990 Ratio Interval 0.948 to 1.033

PRIMARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) 1 hour post-dose (Day 1)	0.950 Ratio Interval 0.781 to 1.154	0.995 Ratio Interval 0.96 to 1.032	0.939 Ratio Interval 0.799 to 1.104	0.989 Ratio Interval 0.879 to 1.114
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) 2 hours post-dose (Day 1)	0.937 Ratio Interval 0.781 to 1.126	0.994 Ratio Interval 0.924 to 1.07	0.910 Ratio Interval 0.766 to 1.081	0.996 Ratio Interval 0.867 to 1.144
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) 4 hours post-dose (Day 1)	0.991 Ratio Interval 0.812 to 1.211	1.029 Ratio Interval 0.881 to 1.202	0.973 Ratio Interval 0.897 to 1.054	1.062 Ratio Interval 0.958 to 1.177

SECONDARY outcome

Timeframe: Up to Day 28

Population: Safety Population comprised of all participants who took at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Number of Participants With Non-serious Adverse Events (AEs)	1 Participants	3 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Number of Participants With Serious Adverse Events (SAEs)	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase Alkaline phosphatase, 24 hours post-dose (Day 1)	4.8 International units per liter Standard Deviation 8.42	-1.4 International units per liter Standard Deviation 7.44	5.3 International units per liter Standard Deviation 3.08	3.1 International units per liter Standard Deviation 3.48
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase Alkaline phosphatase, Day 7 to Day 14	6.5 International units per liter Standard Deviation 5.00	3.2 International units per liter Standard Deviation 4.21	3.0 International units per liter Standard Deviation 3.52	2.6 International units per liter Standard Deviation 4.31
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase ALT, 24 hours post-dose (Day 1)	-2.0 International units per liter Standard Deviation 2.16	0.0 International units per liter Standard Deviation 1.58	-1.8 International units per liter Standard Deviation 3.76	-0.1 International units per liter Standard Deviation 2.17
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase ALT, Day 7 to Day 14	1.3 International units per liter Standard Deviation 0.96	1.8 International units per liter Standard Deviation 3.27	-4.3 International units per liter Standard Deviation 12.94	0.9 International units per liter Standard Deviation 4.85
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase AST, 24 hours post-dose (Day 1)	0.0 International units per liter Standard Deviation 1.63	-0.4 International units per liter Standard Deviation 0.55	0.5 International units per liter Standard Deviation 1.76	-1.8 International units per liter Standard Deviation 3.77
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase AST, Day 7 to Day 14	2.8 International units per liter Standard Deviation 2.50	1.4 International units per liter Standard Deviation 1.67	-0.3 International units per liter Standard Deviation 3.67	-0.9 International units per liter Standard Deviation 6.71

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Direct bilirubin, 24 hours post-dose (Day 1)	2.0 Micromoles per liter Standard Deviation 1.63	0.4 Micromoles per liter Standard Deviation 0.89	0.3 Micromoles per liter Standard Deviation 1.97	1.0 Micromoles per liter Standard Deviation 2.14
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Direct bilirubin, Day 7 to Day 14	1.0 Micromoles per liter Standard Deviation 1.15	0.0 Micromoles per liter Standard Deviation 0.00	0.0 Micromoles per liter Standard Deviation 1.26	0.5 Micromoles per liter Standard Deviation 2.56
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Total bilirubin, 24 hours post-dose (Day 1)	3.0 Micromoles per liter Standard Deviation 4.16	0.8 Micromoles per liter Standard Deviation 1.79	0.7 Micromoles per liter Standard Deviation 4.84	4.8 Micromoles per liter Standard Deviation 6.76
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Total bilirubin, Day 7 to Day 14	1.5 Micromoles per liter Standard Deviation 3.42	0.4 Micromoles per liter Standard Deviation 2.61	-1.7 Micromoles per liter Standard Deviation 3.44	0.0 Micromoles per liter Standard Deviation 4.14
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Creatinine, 24 hours post-dose (Day 1)	5.08 Micromoles per liter Standard Deviation 4.102	10.80 Micromoles per liter Standard Deviation 6.110	12.22 Micromoles per liter Standard Deviation 20.214	1.76 Micromoles per liter Standard Deviation 2.759
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Creatinine, Day 7 to Day 14	-1.12 Micromoles per liter Standard Deviation 6.530	8.68 Micromoles per liter Standard Deviation 13.353	4.57 Micromoles per liter Standard Deviation 9.638	3.20 Micromoles per liter Standard Deviation 4.885

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Calcium, 24 hours post-dose (Day 1)	0.035 Millimoles per liter Standard Deviation 0.1427	0.012 Millimoles per liter Standard Deviation 0.0867	0.047 Millimoles per liter Standard Deviation 0.1033	0.060 Millimoles per liter Standard Deviation 0.0466
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Calcium, Day 7 to Day 14	0.025 Millimoles per liter Standard Deviation 0.1399	0.064 Millimoles per liter Standard Deviation 0.0888	0.047 Millimoles per liter Standard Deviation 0.1250	0.115 Millimoles per liter Standard Deviation 0.0583
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Glucose, 24 hours post-dose (Day 1)	0.85 Millimoles per liter Standard Deviation 0.957	1.10 Millimoles per liter Standard Deviation 1.398	0.50 Millimoles per liter Standard Deviation 1.752	0.89 Millimoles per liter Standard Deviation 2.039
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Glucose, Day 7 to Day 14	0.95 Millimoles per liter Standard Deviation 1.760	-0.32 Millimoles per liter Standard Deviation 0.646	-0.57 Millimoles per liter Standard Deviation 0.635	-0.20 Millimoles per liter Standard Deviation 1.995
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Potassium, 24 hours post-dose (Day 1)	0.28 Millimoles per liter Standard Deviation 0.377	0.18 Millimoles per liter Standard Deviation 0.179	0.08 Millimoles per liter Standard Deviation 0.306	-0.05 Millimoles per liter Standard Deviation 0.239
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Potassium, Day 7 to Day 14	0.10 Millimoles per liter Standard Deviation 0.356	0.22 Millimoles per liter Standard Deviation 0.148	0.25 Millimoles per liter Standard Deviation 0.207	0.18 Millimoles per liter Standard Deviation 0.301
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Sodium, 24 hours post-dose (Day 1)	-1.3 Millimoles per liter Standard Deviation 1.26	-0.6 Millimoles per liter Standard Deviation 2.30	-0.2 Millimoles per liter Standard Deviation 1.47	-1.0 Millimoles per liter Standard Deviation 1.85
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) Sodium, Day 7 to Day 14	-0.3 Millimoles per liter Standard Deviation 4.19	0.0 Millimoles per liter Standard Deviation 1.87	0.5 Millimoles per liter Standard Deviation 1.64	0.0 Millimoles per liter Standard Deviation 1.60
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) BUN, 24 hours post-dose (Day 1)	0.00 Millimoles per liter Standard Deviation 1.080	-0.20 Millimoles per liter Standard Deviation 0.758	0.83 Millimoles per liter Standard Deviation 1.033	-0.25 Millimoles per liter Standard Deviation 0.463
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN) BUN, Day 7 to Day 14	-0.25 Millimoles per liter Standard Deviation 1.258	1.50 Millimoles per liter Standard Deviation 1.541	0.00 Millimoles per liter Standard Deviation 1.000	0.31 Millimoles per liter Standard Deviation 1.067

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Clinical Chemistry Parameter: Total Protein Day 7 to Day 14	1.5 Grams per liter Standard Deviation 2.38	6.2 Grams per liter Standard Deviation 4.55	2.0 Grams per liter Standard Deviation 4.73	4.9 Grams per liter Standard Deviation 3.31
Change From Baseline in Clinical Chemistry Parameter: Total Protein 24 hours post-dose (Day 1)	1.3 Grams per liter Standard Deviation 6.13	0.6 Grams per liter Standard Deviation 3.78	1.8 Grams per liter Standard Deviation 2.93	2.6 Grams per liter Standard Deviation 3.66

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Basophils, 24 hours post-dose (Day 1), n=4,4,6,3	-0.008 Giga cells per liter Standard Deviation 0.0359	0.013 Giga cells per liter Standard Deviation 0.0206	-0.005 Giga cells per liter Standard Deviation 0.0302	0.003 Giga cells per liter Standard Deviation 0.0115
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Basophils, Day 7 to Day 14, n=4,5,6,8	0.000 Giga cells per liter Standard Deviation 0.0327	0.002 Giga cells per liter Standard Deviation 0.0192	0.008 Giga cells per liter Standard Deviation 0.0306	0.003 Giga cells per liter Standard Deviation 0.0238
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Eosinophils, 24 hours post-dose (Day 1), n=4,4,6,3	0.007 Giga cells per liter Standard Deviation 0.0695	0.018 Giga cells per liter Standard Deviation 0.0222	0.012 Giga cells per liter Standard Deviation 0.0662	-0.007 Giga cells per liter Standard Deviation 0.0503
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Eosinophils, Day 7 to Day 14, n=4,5,6,8	-0.035 Giga cells per liter Standard Deviation 0.0835	0.004 Giga cells per liter Standard Deviation 0.0230	-0.025 Giga cells per liter Standard Deviation 0.0807	0.023 Giga cells per liter Standard Deviation 0.1004
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Lymphocytes, 24 hours post-dose (Day 1), n=4,4,6,3	0.000 Giga cells per liter Standard Deviation 0.5509	-0.070 Giga cells per liter Standard Deviation 0.1612	-0.157 Giga cells per liter Standard Deviation 0.1558	0.190 Giga cells per liter Standard Deviation 0.4553
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Lymphocytes, Day 7 to Day 14, n=4,5,6,8	-0.025 Giga cells per liter Standard Deviation 0.4277	-0.054 Giga cells per liter Standard Deviation 0.1422	-0.250 Giga cells per liter Standard Deviation 0.2001	0.130 Giga cells per liter Standard Deviation 0.4032
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Monocytes, 24 hours post-dose (Day 1), n=4,4,6,3	0.050 Giga cells per liter Standard Deviation 0.0673	-0.028 Giga cells per liter Standard Deviation 0.0914	0.098 Giga cells per liter Standard Deviation 0.1125	0.140 Giga cells per liter Standard Deviation 0.0700
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Monocytes, Day 7 to Day 14, n=4,5,6,8	0.038 Giga cells per liter Standard Deviation 0.1066	0.038 Giga cells per liter Standard Deviation 0.0998	0.047 Giga cells per liter Standard Deviation 0.1263	0.091 Giga cells per liter Standard Deviation 0.1654
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count T.neutrophils, 24 hours post-dose(Day1),n=4,4,6,3	0.643 Giga cells per liter Standard Deviation 1.0052	0.415 Giga cells per liter Standard Deviation 0.3924	0.738 Giga cells per liter Standard Deviation 0.5615	0.727 Giga cells per liter Standard Deviation 0.7298
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count T.neutrophils, Day 7 to Day 14, n=4,5,6,8	0.185 Giga cells per liter Standard Deviation 0.9008	0.504 Giga cells per liter Standard Deviation 0.4884	0.397 Giga cells per liter Standard Deviation 1.3173	0.366 Giga cells per liter Standard Deviation 0.7204
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Platelets, 24 hours post-dose (Day 1), n=4,4,6,5	11.8 Giga cells per liter Standard Deviation 36.28	-33.0 Giga cells per liter Standard Deviation 73.51	7.8 Giga cells per liter Standard Deviation 16.65	12.6 Giga cells per liter Standard Deviation 27.74
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Platelets, Day 7 to Day 14, n=4,5,6,8	35.3 Giga cells per liter Standard Deviation 17.40	19.8 Giga cells per liter Standard Deviation 45.03	14.3 Giga cells per liter Standard Deviation 52.89	23.4 Giga cells per liter Standard Deviation 24.44
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count WBC count, 24 hours post-dose (Day 1), n=4,4,6,5	0.35 Giga cells per liter Standard Deviation 1.330	0.30 Giga cells per liter Standard Deviation 0.183	0.68 Giga cells per liter Standard Deviation 0.542	2.16 Giga cells per liter Standard Deviation 2.492
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count WBC count, Day 7 to Day 14, n=4,5,6,8	-0.20 Giga cells per liter Standard Deviation 1.334	0.46 Giga cells per liter Standard Deviation 0.498	0.20 Giga cells per liter Standard Deviation 1.355	0.64 Giga cells per liter Standard Deviation 0.588

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Hemoglobin 24 hours post-dose (Day 1), n=4,4,6,5	1.8 Grams per liter Standard Deviation 11.09	2.0 Grams per liter Standard Deviation 5.72	5.0 Grams per liter Standard Deviation 4.77	3.0 Grams per liter Standard Deviation 5.61
Change From Baseline in Hematology Parameter: Hemoglobin Day 7 to Day 14, n=4,5,6,8	-4.3 Grams per liter Standard Deviation 6.55	3.4 Grams per liter Standard Deviation 5.98	-1.5 Grams per liter Standard Deviation 7.09	4.0 Grams per liter Standard Deviation 5.15

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Hematocrit 24 hours post-dose (Day 1), n=4,4,6,5	0.0030 Proportion of red blood cells in blood Standard Deviation 0.02858	0.0053 Proportion of red blood cells in blood Standard Deviation 0.02156	0.0098 Proportion of red blood cells in blood Standard Deviation 0.01546	0.0140 Proportion of red blood cells in blood Standard Deviation 0.02448
Change From Baseline in Hematology Parameter: Hematocrit Day 7 to Day 14, n=4,5,6,8	-0.0225 Proportion of red blood cells in blood Standard Deviation 0.00929	0.0104 Proportion of red blood cells in blood Standard Deviation 0.02173	0.0030 Proportion of red blood cells in blood Standard Deviation 0.02391	0.0135 Proportion of red blood cells in blood Standard Deviation 0.01891

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin 24 hours post-dose (Day 1), n=4,4,6,5	-0.08 Picograms Standard Deviation 0.150	0.05 Picograms Standard Deviation 0.507	0.25 Picograms Standard Deviation 0.302	-0.10 Picograms Standard Deviation 0.235
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin Day 7 to Day 14, n=4,5,6,8	0.10 Picograms Standard Deviation 0.483	0.04 Picograms Standard Deviation 0.182	-0.33 Picograms Standard Deviation 0.314	0.15 Picograms Standard Deviation 0.177

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume 24 hours post-dose (Day 1), n=4,4,6,5	-0.5 Femtoliters Standard Deviation 2.52	0.0 Femtoliters Standard Deviation 0.82	-0.5 Femtoliters Standard Deviation 0.84	0.6 Femtoliters Standard Deviation 1.95
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume Day 7 to Day 14, n=4,5,6,8	-1.5 Femtoliters Standard Deviation 2.08	-0.2 Femtoliters Standard Deviation 0.84	0.7 Femtoliters Standard Deviation 1.03	0.8 Femtoliters Standard Deviation 1.04

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count 24 hours post-dose (Day 1), n=4,4,6,5	0.03 Trillion cells per liter Standard Deviation 0.435	0.03 Trillion cells per liter Standard Deviation 0.287	0.13 Trillion cells per liter Standard Deviation 0.163	0.12 Trillion cells per liter Standard Deviation 0.192
Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count Day 7 to Day 14, n=4,5,6,8	-0.20 Trillion cells per liter Standard Deviation 0.183	0.14 Trillion cells per liter Standard Deviation 0.261	0.00 Trillion cells per liter Standard Deviation 0.310	0.11 Trillion cells per liter Standard Deviation 0.203

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Hematology Parameter: Reticulocytes 24 hours post-dose (Day 1), n=4,4,6,5	0.0012 Percentage of reticulocytes in blood Standard Deviation 0.00330	0.0017 Percentage of reticulocytes in blood Standard Deviation 0.00310	0.0017 Percentage of reticulocytes in blood Standard Deviation 0.00216	0.0000 Percentage of reticulocytes in blood Standard Deviation 0.00100
Change From Baseline in Hematology Parameter: Reticulocytes Day 7 to Day 14, n=4,5,6,8	0.0058 Percentage of reticulocytes in blood Standard Deviation 0.00411	0.0014 Percentage of reticulocytes in blood Standard Deviation 0.00358	0.0025 Percentage of reticulocytes in blood Standard Deviation 0.00333	0.0040 Percentage of reticulocytes in blood Standard Deviation 0.00325

SECONDARY outcome

Timeframe: 24 hours post-dose (Day 1)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Number of Participants With Urinalysis Results by Dipstick Method Bilirubin, 24 hours post-dose (Day 1), negative	4 Participants	5 Participants	6 Participants	8 Participants
Number of Participants With Urinalysis Results by Dipstick Method Bilirubin, 24 hours post-dose (Day 1), trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Bilirubin, 24 hours post-dose (Day 1), 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Bilirubin, 24 hours post-dose (Day 1), 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Bilirubin, 24 hours post-dose (Day 1), 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Occult Blood, 24 hours post-dose (Day 1), negative	2 Participants	5 Participants	4 Participants	7 Participants
Number of Participants With Urinalysis Results by Dipstick Method Occult Blood, 24 hours post-dose (Day 1), trace	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Urinalysis Results by Dipstick Method Occult Blood, 24 hours post-dose (Day 1), 1+	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Occult Blood, 24 hours post-dose (Day 1), 2+	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Occult Blood, 24 hours post-dose (Day 1), 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Glucose, 24 hours post-dose (Day 1), negative	4 Participants	5 Participants	5 Participants	8 Participants
Number of Participants With Urinalysis Results by Dipstick Method Glucose, 24 hours post-dose (Day 1), trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Glucose, 24 hours post-dose (Day 1), 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Glucose, 24 hours post-dose (Day 1), 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Glucose, 24 hours post-dose (Day 1), 3+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Ketones, 24 hours post-dose (Day 1), negative	4 Participants	4 Participants	3 Participants	8 Participants
Number of Participants With Urinalysis Results by Dipstick Method Ketones, 24 hours post-dose (Day 1), trace	0 Participants	1 Participants	3 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Ketones, 24 hours post-dose (Day 1), 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Ketones, 24 hours post-dose (Day 1), 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Ketones, 24 hours post-dose (Day 1), 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Protein, 24 hours post-dose (Day 1), negative	4 Participants	4 Participants	6 Participants	8 Participants
Number of Participants With Urinalysis Results by Dipstick Method Protein, 24 hours post-dose (Day 1), trace	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Protein, 24 hours post-dose (Day 1), 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Protein, 24 hours post-dose (Day 1), 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Urinalysis Results by Dipstick Method Protein, 24 hours post-dose (Day 1), 3+	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Pulse Rate 0.5 hour post-dose (Day 1), n=4,5,6,8	-1.3 Beats per minute Standard Deviation 5.85	-0.8 Beats per minute Standard Deviation 3.42	3.5 Beats per minute Standard Deviation 8.64	3.6 Beats per minute Standard Deviation 6.00
Change From Baseline in Pulse Rate 1 hour post-dose (Day 1), n=4,5,6,8	-3.0 Beats per minute Standard Deviation 6.98	0.8 Beats per minute Standard Deviation 6.69	-0.7 Beats per minute Standard Deviation 3.67	-1.0 Beats per minute Standard Deviation 3.93
Change From Baseline in Pulse Rate 2 hours post-dose (Day 1), n=4,5,6,8	-5.0 Beats per minute Standard Deviation 7.62	-0.4 Beats per minute Standard Deviation 1.95	-1.8 Beats per minute Standard Deviation 6.65	1.0 Beats per minute Standard Deviation 5.93
Change From Baseline in Pulse Rate 4 hours post-dose (Day 1), n=4,5,6,8	-1.8 Beats per minute Standard Deviation 6.80	11.6 Beats per minute Standard Deviation 13.67	-1.2 Beats per minute Standard Deviation 6.40	-0.8 Beats per minute Standard Deviation 7.42
Change From Baseline in Pulse Rate 8 hours post-dose (Day 1), n=4,4,6,8	2.8 Beats per minute Standard Deviation 6.90	1.8 Beats per minute Standard Deviation 5.19	5.7 Beats per minute Standard Deviation 5.85	8.6 Beats per minute Standard Deviation 9.83
Change From Baseline in Pulse Rate 24 hours post-dose (Day 1), n=4,5,6,8	4.3 Beats per minute Standard Deviation 11.27	3.6 Beats per minute Standard Deviation 6.50	7.5 Beats per minute Standard Deviation 7.12	13.0 Beats per minute Standard Deviation 9.20
Change From Baseline in Pulse Rate Day 7 to Day 14, n=4,5,6,8	10.0 Beats per minute Standard Deviation 14.31	4.4 Beats per minute Standard Deviation 5.86	5.3 Beats per minute Standard Deviation 6.25	9.8 Beats per minute Standard Deviation 8.36

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Respiratory Rate 24 hours post-dose (Day 1), n=4,5,6,8	-1.8 Breaths per minute Standard Deviation 0.96	0.8 Breaths per minute Standard Deviation 2.28	0.3 Breaths per minute Standard Deviation 2.58	-0.1 Breaths per minute Standard Deviation 1.81
Change From Baseline in Respiratory Rate Day 7 to Day 14, n=4,5,6,8	-0.5 Breaths per minute Standard Deviation 1.73	-0.4 Breaths per minute Standard Deviation 3.58	2.0 Breaths per minute Standard Deviation 2.28	0.3 Breaths per minute Standard Deviation 1.16
Change From Baseline in Respiratory Rate 0.5 hour post-dose (Day 1), n=4,5,6,8	-2.5 Breaths per minute Standard Deviation 3.11	-3.4 Breaths per minute Standard Deviation 4.39	-2.2 Breaths per minute Standard Deviation 4.92	0.1 Breaths per minute Standard Deviation 1.13
Change From Baseline in Respiratory Rate 1 hour post-dose (Day 1), n=4,5,6,8	-2.8 Breaths per minute Standard Deviation 1.71	-3.2 Breaths per minute Standard Deviation 5.67	1.8 Breaths per minute Standard Deviation 9.22	0.0 Breaths per minute Standard Deviation 0.76
Change From Baseline in Respiratory Rate 2 hours post-dose (Day 1), n=4,5,6,8	-2.0 Breaths per minute Standard Deviation 2.16	-2.6 Breaths per minute Standard Deviation 2.97	-3.0 Breaths per minute Standard Deviation 4.52	-1.0 Breaths per minute Standard Deviation 4.50
Change From Baseline in Respiratory Rate 4 hours post-dose (Day 1), n=4,5,6,8	-2.5 Breaths per minute Standard Deviation 2.08	-2.2 Breaths per minute Standard Deviation 5.63	-2.2 Breaths per minute Standard Deviation 3.54	0.1 Breaths per minute Standard Deviation 0.64
Change From Baseline in Respiratory Rate 8 hours post-dose (Day 1), n=4,4,6,8	-2.0 Breaths per minute Standard Deviation 1.63	-0.3 Breaths per minute Standard Deviation 3.50	0.2 Breaths per minute Standard Deviation 2.56	1.1 Breaths per minute Standard Deviation 2.59

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 0.5 hour post-dose (Day 1), n=4,5,6,8	-3.5 Millimeters of mercury Standard Deviation 8.58	-1.0 Millimeters of mercury Standard Deviation 10.42	-5.0 Millimeters of mercury Standard Deviation 14.67	-3.3 Millimeters of mercury Standard Deviation 4.53
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 1 hour post-dose (Day 1), n=4,5,6,8	-2.0 Millimeters of mercury Standard Deviation 6.22	0.6 Millimeters of mercury Standard Deviation 8.56	-4.3 Millimeters of mercury Standard Deviation 9.73	-2.3 Millimeters of mercury Standard Deviation 3.73
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 2 hours post-dose (Day 1), n=4,5,6,8	0.5 Millimeters of mercury Standard Deviation 12.40	1.2 Millimeters of mercury Standard Deviation 10.55	-5.8 Millimeters of mercury Standard Deviation 8.80	3.3 Millimeters of mercury Standard Deviation 5.87
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 4 hours post-dose (Day 1), n=4,5,6,8	-1.5 Millimeters of mercury Standard Deviation 2.65	3.0 Millimeters of mercury Standard Deviation 8.37	-2.7 Millimeters of mercury Standard Deviation 13.22	1.6 Millimeters of mercury Standard Deviation 6.07
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 8 hours post-dose (Day 1), n=4,4,6,8	-12.3 Millimeters of mercury Standard Deviation 6.65	-6.3 Millimeters of mercury Standard Deviation 8.66	-10.2 Millimeters of mercury Standard Deviation 9.15	-1.0 Millimeters of mercury Standard Deviation 9.32
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, 24 hours post-dose (Day 1), n=4,5,6,8	-7.5 Millimeters of mercury Standard Deviation 7.94	-8.6 Millimeters of mercury Standard Deviation 9.61	-2.8 Millimeters of mercury Standard Deviation 10.61	-3.1 Millimeters of mercury Standard Deviation 8.46
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP, Day 7 to Day 14, n=4,5,6,8	-4.5 Millimeters of mercury Standard Deviation 7.19	-2.2 Millimeters of mercury Standard Deviation 6.91	-2.5 Millimeters of mercury Standard Deviation 11.78	2.8 Millimeters of mercury Standard Deviation 12.83
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 0.5 hour post-dose (Day 1), n=4,5,6,8	-2.3 Millimeters of mercury Standard Deviation 12.28	-0.2 Millimeters of mercury Standard Deviation 12.60	-5.2 Millimeters of mercury Standard Deviation 6.11	-0.1 Millimeters of mercury Standard Deviation 5.03
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 1 hour post-dose (Day 1), n=4,5,6,8	-1.8 Millimeters of mercury Standard Deviation 9.91	3.4 Millimeters of mercury Standard Deviation 12.68	-2.7 Millimeters of mercury Standard Deviation 9.37	3.0 Millimeters of mercury Standard Deviation 8.07
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 2 hours post-dose (Day 1), n=4,5,6,8	1.0 Millimeters of mercury Standard Deviation 15.12	2.0 Millimeters of mercury Standard Deviation 10.20	-0.7 Millimeters of mercury Standard Deviation 18.84	2.0 Millimeters of mercury Standard Deviation 11.80
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 4 hours post-dose (Day 1), n=4,5,6,8	5.5 Millimeters of mercury Standard Deviation 19.69	4.2 Millimeters of mercury Standard Deviation 9.34	6.3 Millimeters of mercury Standard Deviation 13.03	6.1 Millimeters of mercury Standard Deviation 13.53
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 8 hours post-dose (Day 1), n=4,4,6,8	-4.5 Millimeters of mercury Standard Deviation 10.38	3.0 Millimeters of mercury Standard Deviation 16.57	-5.2 Millimeters of mercury Standard Deviation 7.63	-4.8 Millimeters of mercury Standard Deviation 9.65
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, 24 hours post-dose (Day 1), n=4,5,6,8	-2.5 Millimeters of mercury Standard Deviation 4.51	-0.2 Millimeters of mercury Standard Deviation 14.72	-4.7 Millimeters of mercury Standard Deviation 11.41	-3.8 Millimeters of mercury Standard Deviation 14.85
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP, Day 7 to Day 14, n=4,5,6,8	2.0 Millimeters of mercury Standard Deviation 21.37	6.0 Millimeters of mercury Standard Deviation 6.78	-5.8 Millimeters of mercury Standard Deviation 15.07	-2.1 Millimeters of mercury Standard Deviation 9.63

SECONDARY outcome

Timeframe: 4 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8	1 Participants	3 Participants	3 Participants	7 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8	1 Participants	3 Participants	4 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal NCS, Day 7 to Day 14, n=4,5,6,8	1 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal CS, Day 7 to Day 14, n=4,5,6,8	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 0.5 hour post-dose (Day 1), n=4,5,6,8	-1.0 Percentage of oxygen in blood Standard Deviation 2.30	-1.7 Percentage of oxygen in blood Standard Deviation 2.77	0.8 Percentage of oxygen in blood Standard Deviation 2.31	-0.5 Percentage of oxygen in blood Standard Deviation 2.03
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 1 hour post-dose (Day 1), n=4,5,6,8	-0.7 Percentage of oxygen in blood Standard Deviation 2.87	-2.1 Percentage of oxygen in blood Standard Deviation 2.79	-0.3 Percentage of oxygen in blood Standard Deviation 1.03	-0.9 Percentage of oxygen in blood Standard Deviation 2.48
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 2 hours post-dose (Day 1), n=4,5,6,8	-1.5 Percentage of oxygen in blood Standard Deviation 1.91	-0.7 Percentage of oxygen in blood Standard Deviation 1.99	0.6 Percentage of oxygen in blood Standard Deviation 1.21	0.9 Percentage of oxygen in blood Standard Deviation 1.37
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 4 hours post-dose (Day 1), n=4,5,6,8	-0.7 Percentage of oxygen in blood Standard Deviation 2.21	-1.0 Percentage of oxygen in blood Standard Deviation 1.87	-0.3 Percentage of oxygen in blood Standard Deviation 1.96	0.5 Percentage of oxygen in blood Standard Deviation 2.13
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 8 hours post-dose (Day 1), n=4,4,6,8	-0.7 Percentage of oxygen in blood Standard Deviation 2.50	-0.2 Percentage of oxygen in blood Standard Deviation 3.58	0.8 Percentage of oxygen in blood Standard Deviation 2.31	0.4 Percentage of oxygen in blood Standard Deviation 2.98
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood 24 hours post-dose (Day 1), n=4,5,6,8	-1.0 Percentage of oxygen in blood Standard Deviation 2.00	-2.3 Percentage of oxygen in blood Standard Deviation 3.06	2.1 Percentage of oxygen in blood Standard Deviation 1.60	1.0 Percentage of oxygen in blood Standard Deviation 3.28
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood Day 7 to Day 14, n=4,5,6,8	-0.2 Percentage of oxygen in blood Standard Deviation 0.95	-2.9 Percentage of oxygen in blood Standard Deviation 2.37	0.5 Percentage of oxygen in blood Standard Deviation 3.33	0.8 Percentage of oxygen in blood Standard Deviation 2.49

SECONDARY outcome

Timeframe: Up to Day 28

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Number of Participants With Positive Immunogenicity Results	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 0.08 hour post-dose (Day 1), n=4,5,5,8	0.143 Ratio Interval 0.028 to 0.723	0.185 Ratio NA indicates confidence interval could not be estimated as more than 75 percentage (%) of the values were below lower limit of quantification.	1.020 Ratio Interval 0.063 to 16.661	0.254 Ratio Interval 0.078 to 0.831
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 0.5 hour post-dose (Day 1), n=4,5,5,8	0.179 Ratio Interval 0.04 to 0.792	0.210 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.500 Ratio Interval 0.065 to 3.825	0.211 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 1 hour post-dose (Day 1), n=4,5,5,8	0.238 Ratio Interval 0.097 to 0.582	0.162 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.420 Ratio Interval 0.086 to 2.062	0.235 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 2 hours post-dose (Day 1), n=4,5,5,8	0.230 Ratio Interval 0.041 to 1.28	0.166 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.393 Ratio Interval 0.159 to 0.97	0.211 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 4 hours post-dose (Day 1), n=4,5,5,8	0.372 Ratio Interval 0.159 to 0.872	0.187 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.398 Ratio Interval 0.161 to 0.98	0.387 Ratio Interval 0.16 to 0.933
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 8 hours post-dose (Day 1), n=4,5,5,8	0.889 Ratio Interval 0.148 to 5.327	0.669 Ratio Interval 0.249 to 1.798	0.503 Ratio Interval 0.311 to 0.813	0.277 Ratio Interval 0.08 to 0.963
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 24 hours post-dose (Day 1), n=4,5,5,8	2.329 Ratio Interval 0.692 to 7.836	1.372 Ratio Interval 0.462 to 4.07	0.763 Ratio Interval 0.267 to 2.184	0.939 Ratio Interval 0.186 to 4.751
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, Day 7 to Day 14, n=4,5,5,7	1.625 Ratio Interval 0.084 to 31.3	2.380 Ratio Interval 0.703 to 8.063	0.616 Ratio Interval 0.115 to 3.307	1.826 Ratio Interval 0.399 to 8.354
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 0.08 hour post-dose (Day 1), n=4,5,4,6	1.884 Ratio Interval 0.505 to 7.026	4.696 Ratio Interval 1.303 to 16.923	2.222 Ratio Interval 0.774 to 6.373	2.982 Ratio Interval 1.36 to 6.535
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 0.5 hour post-dose (Day 1), n=4,5,4,6	2.342 Ratio Interval 0.435 to 12.622	5.325 Ratio Interval 1.427 to 19.873	2.895 Ratio Interval 1.206 to 6.95	3.187 Ratio Interval 1.303 to 7.797
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 1 hour post-dose (Day 1), n=4,5,4,6	2.427 Ratio Interval 0.414 to 14.225	4.263 Ratio Interval 1.463 to 12.418	2.572 Ratio Interval 0.775 to 8.539	3.264 Ratio Interval 1.134 to 9.396
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 2 hours post-dose (Day 1), n=4,5,4,6	2.269 Ratio Interval 0.344 to 14.945	3.499 Ratio Interval 1.377 to 8.89	3.423 Ratio Interval 0.698 to 16.789	2.463 Ratio Interval 0.982 to 6.174
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 4 hours post-dose (Day 1), n=4,5,4,6	2.442 Ratio Interval 0.344 to 17.34	2.740 Ratio Interval 1.245 to 6.033	3.513 Ratio Interval 0.75 to 16.459	2.717 Ratio Interval 1.033 to 7.146
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 8 hours post-dose (Day 1), n=4,5,4,6	4.365 Ratio Interval 1.094 to 17.42	4.125 Ratio Interval 0.716 to 23.775	6.691 Ratio Interval 0.812 to 55.117	4.882 Ratio Interval 1.581 to 15.072
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 24 hours post-dose (Day 1), n=4,5,4,6	2.397 Ratio Interval 0.879 to 6.536	3.701 Ratio Interval 1.413 to 9.69	2.573 Ratio Interval 0.403 to 16.426	5.117 Ratio Interval 1.91 to 13.712
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), Day 7 to Day 14, n=4,5,3,6	1.469 Ratio Interval 0.714 to 3.02	2.110 Ratio Interval 0.775 to 5.744	0.548 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.642 Ratio Interval 0.781 to 3.45
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 0.08 hour post-dose (Day 1), n=4,5,5,7	2.252 Ratio Interval 0.366 to 13.855	4.392 Ratio Interval 1.405 to 13.732	3.465 Ratio Interval 1.025 to 11.719	1.817 Ratio Interval 0.969 to 3.405
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 0.5 hour post-dose (Day 1), n=4,5,5,7	2.943 Ratio Interval 0.335 to 25.843	4.935 Ratio Interval 1.383 to 17.617	2.242 Ratio Interval 0.639 to 7.865	2.205 Ratio Interval 1.26 to 3.859
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 1 hour post-dose (Day 1), n=4,5,5,7	3.002 Ratio Interval 0.318 to 28.319	3.494 Ratio Interval 1.438 to 8.49	2.362 Ratio Interval 0.542 to 10.291	1.780 Ratio Interval 0.783 to 4.047
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 2 hours post-dose (Day 1), n=4,5,5,7	2.311 Ratio Interval 0.161 to 33.222	4.025 Ratio Interval 1.393 to 11.63	3.471 Ratio Interval 0.651 to 18.5	1.949 Ratio Interval 1.012 to 3.756
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 4 hours post-dose (Day 1), n=4,5,5,7	3.350 Ratio Interval 0.23 to 48.748	3.115 Ratio Interval 1.349 to 7.19	3.623 Ratio Interval 0.679 to 19.331	1.818 Ratio Interval 0.715 to 4.623
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 8 hours post-dose (Day 1), n=4,5,5,7	4.910 Ratio Interval 0.654 to 36.845	3.517 Ratio Interval 0.635 to 19.477	6.002 Ratio Interval 0.762 to 47.289	4.229 Ratio Interval 1.433 to 12.477
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 24 hours post-dose (Day 1), n=4,5,5,7	3.423 Ratio Interval 0.618 to 18.944	4.096 Ratio Interval 1.43 to 11.73	2.812 Ratio Interval 0.503 to 15.732	7.095 Ratio Interval 2.426 to 20.752
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), Day 7 to Day 14, n=4,5,5,6	1.190 Ratio Interval 0.684 to 2.073	1.904 Ratio Interval 0.596 to 6.089	0.925 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.932 Ratio Interval 1.111 to 3.362

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=4 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=4 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 1 hour post-dose (Day 1), n=4,4,4,8	0.270 Ratio Interval 0.059 to 1.244	0.190 Ratio Interval 0.025 to 1.475	0.394 Ratio Interval 0.046 to 3.414	0.369 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 2 hours post-dose (Day 1), n=4,4,4,8	0.310 Ratio Interval 0.068 to 1.419	0.193 Ratio Interval 0.025 to 1.476	0.505 Ratio Interval 0.147 to 1.738	0.369 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang II, 4 hours post-dose (Day 1), n=4,4,3,8	0.332 Ratio Interval 0.089 to 1.24	0.191 Ratio Interval 0.025 to 1.475	0.183 Ratio Interval 0.038 to 0.879	0.420 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 1 hour post-dose (Day 1), n=4,4,4,7	2.985 Ratio Interval 0.279 to 31.931	3.313 Ratio Interval 0.892 to 12.31	2.709 Ratio Interval 0.792 to 9.269	1.834 Ratio Interval 0.743 to 4.528
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 2 hours post-dose (Day 1), n=4,4,3,7	3.443 Ratio Interval 0.282 to 42.025	4.621 Ratio Interval 0.803 to 26.6	5.246 Ratio Interval 1.386 to 19.859	1.562 Ratio Interval 0.566 to 4.312
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-5), 4 hours post-dose (Day 1), n=4,4,3,7	2.373 Ratio Interval 0.401 to 14.05	3.213 Ratio Interval 0.757 to 13.646	5.239 Ratio Interval 1.565 to 17.541	1.472 Ratio Interval 0.575 to 3.768
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 1 hour post-dose (Day 1), n=4,4,4,8	2.840 Ratio Interval 0.353 to 22.846	4.150 Ratio Interval 0.912 to 18.88	2.993 Ratio Interval 0.356 to 25.136	1.558 Ratio Interval 0.969 to 2.504
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 2 hours post-dose (Day 1), n=4,4,4,8	3.376 Ratio Interval 0.279 to 40.91	3.792 Ratio Interval 0.878 to 16.368	4.476 Ratio Interval 0.612 to 32.754	1.589 Ratio Interval 0.83 to 3.043
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7) Ang (1-7), 4 hours post-dose (Day 1), n=4,4,3,8	2.857 Ratio Interval 0.362 to 22.55	3.151 Ratio Interval 0.849 to 11.693	8.521 Ratio Interval 0.733 to 99.048	1.693 Ratio Interval 0.818 to 3.504

SECONDARY outcome

Timeframe: 0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 0.08 hour post-dose (Day 1), n=4,5,5,8	0.752 Ratio Interval 0.175 to 3.239	0.463 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.450 Ratio Interval 0.313 to 6.711	0.843 Ratio Interval 0.491 to 1.447
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 0.5 hour post-dose (Day 1), n=4,5,5,8	0.718 Ratio Interval 0.186 to 2.779	0.468 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.097 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.590 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 1 hour post-dose (Day 1), n=4,5,5,8	0.937 Ratio Interval 0.351 to 2.504	0.509 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.875 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.794 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 2 hours post-dose (Day 1), n=4,5,5,8	1.174 Ratio Interval 0.539 to 2.559	0.455 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.558 Ratio Interval 0.15 to 2.077	0.657 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 4 hours post-dose (Day 1), n=4,5,5,8	1.312 Ratio Interval 0.571 to 3.011	0.659 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	0.540 Ratio Interval 0.136 to 2.144	1.283 Ratio Interval 0.53 to 3.102
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 8 hours post-dose (Day 1), n=4,5,5,8	2.139 Ratio Interval 0.623 to 7.339	2.093 Ratio Interval 0.778 to 5.625	0.412 Ratio Interval 0.083 to 2.055	0.439 Ratio Interval 0.181 to 1.062
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 24 hours post-dose (Day 1), n=4,5,5,8	8.041 Ratio Interval 2.416 to 26.757	3.682 Ratio Interval 1.929 to 7.03	1.335 Ratio Interval 0.908 to 1.965	0.946 Ratio Interval 0.435 to 2.054
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points Day 7 to Day 14, n=4,5,5,7	16.132 Ratio Interval 1.204 to 216.087	13.742 Ratio Interval 3.829 to 49.326	3.278 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	6.156 Ratio Interval 2.618 to 14.479

SECONDARY outcome

Timeframe: 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=4 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=4 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 1 hour post-dose (Day 1), n=4,4,4,8	0.888 Ratio Interval 0.275 to 2.866	0.443 Ratio Interval 0.108 to 1.821	0.620 Ratio Interval 0.058 to 6.65	0.789 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 2 hours post-dose (Day 1), n=4,4,4,8	0.858 Ratio Interval 0.253 to 2.908	0.493 Ratio Interval 0.116 to 2.096	0.531 Ratio Interval 0.117 to 2.403	0.774 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.
Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points 4 hours post-dose (Day 1), n=4,4,3,8	1.085 Ratio Interval 0.478 to 2.462	0.587 Ratio Interval 0.172 to 2.003	0.148 Ratio Interval 0.012 to 1.759	0.826 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=4 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP) 2 hours post-dose (Day 1)	1.034 Ratio Interval 0.955 to 1.119	1.005 Ratio Interval 0.842 to 1.199	0.923 Ratio Interval 0.795 to 1.071	1.015 Ratio Interval 0.841 to 1.224
Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP) 4 hours post-dose (Day 1)	1.025 Ratio Interval 0.924 to 1.138	1.042 Ratio Interval 0.852 to 1.276	0.944 Ratio Interval 0.795 to 1.12	1.074 Ratio Interval 0.84 to 1.373
Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP) 24 hours post-dose (Day 1)	0.606 Ratio Interval 0.253 to 1.453	0.896 Ratio Interval 0.481 to 1.67	0.703 Ratio Interval 0.43 to 1.151	0.810 Ratio Interval 0.539 to 1.217

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=4 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrite, 24 hours post-dose (Day 1), n=4,4,4,7	1.038 Ratio Interval 0.898 to 1.199	1.146 Ratio Interval 1.044 to 1.259	0.667 Ratio Interval 0.245 to 1.814	0.914 Ratio Interval 0.605 to 1.381
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrate, 2 hours post-dose (Day 1), n=4,4,5,8	1.251 Ratio Interval 0.432 to 3.623	1.025 Ratio Interval 0.862 to 1.218	0.485 Ratio Interval 0.108 to 2.177	0.836 Ratio Interval 0.768 to 0.91
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrite, 2 hours post-dose (Day 1), n=4,4,5,8	1.246 Ratio Interval 0.44 to 3.533	1.029 Ratio Interval 0.87 to 1.216	0.530 Ratio Interval 0.145 to 1.931	0.858 Ratio Interval 0.797 to 0.923
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrite, 4 hours post-dose (Day 1), n=4,4,5,8	0.760 Ratio Interval 0.635 to 0.91	0.992 Ratio Interval 0.749 to 1.312	0.679 Ratio Interval 0.42 to 1.096	0.770 Ratio Interval 0.654 to 0.907
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrate, 4 hours post-dose (Day 1), n=4,4,5,8	0.739 Ratio Interval 0.595 to 0.917	0.977 Ratio Interval 0.7 to 1.362	0.655 Ratio Interval 0.395 to 1.086	0.762 Ratio Interval 0.649 to 0.895
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) Nitrate, 24 hours post-dose (Day 1), n=4,4,4,7	1.017 Ratio Interval 0.853 to 1.212	1.149 Ratio Interval 1.049 to 1.259	0.641 Ratio Interval 0.222 to 1.854	0.911 Ratio Interval 0.597 to 1.39
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) En. nitrite, 2 hours post-dose (Day 1), n=4,4,5,8	1.099 Ratio Interval 0.798 to 1.512	2.036 Ratio Interval 0.309 to 13.411	1.171 Ratio Interval 0.878 to 1.563	0.975 Ratio Interval 0.647 to 1.469
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) En. nitrite, 4 hours post-dose (Day 1), n=4,4,5,8	1.245 Ratio Interval 0.665 to 2.33	2.819 Ratio Interval 0.079 to 100.021	1.329 Ratio Interval 0.643 to 2.747	0.820 Ratio Interval 0.466 to 1.443
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO]) En. nitrite, 24 hours post-dose (Day 1), n=4,4,4,7	1.290 Ratio Interval 0.543 to 3.063	1.399 Ratio Interval 0.503 to 3.894	1.289 Ratio Interval 0.501 to 3.316	1.271 Ratio Interval 0.614 to 2.634

SECONDARY outcome

Timeframe: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Disease Biomarker: Cardiac Troponin-I 2 hours post-dose (Day 1)	1.565 Ratio Interval 0.66 to 3.714	1.320 Ratio Interval 0.824 to 2.114	1.585 Ratio Interval 0.657 to 3.822	1.414 Ratio Interval 0.761 to 2.628
Change From Baseline in Disease Biomarker: Cardiac Troponin-I 4 hours post-dose (Day 1)	1.968 Ratio Interval 0.543 to 7.131	1.149 Ratio Interval 0.782 to 1.688	1.695 Ratio Interval 0.592 to 4.856	2.030 Ratio Interval 1.064 to 3.873
Change From Baseline in Disease Biomarker: Cardiac Troponin-I 24 hours post-dose (Day 1)	1.316 Ratio Interval 0.549 to 3.154	1.000 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.000 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.	1.000 Ratio NA indicates confidence interval could not be estimated as more than 75% of the values were below lower limit of quantification.

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic population comprised of participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.

Blood samples were collected at indicated time points for evaluation of Cmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Maximum Observed Plasma Concentration (Cmax) of GSK2586881	1.5159 Micrograms per milliliter Geometric Coefficient of Variation 37.0	4.0229 Micrograms per milliliter Geometric Coefficient of Variation 37.4	8.9701 Micrograms per milliliter Geometric Coefficient of Variation 26.1	14.8042 Micrograms per milliliter Geometric Coefficient of Variation 33.1

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population

Blood samples were collected at indicated time points for evaluation of tmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Time to Cmax (Tmax) of GSK2586881	0.08333 Hours Interval 0.0833 to 0.1333	0.16667 Hours Interval 0.0667 to 0.5	0.10000 Hours Interval 0.0667 to 0.55	0.13333 Hours Interval 0.0833 to 0.6333

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population

Blood samples were collected at indicated time points for evaluation of AUC(0-t). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881	3.941 Hours*micrograms per milliliter Geometric Coefficient of Variation 53.6	17.874 Hours*micrograms per milliliter Geometric Coefficient of Variation 30.9	46.789 Hours*micrograms per milliliter Geometric Coefficient of Variation 16.3	68.042 Hours*micrograms per milliliter Geometric Coefficient of Variation 37.0

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for evaluation of AUC(0-inf). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=2 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=7 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881	NA Hours*micrograms per milliliter Geometric Coefficient of Variation NA 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.	25.26 Hours*micrograms per milliliter Geometric Coefficient of Variation 7.7	52.46 Hours*micrograms per milliliter Geometric Coefficient of Variation 20.0	76.87 Hours*micrograms per milliliter Geometric Coefficient of Variation 42.1

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population

Blood samples were collected at indicated time points for evaluation of Ct. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Last Observed Quantifiable Concentration (Ct) of GSK2586881	0.2563 Micrograms per milliliter Geometric Coefficient of Variation 22.8	0.3327 Micrograms per milliliter Geometric Coefficient of Variation 54.4	0.4800 Micrograms per milliliter Geometric Coefficient of Variation 44.9	0.6380 Micrograms per milliliter Geometric Coefficient of Variation 54.9

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population

Blood samples were collected at indicated time points for evaluation of tlast. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	8.000 Hours Interval 4.2 to 8.47	24.000 Hours Interval 8.18 to 24.25	24.017 Hours Interval 23.73 to 24.15	24.117 Hours Interval 23.97 to 24.28

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for evaluation of CL. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=2 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=7 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Plasma Clearance (CL) of GSK2586881	NA Liters per hour Geometric Coefficient of Variation NA 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.	0.5838 Liters per hour Geometric Coefficient of Variation 10.1	0.6207 Liters per hour Geometric Coefficient of Variation 16.8	0.8170 Liters per hour Geometric Coefficient of Variation 30.8

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for evaluation of apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=2 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=7 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Apparent Volume of Distribution of GSK2586881	NA Liters Geometric Coefficient of Variation NA 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.	6.443 Liters Geometric Coefficient of Variation 2.4	6.593 Liters Geometric Coefficient of Variation 20.5	8.084 Liters Geometric Coefficient of Variation 20.6

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for evaluation of t1/2. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=2 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=7 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Apparent Terminal Phase Half-life (t1/2) of GSK2586881	NA Hours Geometric Coefficient of Variation NA 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.	7.651 Hours Geometric Coefficient of Variation 7.7	7.362 Hours Geometric Coefficient of Variation 23.2	6.858 Hours Geometric Coefficient of Variation 19.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

Population: Evaluable Population. Only those participants with data available at the specified time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	GSK2586881 0.1 mg/kg n=4 Participants Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 Participants Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=5 Participants Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 Participants Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Change From Baseline in Cardiac Index (CI) 1 hour post-dose (Day 1)	1.045 Ratio Interval 0.874 to 1.248	1.076 Ratio Interval 0.947 to 1.223	1.084 Ratio Interval 0.766 to 1.533	0.990 Ratio Interval 0.948 to 1.034
Change From Baseline in Cardiac Index (CI) 2 hours post-dose (Day 1)	1.021 Ratio Interval 0.816 to 1.278	1.029 Ratio Interval 0.951 to 1.113	0.926 Ratio Interval 0.719 to 1.193	1.020 Ratio Interval 0.948 to 1.097
Change From Baseline in Cardiac Index (CI) 4 hours post-dose (Day 1)	1.107 Ratio Interval 0.801 to 1.53	1.128 Ratio Interval 0.941 to 1.352	0.889 Ratio Interval 0.74 to 1.068	1.000 Ratio Interval 0.933 to 1.072

Adverse Events

GSK2586881 0.1 mg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

GSK2586881 0.2 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK2586881 0.4 mg/kg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2586881 0.8 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	GSK2586881 0.1 mg/kg n=4 participants at risk Participants received a single IV dose of 0.1 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.2 mg/kg n=5 participants at risk Participants received a single IV dose of 0.2 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.4 mg/kg n=6 participants at risk Participants received a single IV dose of 0.4 mg/kg GSK2586881 and were followed up till 28 days post-dose.	GSK2586881 0.8 mg/kg n=8 participants at risk Participants received a single IV dose of 0.8 mg/kg GSK2586881 and were followed up till 28 days post-dose.
Musculoskeletal and connective tissue disorders Back pain	25.0% 1/4 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	33.3% 2/6 • Number of events 2 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	16.7% 1/6 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Infections and infestations Pneumonia	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	16.7% 1/6 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	20.0% 1/5 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/6 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	16.7% 1/6 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Cardiac disorders Bradycardia	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/6 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	12.5% 1/8 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Nervous system disorders Headache	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/5 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/6 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	12.5% 1/8 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	20.0% 1/5 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/6 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	20.0% 1/5 • Number of events 1 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/6 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.	0.00% 0/8 • Non-SAEs and SAEs were reported from start of study treatment and up to Day 28 Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER