Trial Outcomes & Findings for The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury (NCT NCT01597635)

Last Updated: 2017-09-28

Results Overview

Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Up to Day 7

Results posted on

2017-09-28

Participant Flow

This study was conducted across 5 centers in United States and 5 centers in Canada from 20 September 2012 to 06 October 2014.

A total of 46 participants were randomized for this study of which 44 participants (5 participants in Part A and 39 participants in Part B) received at least one dose of study medication.

Participant milestones

Participant milestones
Measure	Part A Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kilograms \[mg/kg\], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.	Part B (Placebo BID) Eligible participants received intravenous matching placebo (saline solution) twice daily (BID) as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Part A STARTED	5	0	0
Part A COMPLETED	2	0	0
Part A NOT COMPLETED	3	0	0
Part B STARTED	0	20	19
Part B COMPLETED	0	14	15
Part B NOT COMPLETED	0	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kilograms \[mg/kg\], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.	Part B (Placebo BID) Eligible participants received intravenous matching placebo (saline solution) twice daily (BID) as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Part A Adverse Event	3	0	0
Part B Adverse Event	0	0	1
Part B Protocol Violation	0	1	0
Part B Protocol-defined stopping criteria	0	4	3
Part B Withdrawal by Subject	0	1	0

Baseline Characteristics

The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A n=5 Participants Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.	Total n=44 Participants Total of all reporting groups
Age, Customized 18-80 years	5 Participants n=5 Participants	20 Participants n=7 Participants	19 Participants n=5 Participants	44 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	13 Participants n=7 Participants	13 Participants n=5 Participants	29 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	40 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population was defined as all participants in Part B who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 1 at Pre-dose	87.4 Beats per minute Standard Deviation 16.32	97.7 Beats per minute Standard Deviation 16.25
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 1 at 0.5 hours	87.9 Beats per minute Standard Deviation 17.08	95.3 Beats per minute Standard Deviation 15.10
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 1 at 2 hours	88.8 Beats per minute Standard Deviation 18.22	94.7 Beats per minute Standard Deviation 17.59
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 1 at 6 hours	90.0 Beats per minute Standard Deviation 18.03	96.5 Beats per minute Standard Deviation 18.58
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 1 at 12 hours	87.6 Beats per minute Standard Deviation 20.60	97.1 Beats per minute Standard Deviation 18.46
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 2 at 0 hours	92.2 Beats per minute Standard Deviation 19.02	93.4 Beats per minute Standard Deviation 16.98
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 0 hours	93.3 Beats per minute Standard Deviation 19.20	97.7 Beats per minute Standard Deviation 14.11
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 0.5 hours	91.7 Beats per minute Standard Deviation 16.29	97.2 Beats per minute Standard Deviation 12.81
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 2 hours	93.2 Beats per minute Standard Deviation 16.51	95.2 Beats per minute Standard Deviation 13.31
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 6 hours	93.2 Beats per minute Standard Deviation 16.63	97.5 Beats per minute Standard Deviation 14.44
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 12 hours	93.8 Beats per minute Standard Deviation 20.12	93.6 Beats per minute Standard Deviation 16.08
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 18 hours	98.1 Beats per minute Standard Deviation 19.34	88.9 Beats per minute Standard Deviation 15.69
Heart Rate Assessments Upto Day 7 (Part B) Heart rate on Day 3 at 24 hours	90.8 Beats per minute Standard Deviation 15.46	95.1 Beats per minute Standard Deviation 13.25
Heart Rate Assessments Upto Day 7 (Part B) Heart rate at follow-up Day 7	91.6 Beats per minute Standard Deviation 19.06	94.2 Beats per minute Standard Deviation 15.17

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

Outcome measures

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) PR interval on Day 1,Pre-dose	136.8 millisecond Standard Deviation 24.19	139.0 millisecond Standard Deviation 25.09
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) PR interval on Day 3,12 hours	128.5 millisecond Standard Deviation 42.09	149.3 millisecond Standard Deviation 19.76
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) PR interval at follow-up	140.4 millisecond Standard Deviation 17.81	144.8 millisecond Standard Deviation 20.73
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QRS duration on Day 1,Pre-dose	98.0 millisecond Standard Deviation 9.27	95.5 millisecond Standard Deviation 16.62
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QRS duration on Day 3,12 hours	82.8 millisecond Standard Deviation 8.66	98.8 millisecond Standard Deviation 15.86
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QRS duration at follow-up Day 7	84.4 millisecond Standard Deviation 9.01	88.6 millisecond Standard Deviation 16.86
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Uncorrected QT interval on Day 1,Pre-dose	350.0 millisecond Standard Deviation 27.96	357.5 millisecond Standard Deviation 44.13
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Uncorrected QT interval on Day 3,12 hours	357.8 millisecond Standard Deviation 48.90	369.8 millisecond Standard Deviation 33.92
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Uncorrected QT interval at follow-up Day 7	354.3 millisecond Standard Deviation 37.12	377.5 millisecond Standard Deviation 49.46
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Basett) on Day 1,Pre-dose	463.0 millisecond Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	469.4 millisecond Standard Deviation 66.08
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Basett) on Day 3,12 hours	438.9 millisecond Standard Deviation 13.02	468.9 millisecond Standard Deviation 41.59
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Basett) at follow-up Day 7	453.5 millisecond Standard Deviation 31.57	483.5 millisecond Standard Deviation 46.51
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Fridericia), Day 1,Pre-dose	423.4 millisecond Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	418.1 millisecond Standard Deviation 49.03
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Fridericia), Day 3,12 hours	406.3 millisecond Standard Deviation 20.18	432.7 millisecond Standard Deviation 35.92
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) Corrected QT interval(Fridericia),follow-up Day 7	419.5 millisecond Standard Deviation 12.66	439.6 millisecond Standard Deviation 36.29
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QTCU on Day 1,Pre-dose	458.3 millisecond Standard Deviation 8.81	447.3 millisecond Standard Deviation 27.65
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QTCU on Day 3,12 hours	440.3 millisecond Standard Deviation 40.07	445.4 millisecond Standard Deviation 28.11
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) QTCU at follow-up Day 7	441.6 millisecond Standard Deviation 17.72	457.3 millisecond Standard Deviation 26.12
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) RR interval on Day 1,Pre-dose	584.6 millisecond Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	513.6 millisecond Standard Deviation 97.25
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) RR interval on Day 3,12 hours	638.8 millisecond Standard Deviation 135.85	623.2 millisecond Standard Deviation 76.02
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) RR interval at follow-up Day 7	661.7 millisecond Standard Deviation 203.97	582.9 millisecond Standard Deviation 128.96

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Basophils on Day 1 at Pre-dose	0.020 giga per liter Standard Deviation NA Standard deviation was not calculated as a single participant was analyzed.	0.000 giga per liter Standard Deviation 0.0000
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Basophils on Day 3 at 12 hours	0.015 giga per liter Standard Deviation 0.0296	0.011 giga per liter Standard Deviation 0.0277
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Basophils on Follow-up Day 7	0.025 giga per liter Standard Deviation 0.0431	0.113 giga per liter Standard Deviation 0.1848
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Eosinophils on Day 1 at Pre-dose	0.110 giga per liter Standard Deviation NA Standard deviation was not calculated as a single participant was analyzed.	0.233 giga per liter Standard Deviation 0.4041
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Eosinophils on Day 3 at 12 hours	0.096 giga per liter Standard Deviation 0.1624	0.163 giga per liter Standard Deviation 0.2280
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Eosinophils on Follow-up Day 7	0.137 giga per liter Standard Deviation 0.1074	0.324 giga per liter Standard Deviation 0.4957
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Lymphocytes on Day 1 at Pre-dose	4.81 giga per liter Standard Deviation 4.603	0.52 giga per liter Standard Deviation 0.266
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Lymphocytes on Day 3 at 12 hours	1.08 giga per liter Standard Deviation 0.948	0.60 giga per liter Standard Deviation 0.380
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Lymphocytes on Follow-up Day 7	1.61 giga per liter Standard Deviation 1.244	1.04 giga per liter Standard Deviation 0.663
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Monocytes on Day 1 at Pre-dose	1.760 giga per liter Standard Deviation 1.7112	0.377 giga per liter Standard Deviation 0.3356
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Monocytes on Day 3 at 12 hours	0.503 giga per liter Standard Deviation 0.4046	0.571 giga per liter Standard Deviation 0.6336
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Monocytes on Follow-up Day 7	0.669 giga per liter Standard Deviation 0.3986	0.727 giga per liter Standard Deviation 0.5812
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Total neutrophils on Day 1 at Pre-dose	6.990 giga per liter Standard Deviation 4.5113	7.807 giga per liter Standard Deviation 9.3471
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Total neutrophils on Day 3 at 12 hours	11.563 giga per liter Standard Deviation 6.0785	9.931 giga per liter Standard Deviation 6.8583
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Total neutrophils on Follow-up Day 7	16.775 giga per liter Standard Deviation 21.6419	11.761 giga per liter Standard Deviation 5.5496
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Platelet count on Day 1 at Pre-dose	170.3 giga per liter Standard Deviation 67.26	236.0 giga per liter Standard Deviation 158.73
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Platelet count on Day 3 at 12 hours	218.9 giga per liter Standard Deviation 120.68	235.9 giga per liter Standard Deviation 134.43
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) Platelet count on Follow-up Day 7	334.1 giga per liter Standard Deviation 169.06	369.8 giga per liter Standard Deviation 169.70
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) White blood cell count on Day 1 at Pre-dose	15.15 giga per liter Standard Deviation 14.289	10.72 giga per liter Standard Deviation 8.829
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) White blood cell count on Day 3 at 12 hours	14.82 giga per liter Standard Deviation 5.927	11.82 giga per liter Standard Deviation 6.618
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) White blood cell count on Follow-up Day 7	14.09 giga per liter Standard Deviation 5.197	36.56 giga per liter Standard Deviation 84.293

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Red blood cell count on Day 1 at Pre-dose	3.207 trillion cells per liter Standard Deviation 0.7733	2.678 trillion cells per liter Standard Deviation 0.5117
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Red blood cell count on Day 3 at 12 hours	3.271 trillion cells per liter Standard Deviation 0.5725	3.076 trillion cells per liter Standard Deviation 0.5001
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Red blood cell count on Follow-up Day 7	3.352 trillion cells per liter Standard Deviation 0.6374	3.314 trillion cells per liter Standard Deviation 0.7700
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Reticulocyte count on Day 1 at Pre-dose	0.025 trillion cells per liter Standard Deviation 0.0195	0.044 trillion cells per liter Standard Deviation NA Standard deviation was not calculated as a single participant was analyzed.
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Reticulocyte count on Day 3 at 12 hours	0.832 trillion cells per liter Standard Deviation 2.5186	3.697 trillion cells per liter Standard Deviation 12.6920
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) Reticulocyte count on Follow-up Day 7	1.607 trillion cells per liter Standard Deviation 5.1055	8.629 trillion cells per liter Standard Deviation 25.6392

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) Hemoglobin on Day 1 at Pre-dose	99.5 grams per liter Standard Deviation 24.83	84.0 grams per liter Standard Deviation 13.09
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) Hemoglobin on Day 3 at 12 hours	195.8 grams per liter Standard Deviation 286.77	180.8 grams per liter Standard Deviation 266.16
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) Hemoglobin on Follow-up Day 7	244.7 grams per liter Standard Deviation 401.03	213.6 grams per liter Standard Deviation 301.50
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) MCHC on Day 1 at Pre-dose	331.8 grams per liter Standard Deviation 10.68	339.5 grams per liter Standard Deviation 19.12
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) MCHC on Day 3 at 12 hours	328.4 grams per liter Standard Deviation 14.73	330.8 grams per liter Standard Deviation 16.82
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) MCHC on Follow-up Day 7	327.8 grams per liter Standard Deviation 12.35	325.4 grams per liter Standard Deviation 6.82

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) MCV on Day 1 at Pre-dose	77.37 femtoliters Standard Deviation 33.654	93.87 femtoliters Standard Deviation 0.971
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) MCV on Day 3 at 12 hours	91.28 femtoliters Standard Deviation 5.611	90.69 femtoliters Standard Deviation 5.976
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) MCV on Follow-up Day 7	92.53 femtoliters Standard Deviation 7.234	90.46 femtoliters Standard Deviation 7.063

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) MCH on Day 1 at Pre-dose	30.30 picograms Standard Deviation 4.493	30.40 picograms Standard Deviation 0.361
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) MCH on Day 3 at 12 hours	30.02 picograms Standard Deviation 2.695	30.32 picograms Standard Deviation 1.955
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) MCH on Follow-up Day 7	30.49 picograms Standard Deviation 2.545	30.25 picograms Standard Deviation 2.071

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) Hematocrit on Day 1 at Pre-dose	0.201 Fraction Standard Deviation 0.1666	0.196 Fraction Standard Deviation 0.1333
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) Hematocrit on Day 3 at 12 hours	0.271 Fraction Standard Deviation 0.1071	1.519 Fraction Standard Deviation 5.3867
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) Hematocrit on Follow-up Day 7	0.254 Fraction Standard Deviation 0.1298	2.270 Fraction Standard Deviation 7.5504

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Direct bilirubin on Day 1 at Pre-dose	10.663 micromoles per liter Standard Deviation 7.8146	13.792 micromoles per liter Standard Deviation 17.7932
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Direct bilirubin on Day 3 at 12 hours	10.446 micromoles per liter Standard Deviation 14.2406	10.428 micromoles per liter Standard Deviation 22.4573
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Direct bilirubin on Follow-up Day 7	4.140 micromoles per liter Standard Deviation 3.5564	2.576 micromoles per liter Standard Deviation 1.6103
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Total bilirubin on Day 1 at Pre-dose	16.672 micromoles per liter Standard Deviation 11.1375	21.926 micromoles per liter Standard Deviation 20.4768
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Total bilirubin on Day 3 at 12 hours	16.803 micromoles per liter Standard Deviation 15.8462	14.119 micromoles per liter Standard Deviation 24.8465
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Total bilirubin on Follow-up Day 7	12.547 micromoles per liter Standard Deviation 10.7837	5.818 micromoles per liter Standard Deviation 3.0149
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Creatinine on Day 1 at Pre-dose	85.194 micromoles per liter Standard Deviation 19.9261	126.228 micromoles per liter Standard Deviation 71.9085
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Creatinine on Day 3 at 12 hours	108.189 micromoles per liter Standard Deviation 102.4388	103.066 micromoles per liter Standard Deviation 90.6252
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Creatinine on Follow-up Day 7	91.726 micromoles per liter Standard Deviation 45.2713	90.516 micromoles per liter Standard Deviation 71.8052
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Uric acid on Day 1 at Pre-dose	233.432 micromoles per liter Standard Deviation 67.9909	181.453 micromoles per liter Standard Deviation 203.5924
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Uric acid on Day 3 at 12 hours	192.925 micromoles per liter Standard Deviation 143.7971	228.144 micromoles per liter Standard Deviation 134.9558
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) Uric acid on Follow-up Day 7	241.766 micromoles per liter Standard Deviation 72.0137	225.326 micromoles per liter Standard Deviation 144.4626

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alkaline phosphatase on Day 1 at Pre-dose	76.6 International units per liter Standard Deviation 18.57	94.0 International units per liter Standard Deviation 50.86
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alkaline phosphatase on Day 3 at 12 hours	130.9 International units per liter Standard Deviation 68.16	109.2 International units per liter Standard Deviation 63.02
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alkaline phosphatase on Follow-up Day 7	101.1 International units per liter Standard Deviation 40.15	117.0 International units per liter Standard Deviation 56.07
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alanine amino transferase on Day 1 at Pre-dose	101.8 International units per liter Standard Deviation 105.98	56.8 International units per liter Standard Deviation 42.20
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alanine amino transferase on Day 3 at 12 hours	73.4 International units per liter Standard Deviation 71.27	43.6 International units per liter Standard Deviation 50.72
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Alanine amino transferase on Follow-up Day 7	44.9 International units per liter Standard Deviation 42.74	117.9 International units per liter Standard Deviation 224.94
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Asparatate amino transferase on Day 1 at Pre-dose	96.8 International units per liter Standard Deviation 46.09	64.6 International units per liter Standard Deviation 37.14
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Asparatate amino transferase on Day 3 at 12 hours	56.2 International units per liter Standard Deviation 34.60	62.0 International units per liter Standard Deviation 71.54
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Asparatate amino transferase on Follow-up Day 7	35.6 International units per liter Standard Deviation 20.25	76.5 International units per liter Standard Deviation 106.39
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Gamma glutamyl transferase on Day 1 at Pre-dose	96.0 International units per liter Standard Deviation 22.63	40.7 International units per liter Standard Deviation 25.89
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Gamma glutamyl transferase on Day 3 at 12 hours	156.5 International units per liter Standard Deviation 149.89	98.4 International units per liter Standard Deviation 71.85
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) Gamma glutamyl transferase on Follow-up Day 7	116.4 International units per liter Standard Deviation 105.36	143.0 International units per liter Standard Deviation 138.22

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Albumin on Day 1 at Pre-dose	25.6 grams per liter Standard Deviation 2.19	18.6 grams per liter Standard Deviation 3.21
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Albumin on Day 3 at 12 hours	25.5 grams per liter Standard Deviation 5.05	22.3 grams per liter Standard Deviation 4.88
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Albumin on Follow-up Day 7	27.9 grams per liter Standard Deviation 6.62	25.5 grams per liter Standard Deviation 6.27
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Total protein on Day 1 at Pre-dose	54.60 grams per liter Standard Deviation 5.983	50.20 grams per liter Standard Deviation 2.775
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Total protein on Day 3 at 12 hours	55.06 grams per liter Standard Deviation 7.122	52.12 grams per liter Standard Deviation 7.457
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) Total protein on Follow-up Day 7	60.86 grams per liter Standard Deviation 8.646	58.18 grams per liter Standard Deviation 10.323

PRIMARY outcome

Timeframe: Up to Day 7

Population: The All Subjects - Part A Population was defined as all participants in Part A who received at least one dose of study medication.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A) Any AE	5 Participants	—
Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A) Anys SAE	3 Participants	—

PRIMARY outcome

Timeframe: Up to Day 7

Population: All Subjects - Part B Population.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) Any AE	14 Participant	15 Participant
Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) Any SAE	4 Participant	3 Participant

SECONDARY outcome

Timeframe: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)

Population: The Pharmacokinetic - Part A Population was defined as participants in the All Subjects - Part A population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881.

Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part A

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at Pre-dose on Day 1	NA nano grams per milliliter Standard Deviation NA No concentration values detected for Pre-dose.	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 5 minutes on Day 1	2854.0 nano grams per milliliter Standard Deviation 595.47	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 10 minutes on Day 1	2692.8 nano grams per milliliter Standard Deviation 629.78	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 2 hours on Day 1	2047.4 nano grams per milliliter Standard Deviation 497.19	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 6 hours on Day 1	5460.0 nano grams per milliliter Standard Deviation 3213.96	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 10 hours on Day 1	10276.6 nano grams per milliliter Standard Deviation 2641.49	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 12 hours on Day 1	8265.4 nano grams per milliliter Standard Deviation 1905.29	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 0 hours on Day 2	3621.6 nano grams per milliliter Standard Deviation 2654.21	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 1 hour on Day 2	17558.6 nano grams per milliliter Standard Deviation 4359.04	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 12 hours on Day 2	7237.8 nano grams per milliliter Standard Deviation 4281.27	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) GSK2586881 concentration at 24 hours on Day 2	3517.8 nano grams per milliliter Standard Deviation 2433.49	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)

Population: The Pharmacokinetic - Part B Population was defined as participants in the All Subjects - Part B population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881. Only those participants with data available at the indicated time points were analyzed.

Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part B.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=19 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at Pre-dose on Day 1	NA nanograms per milliliter Standard Deviation NA No concentration values detected for Pre-dose.	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 0.5 hours on Day 1	5489.3 nanograms per milliliter Standard Deviation 1727.81	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 2 hours on Day 1	4334.0 nanograms per milliliter Standard Deviation 1880.42	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 6 hours on Day 1	5065.4 nanograms per milliliter Standard Deviation 8679.92	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 12 hours on Day 1	1815.9 nanograms per milliliter Standard Deviation 809.52	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 0 hours on Day 2	2115.3 nanograms per milliliter Standard Deviation 1164.12	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 0 hours on Day 3	2306.6 nanograms per milliliter Standard Deviation 1356.75	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 0.5 hours on Day 3	6810.4 nanograms per milliliter Standard Deviation 3135.66	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 2 hours on Day 3	6060.7 nanograms per milliliter Standard Deviation 2956.33	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 6 hours on Day 3	3808.9 nanograms per milliliter Standard Deviation 1953.82	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 12 hours on Day 3	2416.6 nanograms per milliliter Standard Deviation 1601.08	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 18 hours on Day 3	2701.6 nanograms per milliliter Standard Deviation 1874.28	—
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) GSK2586881 concentration at 24 hours on Day 3	2254.7 nanograms per milliliter Standard Deviation 1233.58	—

SECONDARY outcome

Timeframe: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours

Population: Pharmacokinetic - Part A Population.

Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)	0.384 liters per hour Standard Error 0.0886	—

SECONDARY outcome

Timeframe: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours

Population: Pharmacokinetic - Part B Population.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=19 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)	0.698 liters per hour Standard Error 0.0608	—

SECONDARY outcome

Timeframe: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).

Population: All Subjects - Part A Population

Renin-angiotensin system cascade biomarkers included Ang II and Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at Pre-dose on Day 1	26.5 picograms per milliliter Interval 14.0 to 50.1	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 5 minutes on Day 1	7.7 picograms per milliliter Interval 3.2 to 18.4	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 10 minutes on Day 1	6.2 picograms per milliliter Interval 3.4 to 11.3	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 2 hours on Day 1	3.9 picograms per milliliter Interval 0.9 to 17.4	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 6 hours on Day 1	4.3 picograms per milliliter Interval 0.8 to 22.3	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 10 hours on Day 1	2.0 picograms per milliliter Interval 0.4 to 10.3	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 12 hours on Day 1	3.3 picograms per milliliter Interval 0.8 to 13.9	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 0 hours on Day 2	1.7 picograms per milliliter Interval 0.2 to 13.3	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 1 hour on Day 2	4.3 picograms per milliliter Interval 0.3 to 70.9	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 12 hours on Day 2	1.8 picograms per milliliter Interval 0.2 to 15.5	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) AngII at 24 hours on Day 2	1.5 picograms per milliliter Interval 0.2 to 10.5	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at Pre-dose on Day 1	4.3 picograms per milliliter Interval 0.9 to 21.4	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 5 minutes on Day 1	28.7 picograms per milliliter Interval 10.9 to 75.8	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 10 minutes on Day 1	25.7 picograms per milliliter Interval 11.6 to 56.8	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 2 hours on Day 1	18.7 picograms per milliliter Interval 6.4 to 54.1	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 6 hours on Day 1	22.8 picograms per milliliter Interval 5.3 to 97.9	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 10 hours on Day 1	16.8 picograms per milliliter Interval 1.2 to 243.5	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 12 hours on Day 1	15.1 picograms per milliliter Interval 1.2 to 183.2	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 0 hours on Day 2	9.1 picograms per milliliter Interval 0.6 to 130.1	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 1 hour on Day 2	20.9 picograms per milliliter Interval 1.3 to 331.3	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 12 hours on Day 2	18.8 picograms per milliliter Interval 2.6 to 138.4	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) Ang1-7 at 24 hours on Day 2	5.2 picograms per milliliter Interval 0.2 to 122.2	—

SECONDARY outcome

Timeframe: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).

Population: All Subjects - Part A Population.

Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours on Day 1 and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at Pre-dose on Day 1	6.167 Ratio Interval 1.372 to 27.721	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 5 minutes on Day 1	0.268 Ratio Interval 0.099 to 0.722	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 10 minutes on Day 1	0.241 Ratio Interval 0.095 to 0.608	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 2 hours on Day 1	0.210 Ratio Interval 0.036 to 1.226	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 6 hours on Day 1	0.190 Ratio Interval 0.032 to 1.138	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 10 hours on Day 1	0.118 Ratio Interval 0.024 to 0.583	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 12 hours on Day 1	0.221 Ratio Interval 0.012 to 3.959	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 0 hours on Day 2	0.182 Ratio Interval 0.018 to 1.831	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 1 hour on Day 2	0.206 Ratio Interval 0.017 to 2.421	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 12 hours on Day 2	0.094 Ratio Interval 0.007 to 1.268	—
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) AngII/ Ang1-7 at 24 hours on Day 2	0.290 Ratio Interval 0.03 to 2.801	—

SECONDARY outcome

Timeframe: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Renin-angiotensin system cascade biomarkers included Ang II, Ang (1-7) and Ang (1-5). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 0.5 hours	14.14 picograms per milliliter Interval 7.89 to 25.065	2.44 picograms per milliliter Interval 1.4 to 4.095
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 2 hours	12.05 picograms per milliliter Interval 6.658 to 21.146	2.80 picograms per milliliter Interval 1.585 to 4.735
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 6 hours	11.00 picograms per milliliter Interval 6.084 to 19.518	2.89 picograms per milliliter Interval 1.62 to 4.997
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 12 hours	10.90 picograms per milliliter Interval 5.92 to 19.824	3.33 picograms per milliliter Interval 1.853 to 5.727
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 24 hours	8.35 picograms per milliliter Interval 4.506 to 15.378	2.41 picograms per milliliter Interval 1.389 to 4.178
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 48 hours	8.10 picograms per milliliter Interval 4.219 to 15.071	3.74 picograms per milliliter Interval 2.232 to 6.677
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 48.5 hours	8.63 picograms per milliliter Interval 4.514 to 15.961	2.89 picograms per milliliter Interval 1.727 to 5.178
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 50 hours	6.82 picograms per milliliter Interval 3.551 to 12.51	2.58 picograms per milliliter Interval 1.534 to 4.57
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 54 hours	7.03 picograms per milliliter Interval 3.77 to 12.85	2.32 picograms per milliliter Interval 1.338 to 4.146
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 60 hours	7.02 picograms per milliliter Interval 3.883 to 12.768	2.38 picograms per milliliter Interval 1.374 to 4.179
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 66 hours	7.33 picograms per milliliter Interval 4.156 to 13.262	1.84 picograms per milliliter Interval 1.046 to 3.161
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 72 hours	6.62 picograms per milliliter Interval 3.701 to 12.174	1.93 picograms per milliliter Interval 1.067 to 3.441
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 96 hours	4.72 picograms per milliliter Interval 2.325 to 9.769	1.70 picograms per milliliter Interval 0.881 to 3.209
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) AngII at 120 hours	5.21 picograms per milliliter Interval 3.036 to 10.126	2.64 picograms per milliliter Interval 1.437 to 5.586
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 0.5 hours	2.17 picograms per milliliter Interval 1.408 to 3.376	8.58 picograms per milliliter Interval 5.873 to 12.988
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 2 hours	2.18 picograms per milliliter Interval 1.41 to 3.383	7.50 picograms per milliliter Interval 5.124 to 11.367
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 6 hours	2.34 picograms per milliliter Interval 1.508 to 3.643	8.38 picograms per milliliter Interval 5.697 to 12.661
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 12 hours	2.78 picograms per milliliter Interval 1.784 to 4.363	5.07 picograms per milliliter Interval 3.37 to 7.533
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 24 hours	2.38 picograms per milliliter Interval 1.512 to 3.763	3.57 picograms per milliliter Interval 2.331 to 5.363
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 48 hours	2.39 picograms per milliliter Interval 1.519 to 3.724	4.59 picograms per milliliter Interval 3.03 to 6.854
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 48.5 hours	2.30 picograms per milliliter Interval 1.465 to 3.568	5.26 picograms per milliliter Interval 3.466 to 7.829
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 50 hours	2.53 picograms per milliliter Interval 1.619 to 3.924	4.91 picograms per milliliter Interval 3.213 to 7.268
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 54 hours	2.52 picograms per milliliter Interval 1.629 to 3.936	3.21 picograms per milliliter Interval 2.106 to 4.721
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 60 hours	2.26 picograms per milliliter Interval 1.478 to 3.49	2.78 picograms per milliliter Interval 1.868 to 4.143
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 66 hours	2.19 picograms per milliliter Interval 1.454 to 3.366	2.71 picograms per milliliter Interval 1.804 to 4.071
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 72 hours	1.72 picograms per milliliter Interval 1.125 to 2.662	2.50 picograms per milliliter Interval 1.64 to 3.884
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 96 hours	2.23 picograms per milliliter Interval 1.315 to 3.822	1.28 picograms per milliliter Interval 0.791 to 2.077
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-5 at 120 hours	2.19 picograms per milliliter Interval 1.451 to 3.412	1.38 picograms per milliliter Interval 0.868 to 2.403
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 0.5 hours	3.12 picograms per milliliter Interval 1.702 to 5.665	13.15 picograms per milliliter Interval 7.384 to 22.894
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 2 hours	3.29 picograms per milliliter Interval 1.786 to 5.965	12.05 picograms per milliliter Interval 6.774 to 21.245
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 6 hours	2.92 picograms per milliliter Interval 1.578 to 5.361	15.33 picograms per milliliter Interval 8.369 to 27.742
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 12 hours	3.03 picograms per milliliter Interval 1.607 to 5.711	6.82 picograms per milliliter Interval 3.8 to 12.383
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 24 hours	2.87 picograms per milliliter Interval 1.514 to 5.41	6.25 picograms per milliliter Interval 3.342 to 11.563
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 48 hours	3.58 picograms per milliliter Interval 1.878 to 6.875	5.71 picograms per milliliter Interval 3.154 to 9.797
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 48.5 hours	2.77 picograms per milliliter Interval 1.472 to 5.289	5.54 picograms per milliliter Interval 3.063 to 9.544
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 50 hours	3.20 picograms per milliliter Interval 1.696 to 6.064	6.13 picograms per milliliter Interval 3.399 to 10.648
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 54 hours	3.16 picograms per milliliter Interval 1.686 to 6.031	5.78 picograms per milliliter Interval 3.099 to 10.144
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 60 hours	3.57 picograms per milliliter Interval 1.907 to 6.701	4.74 picograms per milliliter Interval 2.542 to 8.631
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 66 hours	3.40 picograms per milliliter Interval 1.837 to 6.298	3.97 picograms per milliliter Interval 2.157 to 7.262
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 72 hours	2.66 picograms per milliliter Interval 1.389 to 5.051	4.70 picograms per milliliter Interval 2.51 to 8.532
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 96 hours	1.77 picograms per milliliter Interval 0.796 to 3.823	2.43 picograms per milliliter Interval 1.225 to 4.759
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) Ang1-7 at 120 hours	2.38 picograms per milliliter Interval 1.213 to 4.155	3.21 picograms per milliliter Interval 1.857 to 6.147

SECONDARY outcome

Timeframe: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-5) and Ang II/Ang (1-7) and). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 0.5 hours	4.35 Ratio Interval 2.463 to 7.664	0.29 Ratio Interval 0.175 to 0.488
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 2 hours	3.82 Ratio Interval 2.15 to 6.713	0.38 Ratio Interval 0.227 to 0.645
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 6 hours	3.20 Ratio Interval 1.793 to 5.619	0.36 Ratio Interval 0.211 to 0.629
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 12 hours	2.90 Ratio Interval 1.605 to 5.215	0.72 Ratio Interval 0.414 to 1.27
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 24 hours	2.35 Ratio Interval 1.296 to 4.276	0.68 Ratio Interval 0.383 to 1.182
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 48 hours	2.68 Ratio Interval 1.481 to 4.757	0.85 Ratio Interval 0.497 to 1.445
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 48.5 hours	2.90 Ratio Interval 1.606 to 5.164	0.56 Ratio Interval 0.328 to 0.959
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 50 hours	2.11 Ratio Interval 1.181 to 3.74	0.53 Ratio Interval 0.311 to 0.909
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 54 hours	2.21 Ratio Interval 1.249 to 3.885	0.68 Ratio Interval 0.385 to 1.191
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 60 hours	2.52 Ratio Interval 1.445 to 4.412	0.86 Ratio Interval 0.496 to 1.501
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 66 hours	2.90 Ratio Interval 1.669 to 5.036	0.64 Ratio Interval 0.37 to 1.105
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 72 hours	2.91 Ratio Interval 1.62 to 5.153	0.76 Ratio Interval 0.429 to 1.335
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 96 hours	1.72 Ratio Interval 0.87 to 3.387	1.41 Ratio Interval 0.738 to 2.695
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-5 at 120 hours	1.93 Ratio Interval 1.058 to 3.508	1.53 Ratio Interval 0.768 to 2.872
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 0.5 hours	3.10 Ratio Interval 1.681 to 5.669	0.19 Ratio Interval 0.11 to 0.342
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 2 hours	2.52 Ratio Interval 1.379 to 4.611	0.24 Ratio Interval 0.135 to 0.432
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 6 hours	2.63 Ratio Interval 1.456 to 4.767	0.20 Ratio Interval 0.109 to 0.378
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 12 hours	2.50 Ratio Interval 1.352 to 4.675	0.49 Ratio Interval 0.267 to 0.913
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 24 hours	2.11 Ratio Interval 1.127 to 3.99	0.37 Ratio Interval 0.2 to 0.671
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 48 hours	1.61 Ratio Interval 0.843 to 3.105	0.65 Ratio Interval 0.363 to 1.146
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 48.5 hours	2.18 Ratio Interval 1.147 to 4.165	0.51 Ratio Interval 0.291 to 0.917
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 50 hours	1.51 Ratio Interval 0.799 to 2.887	0.42 Ratio Interval 0.233 to 0.747
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Row 23Ang II/Ang1-7 at 54 hours	1.64 Ratio Interval 0.872 to 3.105	0.40 Ratio Interval 0.213 to 0.719
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 60 hours	1.55 Ratio Interval 0.817 to 2.945	0.48 Ratio Interval 0.264 to 0.878
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 66 hours	1.81 Ratio Interval 0.964 to 3.354	0.45 Ratio Interval 0.246 to 0.825
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 72 hours	1.75 Ratio Interval 0.931 to 3.295	0.42 Ratio Interval 0.219 to 0.796
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 96 hours	2.02 Ratio Interval 0.951 to 4.323	0.69 Ratio Interval 0.335 to 1.406
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) Ang II/Ang1-7 at 120 hours	1.66 Ratio Interval 0.826 to 3.178	0.64 Ratio Interval 0.311 to 1.568

SECONDARY outcome

Timeframe: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Measures of oxygenation included PEEP the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration, peak ventilator pressure highest level of pressure applied to the lungs during inhalation and plateau ventilatory pressure the pressure applied to small airways and alveoli measured during an inspiratory pause on the ventilator. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 66 hours	24.3 centimeters of water pressure Interval 21.48 to 27.38	25.9 centimeters of water pressure Interval 23.08 to 28.92
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 72 hours	22.9 centimeters of water pressure Interval 20.08 to 26.34	29.3 centimeters of water pressure Interval 25.85 to 32.87
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 168 hours	19.9 centimeters of water pressure Interval 17.35 to 24.63	25.2 centimeters of water pressure Interval 20.7 to 30.23
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 0.5 hours	24.2 centimeters of water pressure Interval 21.41 to 27.12	25.9 centimeters of water pressure Interval 23.02 to 29.17
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 1 hour	24.8 centimeters of water pressure Interval 22.06 to 27.85	24.7 centimeters of water pressure Interval 21.9 to 27.72
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 2 hours	23.9 centimeters of water pressure Interval 21.22 to 26.96	24.8 centimeters of water pressure Interval 21.92 to 27.89
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 4 hours	24.3 centimeters of water pressure Interval 21.65 to 27.49	24.9 centimeters of water pressure Interval 21.95 to 28.22
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 6 hours	24.8 centimeters of water pressure Interval 22.15 to 27.77	25.2 centimeters of water pressure Interval 22.07 to 28.62
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 8 hours	25.9 centimeters of water pressure Interval 23.2 to 29.05	21.9 centimeters of water pressure Interval 19.22 to 24.84
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 12 hours	24.1 centimeters of water pressure Interval 21.38 to 27.26	24.0 centimeters of water pressure Interval 20.96 to 27.38
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 18 hours	25.3 centimeters of water pressure Interval 22.45 to 28.64	21.5 centimeters of water pressure Interval 18.63 to 24.95
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 24 hours	24.1 centimeters of water pressure Interval 21.46 to 27.25	24.2 centimeters of water pressure Interval 21.16 to 27.44
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 24.5 hours	23.8 centimeters of water pressure Interval 21.22 to 26.84	23.2 centimeters of water pressure Interval 20.36 to 26.37
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 25 hours	24.4 centimeters of water pressure Interval 21.74 to 27.49	22.2 centimeters of water pressure Interval 19.44 to 25.35
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 26 hours	23.3 centimeters of water pressure Interval 20.7 to 26.42	23.2 centimeters of water pressure Interval 20.26 to 26.72
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 28 hours	23.1 centimeters of water pressure Interval 20.47 to 26.03	23.4 centimeters of water pressure Interval 20.43 to 26.9
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 30 hours	23.3 centimeters of water pressure Interval 20.44 to 26.61	23.6 centimeters of water pressure Interval 20.71 to 27.01
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 32 hours	23.2 centimeters of water pressure Interval 20.38 to 26.41	23.2 centimeters of water pressure Interval 20.44 to 26.55
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 36 hours	23.4 centimeters of water pressure Interval 20.63 to 26.59	23.7 centimeters of water pressure Interval 20.55 to 27.29
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 42 hours	24.8 centimeters of water pressure Interval 21.36 to 28.57	23.3 centimeters of water pressure Interval 20.18 to 26.82
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 48 hours	23.6 centimeters of water pressure Interval 20.32 to 27.73	23.1 centimeters of water pressure Interval 20.1 to 27.18
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 48.5 hours	23.1 centimeters of water pressure Interval 19.89 to 27.11	25.2 centimeters of water pressure Interval 22.01 to 29.38
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 49 hours	22.8 centimeters of water pressure Interval 19.34 to 26.73	24.6 centimeters of water pressure Interval 21.44 to 28.66
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 50 hours	22.3 centimeters of water pressure Interval 19.01 to 26.27	25.2 centimeters of water pressure Interval 21.93 to 29.33
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 52 hours	23.9 centimeters of water pressure Interval 20.46 to 28.73	25.4 centimeters of water pressure Interval 22.0 to 29.64
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 54 hours	23.1 centimeters of water pressure Interval 19.75 to 27.63	23.1 centimeters of water pressure Interval 20.06 to 26.94
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 56 hours	23.2 centimeters of water pressure Interval 19.87 to 27.85	22.4 centimeters of water pressure Interval 19.5 to 25.86
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 60 hours	22.5 centimeters of water pressure Interval 18.69 to 27.06	23.4 centimeters of water pressure Interval 20.18 to 26.99
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 66 hours	24.5 centimeters of water pressure Interval 19.54 to 30.63	23.6 centimeters of water pressure Interval 20.1 to 27.69
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 72 hours	21.7 centimeters of water pressure Interval 17.69 to 26.83	25.3 centimeters of water pressure Interval 21.52 to 29.52
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Plateau ventilatory pressure at 168 hours	15.1 centimeters of water pressure Interval 11.7 to 19.47	17.0 centimeters of water pressure Interval 14.62 to 20.3
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 0.5 hours	10.3 centimeters of water pressure Interval 8.87 to 12.18	9.6 centimeters of water pressure Interval 8.23 to 11.54
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 1 hour	9.9 centimeters of water pressure Interval 8.51 to 11.69	9.6 centimeters of water pressure Interval 8.23 to 11.6
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 2 hours	9.9 centimeters of water pressure Interval 8.48 to 11.62	9.7 centimeters of water pressure Interval 8.26 to 11.72
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 4 hours	9.7 centimeters of water pressure Interval 8.3 to 11.29	9.6 centimeters of water pressure Interval 8.21 to 11.56
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 6 hours	9.6 centimeters of water pressure Interval 8.28 to 11.14	9.5 centimeters of water pressure Interval 8.21 to 11.32
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 8 hours	9.7 centimeters of water pressure Interval 8.38 to 11.18	9.6 centimeters of water pressure Interval 8.25 to 11.19
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 12 hours	9.8 centimeters of water pressure Interval 8.56 to 11.38	9.5 centimeters of water pressure Interval 8.13 to 10.87
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 18 hours	10.1 centimeters of water pressure Interval 8.79 to 11.71	9.6 centimeters of water pressure Interval 8.23 to 11.13
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 24 hours	9.7 centimeters of water pressure Interval 8.39 to 11.36	9.3 centimeters of water pressure Interval 8.13 to 10.76
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 24.5 hours	9.7 centimeters of water pressure Interval 8.39 to 11.37	9.3 centimeters of water pressure Interval 8.14 to 10.78
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 25 hours	9.7 centimeters of water pressure Interval 8.41 to 11.38	8.6 centimeters of water pressure Interval 7.47 to 9.89
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 26 hours	9.4 centimeters of water pressure Interval 8.13 to 11.01	9.3 centimeters of water pressure Interval 8.11 to 10.78
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 28 hours	9.1 centimeters of water pressure Interval 7.89 to 10.7	9.4 centimeters of water pressure Interval 8.02 to 10.79
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 30 hours	9.5 centimeters of water pressure Interval 8.2 to 11.11	9.3 centimeters of water pressure Interval 7.89 to 10.78
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 32 hours	9.1 centimeters of water pressure Interval 7.84 to 10.63	9.2 centimeters of water pressure Interval 7.79 to 10.66
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 36 hours	9.3 centimeters of water pressure Interval 7.91 to 10.96	9.0 centimeters of water pressure Interval 7.75 to 10.55
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 42 hours	9.6 centimeters of water pressure Interval 8.21 to 11.31	8.9 centimeters of water pressure Interval 7.59 to 10.39
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 48 hours	9.6 centimeters of water pressure Interval 8.2 to 11.38	8.8 centimeters of water pressure Interval 7.52 to 10.4
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 48.5 hours	9.6 centimeters of water pressure Interval 8.19 to 11.42	8.8 centimeters of water pressure Interval 7.57 to 10.47
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 49 hours	9.6 centimeters of water pressure Interval 8.17 to 11.44	8.6 centimeters of water pressure Interval 7.43 to 10.26
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 50 hours	9.6 centimeters of water pressure Interval 8.12 to 11.39	8.7 centimeters of water pressure Interval 7.5 to 10.34
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 52 hours	9.6 centimeters of water pressure Interval 8.18 to 11.48	8.8 centimeters of water pressure Interval 7.56 to 10.45
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 54 hours	9.4 centimeters of water pressure Interval 7.98 to 11.25	8.7 centimeters of water pressure Interval 7.41 to 10.19
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 56 hours	9.2 centimeters of water pressure Interval 7.85 to 11.12	8.7 centimeters of water pressure Interval 7.38 to 10.16
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 60 hours	8.9 centimeters of water pressure Interval 7.55 to 10.62	8.2 centimeters of water pressure Interval 6.91 to 9.63
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 66 hours	9.4 centimeters of water pressure Interval 7.85 to 11.04	9.1 centimeters of water pressure Interval 7.56 to 10.63
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 72 hours	9.6 centimeters of water pressure Interval 7.98 to 11.34	8.8 centimeters of water pressure Interval 7.53 to 10.25
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) PEEP at 168 hours	6.9 centimeters of water pressure Interval 5.83 to 9.05	7.5 centimeters of water pressure Interval 6.19 to 9.36
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 0.5 hours	29.3 centimeters of water pressure Interval 26.72 to 32.02	29.7 centimeters of water pressure Interval 27.0 to 32.7
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 1 hour	28.3 centimeters of water pressure Interval 25.83 to 30.98	30.4 centimeters of water pressure Interval 27.58 to 33.38
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 12 hours	28.5 centimeters of water pressure Interval 25.94 to 31.18	29.7 centimeters of water pressure Interval 27.04 to 32.59
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 2 hours	27.7 centimeters of water pressure Interval 25.37 to 30.43	29.7 centimeters of water pressure Interval 26.78 to 32.67
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 4 hours	28.4 centimeters of water pressure Interval 25.94 to 31.06	28.8 centimeters of water pressure Interval 25.99 to 31.64
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 6 hours	28.1 centimeters of water pressure Interval 25.77 to 30.74	29.4 centimeters of water pressure Interval 26.63 to 32.33
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 8 hours	28.2 centimeters of water pressure Interval 25.78 to 30.91	29.3 centimeters of water pressure Interval 26.48 to 32.15
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 18 hours	29.5 centimeters of water pressure Interval 26.87 to 32.31	28.9 centimeters of water pressure Interval 26.21 to 31.79
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 24 hours	28.8 centimeters of water pressure Interval 26.3 to 31.56	28.3 centimeters of water pressure Interval 25.66 to 31.08
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 24.5 hours	29.1 centimeters of water pressure Interval 26.61 to 31.96	28.2 centimeters of water pressure Interval 25.66 to 31.04
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 25 hours	29.4 centimeters of water pressure Interval 26.8 to 32.24	27.2 centimeters of water pressure Interval 24.74 to 29.92
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 26 hours	27.6 centimeters of water pressure Interval 25.1 to 30.26	27.4 centimeters of water pressure Interval 24.87 to 30.15
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 28 hours	29.3 centimeters of water pressure Interval 26.64 to 32.27	26.9 centimeters of water pressure Interval 24.32 to 29.57
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 30 hours	29.5 centimeters of water pressure Interval 26.81 to 32.52	28.6 centimeters of water pressure Interval 26.0 to 31.36
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 32 hours	30.7 centimeters of water pressure Interval 27.98 to 33.72	28.1 centimeters of water pressure Interval 25.44 to 30.81
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 36 hours	30.7 centimeters of water pressure Interval 27.79 to 33.74	27.0 centimeters of water pressure Interval 24.29 to 29.68
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 42 hours	28.2 centimeters of water pressure Interval 25.52 to 31.26	27.6 centimeters of water pressure Interval 25.01 to 30.23
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 48 hours	25.7 centimeters of water pressure Interval 23.17 to 28.4	26.7 centimeters of water pressure Interval 24.13 to 29.47
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 48.5 hours	26.0 centimeters of water pressure Interval 23.41 to 28.78	28.1 centimeters of water pressure Interval 25.4 to 31.03
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 49 hours	26.4 centimeters of water pressure Interval 23.71 to 29.23	28.1 centimeters of water pressure Interval 25.34 to 30.97
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 50 hours	24.2 centimeters of water pressure Interval 21.79 to 26.86	27.3 centimeters of water pressure Interval 24.59 to 30.19
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 52 hours	26.6 centimeters of water pressure Interval 23.87 to 29.57	26.7 centimeters of water pressure Interval 24.12 to 29.47
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 54 hours	25.3 centimeters of water pressure Interval 22.87 to 27.95	27.3 centimeters of water pressure Interval 24.76 to 30.15
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 56 hours	25.6 centimeters of water pressure Interval 23.14 to 28.43	27.9 centimeters of water pressure Interval 25.22 to 31.07
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) Peak ventilatory pressure at 60 hours	24.1 centimeters of water pressure Interval 21.79 to 26.75	26.8 centimeters of water pressure Interval 24.09 to 29.82

SECONDARY outcome

Timeframe: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Measure of oxygenation included PaO2/FiO2 ratio defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen by pulse oximeter a device that measured the oxygen saturation of arterial blood in a participant by utilizing a sensor attached typically to a finger, toe, or ear to determine the percentage of oxyhemoglobin in blood pulsating through a network of capillaries. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 0.5 hours	166.2 Ratio Interval 139.71 to 201.29	173.7 Ratio Interval 143.97 to 206.37
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 1 hour	178.1 Ratio Interval 149.67 to 215.96	160.2 Ratio Interval 132.71 to 190.93
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 2 hours	181.5 Ratio Interval 153.14 to 216.76	162.3 Ratio Interval 137.17 to 192.34
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 4 hours	182.8 Ratio Interval 153.78 to 218.35	155.1 Ratio Interval 130.45 to 183.88
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 6 hours	173.2 Ratio Interval 146.0 to 205.32	156.7 Ratio Interval 130.95 to 186.82
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 8 hours	160.9 Ratio Interval 135.62 to 191.4	170.6 Ratio Interval 143.85 to 203.91
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 12 hours	173.7 Ratio Interval 144.53 to 208.14	179.6 Ratio Interval 149.68 to 214.58
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 18 hours	180.5 Ratio Interval 151.11 to 214.8	176.8 Ratio Interval 147.25 to 212.12
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 24 hours	183.5 Ratio Interval 153.03 to 219.67	167.3 Ratio Interval 141.36 to 199.09
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 24.5 hours	189.3 Ratio Interval 158.67 to 226.84	175.8 Ratio Interval 147.94 to 209.31
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 25 hours	179.6 Ratio Interval 150.61 to 215.78	167.1 Ratio Interval 139.64 to 198.81
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 26 hours	182.9 Ratio Interval 153.39 to 219.07	183.2 Ratio Interval 153.67 to 217.68
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 28 hours	191.1 Ratio Interval 159.67 to 229.27	167.9 Ratio Interval 140.69 to 200.46
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 30 hours	169.5 Ratio Interval 140.9 to 205.06	169.3 Ratio Interval 139.8 to 204.89
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 32 hours	174.2 Ratio Interval 143.12 to 210.61	155.3 Ratio Interval 128.84 to 186.13
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 36 hours	200.5 Ratio Interval 164.55 to 240.83	159.5 Ratio Interval 132.9 to 191.36
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 42 hours	172.7 Ratio Interval 142.65 to 207.0	171.0 Ratio Interval 143.95 to 203.01
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 48 hours	169.9 Ratio Interval 139.2 to 206.04	178.2 Ratio Interval 148.82 to 214.14
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 48.5 hours	195.8 Ratio Interval 159.95 to 237.96	175.5 Ratio Interval 146.24 to 211.2
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 49 hours	166.5 Ratio Interval 135.67 to 203.47	175.1 Ratio Interval 144.85 to 211.61
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 50 hours	168.3 Ratio Interval 138.07 to 205.14	167.5 Ratio Interval 137.42 to 202.44
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 52 hours	183.9 Ratio Interval 149.96 to 227.12	168.4 Ratio Interval 141.57 to 202.76
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 54 hours	191.6 Ratio Interval 156.36 to 235.76	172.1 Ratio Interval 144.47 to 204.97
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 56 hours	181.6 Ratio Interval 148.45 to 224.06	173.9 Ratio Interval 146.2 to 206.22
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 60 hours	170.8 Ratio Interval 139.25 to 210.58	162.4 Ratio Interval 135.34 to 192.99
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 66 hours	154.6 Ratio Interval 126.25 to 189.63	162.6 Ratio Interval 133.81 to 195.44
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 72 hours	150.4 Ratio Interval 119.68 to 188.02	153.3 Ratio Interval 128.23 to 183.15
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) PaO2/FiO2 at 168 hours	198.9 Ratio Interval 163.04 to 266.41	168.9 Ratio Interval 143.77 to 196.4

SECONDARY outcome

Timeframe: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Oxygenation index was defined as calculation used in intensive care medicine to measure the fraction of inspired oxygen (FiO2) and its usage within the body and was computed using the equation Oxygenation Index= FiO2 x Mean Airway Pressure/Pao2. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 0.5 hours	10.0 Percentage Interval 7.26 to 13.17	10.6 Percentage Interval 7.71 to 14.79
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 1 hour	9.0 Percentage Interval 6.6 to 11.82	12.2 Percentage Interval 8.95 to 16.99
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 2 hours	9.9 Percentage Interval 7.35 to 12.96	11.0 Percentage Interval 7.95 to 15.15
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 4 hours	9.3 Percentage Interval 7.01 to 12.43	11.6 Percentage Interval 8.27 to 16.97
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 6 hours	10.2 Percentage Interval 7.65 to 13.46	12.3 Percentage Interval 8.65 to 18.07
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 8 hours	10.4 Percentage Interval 7.76 to 13.89	12.4 Percentage Interval 8.86 to 17.36
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 12 hours	9.3 Percentage Interval 6.88 to 12.61	11.0 Percentage Interval 7.5 to 16.24
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 18 hours	8.7 Percentage Interval 6.44 to 11.52	10.8 Percentage Interval 7.54 to 16.17
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 24 hours	10.6 Percentage Interval 8.02 to 14.05	10.6 Percentage Interval 8.22 to 14.39
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 24.5 hours	9.0 Percentage Interval 6.79 to 11.9	9.6 Percentage Interval 7.52 to 13.14
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 25 hours	8.9 Percentage Interval 6.74 to 11.93	10.5 Percentage Interval 8.26 to 14.59
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 26 hours	9.2 Percentage Interval 6.92 to 12.16	8.3 Percentage Interval 6.46 to 11.75
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 28 hours	9.0 Percentage Interval 6.86 to 12.01	9.4 Percentage Interval 6.95 to 13.27
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 30 hours	9.8 Percentage Interval 7.42 to 13.33	9.6 Percentage Interval 7.23 to 13.14
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 32 hours	9.7 Percentage Interval 7.21 to 13.16	10.4 Percentage Interval 7.61 to 14.11
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 36 hours	8.7 Percentage Interval 6.31 to 11.81	10.1 Percentage Interval 7.29 to 13.79
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 42 hours	9.4 Percentage Interval 6.98 to 12.7	10.2 Percentage Interval 7.13 to 14.75
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 48 hours	10.2 Percentage Interval 7.58 to 14.29	8.8 Percentage Interval 6.49 to 13.06
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 48.5 hours	9.2 Percentage Interval 6.78 to 12.79	8.4 Percentage Interval 6.25 to 12.37
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 49 hours	10.8 Percentage Interval 7.9 to 15.04	8.9 Percentage Interval 6.67 to 12.91
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 50 hours	10.4 Percentage Interval 7.63 to 14.64	9.2 Percentage Interval 6.84 to 12.96
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 52 hours	9.8 Percentage Interval 7.07 to 13.78	9.4 Percentage Interval 6.68 to 13.1
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 54 hours	9.4 Percentage Interval 6.83 to 12.99	9.7 Percentage Interval 6.32 to 13.92
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 56 hours	9.3 Percentage Interval 6.86 to 12.97	8.5 Percentage Interval 5.75 to 12.35
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 60 hours	8.9 Percentage Interval 6.33 to 12.53	9.9 Percentage Interval 6.92 to 14.34
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 66 hours	10.5 Percentage Interval 7.27 to 14.66	8.2 Percentage Interval 5.59 to 12.88
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 72 hours	10.5 Percentage Interval 6.62 to 16.36	9.7 Percentage Interval 6.63 to 13.41
Measure of Oxygenation Index Upto Day 7 (Part B) Oxygenation index at 168 hours	5.8 Percentage Interval 4.31 to 9.67	6.4 Percentage Interval 4.38 to 9.34

SECONDARY outcome

Timeframe: Upto Day 3

Population: The All Subjects - Part B Population.

The RIFLE score is made up of the glomerular filtration rate criteria (GFRC) and urine output criteria (UOC) and is defined as Risk (Serum Creatinine x 1.5 or GFR decrease \> 25%-GFRC and \< 0.5 milliliter/kilograms/hour \[ml/kg/hour\] x 6 hours-UOC), Injury (Serum Creatinine x 2 or GFR decrease \> 50%-GFRC and \< 0.5 ml/kg/hour x 12 hours), Failure (Serum Creatinine x 3, or GFR decrease \> 75% \[F=Failure\] or Serum Creatinine \>=4 milligrams/deciliter \[mg/dl\] with an acute rise \> 0.5 mg/dl \[Fc=Failure acute on chronic\] and \< 0.3 ml/kg/hour x 24 hours, or anuria x 12 hours \[Fo=Failure oligouria\]). Due to the duration of this study it was not possible to be calculate the designated RIFLE class Loss and RIFLE class End-stage kidney disease. Data has been presented for rifle score total, rifle score GFR and rifle score urine. Abbreviations NAKI= No acute kidney injury, R=risk, I=injury, MISS= Unable to derive score.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, MISS	15 Participants	14 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, NAKI to NAKI	3 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, NAKI to R	1 Participants	0 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, R to NAKI	1 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, I to NAKI	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, I to I	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score total, Fo to I	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score GFR, MISS	15 Participants	14 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score GFR, NAKI to NAKI	5 Participants	2 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score GFR, R to I	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score GFR, I to NAKI	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score GFR, I to I	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, NAKI to NAKI	10 Participants	11 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, NAKI to Fo	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, NAKI to R	2 Participants	0 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, NAKI to I	2 Participants	0 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, R to NAKI	1 Participants	2 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, I to NAKI	3 Participants	2 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, I to R	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, Fo to NAKI	1 Participants	0 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, Fo to R	0 Participants	1 Participants
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) Rifle score urine, Fo to Fo	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 4 and Day 7

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

The SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). The score ranges from 0-24. 0 (normal) to 4 (high degree of dysfunction) is given for each organ system, with a higher score indicating greater severity. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) Total SOFA Score at Day 4	7.4 Score on scale Interval 5.2 to 9.6	8.0 Score on scale Interval 6.3 to 9.7
Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) Total SOFA Score at Day 7	5.4 Score on scale Interval 2.7 to 8.2	6.8 Score on scale Interval 4.1 to 9.5

SECONDARY outcome

Timeframe: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Serum inflammatory biomarkers included CXCL-8 \[IL-8\], IL-6, markers of neutrophil activation included (e.g. myeloperoxidase \[MPO\]), markers of lung epithelial cell injury included receptor for advanced glycation end-products \[RAGE\], Angiopoietin 2, along with rennin, aldosterone levels. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) CXCL-8 (IL-8) at 12 hours	18.7 picograms per milliliter Interval 12.21 to 28.51	16.6 picograms per milliliter Interval 11.73 to 23.39
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) CXCL-8 (IL-8) at 24 hours	17.5 picograms per milliliter Interval 11.52 to 26.66	16.8 picograms per milliliter Interval 11.94 to 23.57
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) CXCL-8 (IL-8) at 48 hours	22.3 picograms per milliliter Interval 12.88 to 39.23	14.6 picograms per milliliter Interval 9.34 to 22.79
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) CXCL-8 (IL-8) at 72 hours	14.5 picograms per milliliter Interval 8.95 to 23.82	14.1 picograms per milliliter Interval 9.79 to 20.39
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) CXCL-8 (IL-8) at 120 hours	10.0 picograms per milliliter Interval 6.11 to 16.82	11.8 picograms per milliliter Interval 7.73 to 17.84
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) IL-6 at 12 hours	316.2 picograms per milliliter Interval 202.69 to 494.51	313.9 picograms per milliliter Interval 210.72 to 450.05
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) IL-6 at 24 hours	317.9 picograms per milliliter Interval 167.09 to 610.13	231.6 picograms per milliliter Interval 130.64 to 402.86
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) IL-6 at 48 hours	310.5 picograms per milliliter Interval 157.27 to 642.58	159.8 picograms per milliliter Interval 88.52 to 293.27
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) IL-6 at 72 hours	249.9 picograms per milliliter Interval 103.53 to 625.68	180.7 picograms per milliliter Interval 87.5 to 383.61
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) IL-6 at 120 hours	142.2 picograms per milliliter Interval 55.63 to 397.01	66.2 picograms per milliliter Interval 27.37 to 156.2
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) RAGE at 12 hours	3746 picograms per milliliter Interval 2994.0 to 4706.5	3461 picograms per milliliter Interval 2886.2 to 4174.2
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) RAGE at 24 hours	3059 picograms per milliliter Interval 2280.9 to 4094.4	3054 picograms per milliliter Interval 2389.0 to 3868.3
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) RAGE at 48 hours	2531 picograms per milliliter Interval 1563.5 to 4073.7	2480 picograms per milliliter Interval 1689.0 to 3665.5
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) RAGE at 72 hours	1936 picograms per milliliter Interval 1149.2 to 3357.7	1755 picograms per milliliter Interval 1140.0 to 2710.0
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) RAGE at 120 hours	1252 picograms per milliliter Interval 724.6 to 2267.7	1292 picograms per milliliter Interval 779.5 to 2135.8
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) MPO at 12 hours	60161.0 picograms per milliliter Interval 47838.62 to 75187.43	65791.2 picograms per milliliter Interval 54185.59 to 79462.44
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) MPO at 24 hours	55141.5 picograms per milliliter Interval 43437.7 to 69808.68	69059.0 picograms per milliliter Interval 56628.25 to 84474.33
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) MPO at 48 hours	58717.0 picograms per milliliter Interval 44179.56 to 77559.82	73790.1 picograms per milliliter Interval 58940.31 to 92336.24
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) MPO at 72 hours	42521.0 picograms per milliliter Interval 28395.5 to 63099.18	60700.1 picograms per milliliter Interval 43874.43 to 84341.04
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) MPO at 120 hours	32313.1 picograms per milliliter Interval 18853.46 to 55926.54	47835.2 picograms per milliliter Interval 29762.7 to 78945.65
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Angiopoietin-2 at 12 hours	10816.2 picograms per milliliter Interval 8386.58 to 13875.32	8981.1 picograms per milliliter Interval 7262.21 to 11069.75
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Angiopoietin-2 at 24 hours	9127.2 picograms per milliliter Interval 7112.04 to 11768.48	8973.9 picograms per milliliter Interval 7307.81 to 11015.23
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Angiopoietin-2 at 48 hours	9546.3 picograms per milliliter Interval 7228.39 to 12627.37	9043.3 picograms per milliliter Interval 7276.97 to 11310.46
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Angiopoietin-2 at 72 hours	8859.1 picograms per milliliter Interval 6597.11 to 11878.9	7773.7 picograms per milliliter Interval 6130.32 to 9864.61
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Angiopoietin-2 at 120 hours	7047.7 picograms per milliliter Interval 4907.43 to 10244.03	6604.4 picograms per milliliter Interval 4861.69 to 9194.97
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Renin at 72 hours	19.95 picograms per milliliter Interval 10.037 to 39.134	13.60 picograms per milliliter Interval 7.093 to 26.212
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) Aldosterone at 72 hours	36.8 picograms per milliliter Interval 7.46 to 179.86	19.5 picograms per milliliter Interval 7.45 to 50.56

SECONDARY outcome

Timeframe: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Serum inflammatory biomarker included CRP. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) CRP at 12 hours	12.99 milligrams per deciliter Interval 8.457 to 19.919	14.58 milligrams per deciliter Interval 10.196 to 20.872
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) CRP at 24 hours	11.26 milligrams per deciliter Interval 8.261 to 15.241	14.68 milligrams per deciliter Interval 11.357 to 18.895
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) CRP at 48 hours	11.19 milligrams per deciliter Interval 7.716 to 16.556	13.71 milligrams per deciliter Interval 9.846 to 19.529
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) CRP at 72 hours	9.96 milligrams per deciliter Interval 5.783 to 17.406	8.96 milligrams per deciliter Interval 5.51 to 14.764
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) CRP at 120 hours	6.81 milligrams per deciliter Interval 3.394 to 14.053	8.78 milligrams per deciliter Interval 4.503 to 17.514

SECONDARY outcome

Timeframe: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Markers of lung epithelial cell injury included CCP16 and SP-D. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) SP-D at 12 hours	304.71 nanograms per milliliter Interval 260.328 to 357.195	384.58 nanograms per milliliter Interval 338.077 to 438.326
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) SP-D at 24 hours	348.51 nanograms per milliliter Interval 287.86 to 421.778	442.35 nanograms per milliliter Interval 377.745 to 518.505
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) SP-D at 48 hours	307.00 nanograms per milliliter Interval 230.616 to 405.042	494.70 nanograms per milliliter Interval 391.578 to 628.342
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) SP-D at 72 hours	281.79 nanograms per milliliter Interval 199.927 to 398.96	465.15 nanograms per milliliter Interval 344.549 to 625.405
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) SP-D at 120 hours	229.94 nanograms per milliliter Interval 149.118 to 349.968	350.31 nanograms per milliliter Interval 238.257 to 518.552
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) CCP-16 at 12 hours	9.24 nanograms per milliliter Interval 7.771 to 10.908	8.45 nanograms per milliliter Interval 7.265 to 9.832
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) CCP-16 at 24 hours	9.18 nanograms per milliliter Interval 7.525 to 11.222	9.25 nanograms per milliliter Interval 7.795 to 11.116
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) CCP-16 at 48 hours	9.91 nanograms per milliliter Interval 6.784 to 14.461	11.04 nanograms per milliliter Interval 7.909 to 15.554
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) CCP-16 at 72 hours	9.04 nanograms per milliliter Interval 7.232 to 11.367	8.94 nanograms per milliliter Interval 7.439 to 10.795
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) CCP-16 at 120 hours	8.94 nanograms per milliliter Interval 7.067 to 11.382	7.22 nanograms per milliliter Interval 5.714 to 9.115

SECONDARY outcome

Timeframe: Follow-up (Day 14) and follow-up (Day 28)

Population: The All Subjects - Part A Population. Only those participants available at the specified time points were analyzed.

Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=5 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Day 14, Screening positive Confirmed negative	1 Participants	—
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Day 14, Screening positive and Confirmed positive	0 Participants	—
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Day 14, Screening negative	1 Participants	—
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Day 28, Screening positive Confirmed negative	0 Participants	—
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Day 28, Screening positive and Confirmed positive	NA Participants As there were no positive values at screening assay.	—
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) Row 6, Screening negative	1 Participants	—

SECONDARY outcome

Timeframe: Follow-up (Day 14 )and follow-up (Day 28)

Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 14, Screening positive Confirmed negative	1 Participants	0 Participants
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 14, Screening positive and Confirmed positive	0 Participants	NA Participants As there were no positive values at screening assay.
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 14, Screening negative	8 Participants	13 Participants
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 28, Screening positive Confirmed negative	0 Participants	0 Participants
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 28, Screening positive and Confirmed positive	NA Participants As there were no positive values at screening assay.	NA Participants As there were no positive values at screening assay.
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) Day 28, Screening negative	10 Participants	11 Participants

Adverse Events

Part A

Serious events: 3 serious events

Other events: 5 other events

Deaths: 3 deaths

Part B (Placebo BID)

Serious events: 4 serious events

Other events: 14 other events

Deaths: 2 deaths

Part B (GSK2586881 BID)

Serious events: 3 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 1 at Pre-dose	64.7 Millimeters of merucry Standard Deviation 12.86	53.9 Millimeters of merucry Standard Deviation 10.36
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 1 at 0.5 hours	64.4 Millimeters of merucry Standard Deviation 13.75	54.3 Millimeters of merucry Standard Deviation 11.39
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 1 at 2 hours	64.4 Millimeters of merucry Standard Deviation 12.59	54.8 Millimeters of merucry Standard Deviation 9.60
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 1 at 6 hours	63.4 Millimeters of merucry Standard Deviation 12.08	57.1 Millimeters of merucry Standard Deviation 9.21
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 1 at 12 hours	64.3 Millimeters of merucry Standard Deviation 12.78	57.6 Millimeters of merucry Standard Deviation 10.05
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 2 at 0 hours	67.0 Millimeters of merucry Standard Deviation 15.17	57.0 Millimeters of merucry Standard Deviation 10.22
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 0 hours	63.9 Millimeters of merucry Standard Deviation 14.50	62.7 Millimeters of merucry Standard Deviation 14.03
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 0.5 hours	65.6 Millimeters of merucry Standard Deviation 13.21	61.1 Millimeters of merucry Standard Deviation 12.83
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 2 hours	65.2 Millimeters of merucry Standard Deviation 10.34	58.1 Millimeters of merucry Standard Deviation 11.20
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 6 hours	65.2 Millimeters of merucry Standard Deviation 13.83	62.2 Millimeters of merucry Standard Deviation 16.59
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 12 hours	70.0 Millimeters of merucry Standard Deviation 16.40	60.6 Millimeters of merucry Standard Deviation 13.20
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 18 hours	73.2 Millimeters of merucry Standard Deviation 16.31	61.8 Millimeters of merucry Standard Deviation 10.50
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on Day 3 at 24 hours	66.4 Millimeters of merucry Standard Deviation 15.19	61.1 Millimeters of merucry Standard Deviation 13.06
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Diastolic blood pressure on follow-up Day 7	66.4 Millimeters of merucry Standard Deviation 11.58	62.7 Millimeters of merucry Standard Deviation 8.52
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 1 at Pre-dose	122.0 Millimeters of merucry Standard Deviation 18.97	106.1 Millimeters of merucry Standard Deviation 12.68
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 1 at 0.5 hours	118.8 Millimeters of merucry Standard Deviation 20.01	105.7 Millimeters of merucry Standard Deviation 12.66
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 1 at 2 hours	122.9 Millimeters of merucry Standard Deviation 14.85	107.5 Millimeters of merucry Standard Deviation 20.49
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 1 at 6 hours	121.6 Millimeters of merucry Standard Deviation 17.80	118.7 Millimeters of merucry Standard Deviation 16.41
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 1 at 12 hours	122.9 Millimeters of merucry Standard Deviation 21.88	116.9 Millimeters of merucry Standard Deviation 24.33
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 2 at 0 hours	131.6 Millimeters of merucry Standard Deviation 23.68	114.8 Millimeters of merucry Standard Deviation 18.94
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 0 hours	124.4 Millimeters of merucry Standard Deviation 16.32	125.2 Millimeters of merucry Standard Deviation 23.70
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 0.5 hours	127.1 Millimeters of merucry Standard Deviation 15.76	121.9 Millimeters of merucry Standard Deviation 23.60
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 2 hours	125.2 Millimeters of merucry Standard Deviation 14.77	118.5 Millimeters of merucry Standard Deviation 20.87
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 6 hours	127.8 Millimeters of merucry Standard Deviation 19.01	118.5 Millimeters of merucry Standard Deviation 19.60
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 12 hours	130.2 Millimeters of merucry Standard Deviation 21.95	123.2 Millimeters of merucry Standard Deviation 24.61
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 18 hours	137.5 Millimeters of merucry Standard Deviation 23.92	129.0 Millimeters of merucry Standard Deviation 17.45
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on Day 3 at 24 hours	128.8 Millimeters of merucry Standard Deviation 20.43	130.3 Millimeters of merucry Standard Deviation 24.97
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) Systolic blood pressure on follow-up Day 7	129.1 Millimeters of merucry Standard Deviation 22.22	129.9 Millimeters of merucry Standard Deviation 17.92

Measure	Part B (Placebo BID) n=20 Participants Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 Participants Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Calcium on Day 1 at Pre-dose	1.927 millimoles per liter Standard Deviation 0.0736	1.894 millimoles per liter Standard Deviation 0.1070
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Calcium on Day 3 at 12 hours	1.983 millimoles per liter Standard Deviation 0.1220	1.982 millimoles per liter Standard Deviation 0.1296
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Calcium on Follow-up Day 7	2.155 millimoles per liter Standard Deviation 0.1016	2.104 millimoles per liter Standard Deviation 0.1448
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Chloride on Day 1 at Pre-dose	108.8 millimoles per liter Standard Deviation 5.93	104.0 millimoles per liter Standard Deviation 7.18
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Chloride on Day 3 at 12 hours	107.7 millimoles per liter Standard Deviation 5.12	106.0 millimoles per liter Standard Deviation 6.05
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Chloride on Follow-up Day 7	104.4 millimoles per liter Standard Deviation 3.76	103.7 millimoles per liter Standard Deviation 5.01
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Carbon dioxide on Day 1 at Pre-dose	24.40 millimoles per liter Standard Deviation 5.273	23.28 millimoles per liter Standard Deviation 6.685
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Carbon dioxide on Day 3 at 12 hours	26.35 millimoles per liter Standard Deviation 3.176	27.83 millimoles per liter Standard Deviation 6.071
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Carbon dioxide on Follow-up Day 7	27.69 millimoles per liter Standard Deviation 3.728	27.39 millimoles per liter Standard Deviation 3.412
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Glucose on Day 1 at Pre-dose	6.015 millimoles per liter Standard Deviation 0.7499	6.159 millimoles per liter Standard Deviation 1.1230
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Glucose on Day 3 at 12 hours	8.095 millimoles per liter Standard Deviation 2.1569	7.411 millimoles per liter Standard Deviation 1.6158
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Glucose on Follow-up Day 7	6.701 millimoles per liter Standard Deviation 1.6354	7.285 millimoles per liter Standard Deviation 1.5159
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Potassium on Day 1 at Pre-dose	3.88 millimoles per liter Standard Deviation 0.444	3.72 millimoles per liter Standard Deviation 0.164
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Potassium on Day 3 at 12 hours	4.20 millimoles per liter Standard Deviation 0.511	3.96 millimoles per liter Standard Deviation 0.578
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Potassium on Follow-up Day 7	3.83 millimoles per liter Standard Deviation 0.505	3.92 millimoles per liter Standard Deviation 0.435
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Sodium on Day 1 at Pre-dose	141.8 millimoles per liter Standard Deviation 3.11	137.6 millimoles per liter Standard Deviation 3.71
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Sodium on Day 3 at 12 hours	143.1 millimoles per liter Standard Deviation 4.46	141.6 millimoles per liter Standard Deviation 4.03
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Sodium on Follow-up Day 7	141.9 millimoles per liter Standard Deviation 4.59	139.7 millimoles per liter Standard Deviation 4.58
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Urea/Blood urea nitrogen on Day 1 at Pre-dose	6.433 millimoles per liter Standard Deviation 3.0512	11.399 millimoles per liter Standard Deviation 7.4163
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Urea/Blood urea nitrogen on Day 3 at 12 hours	10.410 millimoles per liter Standard Deviation 6.5542	9.485 millimoles per liter Standard Deviation 6.5777
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) Urea/Blood urea nitrogen on Follow-up Day 7	11.787 millimoles per liter Standard Deviation 9.3546	9.207 millimoles per liter Standard Deviation 6.5375

Measure	Part A n=5 participants at risk Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.	Part B (Placebo BID) n=20 participants at risk Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.	Part B (GSK2586881 BID) n=19 participants at risk Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Infections and infestations Influenza	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Infections and infestations Sepsis	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.3% 1/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Blood and lymphatic system disorders Disseminated intravascular coagulation	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
General disorders Multi-organ failure	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Immune system disorders Graft versus host disease	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Nervous system disorders Subarachnoid haemorrhage	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Renal and urinary disorders Renal failure acute	20.0% 1/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Infections and infestations Empyema	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Infections and infestations Pneumonia	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.3% 1/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Infections and infestations Septic shock	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Cardiac disorders Cardiac arrest	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.3% 1/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Injury, poisoning and procedural complications Bronchial anastomosis complication	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.3% 1/19 • Upto follow-up Day 7. The All subjects population was used for analysis.
Investigations Hepatic enzyme increased	0.00% 0/5 • Upto follow-up Day 7. The All subjects population was used for analysis.	5.0% 1/20 • Upto follow-up Day 7. The All subjects population was used for analysis.	0.00% 0/19 • Upto follow-up Day 7. The All subjects population was used for analysis.