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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03177603

Enrollment

Registered

2017-06-06

Start date

2018-02-21

Completion date

2019-05-07

Last updated

2020-04-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension, Pulmonary

Keywords

Pulmonary Arterial Hypertension, Dose-escalation, Safety, Tolerability, GSK2586881

Brief summary

GSK2586881, a purified intravenous (IV) formulation of soluble recombinant human Angiotensin Converting Enzyme (rhACE2) is being investigated as a treatment for PAH. This GlaxoSmithKline (GSK) study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK2586881 in subjects with PAH. This open-label, dose-escalation study will comprise of 4 separate groups based on the planned dose range, and subjects in each group will be administered a single dose of GSK2586881 ranging between 0.1, 0.2, 0.4 and 0.8 milligram per kilogram (mg/kg) via IV route. Dose escalation will occur after 4 subjects have been dosed per cohort and review of safety, tolerability, PK and hemodynamic data up to 24 hours post dose has taken place. A maximum of 27 subjects will be included in the study and the total duration of the study will be up to a maximum of 59 days.

Interventions

DRUGGSK2586881

GSK2586881 is a clear colorless liquid for IV infusion over 3- 5 minutes and will be administered a maximum dose of 0.8 mg/kg.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Subjects must be between 18-75 years of age (inclusive), at the time of signing the informed consent. * Documented diagnosis of PAH, defined as mPAP \> 25 millimeter of mercury (mmHg) and pulmonary wedge pressure (PWP) \<= 15. * Idiopathic PAH (IPAH), Hereditary PAH (HPAH), or PAH associated with collagen vascular disease, or appetite suppressant use. * World Health Organization (WHO) functional class I, II, or III, stable for at least 8 weeks prior to enrollment. * Hemodynamically stable on background therapy with no evidence of uncontrolled right heart failure (historic data), as determined by the investigator. * Six minute walk (6MW) distance, as performed at screening or within 6 months prior to screening, of \>= 100 meters (m) and \<= 500 m. * Mean BP of \>60 mmHg. * Receiving stable doses of one or more medications that are approved for treatment of PAH, including endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and/or prostanoids/prostacyclin receptor agonists, for a minimum of 12 consecutive weeks before enrollment. * Diuretic dose stable for 8 weeks. * Body weight \<= 100 kg and body mass index (BMI) within the range 18-35 kg per m square (kg/m\^2) (inclusive). * Male and/or female (following confirmation of negative pregnancy test for Women of Childbearing Potential \[WOCBP\]). Women who are pregnant or breastfeeding are excluded. * Capable of giving signed informed consent.

Exclusion criteria

* History of systemic hypotension, defined as systolic BP \<90 mmHg and/or diastolic BP \<50 mmHg. * Hospitalization for PAH associated deterioration in the previous 6 months. * Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. Concurrent disease or condition that may interfere with study participation or safety include bleeding disorders, arrhythmia, organ transplant, organ failure, current neoplasm, poorly controlled diabetes mellitus, and serious neurological disorders. * Complex repaired and unrepaired congenital heart disease. * Subjects with Eisenmenger physiology. * Alanine transferase (ALT) \>2x upper limit of normal (ULN). * Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Estimated glomerular-filtration-rate (eGFR) \<45 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2). * QTc \>480 millisecond (msec) or QTc \> 500 msec in subjects with bundle branch block. * Any bleeding concerns as evidenced by International normalized ratio (INR) \>1.5 (in subjects not receiving anticoagulation therapy) or platelet count \<80,000. * Hemoglobin (Hb) \<10 gram per deciliter (g/dL). * Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study. * Any use of an Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin receptor blocker or renin inhibitors within 14 days prior to dosing. Therapy can be stopped to enable inclusion if deemed safe by the subject's treating physician. * Use of any investigational product (IP) or device within 30 days prior to dosing, or known requirement for any investigational agent prior to completion of all scheduled study assessments. * Positive human immunodeficiency virus (HIV) antibody test. * Presence of Hepatitis B surface antigen (HBsAg) at screening. * Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment. * Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. * Participation in the study would result in loss of blood or blood products in excess of 300mL within 65 days. * Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. * A known or suspected history of alcohol or drug abuse within the 2 years prior to screening. * Unable to refrain from smoking during the in-house treatment period.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)	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.
Change From Baseline in Pulmonary Vascular Resistance (PVR)	Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)	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.
Change From Baseline in Cardiac Output (CO)	Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Clinical Chemistry Parameter: Total Protein	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Hemoglobin	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Hematocrit	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Hematology Parameter: Reticulocytes	Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Number of Participants With Urinalysis Results by Dipstick Method	24 hours post-dose (Day 1)	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.
Change From Baseline in Pulse Rate	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)	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.
Change From Baseline in Respiratory Rate	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)	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.
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	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)	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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings	4 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)	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.
Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	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)	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.
Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)	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)	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.
Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)	Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)	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.
Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	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)	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.
Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	1 hour, 2 hours and 4 hours post-dose (Day 1)	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.
Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)	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.
Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO])	Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)	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.
Change From Baseline in Disease Biomarker: Cardiac Troponin-I	Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)	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.
Maximum Observed Plasma Concentration (Cmax) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of Cmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time to Cmax (Tmax) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of tmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of AUC(0-t). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of AUC(0-inf). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Last Observed Quantifiable Concentration (Ct) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of Ct. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of tlast. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Plasma Clearance (CL) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of CL. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Apparent Volume of Distribution of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Apparent Terminal Phase Half-life (t1/2) of GSK2586881	Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)	Blood samples were collected at indicated time points for evaluation of t1/2. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Number of Participants With Positive Immunogenicity Results	Up to Day 28	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.
Number of Participants With Non-serious Adverse Events (AEs)	Up to Day 28	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.
Number of Participants With Serious Adverse Events (SAEs)	Up to Day 28	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.

Other

Measure	Time frame	Description
Change From Baseline in Cardiac Index (CI)	Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)	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.

Countries

Germany, Spain, United States

Participant flow

Recruitment details

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

Pre-assignment details

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

Participants by arm

Arm	Count
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.	4
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.	5
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.	6
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.	8
Total	23

Baseline characteristics

Characteristic	GSK2586881 0.1 mg/kg	GSK2586881 0.2 mg/kg	GSK2586881 0.4 mg/kg	GSK2586881 0.8 mg/kg	Total
Age, Continuous	32.0 Years STANDARD_DEVIATION 4.97	55.4 Years STANDARD_DEVIATION 14.96	52.5 Years STANDARD_DEVIATION 8.67	50.3 Years STANDARD_DEVIATION 13.35	48.8 Years STANDARD_DEVIATION 13.55
Race/Ethnicity, Customized Black or African American	0 Participants	1 Participants	1 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants	4 Participants	5 Participants	7 Participants	20 Participants
Sex: Female, Male Female	3 Participants	3 Participants	4 Participants	5 Participants	15 Participants
Sex: Female, Male Male	1 Participants	2 Participants	2 Participants	3 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 5	0 / 6	0 / 8
other Total, other adverse events	1 / 4	3 / 5	5 / 6	2 / 8
serious Total, serious adverse events	0 / 4	0 / 5	0 / 6	0 / 8

Outcome results

Primary

Change From Baseline in Cardiac Output (CO)

CO is the amount of blood pumped by the heart per minute. Pulmonary arterial catheters were placed in participants and CO values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Output (CO)	1 hour post-dose (Day 1)	1.046 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Output (CO)	4 hours post-dose (Day 1)	1.114 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Output (CO)	2 hours post-dose (Day 1)	1.025 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Output (CO)	1 hour post-dose (Day 1)	1.079 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Output (CO)	4 hours post-dose (Day 1)	1.138 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Output (CO)	2 hours post-dose (Day 1)	1.029 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Output (CO)	1 hour post-dose (Day 1)	1.076 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Output (CO)	2 hours post-dose (Day 1)	0.929 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Output (CO)	4 hours post-dose (Day 1)	0.882 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Output (CO)	1 hour post-dose (Day 1)	0.990 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Output (CO)	4 hours post-dose (Day 1)	1.002 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Output (CO)	2 hours post-dose (Day 1)	1.012 Ratio

Primary

Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)

The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Pulmonary arterial catheters were placed in participants and mPAP values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	1 hour post-dose (Day 1)	0.950 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	4 hours post-dose (Day 1)	0.991 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	2 hours post-dose (Day 1)	0.937 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	1 hour post-dose (Day 1)	0.995 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	4 hours post-dose (Day 1)	1.029 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	2 hours post-dose (Day 1)	0.994 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	2 hours post-dose (Day 1)	0.910 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	1 hour post-dose (Day 1)	0.939 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	4 hours post-dose (Day 1)	0.973 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	1 hour post-dose (Day 1)	0.989 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	4 hours post-dose (Day 1)	1.062 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)	2 hours post-dose (Day 1)	0.996 Ratio

Primary

Change From Baseline in Pulmonary Vascular Resistance (PVR)

PVR is the resistance generated by pulmonary circulation. Pulmonary arterial catheters were placed in participants and PVR values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	2 hours post-dose (Day 1)	0.926 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	4 hours post-dose (Day 1)	0.907 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	1 hour post-dose (Day 1)	0.936 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	1 hour post-dose (Day 1)	0.885 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	4 hours post-dose (Day 1)	0.895 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	2 hours post-dose (Day 1)	1.043 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	2 hours post-dose (Day 1)	0.945 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	1 hour post-dose (Day 1)	0.813 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	4 hours post-dose (Day 1)	0.924 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	1 hour post-dose (Day 1)	1.017 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	4 hours post-dose (Day 1)	1.116 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Pulmonary Vascular Resistance (PVR)	2 hours post-dose (Day 1)	0.974 Ratio

Secondary

Apparent Terminal Phase Half-life (t1/2) of GSK2586881

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

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Apparent Terminal Phase Half-life (t1/2) of GSK2586881	NA Hours	—
GSK2586881 0.2 mg/kg	Apparent Terminal Phase Half-life (t1/2) of GSK2586881	7.651 Hours	Geometric Coefficient of Variation 7.7
GSK2586881 0.4 mg/kg	Apparent Terminal Phase Half-life (t1/2) of GSK2586881	7.362 Hours	Geometric Coefficient of Variation 23.2
GSK2586881 0.8 mg/kg	Apparent Terminal Phase Half-life (t1/2) of GSK2586881	6.858 Hours	Geometric Coefficient of Variation 19.6

Secondary

Apparent Volume of Distribution of GSK2586881

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

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Apparent Volume of Distribution of GSK2586881	NA Liters	—
GSK2586881 0.2 mg/kg	Apparent Volume of Distribution of GSK2586881	6.443 Liters	Geometric Coefficient of Variation 2.4
GSK2586881 0.4 mg/kg	Apparent Volume of Distribution of GSK2586881	6.593 Liters	Geometric Coefficient of Variation 20.5
GSK2586881 0.8 mg/kg	Apparent Volume of Distribution of GSK2586881	8.084 Liters	Geometric Coefficient of Variation 20.6

Secondary

Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881

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

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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	—
GSK2586881 0.2 mg/kg	Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881	25.26 Hours*micrograms per milliliter	Geometric Coefficient of Variation 7.7
GSK2586881 0.4 mg/kg	Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881	52.46 Hours*micrograms per milliliter	Geometric Coefficient of Variation 20
GSK2586881 0.8 mg/kg	Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881	76.87 Hours*micrograms per milliliter	Geometric Coefficient of Variation 42.1

Secondary

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881

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

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

Population: Pharmacokinetic Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881	17.874 Hours*micrograms per milliliter	Geometric Coefficient of Variation 30.9
GSK2586881 0.4 mg/kg	Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881	46.789 Hours*micrograms per milliliter	Geometric Coefficient of Variation 16.3
GSK2586881 0.8 mg/kg	Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881	68.042 Hours*micrograms per milliliter	Geometric Coefficient of Variation 37

Secondary

Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase

Blood samples were collected for the assessment of clinical chemistry parameters: alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 2.5
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, Day 7 to Day 14	1.4 International units per liter	Standard Deviation 1.67
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, Day 7 to Day 14	1.8 International units per liter	Standard Deviation 3.27
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, 24 hours post-dose (Day 1)	-1.4 International units per liter	Standard Deviation 7.44
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, 24 hours post-dose (Day 1)	0.0 International units per liter	Standard Deviation 1.58
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, Day 7 to Day 14	3.2 International units per liter	Standard Deviation 4.21
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, 24 hours post-dose (Day 1)	-0.4 International units per liter	Standard Deviation 0.55
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, Day 7 to Day 14	3.0 International units per liter	Standard Deviation 3.52
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, 24 hours post-dose (Day 1)	-1.8 International units per liter	Standard Deviation 3.76
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, Day 7 to Day 14	-4.3 International units per liter	Standard Deviation 12.94
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, Day 7 to Day 14	-0.3 International units per liter	Standard Deviation 3.67
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, 24 hours post-dose (Day 1)	0.5 International units per liter	Standard Deviation 1.76
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, 24 hours post-dose (Day 1)	5.3 International units per liter	Standard Deviation 3.08
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, 24 hours post-dose (Day 1)	-1.8 International units per liter	Standard Deviation 3.77
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	AST, Day 7 to Day 14	-0.9 International units per liter	Standard Deviation 6.71
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, Day 7 to Day 14	2.6 International units per liter	Standard Deviation 4.31
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, Day 7 to Day 14	0.9 International units per liter	Standard Deviation 4.85
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	Alkaline phosphatase, 24 hours post-dose (Day 1)	3.1 International units per liter	Standard Deviation 3.48
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase	ALT, 24 hours post-dose (Day 1)	-0.1 International units per liter	Standard Deviation 2.17

Secondary

Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)

Blood samples were collected for the assessment of clinical chemistry parameters: calcium, glucose, potassium, sodium and BUN. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 1.76
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 1.08
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, 24 hours post-dose (Day 1)	1.10 Millimoles per liter	Standard Deviation 1.398
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, 24 hours post-dose (Day 1)	-0.20 Millimoles per liter	Standard Deviation 0.758
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, Day 7 to Day 14	-0.32 Millimoles per liter	Standard Deviation 0.646
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, 24 hours post-dose (Day 1)	0.18 Millimoles per liter	Standard Deviation 0.179
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, Day 7 to Day 14	0.22 Millimoles per liter	Standard Deviation 0.148
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, 24 hours post-dose (Day 1)	-0.6 Millimoles per liter	Standard Deviation 2.3
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, Day 7 to Day 14	1.50 Millimoles per liter	Standard Deviation 1.541
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, Day 7 to Day 14	0.0 Millimoles per liter	Standard Deviation 1.87
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, 24 hours post-dose (Day 1)	0.012 Millimoles per liter	Standard Deviation 0.0867
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, Day 7 to Day 14	0.064 Millimoles per liter	Standard Deviation 0.0888
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, Day 7 to Day 14	0.5 Millimoles per liter	Standard Deviation 1.64
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, 24 hours post-dose (Day 1)	-0.2 Millimoles per liter	Standard Deviation 1.47
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, Day 7 to Day 14	0.00 Millimoles per liter	Standard Deviation 1
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, 24 hours post-dose (Day 1)	0.047 Millimoles per liter	Standard Deviation 0.1033
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, Day 7 to Day 14	-0.57 Millimoles per liter	Standard Deviation 0.635
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, Day 7 to Day 14	0.25 Millimoles per liter	Standard Deviation 0.207
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, 24 hours post-dose (Day 1)	0.83 Millimoles per liter	Standard Deviation 1.033
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, Day 7 to Day 14	0.047 Millimoles per liter	Standard Deviation 0.125
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, 24 hours post-dose (Day 1)	0.08 Millimoles per liter	Standard Deviation 0.306
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, 24 hours post-dose (Day 1)	0.50 Millimoles per liter	Standard Deviation 1.752
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, 24 hours post-dose (Day 1)	-0.05 Millimoles per liter	Standard Deviation 0.239
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, Day 7 to Day 14	0.0 Millimoles per liter	Standard Deviation 1.6
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Potassium, Day 7 to Day 14	0.18 Millimoles per liter	Standard Deviation 0.301
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, Day 7 to Day 14	0.31 Millimoles per liter	Standard Deviation 1.067
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Sodium, 24 hours post-dose (Day 1)	-1.0 Millimoles per liter	Standard Deviation 1.85
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, Day 7 to Day 14	0.115 Millimoles per liter	Standard Deviation 0.0583
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, 24 hours post-dose (Day 1)	0.89 Millimoles per liter	Standard Deviation 2.039
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Glucose, Day 7 to Day 14	-0.20 Millimoles per liter	Standard Deviation 1.995
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Calcium, 24 hours post-dose (Day 1)	0.060 Millimoles per liter	Standard Deviation 0.0466
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	BUN, 24 hours post-dose (Day 1)	-0.25 Millimoles per liter	Standard Deviation 0.463

Secondary

Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine

Blood samples were collected for the assessment of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 6.53
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, Day 7 to Day 14	8.68 Micromoles per liter	Standard Deviation 13.353
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, Day 7 to Day 14	0.4 Micromoles per liter	Standard Deviation 2.61
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, 24 hours post-dose (Day 1)	0.4 Micromoles per liter	Standard Deviation 0.89
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, 24 hours post-dose (Day 1)	0.8 Micromoles per liter	Standard Deviation 1.79
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, Day 7 to Day 14	0.0 Micromoles per liter	Standard Deviation 0
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, 24 hours post-dose (Day 1)	10.80 Micromoles per liter	Standard Deviation 6.11
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, Day 7 to Day 14	0.0 Micromoles per liter	Standard Deviation 1.26
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, 24 hours post-dose (Day 1)	0.7 Micromoles per liter	Standard Deviation 4.84
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, Day 7 to Day 14	-1.7 Micromoles per liter	Standard Deviation 3.44
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, Day 7 to Day 14	4.57 Micromoles per liter	Standard Deviation 9.638
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, 24 hours post-dose (Day 1)	12.22 Micromoles per liter	Standard Deviation 20.214
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, 24 hours post-dose (Day 1)	0.3 Micromoles per liter	Standard Deviation 1.97
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, 24 hours post-dose (Day 1)	1.76 Micromoles per liter	Standard Deviation 2.759
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Creatinine, Day 7 to Day 14	3.20 Micromoles per liter	Standard Deviation 4.885
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, Day 7 to Day 14	0.5 Micromoles per liter	Standard Deviation 2.56
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, Day 7 to Day 14	0.0 Micromoles per liter	Standard Deviation 4.14
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Direct bilirubin, 24 hours post-dose (Day 1)	1.0 Micromoles per liter	Standard Deviation 2.14
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Total bilirubin, 24 hours post-dose (Day 1)	4.8 Micromoles per liter	Standard Deviation 6.76

Secondary

Change From Baseline in Clinical Chemistry Parameter: Total Protein

Blood samples were collected for the assessment of clinical chemistry parameter, total protein. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	24 hours post-dose (Day 1)	1.3 Grams per liter	Standard Deviation 6.13
GSK2586881 0.1 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	Day 7 to Day 14	1.5 Grams per liter	Standard Deviation 2.38
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	Day 7 to Day 14	6.2 Grams per liter	Standard Deviation 4.55
GSK2586881 0.2 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	24 hours post-dose (Day 1)	0.6 Grams per liter	Standard Deviation 3.78
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	24 hours post-dose (Day 1)	1.8 Grams per liter	Standard Deviation 2.93
GSK2586881 0.4 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	Day 7 to Day 14	2.0 Grams per liter	Standard Deviation 4.73
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	24 hours post-dose (Day 1)	2.6 Grams per liter	Standard Deviation 3.66
GSK2586881 0.8 mg/kg	Change From Baseline in Clinical Chemistry Parameter: Total Protein	Day 7 to Day 14	4.9 Grams per liter	Standard Deviation 3.31

Secondary

Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

DBP and SBP were measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 12.4
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	DBP, Day 7 to Day 14, n=4,5,6,8	-2.2 Millimeters of mercury	Standard Deviation 6.91
GSK2586881 0.2 mg/kg	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	2.0 Millimeters of mercury	Standard Deviation 10.2
GSK2586881 0.2 mg/kg	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	-0.2 Millimeters of mercury	Standard Deviation 12.6
GSK2586881 0.2 mg/kg	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	3.4 Millimeters of mercury	Standard Deviation 12.68
GSK2586881 0.2 mg/kg	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	0.6 Millimeters of mercury	Standard Deviation 8.56
GSK2586881 0.2 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	SBP, Day 7 to Day 14, n=4,5,6,8	6.0 Millimeters of mercury	Standard Deviation 6.78
GSK2586881 0.2 mg/kg	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	-0.2 Millimeters of mercury	Standard Deviation 14.72
GSK2586881 0.2 mg/kg	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	1.2 Millimeters of mercury	Standard Deviation 10.55
GSK2586881 0.2 mg/kg	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	-6.3 Millimeters of mercury	Standard Deviation 8.66
GSK2586881 0.2 mg/kg	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	3.0 Millimeters of mercury	Standard Deviation 8.37
GSK2586881 0.2 mg/kg	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	3.0 Millimeters of mercury	Standard Deviation 16.57
GSK2586881 0.2 mg/kg	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	4.2 Millimeters of mercury	Standard Deviation 9.34
GSK2586881 0.2 mg/kg	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	-8.6 Millimeters of mercury	Standard Deviation 9.61
GSK2586881 0.2 mg/kg	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	-1.0 Millimeters of mercury	Standard Deviation 10.42
GSK2586881 0.4 mg/kg	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	-5.0 Millimeters of mercury	Standard Deviation 14.67
GSK2586881 0.4 mg/kg	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	-4.3 Millimeters of mercury	Standard Deviation 9.73
GSK2586881 0.4 mg/kg	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	-5.8 Millimeters of mercury	Standard Deviation 8.8
GSK2586881 0.4 mg/kg	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	-2.7 Millimeters of mercury	Standard Deviation 13.22
GSK2586881 0.4 mg/kg	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	-10.2 Millimeters of mercury	Standard Deviation 9.15
GSK2586881 0.4 mg/kg	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	-2.8 Millimeters of mercury	Standard Deviation 10.61
GSK2586881 0.4 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	DBP, Day 7 to Day 14, n=4,5,6,8	-2.5 Millimeters of mercury	Standard Deviation 11.78
GSK2586881 0.4 mg/kg	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	-5.2 Millimeters of mercury	Standard Deviation 6.11
GSK2586881 0.4 mg/kg	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	-2.7 Millimeters of mercury	Standard Deviation 9.37
GSK2586881 0.4 mg/kg	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	-0.7 Millimeters of mercury	Standard Deviation 18.84
GSK2586881 0.4 mg/kg	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	6.3 Millimeters of mercury	Standard Deviation 13.03
GSK2586881 0.4 mg/kg	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	-5.2 Millimeters of mercury	Standard Deviation 7.63
GSK2586881 0.4 mg/kg	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	-4.7 Millimeters of mercury	Standard Deviation 11.41
GSK2586881 0.4 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	SBP, Day 7 to Day 14, n=4,5,6,8	-5.8 Millimeters of mercury	Standard Deviation 15.07
GSK2586881 0.8 mg/kg	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	-3.1 Millimeters of mercury	Standard Deviation 8.46
GSK2586881 0.8 mg/kg	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	-1.0 Millimeters of mercury	Standard Deviation 9.32
GSK2586881 0.8 mg/kg	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	-3.8 Millimeters of mercury	Standard Deviation 14.85
GSK2586881 0.8 mg/kg	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	6.1 Millimeters of mercury	Standard Deviation 13.53
GSK2586881 0.8 mg/kg	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	1.6 Millimeters of mercury	Standard Deviation 6.07
GSK2586881 0.8 mg/kg	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	-3.3 Millimeters of mercury	Standard Deviation 4.53
GSK2586881 0.8 mg/kg	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	-4.8 Millimeters of mercury	Standard Deviation 9.65
GSK2586881 0.8 mg/kg	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	3.3 Millimeters of mercury	Standard Deviation 5.87
GSK2586881 0.8 mg/kg	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	-2.3 Millimeters of mercury	Standard Deviation 3.73
GSK2586881 0.8 mg/kg	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	3.0 Millimeters of mercury	Standard Deviation 8.07
GSK2586881 0.8 mg/kg	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	-0.1 Millimeters of mercury	Standard Deviation 5.03
GSK2586881 0.8 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	DBP, Day 7 to Day 14, n=4,5,6,8	2.8 Millimeters of mercury	Standard Deviation 12.83
GSK2586881 0.8 mg/kg	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	SBP, Day 7 to Day 14, n=4,5,6,8	-2.1 Millimeters of mercury	Standard Deviation 9.63
GSK2586881 0.8 mg/kg	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	2.0 Millimeters of mercury	Standard Deviation 11.8

Secondary

Change From Baseline in Disease Biomarker: Cardiac Troponin-I

Blood samples were collected at specific time points to assess cardiac troponin I. Cardiac troponin I is a biomarker of cardiac stress. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	4 hours post-dose (Day 1)	1.968 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	24 hours post-dose (Day 1)	1.316 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	2 hours post-dose (Day 1)	1.565 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	24 hours post-dose (Day 1)	1.000 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	4 hours post-dose (Day 1)	1.149 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	2 hours post-dose (Day 1)	1.320 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	2 hours post-dose (Day 1)	1.585 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	24 hours post-dose (Day 1)	1.000 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	4 hours post-dose (Day 1)	1.695 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	24 hours post-dose (Day 1)	1.000 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	4 hours post-dose (Day 1)	2.030 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarker: Cardiac Troponin-I	2 hours post-dose (Day 1)	1.414 Ratio

Secondary

Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)

Blood samples were collected at specific time points to evaluate NT pro-BNP, a biomarker of disease activity. NT-pro-BNP is a biomarker of cardiac stress or ventricular workload and decreases as a result of reduced force of contraction if pulmonary blood pressure is reduced. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	4 hours post-dose (Day 1)	1.042 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	24 hours post-dose (Day 1)	0.896 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	2 hours post-dose (Day 1)	1.005 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	2 hours post-dose (Day 1)	0.923 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	4 hours post-dose (Day 1)	0.944 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	24 hours post-dose (Day 1)	0.703 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	24 hours post-dose (Day 1)	0.810 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	4 hours post-dose (Day 1)	1.074 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)	2 hours post-dose (Day 1)	1.015 Ratio

Secondary

Change From Baseline in Hematology Parameter: Hematocrit

Blood samples were collected for the assessment of hematology parameter, hematocrit. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	Day 7 to Day 14, n=4,5,6,8	0.0104 Proportion of red blood cells in blood	Standard Deviation 0.02173
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	24 hours post-dose (Day 1), n=4,4,6,5	0.0053 Proportion of red blood cells in blood	Standard Deviation 0.02156
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	Day 7 to Day 14, n=4,5,6,8	0.0030 Proportion of red blood cells in blood	Standard Deviation 0.02391
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	24 hours post-dose (Day 1), n=4,4,6,5	0.0098 Proportion of red blood cells in blood	Standard Deviation 0.01546
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	24 hours post-dose (Day 1), n=4,4,6,5	0.0140 Proportion of red blood cells in blood	Standard Deviation 0.02448
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Hematocrit	Day 7 to Day 14, n=4,5,6,8	0.0135 Proportion of red blood cells in blood	Standard Deviation 0.01891

Secondary

Change From Baseline in Hematology Parameter: Hemoglobin

Blood samples were collected for the assessment of hematology parameter, hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	Day 7 to Day 14, n=4,5,6,8	3.4 Grams per liter	Standard Deviation 5.98
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	2.0 Grams per liter	Standard Deviation 5.72
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	5.0 Grams per liter	Standard Deviation 4.77
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	Day 7 to Day 14, n=4,5,6,8	-1.5 Grams per liter	Standard Deviation 7.09
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	3.0 Grams per liter	Standard Deviation 5.61
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Hemoglobin	Day 7 to Day 14, n=4,5,6,8	4.0 Grams per liter	Standard Deviation 5.15

Secondary

Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin

Blood samples were collected for the assessment of hematology parameter, mean corpuscle hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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 0.15
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	Day 7 to Day 14, n=4,5,6,8	0.04 Picograms	Standard Deviation 0.182
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	0.05 Picograms	Standard Deviation 0.507
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	0.25 Picograms	Standard Deviation 0.302
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	Day 7 to Day 14, n=4,5,6,8	-0.33 Picograms	Standard Deviation 0.314
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	24 hours post-dose (Day 1), n=4,4,6,5	-0.10 Picograms	Standard Deviation 0.235
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	Day 7 to Day 14, n=4,5,6,8	0.15 Picograms	Standard Deviation 0.177

Secondary

Change From Baseline in Hematology Parameter: Mean Corpuscle Volume

Blood samples were collected for the assessment of hematology parameter, mean corpuscle volume. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	Day 7 to Day 14, n=4,5,6,8	-0.2 Femtoliters	Standard Deviation 0.84
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	24 hours post-dose (Day 1), n=4,4,6,5	0.0 Femtoliters	Standard Deviation 0.82
GSK2586881 0.4 mg/kg	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 0.84
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	Day 7 to Day 14, n=4,5,6,8	0.7 Femtoliters	Standard Deviation 1.03
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	24 hours post-dose (Day 1), n=4,4,6,5	0.6 Femtoliters	Standard Deviation 1.95
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	Day 7 to Day 14, n=4,5,6,8	0.8 Femtoliters	Standard Deviation 1.04

Secondary

Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count

Blood samples were collected for the assessment of hematology parameter: RBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	Day 7 to Day 14, n=4,5,6,8	0.14 Trillion cells per liter	Standard Deviation 0.261
GSK2586881 0.2 mg/kg	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 0.287
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	24 hours post-dose (Day 1), n=4,4,6,5	0.13 Trillion cells per liter	Standard Deviation 0.163
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	Day 7 to Day 14, n=4,5,6,8	0.00 Trillion cells per liter	Standard Deviation 0.31
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	24 hours post-dose (Day 1), n=4,4,6,5	0.12 Trillion cells per liter	Standard Deviation 0.192
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count	Day 7 to Day 14, n=4,5,6,8	0.11 Trillion cells per liter	Standard Deviation 0.203

Secondary

Change From Baseline in Hematology Parameter: Reticulocytes

Blood samples were collected for the assessment of hematology parameter: reticulocytes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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 0.0033
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	Day 7 to Day 14, n=4,5,6,8	0.0014 Percentage of reticulocytes in blood	Standard Deviation 0.00358
GSK2586881 0.2 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	24 hours post-dose (Day 1), n=4,4,6,5	0.0017 Percentage of reticulocytes in blood	Standard Deviation 0.0031
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	24 hours post-dose (Day 1), n=4,4,6,5	0.0017 Percentage of reticulocytes in blood	Standard Deviation 0.00216
GSK2586881 0.4 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	Day 7 to Day 14, n=4,5,6,8	0.0025 Percentage of reticulocytes in blood	Standard Deviation 0.00333
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	24 hours post-dose (Day 1), n=4,4,6,5	0.0000 Percentage of reticulocytes in blood	Standard Deviation 0.001
GSK2586881 0.8 mg/kg	Change From Baseline in Hematology Parameter: Reticulocytes	Day 7 to Day 14, n=4,5,6,8	0.0040 Percentage of reticulocytes in blood	Standard Deviation 0.00325

Secondary

Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count

Blood samples were collected for the assessment of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils (T.neutrophils), platelet count and WBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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 17.4
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 1.33
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	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	0.004 Giga cells per liter	Standard Deviation 0.023
GSK2586881 0.2 mg/kg	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	0.013 Giga cells per liter	Standard Deviation 0.0206
GSK2586881 0.2 mg/kg	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	0.002 Giga cells per liter	Standard Deviation 0.0192
GSK2586881 0.2 mg/kg	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	0.018 Giga cells per liter	Standard Deviation 0.0222
GSK2586881 0.2 mg/kg	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	-0.070 Giga cells per liter	Standard Deviation 0.1612
GSK2586881 0.2 mg/kg	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	-0.054 Giga cells per liter	Standard Deviation 0.1422
GSK2586881 0.2 mg/kg	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	-0.028 Giga cells per liter	Standard Deviation 0.0914
GSK2586881 0.2 mg/kg	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 0.0998
GSK2586881 0.2 mg/kg	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	0.415 Giga cells per liter	Standard Deviation 0.3924
GSK2586881 0.2 mg/kg	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	0.504 Giga cells per liter	Standard Deviation 0.4884
GSK2586881 0.2 mg/kg	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	-33.0 Giga cells per liter	Standard Deviation 73.51
GSK2586881 0.2 mg/kg	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	19.8 Giga cells per liter	Standard Deviation 45.03
GSK2586881 0.2 mg/kg	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	0.30 Giga cells per liter	Standard Deviation 0.183
GSK2586881 0.2 mg/kg	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	0.46 Giga cells per liter	Standard Deviation 0.498
GSK2586881 0.4 mg/kg	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	0.098 Giga cells per liter	Standard Deviation 0.1125
GSK2586881 0.4 mg/kg	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 1.355
GSK2586881 0.4 mg/kg	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	0.047 Giga cells per liter	Standard Deviation 0.1263
GSK2586881 0.4 mg/kg	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	0.012 Giga cells per liter	Standard Deviation 0.0662
GSK2586881 0.4 mg/kg	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	0.68 Giga cells per liter	Standard Deviation 0.542
GSK2586881 0.4 mg/kg	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	0.738 Giga cells per liter	Standard Deviation 0.5615
GSK2586881 0.4 mg/kg	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	0.397 Giga cells per liter	Standard Deviation 1.3173
GSK2586881 0.4 mg/kg	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	0.008 Giga cells per liter	Standard Deviation 0.0306
GSK2586881 0.4 mg/kg	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	-0.005 Giga cells per liter	Standard Deviation 0.0302
GSK2586881 0.4 mg/kg	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	7.8 Giga cells per liter	Standard Deviation 16.65
GSK2586881 0.4 mg/kg	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	14.3 Giga cells per liter	Standard Deviation 52.89
GSK2586881 0.4 mg/kg	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	-0.157 Giga cells per liter	Standard Deviation 0.1558
GSK2586881 0.4 mg/kg	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	-0.250 Giga cells per liter	Standard Deviation 0.2001
GSK2586881 0.4 mg/kg	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	-0.025 Giga cells per liter	Standard Deviation 0.0807
GSK2586881 0.8 mg/kg	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	23.4 Giga cells per liter	Standard Deviation 24.44
GSK2586881 0.8 mg/kg	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 0.0503
GSK2586881 0.8 mg/kg	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	0.003 Giga cells per liter	Standard Deviation 0.0115
GSK2586881 0.8 mg/kg	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	12.6 Giga cells per liter	Standard Deviation 27.74
GSK2586881 0.8 mg/kg	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	0.091 Giga cells per liter	Standard Deviation 0.1654
GSK2586881 0.8 mg/kg	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	0.64 Giga cells per liter	Standard Deviation 0.588
GSK2586881 0.8 mg/kg	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	0.130 Giga cells per liter	Standard Deviation 0.4032
GSK2586881 0.8 mg/kg	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	0.140 Giga cells per liter	Standard Deviation 0.07
GSK2586881 0.8 mg/kg	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	0.727 Giga cells per liter	Standard Deviation 0.7298
GSK2586881 0.8 mg/kg	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	0.003 Giga cells per liter	Standard Deviation 0.0238
GSK2586881 0.8 mg/kg	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	2.16 Giga cells per liter	Standard Deviation 2.492
GSK2586881 0.8 mg/kg	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	0.190 Giga cells per liter	Standard Deviation 0.4553
GSK2586881 0.8 mg/kg	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	0.366 Giga cells per liter	Standard Deviation 0.7204
GSK2586881 0.8 mg/kg	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	0.023 Giga cells per liter	Standard Deviation 0.1004

Secondary

Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO])

Blood samples were collected at specific time points to evaluate levels of nitrite, nitrate and endogenous nitrite (En. nitrite) (biomarkers of NO). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	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	1.029 Ratio
GSK2586881 0.2 mg/kg	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	1.025 Ratio
GSK2586881 0.2 mg/kg	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	1.149 Ratio
GSK2586881 0.2 mg/kg	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	0.992 Ratio
GSK2586881 0.2 mg/kg	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	1.146 Ratio
GSK2586881 0.2 mg/kg	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	0.977 Ratio
GSK2586881 0.2 mg/kg	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	2.036 Ratio
GSK2586881 0.2 mg/kg	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	2.819 Ratio
GSK2586881 0.2 mg/kg	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	1.399 Ratio
GSK2586881 0.4 mg/kg	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	1.171 Ratio
GSK2586881 0.4 mg/kg	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	1.329 Ratio
GSK2586881 0.4 mg/kg	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	0.667 Ratio
GSK2586881 0.4 mg/kg	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	0.641 Ratio
GSK2586881 0.4 mg/kg	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	1.289 Ratio
GSK2586881 0.4 mg/kg	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	0.655 Ratio
GSK2586881 0.4 mg/kg	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	0.679 Ratio
GSK2586881 0.4 mg/kg	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	0.530 Ratio
GSK2586881 0.4 mg/kg	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	0.485 Ratio
GSK2586881 0.8 mg/kg	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	0.858 Ratio
GSK2586881 0.8 mg/kg	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	0.820 Ratio
GSK2586881 0.8 mg/kg	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	0.914 Ratio
GSK2586881 0.8 mg/kg	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	0.770 Ratio
GSK2586881 0.8 mg/kg	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	0.975 Ratio
GSK2586881 0.8 mg/kg	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	0.911 Ratio
GSK2586881 0.8 mg/kg	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	1.271 Ratio
GSK2586881 0.8 mg/kg	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	0.762 Ratio
GSK2586881 0.8 mg/kg	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	0.836 Ratio

Secondary

Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

Blood samples were collected to evaluate pulmonary wedge RAS peptides: Ang II, Ang (1-5) and Ang (1-7). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	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	4.150 Ratio
GSK2586881 0.2 mg/kg	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	3.792 Ratio
GSK2586881 0.2 mg/kg	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	3.151 Ratio
GSK2586881 0.2 mg/kg	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	0.191 Ratio
GSK2586881 0.2 mg/kg	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	0.193 Ratio
GSK2586881 0.2 mg/kg	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	3.313 Ratio
GSK2586881 0.2 mg/kg	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	0.190 Ratio
GSK2586881 0.2 mg/kg	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	3.213 Ratio
GSK2586881 0.2 mg/kg	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	4.621 Ratio
GSK2586881 0.4 mg/kg	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	5.239 Ratio
GSK2586881 0.4 mg/kg	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	0.394 Ratio
GSK2586881 0.4 mg/kg	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	5.246 Ratio
GSK2586881 0.4 mg/kg	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	8.521 Ratio
GSK2586881 0.4 mg/kg	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	4.476 Ratio
GSK2586881 0.4 mg/kg	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	0.183 Ratio
GSK2586881 0.4 mg/kg	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	0.505 Ratio
GSK2586881 0.4 mg/kg	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	2.993 Ratio
GSK2586881 0.4 mg/kg	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	2.709 Ratio
GSK2586881 0.8 mg/kg	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	1.693 Ratio
GSK2586881 0.8 mg/kg	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	0.420 Ratio
GSK2586881 0.8 mg/kg	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	0.369 Ratio
GSK2586881 0.8 mg/kg	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	0.369 Ratio
GSK2586881 0.8 mg/kg	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	1.834 Ratio
GSK2586881 0.8 mg/kg	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	1.562 Ratio
GSK2586881 0.8 mg/kg	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	1.472 Ratio
GSK2586881 0.8 mg/kg	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	1.558 Ratio
GSK2586881 0.8 mg/kg	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	1.589 Ratio

Secondary

Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood

Percent oxygen in blood was measured using pulse oximetry after the participant had rested for at least 5 minutes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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 2.3
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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 2.5
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	24 hours post-dose (Day 1), n=4,5,6,8	-2.3 Percentage of oxygen in blood	Standard Deviation 3.06
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	4 hours post-dose (Day 1), n=4,5,6,8	-1.0 Percentage of oxygen in blood	Standard Deviation 1.87
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	2 hours post-dose (Day 1), n=4,5,6,8	-0.7 Percentage of oxygen in blood	Standard Deviation 1.99
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	8 hours post-dose (Day 1), n=4,4,6,8	-0.2 Percentage of oxygen in blood	Standard Deviation 3.58
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	Day 7 to Day 14, n=4,5,6,8	-2.9 Percentage of oxygen in blood	Standard Deviation 2.37
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	1 hour post-dose (Day 1), n=4,5,6,8	-2.1 Percentage of oxygen in blood	Standard Deviation 2.79
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	0.5 hour post-dose (Day 1), n=4,5,6,8	-1.7 Percentage of oxygen in blood	Standard Deviation 2.77
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	4 hours post-dose (Day 1), n=4,5,6,8	-0.3 Percentage of oxygen in blood	Standard Deviation 1.96
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	0.5 hour post-dose (Day 1), n=4,5,6,8	0.8 Percentage of oxygen in blood	Standard Deviation 2.31
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	1 hour post-dose (Day 1), n=4,5,6,8	-0.3 Percentage of oxygen in blood	Standard Deviation 1.03
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	2 hours post-dose (Day 1), n=4,5,6,8	0.6 Percentage of oxygen in blood	Standard Deviation 1.21
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	8 hours post-dose (Day 1), n=4,4,6,8	0.8 Percentage of oxygen in blood	Standard Deviation 2.31
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	24 hours post-dose (Day 1), n=4,5,6,8	2.1 Percentage of oxygen in blood	Standard Deviation 1.6
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	Day 7 to Day 14, n=4,5,6,8	0.5 Percentage of oxygen in blood	Standard Deviation 3.33
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	2 hours post-dose (Day 1), n=4,5,6,8	0.9 Percentage of oxygen in blood	Standard Deviation 1.37
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	Day 7 to Day 14, n=4,5,6,8	0.8 Percentage of oxygen in blood	Standard Deviation 2.49
GSK2586881 0.8 mg/kg	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 3.28
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	1 hour post-dose (Day 1), n=4,5,6,8	-0.9 Percentage of oxygen in blood	Standard Deviation 2.48
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	0.5 hour post-dose (Day 1), n=4,5,6,8	-0.5 Percentage of oxygen in blood	Standard Deviation 2.03
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	8 hours post-dose (Day 1), n=4,4,6,8	0.4 Percentage of oxygen in blood	Standard Deviation 2.98
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood	4 hours post-dose (Day 1), n=4,5,6,8	0.5 Percentage of oxygen in blood	Standard Deviation 2.13

Secondary

Change From Baseline in Pulse Rate

Pulse rate was measured in supine position after at least a 5-minute rest. Change from Baseline in pulse rate was evaluated. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	Change From Baseline in Pulse Rate	8 hours post-dose (Day 1), n=4,4,6,8	2.8 Beats per minute	Standard Deviation 6.9
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	Change From Baseline in Pulse Rate	4 hours post-dose (Day 1), n=4,5,6,8	-1.8 Beats per minute	Standard Deviation 6.8
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	24 hours post-dose (Day 1), n=4,5,6,8	3.6 Beats per minute	Standard Deviation 6.5
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	4 hours post-dose (Day 1), n=4,5,6,8	11.6 Beats per minute	Standard Deviation 13.67
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	2 hours post-dose (Day 1), n=4,5,6,8	-0.4 Beats per minute	Standard Deviation 1.95
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	8 hours post-dose (Day 1), n=4,4,6,8	1.8 Beats per minute	Standard Deviation 5.19
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	Day 7 to Day 14, n=4,5,6,8	4.4 Beats per minute	Standard Deviation 5.86
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	1 hour post-dose (Day 1), n=4,5,6,8	0.8 Beats per minute	Standard Deviation 6.69
GSK2586881 0.2 mg/kg	Change From Baseline in Pulse Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	-0.8 Beats per minute	Standard Deviation 3.42
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	4 hours post-dose (Day 1), n=4,5,6,8	-1.2 Beats per minute	Standard Deviation 6.4
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	3.5 Beats per minute	Standard Deviation 8.64
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	1 hour post-dose (Day 1), n=4,5,6,8	-0.7 Beats per minute	Standard Deviation 3.67
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	2 hours post-dose (Day 1), n=4,5,6,8	-1.8 Beats per minute	Standard Deviation 6.65
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	8 hours post-dose (Day 1), n=4,4,6,8	5.7 Beats per minute	Standard Deviation 5.85
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	24 hours post-dose (Day 1), n=4,5,6,8	7.5 Beats per minute	Standard Deviation 7.12
GSK2586881 0.4 mg/kg	Change From Baseline in Pulse Rate	Day 7 to Day 14, n=4,5,6,8	5.3 Beats per minute	Standard Deviation 6.25
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	2 hours post-dose (Day 1), n=4,5,6,8	1.0 Beats per minute	Standard Deviation 5.93
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	Day 7 to Day 14, n=4,5,6,8	9.8 Beats per minute	Standard Deviation 8.36
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	24 hours post-dose (Day 1), n=4,5,6,8	13.0 Beats per minute	Standard Deviation 9.2
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	1 hour post-dose (Day 1), n=4,5,6,8	-1.0 Beats per minute	Standard Deviation 3.93
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	3.6 Beats per minute	Standard Deviation 6
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	8 hours post-dose (Day 1), n=4,4,6,8	8.6 Beats per minute	Standard Deviation 9.83
GSK2586881 0.8 mg/kg	Change From Baseline in Pulse Rate	4 hours post-dose (Day 1), n=4,5,6,8	-0.8 Beats per minute	Standard Deviation 7.42

Secondary

Change From Baseline in Respiratory Rate

Respiratory rate was measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	Day 7 to Day 14, n=4,5,6,8	-0.4 Breaths per minute	Standard Deviation 3.58
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	24 hours post-dose (Day 1), n=4,5,6,8	0.8 Breaths per minute	Standard Deviation 2.28
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	4 hours post-dose (Day 1), n=4,5,6,8	-2.2 Breaths per minute	Standard Deviation 5.63
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	8 hours post-dose (Day 1), n=4,4,6,8	-0.3 Breaths per minute	Standard Deviation 3.5
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	-3.4 Breaths per minute	Standard Deviation 4.39
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	1 hour post-dose (Day 1), n=4,5,6,8	-3.2 Breaths per minute	Standard Deviation 5.67
GSK2586881 0.2 mg/kg	Change From Baseline in Respiratory Rate	2 hours post-dose (Day 1), n=4,5,6,8	-2.6 Breaths per minute	Standard Deviation 2.97
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	1 hour post-dose (Day 1), n=4,5,6,8	1.8 Breaths per minute	Standard Deviation 9.22
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	-2.2 Breaths per minute	Standard Deviation 4.92
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	4 hours post-dose (Day 1), n=4,5,6,8	-2.2 Breaths per minute	Standard Deviation 3.54
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	Day 7 to Day 14, n=4,5,6,8	2.0 Breaths per minute	Standard Deviation 2.28
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	24 hours post-dose (Day 1), n=4,5,6,8	0.3 Breaths per minute	Standard Deviation 2.58
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	8 hours post-dose (Day 1), n=4,4,6,8	0.2 Breaths per minute	Standard Deviation 2.56
GSK2586881 0.4 mg/kg	Change From Baseline in Respiratory Rate	2 hours post-dose (Day 1), n=4,5,6,8	-3.0 Breaths per minute	Standard Deviation 4.52
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	8 hours post-dose (Day 1), n=4,4,6,8	1.1 Breaths per minute	Standard Deviation 2.59
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	Day 7 to Day 14, n=4,5,6,8	0.3 Breaths per minute	Standard Deviation 1.16
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	4 hours post-dose (Day 1), n=4,5,6,8	0.1 Breaths per minute	Standard Deviation 0.64
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	2 hours post-dose (Day 1), n=4,5,6,8	-1.0 Breaths per minute	Standard Deviation 4.5
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	1 hour post-dose (Day 1), n=4,5,6,8	0.0 Breaths per minute	Standard Deviation 0.76
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	24 hours post-dose (Day 1), n=4,5,6,8	-0.1 Breaths per minute	Standard Deviation 1.81
GSK2586881 0.8 mg/kg	Change From Baseline in Respiratory Rate	0.5 hour post-dose (Day 1), n=4,5,6,8	0.1 Breaths per minute	Standard Deviation 1.13

Secondary

Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

Blood samples were collected to evaluate systemic RAS peptides: Angiotensin (Ang) II, Ang (1-7) and Ang (1-5). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	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	0.162 Ratio
GSK2586881 0.2 mg/kg	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	0.669 Ratio
GSK2586881 0.2 mg/kg	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	4.935 Ratio
GSK2586881 0.2 mg/kg	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	2.380 Ratio
GSK2586881 0.2 mg/kg	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	4.096 Ratio
GSK2586881 0.2 mg/kg	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	4.125 Ratio
GSK2586881 0.2 mg/kg	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	3.115 Ratio
GSK2586881 0.2 mg/kg	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	4.392 Ratio
GSK2586881 0.2 mg/kg	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	2.740 Ratio
GSK2586881 0.2 mg/kg	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	3.499 Ratio
GSK2586881 0.2 mg/kg	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	0.166 Ratio
GSK2586881 0.2 mg/kg	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	3.494 Ratio
GSK2586881 0.2 mg/kg	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	0.210 Ratio
GSK2586881 0.2 mg/kg	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	4.263 Ratio
GSK2586881 0.2 mg/kg	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	4.025 Ratio
GSK2586881 0.2 mg/kg	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	0.185 Ratio
GSK2586881 0.2 mg/kg	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	0.187 Ratio
GSK2586881 0.2 mg/kg	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	3.701 Ratio
GSK2586881 0.2 mg/kg	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	2.110 Ratio
GSK2586881 0.2 mg/kg	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	5.325 Ratio
GSK2586881 0.2 mg/kg	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	1.904 Ratio
GSK2586881 0.2 mg/kg	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	4.696 Ratio
GSK2586881 0.2 mg/kg	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	3.517 Ratio
GSK2586881 0.2 mg/kg	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	1.372 Ratio
GSK2586881 0.4 mg/kg	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	1.020 Ratio
GSK2586881 0.4 mg/kg	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	0.500 Ratio
GSK2586881 0.4 mg/kg	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	3.623 Ratio
GSK2586881 0.4 mg/kg	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	0.420 Ratio
GSK2586881 0.4 mg/kg	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	0.393 Ratio
GSK2586881 0.4 mg/kg	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	3.465 Ratio
GSK2586881 0.4 mg/kg	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	0.398 Ratio
GSK2586881 0.4 mg/kg	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	0.503 Ratio
GSK2586881 0.4 mg/kg	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	0.763 Ratio
GSK2586881 0.4 mg/kg	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	0.616 Ratio
GSK2586881 0.4 mg/kg	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	2.242 Ratio
GSK2586881 0.4 mg/kg	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	2.222 Ratio
GSK2586881 0.4 mg/kg	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	2.895 Ratio
GSK2586881 0.4 mg/kg	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	6.002 Ratio
GSK2586881 0.4 mg/kg	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	2.572 Ratio
GSK2586881 0.4 mg/kg	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	3.423 Ratio
GSK2586881 0.4 mg/kg	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	2.362 Ratio
GSK2586881 0.4 mg/kg	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	3.513 Ratio
GSK2586881 0.4 mg/kg	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	6.691 Ratio
GSK2586881 0.4 mg/kg	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	0.548 Ratio
GSK2586881 0.4 mg/kg	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	3.471 Ratio
GSK2586881 0.4 mg/kg	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	2.812 Ratio
GSK2586881 0.4 mg/kg	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	2.573 Ratio
GSK2586881 0.4 mg/kg	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	0.925 Ratio
GSK2586881 0.8 mg/kg	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	1.826 Ratio
GSK2586881 0.8 mg/kg	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	0.939 Ratio
GSK2586881 0.8 mg/kg	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	0.277 Ratio
GSK2586881 0.8 mg/kg	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	1.817 Ratio
GSK2586881 0.8 mg/kg	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	5.117 Ratio
GSK2586881 0.8 mg/kg	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	0.254 Ratio
GSK2586881 0.8 mg/kg	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	0.387 Ratio
GSK2586881 0.8 mg/kg	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	7.095 Ratio
GSK2586881 0.8 mg/kg	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	1.642 Ratio
GSK2586881 0.8 mg/kg	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	0.211 Ratio
GSK2586881 0.8 mg/kg	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	1.932 Ratio
GSK2586881 0.8 mg/kg	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	1.949 Ratio
GSK2586881 0.8 mg/kg	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	4.882 Ratio
GSK2586881 0.8 mg/kg	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	0.235 Ratio
GSK2586881 0.8 mg/kg	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	1.818 Ratio
GSK2586881 0.8 mg/kg	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	3.264 Ratio
GSK2586881 0.8 mg/kg	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	3.187 Ratio
GSK2586881 0.8 mg/kg	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	2.205 Ratio
GSK2586881 0.8 mg/kg	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	4.229 Ratio
GSK2586881 0.8 mg/kg	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	2.463 Ratio
GSK2586881 0.8 mg/kg	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	0.211 Ratio
GSK2586881 0.8 mg/kg	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	2.982 Ratio
GSK2586881 0.8 mg/kg	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	2.717 Ratio
GSK2586881 0.8 mg/kg	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	1.780 Ratio

Secondary

Last Observed Quantifiable Concentration (Ct) of GSK2586881

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

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

Population: Pharmacokinetic Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Last Observed Quantifiable Concentration (Ct) of GSK2586881	0.2563 Micrograms per milliliter	Geometric Coefficient of Variation 22.8
GSK2586881 0.2 mg/kg	Last Observed Quantifiable Concentration (Ct) of GSK2586881	0.3327 Micrograms per milliliter	Geometric Coefficient of Variation 54.4
GSK2586881 0.4 mg/kg	Last Observed Quantifiable Concentration (Ct) of GSK2586881	0.4800 Micrograms per milliliter	Geometric Coefficient of Variation 44.9
GSK2586881 0.8 mg/kg	Last Observed Quantifiable Concentration (Ct) of GSK2586881	0.6380 Micrograms per milliliter	Geometric Coefficient of Variation 54.9

Secondary

Maximum Observed Plasma Concentration (Cmax) of GSK2586881

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

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Maximum Observed Plasma Concentration (Cmax) of GSK2586881	1.5159 Micrograms per milliliter	Geometric Coefficient of Variation 37
GSK2586881 0.2 mg/kg	Maximum Observed Plasma Concentration (Cmax) of GSK2586881	4.0229 Micrograms per milliliter	Geometric Coefficient of Variation 37.4
GSK2586881 0.4 mg/kg	Maximum Observed Plasma Concentration (Cmax) of GSK2586881	8.9701 Micrograms per milliliter	Geometric Coefficient of Variation 26.1
GSK2586881 0.8 mg/kg	Maximum Observed Plasma Concentration (Cmax) of GSK2586881	14.8042 Micrograms per milliliter	Geometric Coefficient of Variation 33.1

Secondary

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

12-lead ECGs were obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8	1 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8	1 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, Day 7 to Day 14, n=4,5,6,8	1 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, Day 7 to Day 14, n=4,5,6,8	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, Day 7 to Day 14, n=4,5,6,8	3 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, Day 7 to Day 14, n=4,5,6,8	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8	3 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8	3 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, Day 7 to Day 14, n=4,5,6,8	3 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8	3 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8	4 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, Day 7 to Day 14, n=4,5,6,8	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, Day 7 to Day 14, n=4,5,6,8	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 4 hours post-dose (Day 1), n=4,5,6,8	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 24 hours post-dose(Day 1), n=3,5,6,8	5 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal CS, 24 hours post-dose (Day 1), n=3,5,6,8	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, Day 7 to Day 14, n=4,5,6,8	3 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Abnormal NCS, 4 hours post-dose (Day 1), n=4,5,6,8	7 Participants

Secondary

Number of Participants With Non-serious Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Time frame: Up to Day 28

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK2586881 0.1 mg/kg	Number of Participants With Non-serious Adverse Events (AEs)	1 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Non-serious Adverse Events (AEs)	3 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Non-serious Adverse Events (AEs)	5 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Non-serious Adverse Events (AEs)	2 Participants

Secondary

Number of Participants With Positive Immunogenicity Results

Immunogenicity samples were collected into a serum-separating tube, mixed by gentle inversion 5 times and left to coagulate at room temperature for a minimum of 30 minutes and a maximum of 60 minutes. All samples were first tested for anti-angiotensin converting enzyme type 2 (ACE2) binding antibodies by screening and confirmation assay steps. If post-dose samples were found to be positive for anti-ACE2 binding antibodies, they would have been further characterized for anti-ACE2 neutralizing antibodies. Number of participants with positive immunogenicity results post-dosing are presented.

Time frame: Up to Day 28

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK2586881 0.1 mg/kg	Number of Participants With Positive Immunogenicity Results	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Positive Immunogenicity Results	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Positive Immunogenicity Results	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Positive Immunogenicity Results	0 Participants

Secondary

Number of Participants With Serious Adverse Events (SAEs)

Any untoward event resulting in death, life threatening, requiring hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE.

Time frame: Up to Day 28

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK2586881 0.1 mg/kg	Number of Participants With Serious Adverse Events (SAEs)	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Serious Adverse Events (SAEs)	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Serious Adverse Events (SAEs)	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Serious Adverse Events (SAEs)	0 Participants

Secondary

Number of Participants With Urinalysis Results by Dipstick Method

Urine samples were collected to assess urine bilirubin, urine occult blood, urine glucose, urine ketones, and urine protein by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones and urine protein can be read as negative, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample.

Time frame: 24 hours post-dose (Day 1)

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), negative	2 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 1+	1 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 2+	1 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.1 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), trace	1 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), trace	1 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), negative	5 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), negative	5 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.2 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), negative	5 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), negative	6 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), negative	4 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), trace	2 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), negative	5 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 3+	1 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), negative	3 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), trace	3 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), negative	6 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.4 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), negative	8 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), negative	8 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), negative	8 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 2+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), negative	8 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Bilirubin, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), 3+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Protein, 24 hours post-dose (Day 1), 1+	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Ketones, 24 hours post-dose (Day 1), trace	0 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), trace	1 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Occult Blood, 24 hours post-dose (Day 1), negative	7 Participants
GSK2586881 0.8 mg/kg	Number of Participants With Urinalysis Results by Dipstick Method	Glucose, 24 hours post-dose (Day 1), trace	0 Participants

Secondary

Plasma Clearance (CL) of GSK2586881

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

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK2586881 0.1 mg/kg	Plasma Clearance (CL) of GSK2586881	NA Liters per hour	—
GSK2586881 0.2 mg/kg	Plasma Clearance (CL) of GSK2586881	0.5838 Liters per hour	Geometric Coefficient of Variation 10.1
GSK2586881 0.4 mg/kg	Plasma Clearance (CL) of GSK2586881	0.6207 Liters per hour	Geometric Coefficient of Variation 16.8
GSK2586881 0.8 mg/kg	Plasma Clearance (CL) of GSK2586881	0.8170 Liters per hour	Geometric Coefficient of Variation 30.8

Secondary

Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

Blood samples were collected to assess pulmonary wedge RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	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	0.493 Ratio
GSK2586881 0.2 mg/kg	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	0.587 Ratio
GSK2586881 0.2 mg/kg	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	0.443 Ratio
GSK2586881 0.4 mg/kg	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	0.148 Ratio
GSK2586881 0.4 mg/kg	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	0.531 Ratio
GSK2586881 0.4 mg/kg	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	0.620 Ratio
GSK2586881 0.8 mg/kg	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	0.789 Ratio
GSK2586881 0.8 mg/kg	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	0.774 Ratio
GSK2586881 0.8 mg/kg	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	0.826 Ratio

Secondary

Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

Blood samples were collected to assess systemic RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented. Assessment of follow up visit was conducted between any day of Days 7 to 14.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.1 mg/kg	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
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	24 hours post-dose (Day 1), n=4,5,5,8	3.682 Ratio
GSK2586881 0.2 mg/kg	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	0.463 Ratio
GSK2586881 0.2 mg/kg	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	0.468 Ratio
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	Day 7 to Day 14, n=4,5,5,7	13.742 Ratio
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	2 hours post-dose (Day 1), n=4,5,5,8	0.455 Ratio
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	1 hour post-dose (Day 1), n=4,5,5,8	0.509 Ratio
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	8 hours post-dose (Day 1), n=4,5,5,8	2.093 Ratio
GSK2586881 0.2 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	4 hours post-dose (Day 1), n=4,5,5,8	0.659 Ratio
GSK2586881 0.4 mg/kg	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	1.450 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	2 hours post-dose (Day 1), n=4,5,5,8	0.558 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	24 hours post-dose (Day 1), n=4,5,5,8	1.335 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	Day 7 to Day 14, n=4,5,5,7	3.278 Ratio
GSK2586881 0.4 mg/kg	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	1.097 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	1 hour post-dose (Day 1), n=4,5,5,8	0.875 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	4 hours post-dose (Day 1), n=4,5,5,8	0.540 Ratio
GSK2586881 0.4 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	8 hours post-dose (Day 1), n=4,5,5,8	0.412 Ratio
GSK2586881 0.8 mg/kg	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	0.843 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	Day 7 to Day 14, n=4,5,5,7	6.156 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	24 hours post-dose (Day 1), n=4,5,5,8	0.946 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	4 hours post-dose (Day 1), n=4,5,5,8	1.283 Ratio
GSK2586881 0.8 mg/kg	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	0.590 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	8 hours post-dose (Day 1), n=4,5,5,8	0.439 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	1 hour post-dose (Day 1), n=4,5,5,8	0.794 Ratio
GSK2586881 0.8 mg/kg	Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points	2 hours post-dose (Day 1), n=4,5,5,8	0.657 Ratio

Secondary

Time of the Last Quantifiable Concentration (Tlast) of GSK2586881

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

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

Population: Pharmacokinetic Population

Arm	Measure	Value (MEDIAN)
GSK2586881 0.1 mg/kg	Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	8.000 Hours
GSK2586881 0.2 mg/kg	Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	24.000 Hours
GSK2586881 0.4 mg/kg	Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	24.017 Hours
GSK2586881 0.8 mg/kg	Time of the Last Quantifiable Concentration (Tlast) of GSK2586881	24.117 Hours

Secondary

Time to Cmax (Tmax) of GSK2586881

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

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

Population: Pharmacokinetic Population

Arm	Measure	Value (MEDIAN)
GSK2586881 0.1 mg/kg	Time to Cmax (Tmax) of GSK2586881	0.08333 Hours
GSK2586881 0.2 mg/kg	Time to Cmax (Tmax) of GSK2586881	0.16667 Hours
GSK2586881 0.4 mg/kg	Time to Cmax (Tmax) of GSK2586881	0.10000 Hours
GSK2586881 0.8 mg/kg	Time to Cmax (Tmax) of GSK2586881	0.13333 Hours

Other Pre-specified

Change From Baseline in Cardiac Index (CI)

Cardiac index (CI) was measured using thermodilution. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Index (CI)	4 hours post-dose (Day 1)	1.107 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Index (CI)	2 hours post-dose (Day 1)	1.021 Ratio
GSK2586881 0.1 mg/kg	Change From Baseline in Cardiac Index (CI)	1 hour post-dose (Day 1)	1.045 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Index (CI)	2 hours post-dose (Day 1)	1.029 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Index (CI)	4 hours post-dose (Day 1)	1.128 Ratio
GSK2586881 0.2 mg/kg	Change From Baseline in Cardiac Index (CI)	1 hour post-dose (Day 1)	1.076 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Index (CI)	2 hours post-dose (Day 1)	0.926 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Index (CI)	1 hour post-dose (Day 1)	1.084 Ratio
GSK2586881 0.4 mg/kg	Change From Baseline in Cardiac Index (CI)	4 hours post-dose (Day 1)	0.889 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Index (CI)	4 hours post-dose (Day 1)	1.000 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Index (CI)	2 hours post-dose (Day 1)	1.020 Ratio
GSK2586881 0.8 mg/kg	Change From Baseline in Cardiac Index (CI)	1 hour post-dose (Day 1)	0.990 Ratio

Source: ClinicalTrials.gov · Data processed: Feb 13, 2026

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

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Cardiac Output (CO)

Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)

Change From Baseline in Pulmonary Vascular Resistance (PVR)

Apparent Terminal Phase Half-life (t1/2) of GSK2586881

Apparent Volume of Distribution of GSK2586881

Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881

Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase

Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)

Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine

Change From Baseline in Clinical Chemistry Parameter: Total Protein

Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Change From Baseline in Disease Biomarker: Cardiac Troponin-I

Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)

Change From Baseline in Hematology Parameter: Hematocrit

Change From Baseline in Hematology Parameter: Hemoglobin

Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin

Change From Baseline in Hematology Parameter: Mean Corpuscle Volume

Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count

Change From Baseline in Hematology Parameter: Reticulocytes

Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count

Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO])

Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood

Change From Baseline in Pulse Rate

Change From Baseline in Respiratory Rate

Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

Last Observed Quantifiable Concentration (Ct) of GSK2586881

Maximum Observed Plasma Concentration (Cmax) of GSK2586881

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Number of Participants With Non-serious Adverse Events (AEs)

Number of Participants With Positive Immunogenicity Results

Number of Participants With Serious Adverse Events (SAEs)

Number of Participants With Urinalysis Results by Dipstick Method

Plasma Clearance (CL) of GSK2586881

Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

Time of the Last Quantifiable Concentration (Tlast) of GSK2586881

Time to Cmax (Tmax) of GSK2586881

Change From Baseline in Cardiac Index (CI)