Trial Outcomes & Findings for Dose Response of 28 Days of Dosing of GSK962040 in Type I and II Diabetic Male and Female Subjects With Gastroparesis (NCT NCT01262898)

Last Updated: 2021-07-15

Results Overview

Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 28, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes(min) later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28

Results posted on

2021-07-15

Participant Flow

A total of 80 participants were enrolled and randomized from 03 May 2011 to 26 Feb 2013. The study was conducted at 22 centers, 1 center in Australia, 1 center in Sweden, 2 centers in Belgium, 4 centers in Canada, 5 Centers in United Kingdom and 9 centers in United States.

Out of 80 participants randomized, 1 participant withdrew consent prior to dosing in GSK962040 50 milligram (mg) arm. Remaining 79 participants were included in "All subject population"

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Overall Study STARTED	21	18	18	22
Overall Study COMPLETED	18	16	18	22
Overall Study NOT COMPLETED	3	2	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.
Overall Study Protocol Violation	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Dose Response of 28 Days of Dosing of GSK962040 in Type I and II Diabetic Male and Female Subjects With Gastroparesis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.	Total n=79 Participants Total of all reporting groups
Age, Continuous	54.6 Years STANDARD_DEVIATION 14.23 • n=93 Participants	54.0 Years STANDARD_DEVIATION 11.42 • n=4 Participants	55.2 Years STANDARD_DEVIATION 12.17 • n=27 Participants	51.4 Years STANDARD_DEVIATION 11.34 • n=483 Participants	53.7 Years STANDARD_DEVIATION 12.22 • n=36 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	14 Participants n=4 Participants	10 Participants n=27 Participants	9 Participants n=483 Participants	47 Participants n=36 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	4 Participants n=4 Participants	8 Participants n=27 Participants	13 Participants n=483 Participants	32 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	3 Participants n=36 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	4 Participants n=36 Participants
Race (NIH/OMB) White	19 Participants n=93 Participants	15 Participants n=4 Participants	17 Participants n=27 Participants	20 Participants n=483 Participants	71 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants

PRIMARY outcome

Timeframe: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28

Population: The 'All Subjects Population' compromised of all participants who received at least one dose of study medication. Only those participants available at specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Gastric Half Emptying Time (GEt1/2) Baseline	131.2 Minutes Standard Deviation 25.31	106.5 Minutes Standard Deviation 23.42	118.2 Minutes Standard Deviation 31.13	131.1 Minutes Standard Deviation 32.66
Gastric Half Emptying Time (GEt1/2) Day 1	124.1 Minutes Standard Deviation 39.25	106.6 Minutes Standard Deviation 27.07	104.8 Minutes Standard Deviation 21.61	99.4 Minutes Standard Deviation 33.55
Gastric Half Emptying Time (GEt1/2) Day 28	111.8 Minutes Standard Deviation 24.37	111.8 Minutes Standard Deviation 32.23	107.9 Minutes Standard Deviation 29.03	117.8 Minutes Standard Deviation 44.20

SECONDARY outcome

Timeframe: Up to follow-up (5-10 days post last dose)

Population: All Subjects population.

An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Data for on-treatment adverse events is reported.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) Any on-treatment AEs	13 Participants	14 Participants	13 Participants	18 Participants
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) Any on-treatment SAEs	1 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position SBP Day 1 3.5 hours	0.6 Millimeters of mercury (mmHg) Standard Deviation 13.68	-1.8 Millimeters of mercury (mmHg) Standard Deviation 17.50	0.8 Millimeters of mercury (mmHg) Standard Deviation 18.07	-2.3 Millimeters of mercury (mmHg) Standard Deviation 8.85
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position SBP Day 28 3.5 hours	3.2 Millimeters of mercury (mmHg) Standard Deviation 12.09	-1.1 Millimeters of mercury (mmHg) Standard Deviation 15.56	4.6 Millimeters of mercury (mmHg) Standard Deviation 16.47	-7.2 Millimeters of mercury (mmHg) Standard Deviation 11.62
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position DBP Day 1 3.5 hours	-2.5 Millimeters of mercury (mmHg) Standard Deviation 8.09	1.1 Millimeters of mercury (mmHg) Standard Deviation 7.45	-0.7 Millimeters of mercury (mmHg) Standard Deviation 8.50	-2.3 Millimeters of mercury (mmHg) Standard Deviation 5.19
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position DBP Day 28 3.5 hours	-0.3 Millimeters of mercury (mmHg) Standard Deviation 4.69	-0.8 Millimeters of mercury (mmHg) Standard Deviation 8.62	2.7 Millimeters of mercury (mmHg) Standard Deviation 6.33	-6.1 Millimeters of mercury (mmHg) Standard Deviation 7.32

SECONDARY outcome

Timeframe: Baseline, Day 1, and Day 8

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Heart rate measurements were taken at pre-dose and 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values . Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position Heart rate Day 1 3.5 hours	-0.3 Beats per minute (BPM) Standard Deviation 7.60	-0.8 Beats per minute (BPM) Standard Deviation 6.64	-0.3 Beats per minute (BPM) Standard Deviation 8.39	2.1 Beats per minute (BPM) Standard Deviation 6.31
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position Heart rate Day 28 3.5 hours	-3.9 Beats per minute (BPM) Standard Deviation 6.86	-1.5 Beats per minute (BPM) Standard Deviation 6.94	1.0 Beats per minute (BPM) Standard Deviation 9.09	0.7 Beats per minute (BPM) Standard Deviation 8.26

SECONDARY outcome

Timeframe: Baseline, Day 1 and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The Baseline value was the Day 1 pre-dose value. ECG parameters included PR interval, QRS duration, QT interval, QTcB, QTcF and RR interval.

Outcome measures

SECONDARY outcome

Timeframe: Screening2/Baseline (Day -30 to -1), Day 1 and 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The clinical concern range (CCR) for SBP was greater than (\<) 85 and less than (\>) 160 and for DBP the range was \<45 and \>100. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Number of Participants Outside the Normal Range for SBP and DBP SBP Screening 3.5 hours < CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP SBP Screening 3.5 hours>CCR	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP SBP Day 1 3.5 hours>CCR	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP SBP Day 28 3.5 hours< CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP SBP Day 28 3.5 hours>CCR	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Day 28 3.5 hours	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP SBP Day 1 3.5 hours< CCR	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Screening 3.5 hours< CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Screening 3.5 hours>CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Day 1 3.5 hours	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Day 1 3.5 hours - 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for SBP and DBP DBP Day 28 3.5 hours - 2	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Screening2/Baseline (Day -30 to -1), Day 1 and 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Heart rate measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The CCR for heart rate was Increase or decrease by less than or equal to (\>=) 15 and \>= 30. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Number of Participants Outside the Normal Range for Heart Rate Heart rate Day 28 3.5 hours> CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for Heart Rate Heart rate Screening 3.5 hours <CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for Heart Rate Heart rate Screening 3.5 hours >CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for Heart Rate Heart rate Day 1 3.5 hours <CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for Heart Rate Heart rate Day 1 3.5 hours >CCR	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for Heart Rate Heart rate Day 28 3.5 hours<CCR	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose), Day 1, Day 14 and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The CCR for ECG parameters were: PR interval (\<110 and \>220), QRS interval (\<75 and \>110), Absolute QTc interval (\>450 to =\< 480) respectively. Baseline was the pre-dose reading for Day 1. Data for abnormal- clinically significant (ACS) and abnormal- not clinically significant (ANCS) has been presented.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Number of Participants Outside the Normal Range for 12-lead ECG Day 28 1.5 hour ANCS	7 Participants	6 Participants	5 Participants	5 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 28 pre-dose ACS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 1 pre-dose ANCS	6 Participants	7 Participants	6 Participants	5 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 1 pre-dose ACS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 1 1.5 hour ANCS	6 Participants	8 Participants	6 Participants	6 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 1 1.5 hour ACS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 14 pre-dose ANCS	7 Participants	7 Participants	5 Participants	7 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 14 pre-dose ACS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 28 pre-dose ANCS	7 Participants	5 Participants	4 Participants	5 Participants
Number of Participants Outside the Normal Range for 12-lead ECG Day 28 1.5 hour ACS	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Alkaline phosphatase, alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase, creatine kinase, lactate dehydrogenase measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Direct Bilirubin, Total Bilirubin, Creatinine, Uric acid measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Direct Bilirubin Day 5	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.75	-0.2 Unit moles per litre (UMOL/L) Standard Deviation 1.27	-0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.62	-0.0 Unit moles per litre (UMOL/L) Standard Deviation 1.38
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Direct Bilirubin Day 10	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.75	0.0 Unit moles per litre (UMOL/L) Standard Deviation 1.65	-0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.75	-0.0 Unit moles per litre (UMOL/L) Standard Deviation 1.10
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Direct Bilirubin Day 14	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.57	0.1 Unit moles per litre (UMOL/L) Standard Deviation 1.19	-0.2 Unit moles per litre (UMOL/L) Standard Deviation 0.70	-0.0 Unit moles per litre (UMOL/L) Standard Deviation 1.21
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Direct Bilirubin Day 21	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.75	0.2 Unit moles per litre (UMOL/L) Standard Deviation 1.35	-0.2 Unit moles per litre (UMOL/L) Standard Deviation 0.90	0.1 Unit moles per litre (UMOL/L) Standard Deviation 1.03
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Direct Bilirubin Day 28	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.74	0.3 Unit moles per litre (UMOL/L) Standard Deviation 1.57	0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.98	-0.1 Unit moles per litre (UMOL/L) Standard Deviation 0.84
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Total Bilirubin Day 5	0.2 Unit moles per litre (UMOL/L) Standard Deviation 2.43	0.4 Unit moles per litre (UMOL/L) Standard Deviation 2.71	-2.6 Unit moles per litre (UMOL/L) Standard Deviation 3.41	-0.5 Unit moles per litre (UMOL/L) Standard Deviation 3.19
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Total Bilirubin Day 10	-0.4 Unit moles per litre (UMOL/L) Standard Deviation 2.25	-0.1 Unit moles per litre (UMOL/L) Standard Deviation 3.13	-1.8 Unit moles per litre (UMOL/L) Standard Deviation 4.83	-0.4 Unit moles per litre (UMOL/L) Standard Deviation 2.57
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Total Bilirubin Day 14	0.5 Unit moles per litre (UMOL/L) Standard Deviation 2.41	0.2 Unit moles per litre (UMOL/L) Standard Deviation 2.99	-2.1 Unit moles per litre (UMOL/L) Standard Deviation 3.15	-0.3 Unit moles per litre (UMOL/L) Standard Deviation 2.99
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Total Bilirubin Day 21	-0.6 Unit moles per litre (UMOL/L) Standard Deviation 2.53	0.4 Unit moles per litre (UMOL/L) Standard Deviation 3.72	-1.2 Unit moles per litre (UMOL/L) Standard Deviation 3.49	-0.2 Unit moles per litre (UMOL/L) Standard Deviation 1.99
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Total Bilirubin, Day 28	0.0 Unit moles per litre (UMOL/L) Standard Deviation 1.87	1.2 Unit moles per litre (UMOL/L) Standard Deviation 3.45	-0.6 Unit moles per litre (UMOL/L) Standard Deviation 2.71	-0.9 Unit moles per litre (UMOL/L) Standard Deviation 3.27
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Creatinine Day 28	-2.91 Unit moles per litre (UMOL/L) Standard Deviation 6.156	0.51 Unit moles per litre (UMOL/L) Standard Deviation 7.415	9.42 Unit moles per litre (UMOL/L) Standard Deviation 17.103	9.80 Unit moles per litre (UMOL/L) Standard Deviation 11.993
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid Uric acid Day 28	-8.61 Unit moles per litre (UMOL/L) Standard Deviation 39.359	3.56 Unit moles per litre (UMOL/L) Standard Deviation 32.183	8.62 Unit moles per litre (UMOL/L) Standard Deviation 25.412	18.29 Unit moles per litre (UMOL/L) Standard Deviation 39.987

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Albumin, Total Protein measurements were taken at Baseline (Day 1 pre-dose), and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein Total Protein Day 28	-0.3 Grams per liter (g/L) Standard Deviation 3.79	0.7 Grams per liter (g/L) Standard Deviation 2.94	1.0 Grams per liter (g/L) Standard Deviation 2.68	-0.5 Grams per liter (g/L) Standard Deviation 4.53
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein Albumin Day 28	-0.68 Grams per liter (g/L) Standard Deviation 2.335	0.49 Grams per liter (g/L) Standard Deviation 2.040	0.11 Grams per liter (g/L) Standard Deviation 1.323	-0.66 Grams per liter (g/L) Standard Deviation 2.308

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon dioxide content/Bicarbonate measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Calcium Day 28	-0.018 Millimoles per liter (MMOL/L) Standard Deviation 0.1067	-0.017 Millimoles per liter (MMOL/L) Standard Deviation 0.0764	0.027 Millimoles per liter (MMOL/L) Standard Deviation 0.0666	-0.031 Millimoles per liter (MMOL/L) Standard Deviation 0.1323
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Glucose Day 28	-0.21 Millimoles per liter (MMOL/L) Standard Deviation 4.343	0.24 Millimoles per liter (MMOL/L) Standard Deviation 3.638	0.66 Millimoles per liter (MMOL/L) Standard Deviation 6.790	-0.25 Millimoles per liter (MMOL/L) Standard Deviation 2.332
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Potassium Day 28	-0.042 Millimoles per liter (MMOL/L) Standard Deviation 0.3564	0.094 Millimoles per liter (MMOL/L) Standard Deviation 0.6002	-0.111 Millimoles per liter (MMOL/L) Standard Deviation 0.5132	-0.068 Millimoles per liter (MMOL/L) Standard Deviation 0.3999
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Chloride Day 28	0.26 Millimoles per liter (MMOL/L) Standard Deviation 3.754	-0.93 Millimoles per liter (MMOL/L) Standard Deviation 3.137	-0.94 Millimoles per liter (MMOL/L) Standard Deviation 2.578	0.15 Millimoles per liter (MMOL/L) Standard Deviation 2.759
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Sodium Day 28	-0.42 Millimoles per liter (MMOL/L) Standard Deviation 3.203	-0.41 Millimoles per liter (MMOL/L) Standard Deviation 2.303	-0.56 Millimoles per liter (MMOL/L) Standard Deviation 2.833	0.00 Millimoles per liter (MMOL/L) Standard Deviation 1.718
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Urea/BUN Day 28	-0.35 Millimoles per liter (MMOL/L) Standard Deviation 2.021	-0.31 Millimoles per liter (MMOL/L) Standard Deviation 1.778	-0.04 Millimoles per liter (MMOL/L) Standard Deviation 1.942	0.26 Millimoles per liter (MMOL/L) Standard Deviation 2.016
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate Carbon dioxide content/Bicarbonate Day 28	-0.21 Millimoles per liter (MMOL/L) Standard Deviation 1.843	-0.79 Millimoles per liter (MMOL/L) Standard Deviation 2.286	1.17 Millimoles per liter (MMOL/L) Standard Deviation 2.526	-0.08 Millimoles per liter (MMOL/L) Standard Deviation 2.298

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet count, White Blood cell count measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Platelet count Day 28	6.4 Giga (10^9) cells per liter (GI/L) Standard Deviation 32.76	1.5 Giga (10^9) cells per liter (GI/L) Standard Deviation 35.37	0.6 Giga (10^9) cells per liter (GI/L) Standard Deviation 28.87	-2.0 Giga (10^9) cells per liter (GI/L) Standard Deviation 21.58
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Basophils Day 28	0.0066 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.03852	-0.0388 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.09539	-0.0322 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.07998	0.1072 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.43592
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Eosinophils Day 28	-0.0167 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.07137	0.0431 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.11412	-0.0040 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.18975	0.1173 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.41877
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Lymphocytes Day 28	0.0485 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.44972	-0.0561 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.45151	0.1887 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.31662	-0.0099 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.34075
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Monocytes Day 28	-0.0327 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.16668	-0.0530 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.09965	-0.0097 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.17272	-0.0298 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.10623
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count Total Neutrophils Day 28	0.1380 Giga (10^9) cells per liter (GI/L) Standard Deviation 0.78256	0.2159 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.28307	0.2949 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.20093	-0.7640 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.97899
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count White Blood cell count Day 28	0.144 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.0951	0.225 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.4369	0.428 Giga (10^9) cells per liter (GI/L) Standard Deviation 1.0110	-0.730 Giga (10^9) cells per liter (GI/L) Standard Deviation 2.0794

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Hematocrit measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=16 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Hematocrit	-0.0025 Ratio Standard Deviation 0.01692	0.0021 Ratio Standard Deviation 0.01053	0.0019 Ratio Standard Deviation 0.01508	-0.0059 Ratio Standard Deviation 0.01637

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Mean Corpuscle Hemoglobin measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=14 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=15 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=19 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin	0.05 Picograms (Pg) Standard Deviation 0.521	0.15 Picograms (Pg) Standard Deviation 0.454	-0.15 Picograms (Pg) Standard Deviation 0.667	-0.14 Picograms (Pg) Standard Deviation 0.643

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Hemoglobin, Mean Corpuscle Hemoglobin concentration measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration Hemoglobin Day 28	0.4 g/L Standard Deviation 5.36	1.1 g/L Standard Deviation 4.63	-0.2 g/L Standard Deviation 5.46	-2.7 g/L Standard Deviation 5.11
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration Mean Corpuscle Hemoglobin concentration Day 28	2.8 g/L Standard Deviation 6.20	1.6 g/L Standard Deviation 4.92	-2.8 g/L Standard Deviation 6.53	-1.9 g/L Standard Deviation 7.81

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Mean Corpuscle Volume measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=16 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume	-0.52 Femtoliters (FL) Standard Deviation 0.952	-0.24 Femtoliters (FL) Standard Deviation 1.163	0.43 Femtoliters (FL) Standard Deviation 1.514	0.13 Femtoliters (FL) Standard Deviation 1.318

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Red Blood Cell count, Reticulocytes measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes Red Blood Cell count Day 28	0.003 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.2015	0.035 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.1399	0.003 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.1597	-0.072 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.1660
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes Reticulocytes Day 28	-0.0080 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.02949	-0.0051 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.01418	0.0070 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.01919	-0.0050 Tera (10^12) cells per liter (TI/L) Standard Deviation 0.01937

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: The 'Pharmacokinetic (PK) Population' was defined as participants in the 'All subjects' population for whom a PK sample was obtained and analyzed. Only those participants available at specified time points were analyzed.

AUC(0-t) was derived from GSK962040 plasma concentration-time data. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.Only participants who received GSK962040 drug were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=22 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points Day 1	854.9 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 36.6	4083.1 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 23.6	12911.9 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 30.0	—
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points Day 28	1908.1 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 46.1	7347.2 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 24.3	22173.3 Nanograms.hour/milliliter (ng.h/mL) Geometric Coefficient of Variation 31.8	—

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: PK population. Only those participants available at specified time points were analyzed.

Cmax is defined as the maximum observed drug concentration after administration. Cmax was determined directly from the raw concentration-time data. Samples were collected at the following times: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=22 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Maximum Observed Concentration (Cmax) at Specified Time Points Day 28	131.71 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.9	530.97 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 34.0	1703.29 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 38.0	—
Maximum Observed Concentration (Cmax) at Specified Time Points Day 1	70.21 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 54.7	385.73 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 27.6	1239.62 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 40.0	—

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: PK population. Only those participants available at specified time points were analyzed.

Tmax is defined as the time to reach the observed maximum concentration. Samples were collected at the following times: Tmax was determined directly from the raw concentration-time data. Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=22 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Time of Occurrence of Cmax (Tmax) at Specified Time Points Day 1	2.174 Hour Standard Deviation 0.9066	2.238 Hour Standard Deviation 1.0697	2.092 Hour Standard Deviation 0.8419	—
Time of Occurrence of Cmax (Tmax) at Specified Time Points Day 28	2.189 Hour Standard Deviation 1.3976	2.168 Hour Standard Deviation 0.7224	2.026 Hour Standard Deviation 1.2038	—

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: PK population.

Analysis of pre-dose (trough) concentration at the end of the dosing interval (Ct) was planned to be performed from the samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=22 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points Day 14	63.73 Liters Standard Deviation 34.853	214.26 Liters Standard Deviation 146.572	537.23 Liters Standard Deviation 290.370	—
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points Day 28	62.60 Liters Standard Deviation 32.830	205.03 Liters Standard Deviation 84.251	597.39 Liters Standard Deviation 321.225	—

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: PK Population. The data for this outcome measure was not collected.

CL/F was calculated as dose/AUC. The parameter was planned to be analyzed from samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however the data for this outcome measure was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28

Population: PK Population. The data for this outcome measure was not collected.

The apparent volume of distribution V/F = CL/F × MRT, where MRT is the mean residence time. The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.

Population: PK Population. The data for this outcome measure was not collected.

This outcome measure was not analyzed in results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Day 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

The time to first bowel movement was calculated as the time of the first bowel movement after the first dose in hours (floored) for each participant. If a participant had fewer than 5 days worth of data then the daily mean for that week was set to missing for the following two parameters: Bowel Movement Count and Stool Consistency. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics of time to first bowel movement.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=12 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=15 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=12 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Time to First Bowel Movement After First Dose	28.94 hours Standard Deviation 25.044	53.98 hours Standard Deviation 67.901	17.52 hours Standard Deviation 19.286	15.73 hours Standard Deviation 15.648

SECONDARY outcome

Timeframe: Up to Week 4 (Day 28)

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Daily bowel movement frequency analyzed number of times passed stools in 24 hours of duration. Following dosing with study medication, stool monitoring was performed up to Day 28. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Daily Bowel Movement Frequency Week 1	1.30 Bowel movements/24 hours Standard Deviation 0.872	1.33 Bowel movements/24 hours Standard Deviation 0.812	1.50 Bowel movements/24 hours Standard Deviation 0.943	1.39 Bowel movements/24 hours Standard Deviation 0.729
Daily Bowel Movement Frequency Week 2	2.23 Bowel movements/24 hours Standard Deviation 3.473	1.59 Bowel movements/24 hours Standard Deviation 0.948	1.55 Bowel movements/24 hours Standard Deviation 1.012	1.45 Bowel movements/24 hours Standard Deviation 0.883
Daily Bowel Movement Frequency Week 3	2.18 Bowel movements/24 hours Standard Deviation 3.269	1.44 Bowel movements/24 hours Standard Deviation 0.830	1.77 Bowel movements/24 hours Standard Deviation 1.172	1.38 Bowel movements/24 hours Standard Deviation 0.770
Daily Bowel Movement Frequency Week 4	2.11 Bowel movements/24 hours Standard Deviation 3.432	1.54 Bowel movements/24 hours Standard Deviation 0.841	1.68 Bowel movements/24 hours Standard Deviation 1.049	1.37 Bowel movements/24 hours Standard Deviation 0.831

SECONDARY outcome

Timeframe: Up to Week 4 (Day 28)

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

Stool consistency was determined on a scale of 1 to 5 (1 = Very hard, 2 = Hard, 3 = Formed, 4 = Loose, 5 = Watery). Following dosing with study medication, stool monitoring was performed up to Day 28. Participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Daily Average Stool Consistency Week 3	2.89 Bowel Movements/ 24 hours Standard Deviation 0.517	2.87 Bowel Movements/ 24 hours Standard Deviation 0.889	2.99 Bowel Movements/ 24 hours Standard Deviation 0.558	3.26 Bowel Movements/ 24 hours Standard Deviation 0.683
Daily Average Stool Consistency Week 1	2.91 Bowel Movements/ 24 hours Standard Deviation 0.817	3.24 Bowel Movements/ 24 hours Standard Deviation 0.524	2.80 Bowel Movements/ 24 hours Standard Deviation 0.815	3.71 Bowel Movements/ 24 hours Standard Deviation 0.874
Daily Average Stool Consistency Week 2	2.98 Bowel Movements/ 24 hours Standard Deviation 0.730	2.81 Bowel Movements/ 24 hours Standard Deviation 0.673	3.05 Bowel Movements/ 24 hours Standard Deviation 0.798	3.29 Bowel Movements/ 24 hours Standard Deviation 0.724
Daily Average Stool Consistency Week 4	2.92 Bowel Movements/ 24 hours Standard Deviation 0.528	2.96 Bowel Movements/ 24 hours Standard Deviation 0.625	2.98 Bowel Movements/ 24 hours Standard Deviation 0.502	3.37 Bowel Movements/ 24 hours Standard Deviation 0.569

SECONDARY outcome

Timeframe: Up to 14 days post last dose (Day 28)

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

GCSI-DD was measured on a 6-point scale. The Total GCSI-DD score was the mean of the following three subscales: Nausea/Vomiting Subscale = mean (nausea, retching, vomiting), Fullness/Early Satiety Subscale = mean (feeling excessively full after meals, not able to finish a normal-sized meal, stomach fullness, loss of appetite), Bloating Subscale = mean (bloating, stomach or belly visibly larger). Each subscale was scored on a severity scale of 0 (none) to 5 (very severe), with lower scores representing less symptom severity. The change from Baseline to each study week in average score was derived and if it improved by 1 point or more, that participant was defined as "responder" for that symptom and on that particular week. Baseline was Screening2/Baseline values (Day -30 to -1). Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 3	-0.75 Score on a scale Standard Deviation 0.770	-1.29 Score on a scale Standard Deviation 0.936	-1.16 Score on a scale Standard Deviation 0.745	-0.77 Score on a scale Standard Deviation 0.654
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 5	-0.87 Score on a scale Standard Deviation 0.951	-1.19 Score on a scale Standard Deviation 0.906	-1.07 Score on a scale Standard Deviation 0.738	-0.74 Score on a scale Standard Deviation 0.728
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 6	-0.85 Score on a scale Standard Deviation 0.943	-0.96 Score on a scale Standard Deviation 1.000	-0.86 Score on a scale Standard Deviation 0.632	-0.59 Score on a scale Standard Deviation 0.776
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 1	-0.48 Score on a scale Standard Deviation 0.645	-0.46 Score on a scale Standard Deviation 0.676	-0.58 Score on a scale Standard Deviation 0.379	-0.57 Score on a scale Standard Deviation 0.491
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 2	-0.68 Score on a scale Standard Deviation 0.728	-1.04 Score on a scale Standard Deviation 1.062	-1.21 Score on a scale Standard Deviation 0.663	-0.72 Score on a scale Standard Deviation 0.597
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) Week 4	-0.86 Score on a scale Standard Deviation 1.001	-1.32 Score on a scale Standard Deviation 0.980	-1.12 Score on a scale Standard Deviation 0.670	-0.82 Score on a scale Standard Deviation 0.727

SECONDARY outcome

Timeframe: Baseline(Screening i.e., Day -30 to -1), Day 1 and 28

Population: All Subjects Population. Only those participants available at specified time points were analyzed.

WMC is an ingestible telemetric capsule which measures pH, pressure and temperature to assess total gastric emptying time, small and large bowel transit time, colonic transit time, and whole gut transit time. The WMC was ingested immediately following the standard test meal for the oral breath test. Data was collected on a data logger, which was worn on a belt clip. The WMC passed naturally in the participant's stools between 2 and 5 days after ingestion. The parameters Whole bowel transit time, 100 % gastric emptying time (truncated at 240 minutes), small bowel transit time, colonic transit time were analyzed. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) 100% Gastric Emptying Time Day 1	-159.9 minutes Standard Deviation 616.67	-240.3 minutes Standard Deviation 567.18	-323.8 minutes Standard Deviation 461.05	-381.0 minutes Standard Deviation 541.73
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) 100% Gastric Emptying Time Day 28	-243.0 minutes Standard Deviation 500.49	-15.4 minutes Standard Deviation 502.80	-162.7 minutes Standard Deviation 558.96	-341.3 minutes Standard Deviation 599.52
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) 100% Gastric Emptying Time(Truncated) Day 1	2.7 minutes Standard Deviation 27.95	3.7 minutes Standard Deviation 28.87	-15.8 minutes Standard Deviation 61.32	-65.5 minutes Standard Deviation 91.11
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) 100% Gastric Emptying Time(Truncated) Day 28	-10.7 minutes Standard Deviation 18.60	19.7 minutes Standard Deviation 42.47	-13.9 minutes Standard Deviation 42.34	-40.2 minutes Standard Deviation 68.66
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Colonic Transit Time Day 1	-331.3 minutes Standard Deviation 1349.11	-92.9 minutes Standard Deviation 1970.38	-170.5 minutes Standard Deviation 1723.01	-598.3 minutes Standard Deviation 1617.05
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Colonic Transit Time Day 28	-518.1 minutes Standard Deviation 2650.06	142.9 minutes Standard Deviation 1326.20	-29.4 minutes Standard Deviation 1702.69	-416.4 minutes Standard Deviation 1447.79
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Small Bowel Transit Time Day 1	-24.5 minutes Standard Deviation 118.39	-47.7 minutes Standard Deviation 94.33	15.7 minutes Standard Deviation 211.88	-6.6 minutes Standard Deviation 149.11
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Small Bowel Transit Time 28	-76.4 minutes Standard Deviation 107.89	-57.3 minutes Standard Deviation 176.42	-7.1 minutes Standard Deviation 148.51	-28.6 minutes Standard Deviation 135.44
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Whole Bowel Transit Time Day 1	-527.6 minutes Standard Deviation 1489.02	-402.1 minutes Standard Deviation 2109.06	-493.1 minutes Standard Deviation 1987.51	-1002.5 minutes Standard Deviation 2045.60
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) Whole Bowel Transit Time 28	-777.6 minutes Standard Deviation 2644.80	-2.4 minutes Standard Deviation 1298.37	-233.5 minutes Standard Deviation 1850.91	-789.1 minutes Standard Deviation 1560.06

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

GSK962040 10 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

GSK962040 50 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

GSK962040 125 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 participants at risk Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 participants at risk Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 participants at risk Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.00% 0/21 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	0.00% 0/18 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	5.6% 1/18 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	0.00% 0/22 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.8% 1/21 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	0.00% 0/18 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	0.00% 0/18 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.	0.00% 0/22 • Up to follow-up i.e., 14 days ± 2 days post last dose (Day 28) All Subjects population was used to assess adverse events.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcB Day 1 1.5 hours	-2.84 Milliseconds (msec) Standard Deviation 13.906	-1.94 Milliseconds (msec) Standard Deviation 13.721	-2.45 Milliseconds (msec) Standard Deviation 13.447	-0.12 Milliseconds (msec) Standard Deviation 15.771
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcF Day 14 pre-dose	-1.02 Milliseconds (msec) Standard Deviation 11.942	-5.57 Milliseconds (msec) Standard Deviation 12.599	-5.91 Milliseconds (msec) Standard Deviation 19.109	-4.37 Milliseconds (msec) Standard Deviation 13.314
Change From Baseline in Electrocardiography Parameters (12-lead ECG) RR interval Day 28 pre-dose	18.15 Milliseconds (msec) Standard Deviation 109.227	-31.14 Milliseconds (msec) Standard Deviation 75.740	-3.31 Milliseconds (msec) Standard Deviation 99.049	-11.51 Milliseconds (msec) Standard Deviation 108.680
Change From Baseline in Electrocardiography Parameters (12-lead ECG) RR interval Day 28 1.5 hours	13.96 Milliseconds (msec) Standard Deviation 76.906	-23.69 Milliseconds (msec) Standard Deviation 96.568	-4.08 Milliseconds (msec) Standard Deviation 114.019	-15.60 Milliseconds (msec) Standard Deviation 108.056
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QRS duration Day 28 pre-dose	2.4 Milliseconds (msec) Standard Deviation 4.93	1.1 Milliseconds (msec) Standard Deviation 4.54	-0.3 Milliseconds (msec) Standard Deviation 3.84	1.0 Milliseconds (msec) Standard Deviation 4.81
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QRS duration Day 28 1.5 hours	0.8 Milliseconds (msec) Standard Deviation 4.29	0.6 Milliseconds (msec) Standard Deviation 3.98	-0.3 Milliseconds (msec) Standard Deviation 4.96	0.0 Milliseconds (msec) Standard Deviation 4.97
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QT interval Day 1 1.5 hours	1.0 Milliseconds (msec) Standard Deviation 12.30	-0.2 Milliseconds (msec) Standard Deviation 17.45	-3.8 Milliseconds (msec) Standard Deviation 13.16	1.6 Milliseconds (msec) Standard Deviation 12.64
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QT interval Day 14 pre-dose	-8.8 Milliseconds (msec) Standard Deviation 18.52	-9.6 Milliseconds (msec) Standard Deviation 19.11	-10.7 Milliseconds (msec) Standard Deviation 25.58	-9.6 Milliseconds (msec) Standard Deviation 19.87
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QT interval Day 28 pre-dose	0.3 Milliseconds (msec) Standard Deviation 21.83	-5.0 Milliseconds (msec) Standard Deviation 21.36	-2.0 Milliseconds (msec) Standard Deviation 23.20	-3.0 Milliseconds (msec) Standard Deviation 20.29
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QT interval Day 28 1.5 hours	4.9 Milliseconds (msec) Standard Deviation 16.37	-2.8 Milliseconds (msec) Standard Deviation 22.18	-1.3 Milliseconds (msec) Standard Deviation 26.49	-4.5 Milliseconds (msec) Standard Deviation 21.38
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcB Day 14 pre-dose	3.23 Milliseconds (msec) Standard Deviation 11.503	-2.97 Milliseconds (msec) Standard Deviation 12.075	-2.68 Milliseconds (msec) Standard Deviation 18.410	-1.42 Milliseconds (msec) Standard Deviation 16.245
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcB Day 28 pre-dose	-3.85 Milliseconds (msec) Standard Deviation 20.907	2.71 Milliseconds (msec) Standard Deviation 9.741	1.31 Milliseconds (msec) Standard Deviation 18.419	-0.20 Milliseconds (msec) Standard Deviation 15.062
Change From Baseline in Electrocardiography Parameters (12-lead ECG) PR interval Day 1 1.5 hours	-2.6 Milliseconds (msec) Standard Deviation 10.40	3.2 Milliseconds (msec) Standard Deviation 7.46	0.5 Milliseconds (msec) Standard Deviation 13.03	-0.9 Milliseconds (msec) Standard Deviation 9.68
Change From Baseline in Electrocardiography Parameters (12-lead ECG) PR interval Day 14 pre-dose	-5.5 Milliseconds (msec) Standard Deviation 7.39	0.6 Milliseconds (msec) Standard Deviation 7.87	-1.6 Milliseconds (msec) Standard Deviation 11.29	-3.1 Milliseconds (msec) Standard Deviation 9.25
Change From Baseline in Electrocardiography Parameters (12-lead ECG) PR interval Day 28 pre-dose	2.4 Milliseconds (msec) Standard Deviation 17.12	-7.1 Milliseconds (msec) Standard Deviation 26.93	2.2 Milliseconds (msec) Standard Deviation 18.32	-0.1 Milliseconds (msec) Standard Deviation 8.14
Change From Baseline in Electrocardiography Parameters (12-lead ECG) PR interval Day 28 1.5 hours	1.2 Milliseconds (msec) Standard Deviation 14.28	0.5 Milliseconds (msec) Standard Deviation 11.48	3.6 Milliseconds (msec) Standard Deviation 16.71	-4.3 Milliseconds (msec) Standard Deviation 9.54
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QRS duration Day 1 1.5 hours	0.2 Milliseconds (msec) Standard Deviation 5.18	-0.6 Milliseconds (msec) Standard Deviation 4.16	0.1 Milliseconds (msec) Standard Deviation 4.07	0.6 Milliseconds (msec) Standard Deviation 5.22
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QRS duration Day 14 pre-dose	0.1 Milliseconds (msec) Standard Deviation 5.26	-0.8 Milliseconds (msec) Standard Deviation 4.33	-0.1 Milliseconds (msec) Standard Deviation 3.57	-0.9 Milliseconds (msec) Standard Deviation 4.97
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcB Day 28 1.5 hours	1.59 Milliseconds (msec) Standard Deviation 24.246	1.86 Milliseconds (msec) Standard Deviation 14.682	-0.16 Milliseconds (msec) Standard Deviation 17.208	-0.88 Milliseconds (msec) Standard Deviation 15.216
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcF Day 1 1.5 hours	-1.52 Milliseconds (msec) Standard Deviation 12.089	-1.26 Milliseconds (msec) Standard Deviation 14.709	-2.84 Milliseconds (msec) Standard Deviation 11.080	0.72 Milliseconds (msec) Standard Deviation 12.418
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcF Day 28 pre-dose	-2.55 Milliseconds (msec) Standard Deviation 18.782	0.04 Milliseconds (msec) Standard Deviation 12.835	0.96 Milliseconds (msec) Standard Deviation 15.942	-1.21 Milliseconds (msec) Standard Deviation 12.490
Change From Baseline in Electrocardiography Parameters (12-lead ECG) QTcF Day 28 1.5 hours	2.70 Milliseconds (msec) Standard Deviation 20.473	-0.24 Milliseconds (msec) Standard Deviation 14.344	-0.64 Milliseconds (msec) Standard Deviation 16.857	-2.17 Milliseconds (msec) Standard Deviation 12.797
Change From Baseline in Electrocardiography Parameters (12-lead ECG) RR interval Day 1 1.5 hours	16.82 Milliseconds (msec) Standard Deviation 56.084	7.26 Milliseconds (msec) Standard Deviation 44.025	-3.26 Milliseconds (msec) Standard Deviation 68.824	8.74 Milliseconds (msec) Standard Deviation 81.926
Change From Baseline in Electrocardiography Parameters (12-lead ECG) RR interval Day 14 pre-dose	-54.61 Milliseconds (msec) Standard Deviation 76.965	-33.95 Milliseconds (msec) Standard Deviation 75.539	-42.92 Milliseconds (msec) Standard Deviation 90.333	-35.25 Milliseconds (msec) Standard Deviation 102.822

Measure	Placebo n=21 Participants Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days.	GSK962040 10 mg n=18 Participants Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days.	GSK962040 50 mg n=18 Participants Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days.	GSK962040 125 mg n=22 Participants Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days.
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alanine Amino Transferase Day 5	0.7 International units per liter (IU/L) Standard Deviation 3.28	2.6 International units per liter (IU/L) Standard Deviation 7.31	2.8 International units per liter (IU/L) Standard Deviation 10.88	-1.1 International units per liter (IU/L) Standard Deviation 16.03
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alanine Amino Transferase Day 28	-1.5 International units per liter (IU/L) Standard Deviation 5.39	1.1 International units per liter (IU/L) Standard Deviation 6.22	-1.2 International units per liter (IU/L) Standard Deviation 6.88	-4.0 International units per liter (IU/L) Standard Deviation 13.60
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Aspartate Amino Transferase Day 10	0.5 International units per liter (IU/L) Standard Deviation 9.08	1.2 International units per liter (IU/L) Standard Deviation 8.27	-2.7 International units per liter (IU/L) Standard Deviation 10.67	2.8 International units per liter (IU/L) Standard Deviation 3.43
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Gamma Glutamyl Transferase Day 28	-1.7 International units per liter (IU/L) Standard Deviation 5.44	0.5 International units per liter (IU/L) Standard Deviation 5.51	0.3 International units per liter (IU/L) Standard Deviation 4.37	4.2 International units per liter (IU/L) Standard Deviation 16.01
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Creatine Kinase Day 28	-4.3 International units per liter (IU/L) Standard Deviation 61.05	41.9 International units per liter (IU/L) Standard Deviation 74.29	42.0 International units per liter (IU/L) Standard Deviation 103.49	0.2 International units per liter (IU/L) Standard Deviation 42.14
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Lactate Dehydrogenase Day 28	-11.5 International units per liter (IU/L) Standard Deviation 38.69	8.6 International units per liter (IU/L) Standard Deviation 31.10	-5.8 International units per liter (IU/L) Standard Deviation 42.29	-16.2 International units per liter (IU/L) Standard Deviation 40.37
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alkaline Phosphatase Day 5	3.0 International units per liter (IU/L) Standard Deviation 7.54	4.3 International units per liter (IU/L) Standard Deviation 7.20	4.0 International units per liter (IU/L) Standard Deviation 9.27	-1.1 International units per liter (IU/L) Standard Deviation 23.56
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alkaline Phosphatase Day 10	2.7 International units per liter (IU/L) Standard Deviation 8.63	5.0 International units per liter (IU/L) Standard Deviation 7.79	2.8 International units per liter (IU/L) Standard Deviation 10.58	-1.3 International units per liter (IU/L) Standard Deviation 26.28
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alkaline Phosphatase Day 14	3.7 International units per liter (IU/L) Standard Deviation 9.17	5.0 International units per liter (IU/L) Standard Deviation 8.16	0.7 International units per liter (IU/L) Standard Deviation 8.70	-4.3 International units per liter (IU/L) Standard Deviation 24.67
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alkaline Phosphatase Day 21	4.3 International units per liter (IU/L) Standard Deviation 15.25	3.9 International units per liter (IU/L) Standard Deviation 9.19	1.7 International units per liter (IU/L) Standard Deviation 11.39	-1.7 International units per liter (IU/L) Standard Deviation 26.96
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alkaline Phosphatase Day 28	1.1 International units per liter (IU/L) Standard Deviation 14.05	3.1 International units per liter (IU/L) Standard Deviation 7.17	-2.5 International units per liter (IU/L) Standard Deviation 14.66	-1.7 International units per liter (IU/L) Standard Deviation 25.23
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alanine Amino Transferase Day 10	0.6 International units per liter (IU/L) Standard Deviation 7.86	2.5 International units per liter (IU/L) Standard Deviation 6.60	-1.2 International units per liter (IU/L) Standard Deviation 4.93	-1.1 International units per liter (IU/L) Standard Deviation 17.05
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alanine Amino Transferase Day 14	2.4 International units per liter (IU/L) Standard Deviation 7.32	2.9 International units per liter (IU/L) Standard Deviation 6.99	-1.0 International units per liter (IU/L) Standard Deviation 6.94	-3.2 International units per liter (IU/L) Standard Deviation 15.94
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Alanine Amino Transferase Day 21	-0.4 International units per liter (IU/L) Standard Deviation 6.74	0.3 International units per liter (IU/L) Standard Deviation 6.09	-0.1 International units per liter (IU/L) Standard Deviation 5.89	-2.9 International units per liter (IU/L) Standard Deviation 14.59
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Aspartate Amino Transferase Day 5	-0.3 International units per liter (IU/L) Standard Deviation 5.68	0.1 International units per liter (IU/L) Standard Deviation 6.73	-1.9 International units per liter (IU/L) Standard Deviation 9.90	1.6 International units per liter (IU/L) Standard Deviation 4.56
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Aspartate Amino Transferase Day 14	2.6 International units per liter (IU/L) Standard Deviation 5.50	-1.1 International units per liter (IU/L) Standard Deviation 6.94	-2.8 International units per liter (IU/L) Standard Deviation 11.35	1.0 International units per liter (IU/L) Standard Deviation 6.36
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Aspartate Amino Transferase Day 21	-1.1 International units per liter (IU/L) Standard Deviation 6.80	-0.3 International units per liter (IU/L) Standard Deviation 6.78	-1.2 International units per liter (IU/L) Standard Deviation 9.55	1.6 International units per liter (IU/L) Standard Deviation 5.12
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Aspartate Amino Transferase Day 28	-0.8 International units per liter (IU/L) Standard Deviation 6.63	0.4 International units per liter (IU/L) Standard Deviation 5.41	-2.7 International units per liter (IU/L) Standard Deviation 9.13	0.5 International units per liter (IU/L) Standard Deviation 6.61
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Gamma Glutamyl Transferase Day 5	-0.5 International units per liter (IU/L) Standard Deviation 2.43	1.8 International units per liter (IU/L) Standard Deviation 4.35	1.6 International units per liter (IU/L) Standard Deviation 6.26	2.4 International units per liter (IU/L) Standard Deviation 8.44
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Gamma Glutamyl Transferase Day 10	-1.1 International units per liter (IU/L) Standard Deviation 2.88	0.5 International units per liter (IU/L) Standard Deviation 4.16	1.8 International units per liter (IU/L) Standard Deviation 7.09	1.2 International units per liter (IU/L) Standard Deviation 6.79
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Gamma Glutamyl Transferase Day 14	-0.2 International units per liter (IU/L) Standard Deviation 4.57	0.4 International units per liter (IU/L) Standard Deviation 3.10	2.1 International units per liter (IU/L) Standard Deviation 6.55	1.5 International units per liter (IU/L) Standard Deviation 8.95
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase Gamma Glutamyl Transferase Day 21	-0.3 International units per liter (IU/L) Standard Deviation 5.11	-1.3 International units per liter (IU/L) Standard Deviation 5.00	1.8 International units per liter (IU/L) Standard Deviation 3.52	2.6 International units per liter (IU/L) Standard Deviation 7.93