Trial Outcomes & Findings for A Study to Evaluate the Effect of the Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure (NCT NCT02497937)

Results Overview

DLco is a measure of the ability of a gas to transfer from alveoli across the alveolar epithelium and capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. Data of DLco (milliliter per millimeter of mercury per minute \[mL/mmHg/min\]) for Mayo site is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Baseline, Day 4, Day 5 and Day 7 of each treatment period

Results posted on

2018-09-05

Participant Flow

This was a randomized, double-blind, sponsor-unblinded, placebo-controlled, 2 by 2 crossover study in adults with heart failure. A total of 11 participants with Congestive Heart Failure were enrolled in the study. Study was conducted in the United States.

Participant milestones

Participant milestones
Measure	Sequence A (GSK2798745 2.4 mg)/P (Placebo) Eligible participants were randomized to one of two treatment sequences AP and PA where A=GSK2798745 2.4 mg and P=Placebo. In this sequence, participants received GSK2798745 2.4 milligrams (mg) once daily orally with 240 milliliter (mL) water in Period 1 and placebo in Period 2 for 7 days. Treatment periods were separated by a washout period of 14 days.	Sequence P (Placebo)/A (GSK2798745 2.4 mg) Eligible participants were randomized to one of two treatment sequences AP and PA where A=GSK2798745 2.4 mg and P=Placebo. In this sequence, participants received placebo in Period 1 and GSK2798745 2.4mg once daily orally with 240 mL water in Period 2 for 7 days. Treatment periods were separated by a washout period of 14 days.
Period 1 (Up to 7 Days) STARTED	6	5
Period 1 (Up to 7 Days) COMPLETED	6	5
Period 1 (Up to 7 Days) NOT COMPLETED	0	0
Washout Period (Up to 14 Days) STARTED	6	5
Washout Period (Up to 14 Days) COMPLETED	6	5
Washout Period (Up to 14 Days) NOT COMPLETED	0	0
Period 2 (Up to 7 Days) STARTED	6	5
Period 2 (Up to 7 Days) COMPLETED	6	5
Period 2 (Up to 7 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Effect of the Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Treatment Combined n=11 Participants Eligible participants were randomized to one of two treatment sequences AP and PA where A=GSK2798745 2.4 mg and P=Placebo. In sequence AP, participants received GSK2798745 2.4 milligrams (mg) once daily orally with 240 milliliter (mL) water in Period 1 and placebo in Period 2 for 7 days. In sequence PA, participants received placebo in Period 1 and GSK2798745 2.4mg once daily orally with 240 mL water in Period 2 for 7 days. In both sequence AP and PA, treatment periods were separated by a washout period of 14 days. Data represents all treatments combined.
Age, Continuous	67.7 Years STANDARD_DEVIATION 12.90 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	4 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 4, Day 5 and Day 7 of each treatment period

Population: Analysis Population comprised of participants in the 'All Subjects' population having Baseline and post-Baseline assessments of the endpoint of interest for both periods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

DLco is a measure of the ability of a gas to transfer from alveoli across the alveolar epithelium and capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. Data of DLco (milliliter per millimeter of mercury per minute \[mL/mmHg/min\]) for Mayo site is presented.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=7 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day 4, n =6,7	-0.4 mL/mmHg/min Standard Deviation 0.85	0.6 mL/mmHg/min Standard Deviation 1.16
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day -1, post exercise,n =7,7	0.6 mL/mmHg/min Standard Deviation 0.98	1.4 mL/mmHg/min Standard Deviation 1.47
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day 5,pre infusion,n =7,7	-1.0 mL/mmHg/min Standard Deviation 0.94	0.4 mL/mmHg/min Standard Deviation 1.31
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day 5,post infusion,n =7,7	-0.8 mL/mmHg/min Standard Deviation 0.65	-0.7 mL/mmHg/min Standard Deviation 0.81
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day 7,pre exercise,n =7,7	-0.6 mL/mmHg/min Standard Deviation 1.63	0.7 mL/mmHg/min Standard Deviation 1.91
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) Day 7,post exercise,n =7,7	0.4 mL/mmHg/min Standard Deviation 1.38	1.6 mL/mmHg/min Standard Deviation 2.45

PRIMARY outcome

Timeframe: Baseline, Day 4, Day 5 and Day 7 of each treatment period

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

DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to the symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 Pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Statistical analysis was not performed as the sample size was too small

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=4 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day 5,pre infusion,n =4,3	0.2 mL/mmHg/min Standard Deviation 0.53	-0.3 mL/mmHg/min Standard Deviation 0.24
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day -1, post exercise, n =4, 3	1.3 mL/mmHg/min Standard Deviation 1.32	1.0 mL/mmHg/min Standard Deviation 0.47
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day 4, n =4, 3	1.5 mL/mmHg/min Standard Deviation 1.11	0.1 mL/mmHg/min Standard Deviation 1.05
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day 5,post infusion,n =4,4	0.7 mL/mmHg/min Standard Deviation 1.47	0.8 mL/mmHg/min Standard Deviation 1.31
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day 7,pre exercise, n =4,3	0.4 mL/mmHg/min Standard Deviation 1.82	-0.6 mL/mmHg/min Standard Deviation 1.20
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) Day 7,post exercise, n =4,3	1.2 mL/mmHg/min Standard Deviation 1.01	0.4 mL/mmHg/min Standard Deviation 1.12

SECONDARY outcome

Timeframe: Baseline, Day 4, Day 5 and Day 7 of each treatment period

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

DLno is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary DM. Since nitric oxide has a greater affinity for hemoglobin, transfer of gas mainly limits the diffusion of nitric oxide across the alveolar capillary membrane. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=7 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day -1,post-exercise, n =7, 7	2.1 mL/mmHg/min Standard Deviation 1.87	3.5 mL/mmHg/min Standard Deviation 3.66
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day 4, n =6, 7	-2.3 mL/mmHg/min Standard Deviation 4.01	5.0 mL/mmHg/min Standard Deviation 5.51
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day 5,pre-infusion, n =7, 7	-6.0 mL/mmHg/min Standard Deviation 6.50	2.4 mL/mmHg/min Standard Deviation 8.56
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day 5,post-infusion, n =7, 7	-2.7 mL/mmHg/min Standard Deviation 3.83	-3.3 mL/mmHg/min Standard Deviation 3.27
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day 7,pre-exercise, n =7, 7	-1.9 mL/mmHg/min Standard Deviation 6.19	6.0 mL/mmHg/min Standard Deviation 9.96
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DLno,Day 7, post-exercise,n =7,7	1.5 mL/mmHg/min Standard Deviation 5.37	8.6 mL/mmHg/min Standard Deviation 10.19
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day -1,post-exercise, n =7, 7	1.0 mL/mmHg/min Standard Deviation 0.85	1.7 mL/mmHg/min Standard Deviation 1.53
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day 4, n =6, 7	-1.0 mL/mmHg/min Standard Deviation 1.82	2.4 mL/mmHg/min Standard Deviation 2.61
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day 5,pre-infusion, n =7, 7	-2.7 mL/mmHg/min Standard Deviation 2.95	1.2 mL/mmHg/min Standard Deviation 3.92
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day 5,post-infusion, n =7, 7	-1.2 mL/mmHg/min Standard Deviation 1.74	-1.5 mL/mmHg/min Standard Deviation 1.49
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day 7,pre-exercise, n =7, 7	-0.9 mL/mmHg/min Standard Deviation 2.81	2.8 mL/mmHg/min Standard Deviation 4.55
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) DM,Day 7, post-exercise,n =7,7	0.7 mL/mmHg/min Standard Deviation 2.44	4.1 mL/mmHg/min Standard Deviation 4.74

SECONDARY outcome

Timeframe: Baseline, Day 4, Day 5 and Day 7 of each treatment period

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

Vc is defined as volume of blood within the capillaries. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=7 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Capillary Blood Volume (Vc) Day 4, n =6, 7	-2.6 mL Standard Deviation 8.64	-0.2 mL Standard Deviation 9.40
Change From Baseline in Capillary Blood Volume (Vc) Day -1,post exercise, n =7, 7	1.6 mL Standard Deviation 8.39	10.4 mL Standard Deviation 14.77
Change From Baseline in Capillary Blood Volume (Vc) Day 5,pre infusion, n =7, 7	-0.1 mL Standard Deviation 11.60	3.0 mL Standard Deviation 12.99
Change From Baseline in Capillary Blood Volume (Vc) Day 5,post infusion, n =7, 7	-4.9 mL Standard Deviation 14.19	-2.3 mL Standard Deviation 11.70
Change From Baseline in Capillary Blood Volume (Vc) Day 7,pre exercise, n =7, 7	-4.7 mL Standard Deviation 12.86	-2.6 mL Standard Deviation 13.99
Change From Baseline in Capillary Blood Volume (Vc) Day 7, post exercise,n =7,7	0.3 mL Standard Deviation 12.33	3.3 mL Standard Deviation 15.35

SECONDARY outcome

Timeframe: Baseline, Day 5 and Day 7 of each treatment period

Population: Analysis Population.

DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Mayo site.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=7 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) Day 7, post exercise	0.4 mL/mmHg/min Standard Deviation 1.38	1.6 mL/mmHg/min Standard Deviation 2.45
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) Day -1,post exercise	0.6 mL/mmHg/min Standard Deviation 0.98	1.4 mL/mmHg/min Standard Deviation 1.47
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) Day 5,post infusion	-0.8 mL/mmHg/min Standard Deviation 0.65	-0.7 mL/mmHg/min Standard Deviation 0.81

SECONDARY outcome

Timeframe: Baseline, Day 5 and Day 7 of each treatment period

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

DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Hennepin site is presented.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=4 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) Day -1,post exercise,n=4,3	1.3 mL/mmHg/min Standard Deviation 1.32	1.0 mL/mmHg/min Standard Deviation 0.47
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) Day 5,post infusion,n=4,4	0.7 mL/mmHg/min Standard Deviation 1.47	0.8 mL/mmHg/min Standard Deviation 1.31
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) Day 7, post exercise,n=4,3	1.2 mL/mmHg/min Standard Deviation 1.01	0.4 mL/mmHg/min Standard Deviation 1.12

SECONDARY outcome

Timeframe: Baseline and Day 7 of each treatment period

Population: Analysis Population

Participants were asked to participate in a submaximal exercise test that consisted of 3 parts: a 2-minute (min) resting Baseline, a 3-min step exercise and a 1-min recovery period. Throughout the test, breathing pattern, gas exchange, and heart rate were monitored using a simplified gas analysis system. Respiratory exchange ratio and the Borg Rating of Perceived Exertion measures were utilized to ensure participants perform progressive exercise while maintaining a submaximal level throughout the exercise period. Minute ventilation, breath frequency, tidal volume, oxygen consumption, carbon dioxide (CO2) production, Respiratory exchange ratio (RER) and end tidal CO2 were obtained from the breath-by-breath gas measurements. The VE/VCO2 slope and other variables were derived from this data. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day -1,recovery	-5.1 Ratio Standard Deviation 4.17	-5.7 Ratio Standard Deviation 4.31
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day -1,post 1 min	1.3 Ratio Standard Deviation 3.1	0.3 Ratio Standard Deviation 5.0
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day -1,at rest,post 2 min	1.6 Ratio Standard Deviation 6.40	1.8 Ratio Standard Deviation 11.93
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day -1,post 3 min	0.7 Ratio Standard Deviation 9.15	-4.5 Ratio Standard Deviation 6.68
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day 7,at rest	2.4 Ratio Standard Deviation 10.1	0.6 Ratio Standard Deviation 2.1
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day 7,post 1 min	0.7 Ratio Standard Deviation 10.1	0.0 Ratio Standard Deviation 3.8
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day 7,post 2 min	-1.2 Ratio Standard Deviation 11.99	1.6 Ratio Standard Deviation 10.37
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day 7,post 3 min	1.6 Ratio Standard Deviation 13.29	-1.2 Ratio Standard Deviation 3.97
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 1 Day 7,recovery	-8.0 Ratio Standard Deviation 5.68	-5.4 Ratio Standard Deviation 3.26
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day -1,post 1 min	-3.6 Ratio Standard Deviation 4.1	-2.1 Ratio Standard Deviation 4.5
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day -1,post 2 min	-3.7 Ratio Standard Deviation 4.68	-2.8 Ratio Standard Deviation 5.74
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day -1,post 3 min	-4.7 Ratio Standard Deviation 6.65	-4.2 Ratio Standard Deviation 5.86
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day -1,Recovery	-9.3 Ratio Standard Deviation 3.04	-7.6 Ratio Standard Deviation 6.13
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day 7 at rest	-2.5 Ratio Standard Deviation 6.3	-0.9 Ratio Standard Deviation 4.2
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day 7,post 1 min	-4.0 Ratio Standard Deviation 4.4	-2.5 Ratio Standard Deviation 3.7
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day 7,post 2 min	-2.6 Ratio Standard Deviation 4.16	-3.9 Ratio Standard Deviation 4.98
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day 7,post 3 min	-0.7 Ratio Standard Deviation 10.21	-6.4 Ratio Standard Deviation 3.65
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio Period 2 Day 7,Recovery	-2.1 Ratio Standard Deviation 22.58	-7.6 Ratio Standard Deviation 5.17

SECONDARY outcome

Timeframe: Baseline, Day 4 and Day 7 of each treatment period

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

FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FVC is the total amount of air exhaled during the lung function test. FEF is the the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. FEF 25-75, FEF50 and FEF75 is defined as a reduction in forced expiratory flow at 25 to 75 percent of the pulmonary volume. Results presented combines data across all sites. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FVC,Day 4,n=10,11	-0.0 Liters Standard Deviation 0.11	-0.1 Liters Standard Deviation 0.10
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FVC,Day 7,n=11,11	-0.0 Liters Standard Deviation 0.10	-0.0 Liters Standard Deviation 0.19
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEV1,Day 4,n=10,11	-0.1 Liters Standard Deviation 0.09	-0.0 Liters Standard Deviation 0.09
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEV1,Day 7,n=11,11	-0.1 Liters Standard Deviation 0.08	-0.0 Liters Standard Deviation 0.12
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF 25-75,Day 4,n=10,11	-0.2 Liters Standard Deviation 0.26	0.1 Liters Standard Deviation 0.34
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF 25-75,Day 7,n=11,11	-0.1 Liters Standard Deviation 0.16	-0.1 Liters Standard Deviation 0.25
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF50,Day 4,n=10,11	-0.3 Liters Standard Deviation 0.36	0.0 Liters Standard Deviation 0.43
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF50,Day 7,n=11,11	-0.2 Liters Standard Deviation 0.30	-0.0 Liters Standard Deviation 0.32
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF75,Day 4,n=10,11	-0.0 Liters Standard Deviation 0.08	0.0 Liters Standard Deviation 0.14
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 FEF75,Day 7,n=11,11	-0.0 Liters Standard Deviation 0.06	-0.0 Liters Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, Day 4 and Day 7 of each treatment period

Population: Analysis Population. Analysis was planned but not performed. FRC parameter was not collected because other measures which were collected served as reasonable surrogates.

FRC is the volume of air present in the lungs at the end of passive expiration. FRC was planned to be measured by body plethysmography. Analysis was planned but not performed. FRC parameter was not collected because other measures which were collected served as reasonable surrogates.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 4 and Day 7 of each treatment period

Population: Analysis Population. Analysis was planned but not performed. EELV parameter was not collected because other measures which were collected served as reasonable surrogates.

EELV corresponds to FRC in the presence of positive end expiration pressure (PEEP). Analysis was planned but not performed. EELV parameter was not collected because other measures which were collected served as reasonable surrogates.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 5 and Day 7 of each treatment period

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

Dyspnea was assessed using a standardized, validated 5-point Likert scale. Participants were asked to check the box next to the statement that most accurately described their current state of breathlessness or shortness of breath. Scale consisted of 5 points : 1- Not short of breath, 2- Mildly short of breath, 3- Moderately short of breath, 4- Severely short of breath and 5- Very severely short of breath. Participants rated their current state of breathlessness on this 5 point scale. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point .

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Dyspnea Score Period 1 Day-1,post exercise,n=4,2	0.5 Scores on a scale Standard Deviation 0.58	0.5 Scores on a scale Standard Deviation 0.71
Change From Baseline in Dyspnea Score Period 1 Day5,pre infusion,n=5,6	0.2 Scores on a scale Standard Deviation 0.45	-0.2 Scores on a scale Standard Deviation 0.41
Change From Baseline in Dyspnea Score Period 1 Day5,pre infusion-Orthopnea,n=5,6	0.2 Scores on a scale Standard Deviation 0.45	-0.2 Scores on a scale Standard Deviation 0.41
Change From Baseline in Dyspnea Score Period 1 Day7,pre exercise,n=5,6	0.0 Scores on a scale Standard Deviation 0.00	0.0 Scores on a scale Standard Deviation 0.63
Change From Baseline in Dyspnea Score Period 1 Day7,post exercise,n=3,2	1.3 Scores on a scale Standard Deviation 2.31	0.5 Scores on a scale Standard Deviation 0.71
Change From Baseline in Dyspnea Score Period 2 Day -1,post exercise,n=2,3	2.0 Scores on a scale Standard Deviation 2.83	1.3 Scores on a scale Standard Deviation 1.15
Change From Baseline in Dyspnea Score Period 2 Day5,pre infusion,n=6,5	-0.3 Scores on a scale Standard Deviation 1.03	-0.2 Scores on a scale Standard Deviation 1.10
Change From Baseline in Dyspnea Score Period 2 Day5,pre infusion-Orthopnea,n=6,5	-0.3 Scores on a scale Standard Deviation 1.03	-0.4 Scores on a scale Standard Deviation 0.89
Change From Baseline in Dyspnea Score Period 2 Day7,pre exercise,n=6,5	-0.5 Scores on a scale Standard Deviation 0.84	-0.4 Scores on a scale Standard Deviation 0.89
Change From Baseline in Dyspnea Score Period 2 Day7,post exercise,n=3,4	-1.0 Scores on a scale Standard Deviation 1.00	0.3 Scores on a scale Standard Deviation 1.71

SECONDARY outcome

Timeframe: Up to Day 7 of each treatment period

Population: All Subjects population comprised of all randomized participants who received at least one dose of study medication. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Continuous remote monitoring was performed during each 7-day study period utilizing the Preventice BodyGuardian Remote Monitoring System. Participants were instructed to wear the sensor throughout each study period. Respiratory monitoring data was collected in different body positions like standing, leaning, lying and unknown. Data is presented only for participants from Mayo clinic.

Outcome measures

Outcome measures
Measure	Placebo n=7 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=7 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day -1,Not set,n=4,3	22.9 breaths per minute Standard Deviation 5.14	13.3 breaths per minute Standard Deviation 1.58
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day -1,Standing,n=4,4	15.3 breaths per minute Standard Deviation 2.79	16.8 breaths per minute Standard Deviation 3.43
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day -1,Leaning,n=5,4	15.4 breaths per minute Standard Deviation 3.06	17.7 breaths per minute Standard Deviation 3.56
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day -1,Lying,n=4,4	17 breaths per minute Standard Deviation 3.08	15.6 breaths per minute Standard Deviation 2.26
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day -1,Unknown,n=0,2	—	17.5 breaths per minute Standard Deviation 3.75
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 4,Not set,n=6,3	14.9 breaths per minute Standard Deviation 3.64	13.8 breaths per minute Standard Deviation 1.09
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 4,Standing,n=6,6	15.9 breaths per minute Standard Deviation 3.39	15.5 breaths per minute Standard Deviation 3.1
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 4,Leaning,n=6,6	18.6 breaths per minute Standard Deviation 4.19	17.9 breaths per minute Standard Deviation 3.94
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 4,Lying,n=6,5	16.8 breaths per minute Standard Deviation 3.6	16.5 breaths per minute Standard Deviation 3.41
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 4,Unknown,n=2,3	15.5 breaths per minute Standard Deviation 2.18	13.2 breaths per minute Standard Deviation 3.54
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 7,Not set,n=3,4	15.7 breaths per minute Standard Deviation 3.88	15.1 breaths per minute Standard Deviation 2.76
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 7,Standing,n=7,4	15.9 breaths per minute Standard Deviation 3.54	15.5 breaths per minute Standard Deviation 3.53
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 7,Leaning,n=6,4	15.7 breaths per minute Standard Deviation 3.89	17.5 breaths per minute Standard Deviation 3.68
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) Day 7,Lying,n=7,4	16.8 breaths per minute Standard Deviation 3.88	16 breaths per minute Standard Deviation 3.6

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

SBP and DBP were measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Heart rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Heart Rate Period 1, Day 1,n=5,6	-7.0 beats per minute Standard Deviation 7.42	5.2 beats per minute Standard Deviation 11.46
Change From Baseline in Heart Rate Period 1, Day 2,n=5,6	-5.8 beats per minute Standard Deviation 5.36	-2.8 beats per minute Standard Deviation 15.72
Change From Baseline in Heart Rate Period 1, Day 3,n=5,6	-2.4 beats per minute Standard Deviation 9.21	-0.8 beats per minute Standard Deviation 17.60
Change From Baseline in Heart Rate Period 1,Day 4,n=5,6	-4.6 beats per minute Standard Deviation 10.16	-4.0 beats per minute Standard Deviation 16.84
Change From Baseline in Heart Rate Period 1, Day 5,n=5,6	-4.8 beats per minute Standard Deviation 7.79	2.2 beats per minute Standard Deviation 6.31
Change From Baseline in Heart Rate Period 1, Day 6,n=5,6	-6.2 beats per minute Standard Deviation 5.81	0.8 beats per minute Standard Deviation 4.12
Change From Baseline in Heart Rate Period 1, Day 7,n=5,6	-3.2 beats per minute Standard Deviation 7.95	5.2 beats per minute Standard Deviation 5.08
Change From Baseline in Heart Rate Period 2, Day 1,n=6,5	-7.3 beats per minute Standard Deviation 9.46	7.0 beats per minute Standard Deviation 9.08
Change From Baseline in Heart Rate Period 2, Day 2,n=6,5	-8.0 beats per minute Standard Deviation 15.80	-1.0 beats per minute Standard Deviation 2.35
Change From Baseline in Heart Rate Period 2, Day 3,n=6,5	-7.5 beats per minute Standard Deviation 16.34	-4.0 beats per minute Standard Deviation 4.80
Change From Baseline in Heart Rate Period 2, Day 4,n=6,5	-9.0 beats per minute Standard Deviation 13.52	0.6 beats per minute Standard Deviation 5.86
Change From Baseline in Heart Rate Period 2, Day 5,n=6,5	-11.0 beats per minute Standard Deviation 15.67	0.2 beats per minute Standard Deviation 4.15
Change From Baseline in Heart Rate Period 2, Day 6,n=6,5	-11.0 beats per minute Standard Deviation 16.46	2.2 beats per minute Standard Deviation 9.04
Change From Baseline in Heart Rate Period 2, Day 7,n=6,5	-11.2 beats per minute Standard Deviation 14.46	-1.2 beats per minute Standard Deviation 10.52

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Respiration rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Respiration Rate Period 1, Day 1,n=5,6	0.6 breaths per minute Standard Deviation 0.89	1.0 breaths per minute Standard Deviation 3.95
Change From Baseline in Respiration Rate Period 1, Day 2,n=5,6	-0.2 breaths per minute Standard Deviation 2.86	0.7 breaths per minute Standard Deviation 3.01
Change From Baseline in Respiration Rate Period 1, Day 3,n=5,6	0.2 breaths per minute Standard Deviation 1.79	2.0 breaths per minute Standard Deviation 3.46
Change From Baseline in Respiration Rate Period 1,Day 4,n=5,6	0.6 breaths per minute Standard Deviation 1.67	0.8 breaths per minute Standard Deviation 1.79
Change From Baseline in Respiration Rate Period 1, Day 5,n=5,6	1.2 breaths per minute Standard Deviation 2.59	1.8 breaths per minute Standard Deviation 4.58
Change From Baseline in Respiration Rate Period 1, Day 6,n=5,6	-0.2 breaths per minute Standard Deviation 3.63	2.0 breaths per minute Standard Deviation 3.10
Change From Baseline in Respiration Rate Period 1, Day 7,n=5,6	1.2 breaths per minute Standard Deviation 4.38	1.7 breaths per minute Standard Deviation 3.44
Change From Baseline in Respiration Rate Period 2, Day 1,n=6,5	2.3 breaths per minute Standard Deviation 3.67	1.0 breaths per minute Standard Deviation 3.74
Change From Baseline in Respiration Rate Period 2, Day 2,n=6,5	2.7 breaths per minute Standard Deviation 2.73	3.2 breaths per minute Standard Deviation 2.39
Change From Baseline in Respiration Rate Period 2, Day 3,n=6,5	1.7 breaths per minute Standard Deviation 3.88	3.0 breaths per minute Standard Deviation 2.00
Change From Baseline in Respiration Rate Period 2, Day 4,n=6,5	1.7 breaths per minute Standard Deviation 3.67	4.6 breaths per minute Standard Deviation 3.58
Change From Baseline in Respiration Rate Period 2, Day 5,n=6,5	2.3 breaths per minute Standard Deviation 3.44	1.0 breaths per minute Standard Deviation 3.00
Change From Baseline in Respiration Rate Period 2, Day 6,n=6,5	2.7 breaths per minute Standard Deviation 1.03	2.6 breaths per minute Standard Deviation 2.41
Change From Baseline in Respiration Rate Period 2, Day 7,n=6,5	1.0 breaths per minute Standard Deviation 2.45	-1.0 breaths per minute Standard Deviation 1.73

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Body temperature was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Temperature Period 1, Day 1,n=5,6	-0.2 Celsius Standard Deviation 0.55	-0.0 Celsius Standard Deviation 0.10
Change From Baseline in Temperature Period 1, Day 2,n=5,6	-0.1 Celsius Standard Deviation 0.16	-0.0 Celsius Standard Deviation 0.24
Change From Baseline in Temperature Period 1, Day 3,n=5,6	0.0 Celsius Standard Deviation 0.15	-0.0 Celsius Standard Deviation 0.33
Change From Baseline in Temperature Period 1,Day 4,n=5,6	0.2 Celsius Standard Deviation 0.34	-0.2 Celsius Standard Deviation 0.12
Change From Baseline in Temperature Period 1, Day 5,n=5,6	-0.1 Celsius Standard Deviation 0.11	-0.1 Celsius Standard Deviation 0.19
Change From Baseline in Temperature Period 1, Day 6,n=5,6	0.0 Celsius Standard Deviation 0.30	-0.1 Celsius Standard Deviation 0.32
Change From Baseline in Temperature Period 1, Day 7,n=5,6	-0.0 Celsius Standard Deviation 0.16	-0.2 Celsius Standard Deviation 0.29
Change From Baseline in Temperature Period 2, Day 1,n=6,5	0.2 Celsius Standard Deviation 0.55	0.1 Celsius Standard Deviation 0.13
Change From Baseline in Temperature Period 2, Day 2,n=6,5	0.2 Celsius Standard Deviation 0.44	-0.0 Celsius Standard Deviation 0.28
Change From Baseline in Temperature Period 2, Day 3,n=6,5	0.0 Celsius Standard Deviation 0.49	-0.1 Celsius Standard Deviation 0.21
Change From Baseline in Temperature Period 2, Day 4,n=6,5	0.1 Celsius Standard Deviation 0.46	-0.2 Celsius Standard Deviation 0.21
Change From Baseline in Temperature Period 2, Day 5,n=6,5	-0.2 Celsius Standard Deviation 0.26	-0.1 Celsius Standard Deviation 0.19
Change From Baseline in Temperature Period 2, Day 6,n=6,5	0.1 Celsius Standard Deviation 0.42	-0.1 Celsius Standard Deviation 0.24
Change From Baseline in Temperature Period 2, Day 7,n=6,5	0.1 Celsius Standard Deviation 0.39	0.1 Celsius Standard Deviation 0.21

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Percent oxygen in blood was measured using pulse oximetry in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Percent Oxygen in Blood Period 1, Day 1,n=4,6	0.0 Percentage of oxygen Standard Deviation 0.82	-0.3 Percentage of oxygen Standard Deviation 1.37
Change From Baseline in Percent Oxygen in Blood Period 1, Day 2,n=4,5	1.3 Percentage of oxygen Standard Deviation 0.96	-1.2 Percentage of oxygen Standard Deviation 0.84
Change From Baseline in Percent Oxygen in Blood Period 1, Day 3,n=3,6	0.7 Percentage of oxygen Standard Deviation 1.53	-0.7 Percentage of oxygen Standard Deviation 1.75
Change From Baseline in Percent Oxygen in Blood Period 1,Day 4,n=4,6	0.3 Percentage of oxygen Standard Deviation 0.96	0.0 Percentage of oxygen Standard Deviation 1.10
Change From Baseline in Percent Oxygen in Blood Period 1, Day 5,n=4,6	1.0 Percentage of oxygen Standard Deviation 1.63	0.5 Percentage of oxygen Standard Deviation 2.66
Change From Baseline in Percent Oxygen in Blood Period 1, Day 6,n=4,6	0.3 Percentage of oxygen Standard Deviation 0.96	-0.2 Percentage of oxygen Standard Deviation 1.72
Change From Baseline in Percent Oxygen in Blood Period 1, Day 7,n=4,6	-0.3 Percentage of oxygen Standard Deviation 1.71	-0.3 Percentage of oxygen Standard Deviation 1.51
Change From Baseline in Percent Oxygen in Blood Period 2, Day 1,n=6,5	-1.0 Percentage of oxygen Standard Deviation 2.83	-0.6 Percentage of oxygen Standard Deviation 1.82
Change From Baseline in Percent Oxygen in Blood Period 2, Day 2,n=6,5	0.2 Percentage of oxygen Standard Deviation 2.99	0.0 Percentage of oxygen Standard Deviation 1.22
Change From Baseline in Percent Oxygen in Blood Period 2, Day 3,n=6,4	-0.8 Percentage of oxygen Standard Deviation 2.64	-0.3 Percentage of oxygen Standard Deviation 2.36
Change From Baseline in Percent Oxygen in Blood Period 2, Day 4,n=6,5	-1.0 Percentage of oxygen Standard Deviation 2.61	1.4 Percentage of oxygen Standard Deviation 1.82
Change From Baseline in Percent Oxygen in Blood Period 2, Day 5,n=6,5	-0.2 Percentage of oxygen Standard Deviation 1.33	0.2 Percentage of oxygen Standard Deviation 1.30
Change From Baseline in Percent Oxygen in Blood Period 2, Day 6,n=6,5	-0.5 Percentage of oxygen Standard Deviation 2.17	0.2 Percentage of oxygen Standard Deviation 1.79
Change From Baseline in Percent Oxygen in Blood Period 2, Day 7,n=6,5	0.2 Percentage of oxygen Standard Deviation 2.04	0.0 Percentage of oxygen Standard Deviation 1.87

SECONDARY outcome

Timeframe: Up to Day 7 in each treatment period

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

Triplicate 12-lead ECG was obtained using an automated ECG machine at Baseline (Day-1) and single ECG measurements (M) were taken on Day 4 and Day 7. Data for number of participants with abnormal-clinically significant (CS) and abnormal-not clinically significant (NCS) ECG data is presented.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M1, NCS,n=5,6	5 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M1, CS,n=5,6	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M2, NCS,n=5,6	5 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M2, CS,n=5,6	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M3, NCS,n=5,6	5 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day -1, M3, CS,n=5,6	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day 4, NCS,n=5,6	5 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day 4, CS,n=5,6	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day 7, NCS,n=5,6	5 Participants	6 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 1, Day 7, CS,n=5,6	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day -1, M1, NCS,n=6,5	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2 Day -1, M1, CS,n=6,5	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day -1, M2, NCS,n=6,5	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day -1, M2, CS,n=6,5	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day -1, M3, NCS,n=6,5	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day -1, M3, CS,n=6,5	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day 4, NCS,n=6,5	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day 4, CS,n=6,5	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day 7, NCS,n=6,5	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Period 2, Day 7, CS,n=6,5	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the chemistry parameters including ALT, ALP, AST, creatine kinase and GGT. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Blood samples were collected to analyze the chemistry parameters including albumin and total protein. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Albumin and Total Protein Values Albumin,Period 1, Day 4,n=5,6	-1.6 Grams per liter Standard Deviation 1.52	-0.5 Grams per liter Standard Deviation 2.59
Change From Baseline in Albumin and Total Protein Values Albumin,Period 1, Day 7,n=5,6	-0.6 Grams per liter Standard Deviation 2.30	-0.3 Grams per liter Standard Deviation 1.75
Change From Baseline in Albumin and Total Protein Values Albumin,Period 2, Day 4,n=5,5	-0.4 Grams per liter Standard Deviation 0.55	-0.2 Grams per liter Standard Deviation 1.79
Change From Baseline in Albumin and Total Protein Values Albumin,Period 2, Day 7,n=6,5	0.2 Grams per liter Standard Deviation 1.83	0.8 Grams per liter Standard Deviation 1.30
Change From Baseline in Albumin and Total Protein Values Total protein,Period 1, Day 4,n=5,6	-1.0 Grams per liter Standard Deviation 5.15	-1.5 Grams per liter Standard Deviation 5.36
Change From Baseline in Albumin and Total Protein Values Total protein,Period 1, Day 7,n=5,6	0.8 Grams per liter Standard Deviation 5.22	-1.2 Grams per liter Standard Deviation 4.17
Change From Baseline in Albumin and Total Protein Values Total protein,Period 2, Day 4,n=5,5	-1.6 Grams per liter Standard Deviation 2.07	0.4 Grams per liter Standard Deviation 3.58
Change From Baseline in Albumin and Total Protein Values Total protein,Period 2, Day 7,n=6,5	-0.8 Grams per liter Standard Deviation 3.54	2.8 Grams per liter Standard Deviation 1.64

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Blood samples were collected to analyze the chemistry parameters including Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 7 of each treatment period

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

Blood samples were collected to analyze the chemistry parameters including Creatinine, Direct Bilirubin, Total Bilirubin and Uric acid. Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the digoxin levels. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data not available. Standard deviation could not be calculated as a single participant was analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Digoxin Level Period 1 Day 1,n=3,1	-0.17080 Nanomoles per liter Standard Deviation 0.322378	0.38430 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 2,n=3,1	0.17080 Nanomoles per liter Standard Deviation 0.073959	0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 3,n=3,1	0.12810 Nanomoles per liter Standard Deviation 0.128100	0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 4,n=3,1	-0.10248 Nanomoles per liter Standard Deviation 0.419417	0.12810 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 5,n=3,1	0.25620 Nanomoles per liter Standard Deviation 0.221876	0.38430 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 6,n=3,1	0.17080 Nanomoles per liter Standard Deviation 0.147917	0.00000 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 1 Day 7,n=3,1	-0.00000 Nanomoles per liter Standard Deviation 0.128100	0.00000 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Digoxin Level Period 2 Day 1,n=1,3	-0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.34160 Nanomoles per liter Standard Deviation 0.266661
Change From Baseline in Digoxin Level Period 2 Day 2,n=1,3	-0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.46970 Nanomoles per liter Standard Deviation 0.295834
Change From Baseline in Digoxin Level Period 2 Day 3,n=1,3	-0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.17080 Nanomoles per liter Standard Deviation 0.195676
Change From Baseline in Digoxin Level Period 2 Day 4,n=1,3	-0.38430 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.42700 Nanomoles per liter Standard Deviation 0.195676
Change From Baseline in Digoxin Level Period 2 Day 5,n=1,3	-0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.25620 Nanomoles per liter Standard Deviation 0.128100
Change From Baseline in Digoxin Level Period 2 Day 6,n=1,3	-0.12810 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.29890 Nanomoles per liter Standard Deviation 0.391352
Change From Baseline in Digoxin Level Period 2 Day 7,n=1,3	-0.25620 Nanomoles per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.42700 Nanomoles per liter Standard Deviation 0.369793

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the troponin I level and type I collagen cross-linked C-telopeptide (T1CCT). Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 1, Day 2,n=5,6	-0.0044 Microgram per liter Standard Deviation 0.00658	-0.0007 Microgram per liter Standard Deviation 0.00516
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 1, Day 4,n=5,6	-0.0118 Microgram per liter Standard Deviation 0.01117	-0.0008 Microgram per liter Standard Deviation 0.00492
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 1, Day 7,n=5,5	-0.0112 Microgram per liter Standard Deviation 0.01314	-0.0056 Microgram per liter Standard Deviation 0.00876
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 2, Day 2,n=6,5	0.0023 Microgram per liter Standard Deviation 0.00898	0.0002 Microgram per liter Standard Deviation 0.00672
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 2, Day 4,n=5,5	-0.0036 Microgram per liter Standard Deviation 0.00498	-0.0000 Microgram per liter Standard Deviation 0.01225
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide Troponin I,Period 2, Day 7,n=6,4	-0.0012 Microgram per liter Standard Deviation 0.01132	0.0043 Microgram per liter Standard Deviation 0.01902
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide T1CCT,Period 1 Day 7,n=3,3	-0.0133 Microgram per liter Standard Deviation 0.03774	-0.1250 Microgram per liter Standard Deviation 0.16975
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide T1CCT,Period 2 Day 7,n=3,3	-0.0343 Microgram per liter Standard Deviation 0.12948	-0.0447 Microgram per liter Standard Deviation 0.11186

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the Chemistry parameter N-terminal pro-Brain Natriuretic Peptide. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline is calculated by subtracting the baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide Period 1 Day 7,n=5,6	-279.0 Nanograms per liter Standard Deviation 455.83	214.2 Nanograms per liter Standard Deviation 702.54
Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide Period 2 Day 7,n=6,5	-347.7 Nanograms per liter Standard Deviation 1134.08	-121.6 Nanograms per liter Standard Deviation 340.70

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet count, White Blood Cell (WBC) count, Total Neutrophils. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the Hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Hematocrit Period 1, Day 4,n=5,6	-0.0084 Proportion of red blood cells in blood Standard Deviation 0.01910	-0.0092 Proportion of red blood cells in blood Standard Deviation 0.01641
Change From Baseline in Hematocrit Period 1, Day 7,n=5,6	-0.0086 Proportion of red blood cells in blood Standard Deviation 0.02329	-0.0045 Proportion of red blood cells in blood Standard Deviation 0.02336
Change From Baseline in Hematocrit Period 2, Day 4,n=5,5	0.0046 Proportion of red blood cells in blood Standard Deviation 0.00513	-0.0138 Proportion of red blood cells in blood Standard Deviation 0.02905
Change From Baseline in Hematocrit Period 2, Day 7,n=6,5	-0.0120 Proportion of red blood cells in blood Standard Deviation 0.01381	-0.0164 Proportion of red blood cells in blood Standard Deviation 0.02519

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze Hemoglobin. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Hemoglobin Period 1, Day 7,n=5,6	0.8 Gram per liter Standard Deviation 10.87	-2.2 Gram per liter Standard Deviation 6.55
Change From Baseline in Hemoglobin Period 2, Day 4,n=5,5	1.6 Gram per liter Standard Deviation 2.41	-3.8 Gram per liter Standard Deviation 7.85
Change From Baseline in Hemoglobin Period 2, Day 7,n=6,5	-3.5 Gram per liter Standard Deviation 4.93	-3.4 Gram per liter Standard Deviation 7.89
Change From Baseline in Hemoglobin Period 1, Day 4,n=5,6	-1.0 Gram per liter Standard Deviation 6.67	-4.3 Gram per liter Standard Deviation 7.42

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze Mean Corpuscle Volume. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Mean Corpuscle Volume Period 1, Day 4,n=5,6	0.20 Femtoliters Standard Deviation 1.402	0.97 Femtoliters Standard Deviation 1.218
Change From Baseline in Mean Corpuscle Volume Period 1, Day 7,n=5,6	-0.92 Femtoliters Standard Deviation 1.152	0.55 Femtoliters Standard Deviation 0.946
Change From Baseline in Mean Corpuscle Volume Period 2, Day 4,n=5,5	0.04 Femtoliters Standard Deviation 0.493	0.08 Femtoliters Standard Deviation 0.926
Change From Baseline in Mean Corpuscle Volume Period 2, Day 7,n=6,5	0.23 Femtoliters Standard Deviation 1.003	-0.50 Femtoliters Standard Deviation 1.086

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze the Hematology parameters including RBC and Reticulocytes. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes RBC,Period 1, Day 4,n=5,6	-0.100 Trillion cells per liter Standard Deviation 0.1943	-0.160 Trillion cells per liter Standard Deviation 0.2555
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes RBC,Period 1, Day 7,n=5,6	-0.056 Trillion cells per liter Standard Deviation 0.2637	-0.083 Trillion cells per liter Standard Deviation 0.2700
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes RBC,Period 2, Day 4,n=5,5	0.014 Trillion cells per liter Standard Deviation 0.0937	-0.146 Trillion cells per liter Standard Deviation 0.2708
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes RBC,Period 2, Day 7,n=6,5	-0.188 Trillion cells per liter Standard Deviation 0.2360	-0.150 Trillion cells per liter Standard Deviation 0.2270
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes Reticulocytes,Period 1, Day 4,n=5,6	-0.00148 Trillion cells per liter Standard Deviation 0.002167	-0.00388 Trillion cells per liter Standard Deviation 0.012096
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes Reticulocytes,Period 1, Day 7,n=5,6	0.00049 Trillion cells per liter Standard Deviation 0.004412	0.00021 Trillion cells per liter Standard Deviation 0.010985
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes Reticulocytes,Period 2, Day 4,n=5,5	0.00367 Trillion cells per liter Standard Deviation 0.032819	0.00051 Trillion cells per liter Standard Deviation 0.007178
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes Reticulocytes,Period 2, Day 7,n=6,5	0.00868 Trillion cells per liter Standard Deviation 0.019263	0.00086 Trillion cells per liter Standard Deviation 0.001831

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze Mean Corpuscle Hemoglobin concentration . Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Mean Corpuscle Hemoglobin Concentration Period 2, Day 7,n=1,3	-2.0 grams per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	6.0 grams per liter Standard Deviation 8.66
Change From Baseline in Mean Corpuscle Hemoglobin Concentration Period 1, Day 4,n=3,1	8.0 grams per liter Standard Deviation 7.94	-3.0 grams per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Mean Corpuscle Hemoglobin Concentration Period 1, Day 7,n=3,1	13.7 grams per liter Standard Deviation 12.22	-8.0 grams per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Mean Corpuscle Hemoglobin Concentration Period 2, Day 4,n=1,3	-1.0 grams per liter Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	2.7 grams per liter Standard Deviation 6.66

SECONDARY outcome

Timeframe: Baseline and up to Day 7 in each treatment period

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

Blood samples were collected to analyze Mean Corpuscle Hemoglobin. Change from Baseline was presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Mean Corpuscle Hemoglobin Period 1, Day 4,n=3,1	0.70 Picograms Standard Deviation 0.656	0.20 Picograms Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Mean Corpuscle Hemoglobin Period 1, Day 7,n=3,1	0.70 Picograms Standard Deviation 1.044	-0.20 Picograms Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.
Change From Baseline in Mean Corpuscle Hemoglobin Period 2, Day 4,n=1,3	0.00 Picograms Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.27 Picograms Standard Deviation 0.231
Change From Baseline in Mean Corpuscle Hemoglobin Period 2, Day 7,n=1,3	0.40 Picograms Standard Deviation NA Number of participants analyzed is 1, Standard Deviation could not be calculated.	0.33 Picograms Standard Deviation 0.503

SECONDARY outcome

Timeframe: Up to Day 46

Population: All Subjects Population.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AE and SAE are reported.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) Any AE	5 Participants	7 Participants
Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) Any SAE	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Day 7 of each treatment period

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

The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The vitality sub-score assesses energy and fatigue, and ranges from 0 (worst) - 100 (best). Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score General Health,Period 1, Day 7,n=5,6	1.8 Score on a scale Standard Deviation 2.49	-1.5 Score on a scale Standard Deviation 5.79
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score General Health,Period 2, Day 7,n=5,5	0.0 Score on a scale Standard Deviation 0.71	-1.4 Score on a scale Standard Deviation 2.97
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Role- Emotional, Period 2, Day 7,n=5,5	-0.2 Score on a scale Standard Deviation 3.19	1.2 Score on a scale Standard Deviation 4.09
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Physical Health Score,Period 2, Day 7,n=5,5	2.8 Score on a scale Standard Deviation 3.03	-1.0 Score on a scale Standard Deviation 5.61
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Mental Health Score, Period 2, Day 7,n=5,5	0.2 Score on a scale Standard Deviation 4.09	1.4 Score on a scale Standard Deviation 3.85
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Physical Functioning, Period 1, Day 7,n=5,6	3.0 Score on a scale Standard Deviation 4.00	1.2 Score on a scale Standard Deviation 0.75
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Physical Functioning, Period 2, Day 7,n=5,5	1.0 Score on a scale Standard Deviation 1.22	-0.4 Score on a scale Standard Deviation 2.19
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Role-Physical, Period 1, Day 7,n=4,6	-0.5 Score on a scale Standard Deviation 3.11	3.7 Score on a scale Standard Deviation 3.93
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Role-Physical, Period 2, Day 7,n=5,5	2.0 Score on a scale Standard Deviation 3.67	0.4 Score on a scale Standard Deviation 2.70
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Bodily Pain, Period 1, Day 7,n=5,5	-1.0 Score on a scale Standard Deviation 1.41	-1.2 Score on a scale Standard Deviation 1.10
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Bodily Pain, Period 2, Day 7,n=5,5	-0.2 Score on a scale Standard Deviation 1.10	0.4 Score on a scale Standard Deviation 1.14
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Vitality, Period 1, Day 7,n=5,6	1.2 Score on a scale Standard Deviation 1.79	-1.2 Score on a scale Standard Deviation 1.17
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Vitality, Period 2, Day 7,n=5,5	-0.4 Score on a scale Standard Deviation 1.14	-0.8 Score on a scale Standard Deviation 2.17
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Social Functioning, Period 1, Day 7,n=5,6	-0.6 Score on a scale Standard Deviation 0.55	0.5 Score on a scale Standard Deviation 1.22
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Social Functioning, Period 2, Day 7,n=5,5	0.6 Score on a scale Standard Deviation 0.89	-0.2 Score on a scale Standard Deviation 1.10
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Role- Emotional, Period 1, Day 7,n=4,6	1.3 Score on a scale Standard Deviation 2.50	1.0 Score on a scale Standard Deviation 1.55
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Mental Health, Period 1, Day 7,n=5,6	0.6 Score on a scale Standard Deviation 0.55	0.3 Score on a scale Standard Deviation 0.52
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Mental Health, Period 2, Day 7,n=5,5	0.2 Score on a scale Standard Deviation 1.79	1.2 Score on a scale Standard Deviation 1.79
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Physical Health Score,Period 1, Day 7,n=5,6	5.8 Score on a scale Standard Deviation 8.23	1.7 Score on a scale Standard Deviation 3.83
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score Mental Health Score, Period 1, Day 7,n=5,6	5.2 Score on a scale Standard Deviation 6.53	0.7 Score on a scale Standard Deviation 1.97

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)

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

AUC(0-t), AUC(0-tau) and AUCall for GSK2798745 were determined based on intensive Pharmacokinetic (PK) sampling at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours. PK parameter population included all participants in the PK Concentration Population for whom valid and evaluable pharmacokinetic parameters were derived

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-tau), Period 1, Day 1,n=6	128.3513 hour*nanogram per mL Geometric Coefficient of Variation 70.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-tau), Period 1, Day 7,n=5	202.2948 hour*nanogram per mL Geometric Coefficient of Variation 132.1	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-tau), Period 2, Day 1,n=5	137.7473 hour*nanogram per mL Geometric Coefficient of Variation 38.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-tau), Period 2, Day 7,n=5	274.0828 hour*nanogram per mL Geometric Coefficient of Variation 70.9	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUCall, Period 1, Day 1,n=6	127.9049 hour*nanogram per mL Geometric Coefficient of Variation 70.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUCall Period 1, Day 7,n=5	174.7273 hour*nanogram per mL Geometric Coefficient of Variation 121.5	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUCall Period 2, Day 1,n=5	137.5038 hour*nanogram per mL Geometric Coefficient of Variation 38.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUCall, Period 2, Day 7,n=5	269.0902 hour*nanogram per mL Geometric Coefficient of Variation 70.5	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-t), Period 1, Day 1,n=6	127.9049 hour*nanogram per mL Geometric Coefficient of Variation 70.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-t) Period 1, Day 7,n=5	174.7273 hour*nanogram per mL Geometric Coefficient of Variation 121.5	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-t) Period 2, Day 1,n=5	137.5038 hour*nanogram per mL Geometric Coefficient of Variation 38.4	—
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745 AUC(0-t), Period 2, Day 7,n=5	269.0902 hour*nanogram per mL Geometric Coefficient of Variation 70.5	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)

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

Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Cmax was defined as maximum observed plasma concentration of drug.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Maximum Drug Concentration (Cmax) for GSK2798745 Period 1, Day 1,n=6	10.214 Nanograms per milliliter Geometric Coefficient of Variation 36.3	—
Maximum Drug Concentration (Cmax) for GSK2798745 Period 1, Day 7,n=5	15.687 Nanograms per milliliter Geometric Coefficient of Variation 73.6	—
Maximum Drug Concentration (Cmax) for GSK2798745 Period 2, Day 1,n=5	10.017 Nanograms per milliliter Geometric Coefficient of Variation 48.3	—
Maximum Drug Concentration (Cmax) for GSK2798745 Period 2, Day 7,n=5	15.428 Nanograms per milliliter Geometric Coefficient of Variation 68.1	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)

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

Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Tmax was defined as time to maximum observed plasma concentration of drug.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 Period 1, Day 7,n=5	3.0 Hour Interval 1.0 to 3.0	—
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 Period 1, Day 1,n=6	3.0 Hour Interval 2.0 to 3.0	—
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 Period 2, Day 1,n=5	3.0 Hour Interval 3.0 to 12.0	—
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 Period 2, Day 7,n=5	2.0 Hour Interval 1.0 to 3.0	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)

Population: PK Parameter Population. Data is not available for t1/2. The analysis was planned but not performed. PK sampling scheme was not adequate enough to reliably estimate the t1/2 of GSK2798745.

Blood samples for PK analysis were planned to be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. T½ was defined as Elimination half life of drug. Data is not available for t1/2. The analysis was planned but not performed. PK sampling scheme was not adequate enough to reliably estimate the t1/2 of GSK2798745.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2798745 2.4 mg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=11 participants at risk Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 participants at risk Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Vascular disorders Orthostatic hypotension	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 1,n=5,6	-3.4 Millimeters of mercury Standard Deviation 10.14	0.3 Millimeters of mercury Standard Deviation 12.06
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 2,n=6,5	-9.7 Millimeters of mercury Standard Deviation 18.41	-8.0 Millimeters of mercury Standard Deviation 8.43
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 3,n=6,5	-7.2 Millimeters of mercury Standard Deviation 20.47	-2.0 Millimeters of mercury Standard Deviation 6.82
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 4,n=6,5	-9.8 Millimeters of mercury Standard Deviation 12.27	1.2 Millimeters of mercury Standard Deviation 12.79
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 1,n=6,5	-14.0 Millimeters of mercury Standard Deviation 22.45	-9.2 Millimeters of mercury Standard Deviation 17.33
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 2,n=5,6	-7.6 Millimeters of mercury Standard Deviation 8.02	-4.0 Millimeters of mercury Standard Deviation 14.03
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 3,n=5,6	-14.6 Millimeters of mercury Standard Deviation 4.83	-0.3 Millimeters of mercury Standard Deviation 9.99
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1,Day 4,n=5,6	-5.0 Millimeters of mercury Standard Deviation 9.62	-4.3 Millimeters of mercury Standard Deviation 12.21
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 5,n=5,6	-8.0 Millimeters of mercury Standard Deviation 8.03	-5.8 Millimeters of mercury Standard Deviation 11.20
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 6,n=5,6	-9.8 Millimeters of mercury Standard Deviation 5.67	0.2 Millimeters of mercury Standard Deviation 8.23
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 1, Day 7,n=5,6	0.2 Millimeters of mercury Standard Deviation 13.01	6.5 Millimeters of mercury Standard Deviation 12.00
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 1,n=6,5	-9.2 Millimeters of mercury Standard Deviation 13.91	0.4 Millimeters of mercury Standard Deviation 9.50
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 1,n=5,6	-6.8 Millimeters of mercury Standard Deviation 7.12	2.5 Millimeters of mercury Standard Deviation 19.56
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 2,n=5,6	-7.8 Millimeters of mercury Standard Deviation 13.86	-2.5 Millimeters of mercury Standard Deviation 12.49
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 3,n=5,6	-8.8 Millimeters of mercury Standard Deviation 12.52	0.0 Millimeters of mercury Standard Deviation 10.41
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 4,n=5,6	-9.2 Millimeters of mercury Standard Deviation 9.71	0.8 Millimeters of mercury Standard Deviation 14.66
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 5,n=5,6	-10.4 Millimeters of mercury Standard Deviation 11.78	0.3 Millimeters of mercury Standard Deviation 24.91
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 6,n=5,6	-12.8 Millimeters of mercury Standard Deviation 7.05	0.0 Millimeters of mercury Standard Deviation 14.85
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 1, Day 7,n=5,6	-3.2 Millimeters of mercury Standard Deviation 18.74	9.0 Millimeters of mercury Standard Deviation 25.17
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 2,n=6,5	-12.7 Millimeters of mercury Standard Deviation 31.65	-6.4 Millimeters of mercury Standard Deviation 15.92
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 3,n=6,5	-14.5 Millimeters of mercury Standard Deviation 34.88	-8.0 Millimeters of mercury Standard Deviation 11.75
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 4,n=6,5	-13.5 Millimeters of mercury Standard Deviation 25.62	-4.4 Millimeters of mercury Standard Deviation 14.05
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 5,n=6,5	-19.0 Millimeters of mercury Standard Deviation 23.10	-10.8 Millimeters of mercury Standard Deviation 14.57
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 6,n=6,5	-12.5 Millimeters of mercury Standard Deviation 16.38	-7.4 Millimeters of mercury Standard Deviation 10.57
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) SBP,Period 2, Day 7,n=6,5	-11.5 Millimeters of mercury Standard Deviation 27.57	-2.2 Millimeters of mercury Standard Deviation 14.36
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 5,n=6,5	-10.7 Millimeters of mercury Standard Deviation 15.38	-3.6 Millimeters of mercury Standard Deviation 8.41
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 6,n=6,5	-8.2 Millimeters of mercury Standard Deviation 11.62	5.2 Millimeters of mercury Standard Deviation 9.26
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) DBP,Period 2, Day 7,n=6,5	-9.3 Millimeters of mercury Standard Deviation 13.95	1.2 Millimeters of mercury Standard Deviation 11.03

Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALT,Period 1, Day 4,n=5,6	-1.8 International units per liter Standard Deviation 1.92	-5.5 International units per liter Standard Deviation 10.41
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALT,Period 1, Day 7,n=5,6	-1.2 International units per liter Standard Deviation 2.77	-6.2 International units per liter Standard Deviation 8.80
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALT,Period 2, Day 4,n=5,5	2.8 International units per liter Standard Deviation 5.59	-3.6 International units per liter Standard Deviation 2.88
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALT,Period 2, Day 7,n=6,5	5.3 International units per liter Standard Deviation 6.50	-2.6 International units per liter Standard Deviation 2.70
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALP,Period 1, Day 4,n=5,6	0.6 International units per liter Standard Deviation 6.54	-17.8 International units per liter Standard Deviation 35.65
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALP,Period 1, Day 7,n=5,6	-1.0 International units per liter Standard Deviation 7.00	-15.2 International units per liter Standard Deviation 30.96
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALP,Period 2, Day 4,n=5,5	0.4 International units per liter Standard Deviation 6.73	-0.8 International units per liter Standard Deviation 2.39
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values ALP,Period 2, Day 7,n=6,5	8.0 International units per liter Standard Deviation 21.46	1.2 International units per liter Standard Deviation 6.30
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values AST,Period 1, Day 4,n=5,6	-4.0 International units per liter Standard Deviation 4.80	-6.7 International units per liter Standard Deviation 9.65
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values AST,Period 1, Day 7,n=5,5	-3.2 International units per liter Standard Deviation 3.56	-7.2 International units per liter Standard Deviation 8.04
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values AST,Period 2, Day 4,n=5,5	0.0 International units per liter Standard Deviation 9.97	-8.0 International units per liter Standard Deviation 2.92
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values AST,Period 2, Day 7,n=6,5	4.2 International units per liter Standard Deviation 7.00	-4.8 International units per liter Standard Deviation 1.92
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values GGT,Period 1, Day 4,n=5,6	-6.0 International units per liter Standard Deviation 6.86	-12.5 International units per liter Standard Deviation 20.71
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values GGT,Period 1, Day 7,n=5,6	-9.8 International units per liter Standard Deviation 11.82	-9.5 International units per liter Standard Deviation 11.06
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values GGT,Period 2, Day 4,n=5,5	5.8 International units per liter Standard Deviation 16.95	-4.8 International units per liter Standard Deviation 7.73
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values GGT,Period 2, Day 7,n=6,5	9.0 International units per liter Standard Deviation 22.09	-5.2 International units per liter Standard Deviation 5.54
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values Creatine kinase,Period 1, Day 4,n=5,6	-57.4 International units per liter Standard Deviation 90.68	-27.7 International units per liter Standard Deviation 36.14
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values Creatine kinase,Period 1, Day 7,n=5,6	-64.0 International units per liter Standard Deviation 105.02	-19.5 International units per liter Standard Deviation 54.42
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values Creatine kinase,Period 2, Day 4,n=5,4	-18.0 International units per liter Standard Deviation 25.03	-59.0 International units per liter Standard Deviation 68.33
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values Creatine kinase,Period 2, Day 7,n=6,5	-15.8 International units per liter Standard Deviation 22.05	-47.8 International units per liter Standard Deviation 29.20

Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Potassium,Period 1, Day 4,n=5,6	0.22 Millimoles per liter Standard Deviation 0.319	0.33 Millimoles per liter Standard Deviation 0.388
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Potassium,Period 1, Day 7,n=5,6	0.16 Millimoles per liter Standard Deviation 0.270	0.35 Millimoles per liter Standard Deviation 0.619
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Calcium,Period 1, Day 4,n=5,6	0.01497 Millimoles per liter Standard Deviation 0.080074	-0.06653 Millimoles per liter Standard Deviation 0.187817
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Calcium,Period 1, Day 7,n=5,6	0.05988 Millimoles per liter Standard Deviation 0.120434	-0.05822 Millimoles per liter Standard Deviation 0.185817
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Calcium,Period 2, Day 4,n=5,5	-0.05489 Millimoles per liter Standard Deviation 0.020875	0.00998 Millimoles per liter Standard Deviation 0.041749
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Calcium,Period 2, Day 7,n=6,5	-0.06238 Millimoles per liter Standard Deviation 0.071880	0.02994 Millimoles per liter Standard Deviation 0.044632
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Chloride,Period 1, Day 4,n=5,6	-1.8 Millimoles per liter Standard Deviation 1.48	-1.3 Millimoles per liter Standard Deviation 1.97
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Chloride,Period 1, Day 7,n=5,6	-1.0 Millimoles per liter Standard Deviation 1.87	0.5 Millimoles per liter Standard Deviation 1.76
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Chloride,Period 2, Day 4,n=5,5	-0.8 Millimoles per liter Standard Deviation 1.79	-2.0 Millimoles per liter Standard Deviation 2.35
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Chloride,Period 2, Day 7,n=6,5	-2.0 Millimoles per liter Standard Deviation 4.82	-2.4 Millimoles per liter Standard Deviation 1.82
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Glucose,Period 1, Day 4,n=5,6	3.63035 Millimoles per liter Standard Deviation 4.132346	2.04462 Millimoles per liter Standard Deviation 3.557566
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Glucose,Period 1, Day 7,n=5,6	2.04277 Millimoles per liter Standard Deviation 2.486018	0.61986 Millimoles per liter Standard Deviation 5.924289
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Glucose,Period 2, Day 4,n=5,5	1.68750 Millimoles per liter Standard Deviation 2.144009	3.96341 Millimoles per liter Standard Deviation 3.372569
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Glucose,Period 2, Day 7,n=6,5	1.51727 Millimoles per liter Standard Deviation 4.849639	1.23232 Millimoles per liter Standard Deviation 2.196471
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Potassium,Period 2, Day 4,n=5,5	0.04 Millimoles per liter Standard Deviation 0.397	0.26 Millimoles per liter Standard Deviation 0.270
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Potassium,Period 2, Day 7,n=6,5	-0.23 Millimoles per liter Standard Deviation 0.592	0.14 Millimoles per liter Standard Deviation 0.378
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Sodium,Period 1, Day 4,n=5,6	-1.0 Millimoles per liter Standard Deviation 4.00	-2.0 Millimoles per liter Standard Deviation 1.55
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Sodium,Period 1, Day 7,n=5,6	-1.4 Millimoles per liter Standard Deviation 3.36	-1.2 Millimoles per liter Standard Deviation 2.48
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Sodium,Period 2, Day 4,n=5,5	-1.0 Millimoles per liter Standard Deviation 1.58	-0.8 Millimoles per liter Standard Deviation 2.59
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Sodium,Period 2, Day 7,n=6,5	-2.2 Millimoles per liter Standard Deviation 2.32	-1.6 Millimoles per liter Standard Deviation 1.67
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Urea/BUN,Period 1, Day 4,n=5,6	-0.0714 Millimoles per liter Standard Deviation 1.34528	2.2610 Millimoles per liter Standard Deviation 3.82285
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Urea/BUN,Period 1, Day 7,n=5,6	-0.4284 Millimoles per liter Standard Deviation 1.86188	-0.1785 Millimoles per liter Standard Deviation 2.17448
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Urea/BUN,Period 2, Day 4,n=5,5	-1.2852 Millimoles per liter Standard Deviation 3.02504	-0.5712 Millimoles per liter Standard Deviation 2.53193
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) Urea/BUN,Period 2, Day 7,n=6,5	-0.2975 Millimoles per liter Standard Deviation 4.41537	0.0714 Millimoles per liter Standard Deviation 2.84930

Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Creatinine,Period 1, Day 4,n=5,6	-8.1328 Micromoles per liter Standard Deviation 17.06601	11.4920 Micromoles per liter Standard Deviation 29.13179
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Creatinine,Period 1, Day 7,n=5,6	-13.2600 Micromoles per liter Standard Deviation 15.91200	-9.4293 Micromoles per liter Standard Deviation 12.58472
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Creatinine,Period 2, Day 4,n=5,5	-6.0112 Micromoles per liter Standard Deviation 12.84693	-2.6520 Micromoles per liter Standard Deviation 14.83172
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Creatinine,Period 2, Day 7,n=6,5	-4.8620 Micromoles per liter Standard Deviation 26.95113	3.7128 Micromoles per liter Standard Deviation 11.43064
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Direct Bilirubin,Period 1, Day 4,n=5,6	-0.684 Micromoles per liter Standard Deviation 0.9366	-0.572 Micromoles per liter Standard Deviation 0.8856
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Direct Bilirubin,Period 1, Day 7,n=5,5	-0.342 Micromoles per liter Standard Deviation 0.7647	-0.344 Micromoles per liter Standard Deviation 1.4331
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Direct Bilirubin,Period 2, Day 4,n=5,5	-0.340 Micromoles per liter Standard Deviation 0.7659	-1.026 Micromoles per liter Standard Deviation 1.5295
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Direct Bilirubin,Period 2, Day 7,n=6,5	-0.285 Micromoles per liter Standard Deviation 0.6981	-0.684 Micromoles per liter Standard Deviation 0.9366
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Total Bilirubin,Period 1, Day 4,n=5,6	1.368 Micromoles per liter Standard Deviation 2.8098	-1.425 Micromoles per liter Standard Deviation 1.6813
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Total Bilirubin,Period 1, Day 7,n=5,6	0.684 Micromoles per liter Standard Deviation 1.9497	0.002 Micromoles per liter Standard Deviation 2.1646
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Total Bilirubin,Period 2, Day 4,n=5,5	-0.000 Micromoles per liter Standard Deviation 3.1991	-5.472 Micromoles per liter Standard Deviation 9.2403
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Total Bilirubin,Period 2, Day 7,n=6,5	-0.285 Micromoles per liter Standard Deviation 1.9991	-5.130 Micromoles per liter Standard Deviation 10.1885
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Uric acid,Period 1, Day 4,n=5,6	-17.8440 Micromoles per liter Standard Deviation 35.43930	18.8353 Micromoles per liter Standard Deviation 47.19830
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Uric acid,Period 1, Day 7,n=5,6	-42.8256 Micromoles per liter Standard Deviation 40.20954	-29.7400 Micromoles per liter Standard Deviation 51.57983
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Uric acid,Period 2, Day 4,n=5,5	-17.8440 Micromoles per liter Standard Deviation 29.44110	-1.1896 Micromoles per liter Standard Deviation 24.66807
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid Uric acid,Period 2, Day 7,n=6,5	25.7747 Micromoles per liter Standard Deviation 111.31927	9.5168 Micromoles per liter Standard Deviation 19.99448

Measure	Placebo n=11 Participants Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 Participants Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Basophils,Period 1, Day 7,n=5,6	0.000 Giga cells per liter Standard Deviation 0.0100	0.010 Giga cells per liter Standard Deviation 0.0358
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Basophils,Period 1, Day 4,n=5,6	0.004 Giga cells per liter Standard Deviation 0.0089	0.007 Giga cells per liter Standard Deviation 0.0320
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Basophils,Period 2, Day 4,n=5,5	-0.002 Giga cells per liter Standard Deviation 0.0110	0.002 Giga cells per liter Standard Deviation 0.0130
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Basophils,Period 2, Day 7,n=6,5	0.002 Giga cells per liter Standard Deviation 0.0098	-0.004 Giga cells per liter Standard Deviation 0.0089
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Eosinophils,Period 1, Day 4,n=5,6	0.042 Giga cells per liter Standard Deviation 0.0239	0.033 Giga cells per liter Standard Deviation 0.0859
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Eosinophils,Period 1, Day 7,n=5,6	0.058 Giga cells per liter Standard Deviation 0.0512	0.038 Giga cells per liter Standard Deviation 0.0412
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Eosinophils,Period 2, Day 4,n=5,5	-0.012 Giga cells per liter Standard Deviation 0.0482	-0.022 Giga cells per liter Standard Deviation 0.0920
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Eosinophils,Period 2, Day 7,n=6,5	-0.007 Giga cells per liter Standard Deviation 0.0301	-0.018 Giga cells per liter Standard Deviation 0.1154
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Lymphocytes,Period 1, Day 4,n=5,6	0.128 Giga cells per liter Standard Deviation 0.2876	-0.110 Giga cells per liter Standard Deviation 0.4315
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Lymphocytes,Period 1, Day 7,n=5,6	0.054 Giga cells per liter Standard Deviation 0.1014	-0.122 Giga cells per liter Standard Deviation 0.4964
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Lymphocytes,Period 2, Day 4,n=5,5	-0.024 Giga cells per liter Standard Deviation 0.1636	0.098 Giga cells per liter Standard Deviation 0.3725
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Lymphocytes,Period 2, Day 7,n=6,5	0.025 Giga cells per liter Standard Deviation 0.1512	0.126 Giga cells per liter Standard Deviation 0.2508
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Monocytes,Period 1, Day 4,n=5,6	-0.044 Giga cells per liter Standard Deviation 0.0611	-0.082 Giga cells per liter Standard Deviation 0.1628
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Monocytes,Period 1, Day 7,n=5,6	0.006 Giga cells per liter Standard Deviation 0.0853	0.012 Giga cells per liter Standard Deviation 0.1700
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Monocytes,Period 2, Day 4,n=5,5	-0.064 Giga cells per liter Standard Deviation 0.1236	-0.014 Giga cells per liter Standard Deviation 0.1150
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Monocytes,Period 2, Day 7,n=6,5	-0.015 Giga cells per liter Standard Deviation 0.1280	0.008 Giga cells per liter Standard Deviation 0.1087
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Platelet count,Period 1, Day 4,n=5,6	-1.0 Giga cells per liter Standard Deviation 9.87	-3.2 Giga cells per liter Standard Deviation 27.26
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Platelet count,Period 1, Day 7,n=5,6	-0.8 Giga cells per liter Standard Deviation 17.46	-2.7 Giga cells per liter Standard Deviation 25.23
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Platelet count,Period 2, Day 4,n=5,5	-12.8 Giga cells per liter Standard Deviation 9.36	1.0 Giga cells per liter Standard Deviation 12.79
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Platelet count,Period 2, Day 7,n=6,5	-6.7 Giga cells per liter Standard Deviation 21.50	9.0 Giga cells per liter Standard Deviation 18.40
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils WBC,Period 1, Day 4,n=5,6	0.614 Giga cells per liter Standard Deviation 1.2143	-0.100 Giga cells per liter Standard Deviation 1.3130
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils WBC,Period 1, Day 7,n=5,6	0.034 Giga cells per liter Standard Deviation 0.6344	0.250 Giga cells per liter Standard Deviation 0.8118
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils WBC,Period 2, Day 4,n=5,5	0.156 Giga cells per liter Standard Deviation 0.6105	0.252 Giga cells per liter Standard Deviation 1.0176
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils WBC,Period 2, Day 7,n=6,5	-0.252 Giga cells per liter Standard Deviation 0.6902	0.064 Giga cells per liter Standard Deviation 0.3369
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Total Neutrophils,Period 1, Day 4,n=5,6	0.472 Giga cells per liter Standard Deviation 1.0817	0.043 Giga cells per liter Standard Deviation 0.8491
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Total Neutrophils,Period 1, Day 7,n=5,6	-0.064 Giga cells per liter Standard Deviation 0.6789	0.345 Giga cells per liter Standard Deviation 0.4476
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Total Neutrophils,Period 2, Day 4,n=5,5	0.252 Giga cells per liter Standard Deviation 0.6034	0.162 Giga cells per liter Standard Deviation 0.8436
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils Total Neutrophils,Period 2, Day 7,n=6,5	-0.267 Giga cells per liter Standard Deviation 0.6555	-0.080 Giga cells per liter Standard Deviation 0.5928

Measure	Placebo n=11 participants at risk Participants received placebo capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.	GSK2798745 2.4 mg n=11 participants at risk Participants received GSK2798745 2.4 mg capsule orally once daily with 240 mL water for a period of 7 days in Periods 1 and 2.
Musculoskeletal and connective tissue disorders Arthralgia	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Nervous system disorders Dizziness	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Nervous system disorders Headache	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Nervous system disorders Neuropathy peripheral	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Cardiac disorders Ventricular extrasystoles	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Cardiac disorders Ventricular tachycardia	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Eye disorders Lacrimation increased	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Eye disorders Visual impairment	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Eye disorders Vitreous haemorrhage	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
General disorders Chest pain	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
General disorders Cyst	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Vascular disorders Hypotension	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Ear and labyrinth disorders Ear discomfort	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Gastrointestinal disorders Nausea	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Hepatobiliary disorders Liver injury	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Injury, poisoning and procedural complications Fall	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Psychiatric disorders Nightmare	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.	9.1% 1/11 • AEs and SAEs were collected from the start of study treatment until follow-up (Up to 46 days) All subject population was used to collect adverse events.