Trial Outcomes & Findings for GSK1605786A in the Maintenance of Remission in Subjects With Crohn's Disease (NCT NCT01316939)

NCT ID: NCT01316939

Last Updated: 2017-09-07

Results Overview

Clinical remission is defined as a CDAI score \<150 points. In the missing=no effect imputation, participants with missing CDAI scores was considered not to be in clinical remission. Data for percentage of participants in at both Weeks 28 and 52 of the 52-week treatment period have been presented.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 229 participants
• Primary outcome timeframe: Week 28 and 52
• Results posted on: 2017-09-07

Participant Flow

This study was conducted at 128 centers in 28 countries with sites in North America, Europe, Israel, South Africa, Japan, Republic of Korea, Hong Kong, Australia, and New Zealand from 09 May 2011 and 23 October 2013.

The study was planned to randomize approximately 756 participants (252 participants per group) from induction studies CCX114151 and CCX114643. However a total of 229 participants (159 who participated in study CCX114151 and 70 who participated in study CCX114643) were randomized and comprised the analysis population for this study.

Participant milestones

Measure	Placebo Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 milligram (mg) capsules.	GSK1605786A 500 mg Once Daily Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules twice daily (BID).
Overall Study STARTED	76	77	76
Overall Study COMPLETED	13	9	7
Overall Study NOT COMPLETED	63	68	69

Reasons for withdrawal

Measure	Placebo Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 milligram (mg) capsules.	GSK1605786A 500 mg Once Daily Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules twice daily (BID).
Overall Study Study closed/terminated	26	25	23
Overall Study Lack of Efficacy	24	25	25
Overall Study Adverse Event	9	12	11
Overall Study Withdrawal by Subject	1	3	6
Overall Study Physician Decision	2	2	1
Overall Study Lost to Follow-up	0	0	2
Overall Study Met Liver chemistry stopping criteria	1	0	1
Overall Study Protocol Violation	0	1	0

Baseline Characteristics

GSK1605786A in the Maintenance of Remission in Subjects With Crohn's Disease

Baseline characteristics by cohort

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.	Total n=229 Participants Total of all reporting groups
Age, Continuous	38.2 Years STANDARD_DEVIATION 13.20 • n=5 Participants	36.7 Years STANDARD_DEVIATION 13.00 • n=7 Participants	38.8 Years STANDARD_DEVIATION 12.75 • n=5 Participants	37.9 Years STANDARD_DEVIATION 12.96 • n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	35 Participants n=7 Participants	42 Participants n=5 Participants	123 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	42 Participants n=7 Participants	34 Participants n=5 Participants	106 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants	67 Participants n=7 Participants	69 Participants n=5 Participants	206 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 28 and 52

Population: The Intent-to-Treat (ITT) Population comprised of all participants randomized to treatment who achieved a clinical response (CDAI decrease from baseline of \>=100 points) or achieved clinical remission (CDAI \<150 points).

Clinical remission is defined as a CDAI score <150 points. In the missing=no effect imputation, participants with missing CDAI scores was considered not to be in clinical remission. Data for percentage of participants in at both Weeks 28 and 52 of the 52-week treatment period have been presented.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Percentage of Participants in Clinical Remission (Crohn's Disease Activity Index , CDAI Score <150 Points) at Both Weeks 28 and 52 of the 52-week Treatment Period	10.5 Percentage of Participants	6.5 Percentage of Participants	3.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 28 and 52

Population: ITT Population.

Clinical remission is defined as a CDAI score <150 points. A participant was considered to be not taking corticosteroids at Weeks 28 and 52 if the participant had not taken a corticosteroid for the 8 days prior to and the day of the CDAI assessment for each of Weeks 28 and 52. In the missing=no effect imputation, participants with missing CDAI scores was considered not to be in clinical remission. Data for percentage of participants in clinical remission and not taking corticosteroids at both Weeks 28 and 52 of the 52-week treatment period have been presented.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Percentage of Participants in Clinical Remission (CDAI Score <150 Points) and Not Taking Corticosteroids at Both Weeks 28 and 52 of the 52-week Treatment Period	9.2 Percentage of Participants	5.2 Percentage of Participants	3.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Percentage of participants in clinical remission at both Weeks 28 and 52 of the 52-week treatment period among those participants who were in clinical remission at Baseline was not collected.

Clinical remission is defined as a CDAI score <150 points. Among participants in remission at baseline, the percentage of participants with clinical remission at both Weeks 28 and 52 of the treatment period using the no effect imputation for missing data were to be compared between each GSK1605786A dose group and placebo using Fisher's exact test. Participants with missing CDAI scores were to be considered not to be in remission according to the missing=no effect imputation. The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Upto Week 52

Population: ITT Population. Following early termination of study CCX114157 data for Percentage of participants in clinical remission at all visits (continuous clinical remission) during the 52-week treatment period among participants in clinical remission at Baseline was not collected.

The percentage of participants with clinical remission at all visits during the 52-week treatment period were to be summarized by treatment group for the subset of participants in remission at baseline, using the no effect imputation for missing data. Participants with missing CDAI scores were to be considered not to be in remission according to the missing=no effect imputation. Comparisons between each GSK1605786A dose group and placebo were to be made using Fisher's exact test.The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population. Following early termination of study CCX114157 data for Percentage of participants in clinical remission at Week 52 was not collected.

The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Percentage of participants with a clinical response (CDAI decrease \>=100 points) at both Weeks 28 and 52 of the 52-week treatment period was not collected.

Clinical response is defined as a reduction from the induction study baseline CDAI score of >=100 points. The percentage of participants with a clinical response at both Weeks 28 and 52 of the 52-week maintenance treatment period in the ITT population using the no effect imputation for missing data were to be compared between each GSK1605786A dose group and placebo using Fisher's exact test. Participants with missing CDAI scores were to be considered non-responders according to the missing=no effect imputation. The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Upto Week 52

Population: ITT Population. Following early termination of study CCX114157 data for Time to induction of clinical remission in participants who had achieved clinical response during induction therapy but were not in clinical remission at Baseline was not collected.

The duration of time participants maintained clinical remission during the 52-week treatment period was to be defined as the time between Week 0 and the first visit where remission was not observed in those participants in remission at baseline. These time periods were to be summarized by treatment group using quartiles and their corresponding confidence intervals. Comparisons between each GSK1605786A dose group and placebo were to be made using log-rank tests. The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in CDAI score at Weeks 4, 8, 12, 20, 28, 36, 44, and 52 was not collected.

The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity. CDAI scores and changes in CDAI scores during the 52-week treatment period were to be summarized by treatment group at Weeks 4, 8, 12, 20, 28, 36, 44, and 52. The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 52 was not collected.

The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The IBDQ questionnaire was to be completed by each participant at baseline and at Weeks 28, and 52. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life. The limited data resulting from early termination of Study CCX114157 did not allow any conclusions to be drawn about the efficacy of GSK1605786A in the maintenance of clinical remission in participants with Crohn's disease. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Upto 56 weeks

Population: The Safety Population comprised of all participants in the ITT population except those who did not take at least one dose of investigational product.

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

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	55 Participants	50 Participants	54 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	1 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, 52, 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Vital sign assessments included SBP and DBP collected in supine position following 5 minutes of rest. Assessments were carried out at Weeks 4, 8, 12, 20, 28, 36, 44, 52 and Week 56. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 4	-1.6 Millimeters of mercury Standard Deviation 13.08	-0.9 Millimeters of mercury Standard Deviation 10.15	1.2 Millimeters of mercury Standard Deviation 11.06
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 8	-2.7 Millimeters of mercury Standard Deviation 13.75	0.7 Millimeters of mercury Standard Deviation 12.17	0.5 Millimeters of mercury Standard Deviation 12.91
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 12	-0.9 Millimeters of mercury Standard Deviation 11.93	0.9 Millimeters of mercury Standard Deviation 11.31	1.1 Millimeters of mercury Standard Deviation 13.53
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 20	-3.0 Millimeters of mercury Standard Deviation 12.70	-0.7 Millimeters of mercury Standard Deviation 10.52	2.0 Millimeters of mercury Standard Deviation 9.64
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 28	2.2 Millimeters of mercury Standard Deviation 10.62	1.2 Millimeters of mercury Standard Deviation 10.47	4.6 Millimeters of mercury Standard Deviation 11.63
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 36	0.7 Millimeters of mercury Standard Deviation 13.50	2.1 Millimeters of mercury Standard Deviation 9.49	1.8 Millimeters of mercury Standard Deviation 15.76
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 44	-0.1 Millimeters of mercury Standard Deviation 12.59	-1.6 Millimeters of mercury Standard Deviation 13.35	0.0 Millimeters of mercury Standard Deviation 13.18
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 52	-1.6 Millimeters of mercury Standard Deviation 13.80	1.0 Millimeters of mercury Standard Deviation 9.29	2.3 Millimeters of mercury Standard Deviation 13.25
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 SBP at Week 56	-0.5 Millimeters of mercury Standard Deviation 13.19	-1.3 Millimeters of mercury Standard Deviation 11.21	2.0 Millimeters of mercury Standard Deviation 11.09
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 4	-2.0 Millimeters of mercury Standard Deviation 9.90	-2.0 Millimeters of mercury Standard Deviation 9.54	-0.1 Millimeters of mercury Standard Deviation 9.05
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 8	-0.1 Millimeters of mercury Standard Deviation 10.39	-0.6 Millimeters of mercury Standard Deviation 8.78	-1.3 Millimeters of mercury Standard Deviation 8.03
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 12	-0.4 Millimeters of mercury Standard Deviation 10.22	-1.5 Millimeters of mercury Standard Deviation 6.68	-0.8 Millimeters of mercury Standard Deviation 10.12
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 20	-1.1 Millimeters of mercury Standard Deviation 9.33	-2.0 Millimeters of mercury Standard Deviation 8.31	0.1 Millimeters of mercury Standard Deviation 8.17
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 28	2.4 Millimeters of mercury Standard Deviation 8.00	-1.2 Millimeters of mercury Standard Deviation 10.05	2.0 Millimeters of mercury Standard Deviation 6.13
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 36	-0.2 Millimeters of mercury Standard Deviation 9.94	-0.5 Millimeters of mercury Standard Deviation 10.01	0.8 Millimeters of mercury Standard Deviation 9.04
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 44	0.1 Millimeters of mercury Standard Deviation 12.09	-3.0 Millimeters of mercury Standard Deviation 7.91	-0.1 Millimeters of mercury Standard Deviation 10.29
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 52	-0.7 Millimeters of mercury Standard Deviation 8.99	-1.4 Millimeters of mercury Standard Deviation 8.40	2.4 Millimeters of mercury Standard Deviation 8.00
Change From Baseline in Vital Sign Systolic Blood Pressure Systolic (SBP) and Diastolic Blood Pressure (DBP) Upto Week 56 DBP at Week 56	0.2 Millimeters of mercury Standard Deviation 9.05	0.1 Millimeters of mercury Standard Deviation 7.12	1.3 Millimeters of mercury Standard Deviation 9.53

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 4, 8, 12, 20, 28, 36, 44, 52 and 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Vital sign assessment included heart rate collected in supine position following 5 minutes of rest. Assessments were carried out at Weeks 4, 8, 12, 20, 28, 36, 44, 52 and 56. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 4	1.8 beats per minute Standard Deviation 11.06	-2.2 beats per minute Standard Deviation 11.96	0.0 beats per minute Standard Deviation 10.17
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 8	0.9 beats per minute Standard Deviation 10.85	-0.4 beats per minute Standard Deviation 12.23	-0.2 beats per minute Standard Deviation 12.93
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 12	0.9 beats per minute Standard Deviation 10.27	-2.4 beats per minute Standard Deviation 11.25	-0.5 beats per minute Standard Deviation 11.24
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 20	-1.0 beats per minute Standard Deviation 9.59	-0.8 beats per minute Standard Deviation 14.49	-0.4 beats per minute Standard Deviation 13.83
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 28	1.3 beats per minute Standard Deviation 11.65	0.5 beats per minute Standard Deviation 15.07	-0.7 beats per minute Standard Deviation 11.56
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 36	-2.8 beats per minute Standard Deviation 9.92	2.4 beats per minute Standard Deviation 9.45	2.5 beats per minute Standard Deviation 8.11
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 44	2.0 beats per minute Standard Deviation 10.96	2.6 beats per minute Standard Deviation 5.85	1.4 beats per minute Standard Deviation 11.22
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 52	1.6 beats per minute Standard Deviation 8.87	-0.1 beats per minute Standard Deviation 7.77	4.1 beats per minute Standard Deviation 8.55
Change From Baseline in Vital Sign Heart Rate Upto Week 56 Heart rate at Week 56	-1.1 beats per minute Standard Deviation 8.79	1.5 beats per minute Standard Deviation 12.04	-3.1 beats per minute Standard Deviation 8.43

SECONDARY outcome

Timeframe: Upto Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hematocrit, red blood cell count, hemoglobin, white blood cell count and segmented neutrophils . Assessments were carried out at Weeks 4, 8, 12, 20, 28, 36, 44 and 52 and 56. The consolidated data for number of participants with shift from Baseline (change from Baseline) in hematology parameters characterized as high and low have been presented.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Number of Participants With Shift From Baseline in Hematology Parameters Platelets low	1 Participants	1 Participants	0 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Platelets high	6 Participants	12 Participants	14 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Neutrophils low	3 Participants	2 Participants	1 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Neutrophils high	22 Participants	20 Participants	20 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Lymphocytes low	19 Participants	19 Participants	14 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Lymphocytes high	3 Participants	2 Participants	2 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Monocytes high	7 Participants	4 Participants	7 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Eosinophils high	3 Participants	7 Participants	2 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Basophil high	0 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Hematocrit low	13 Participants	10 Participants	11 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Hematocrit high	1 Participants	1 Participants	2 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Red blood cell count low	8 Participants	6 Participants	9 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Red blood cell count high	1 Participants	0 Participants	2 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Hemoglobin low	15 Participants	13 Participants	11 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Hemoglobin high	1 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline in Hematology Parameters White blood cell count low	4 Participants	5 Participants	7 Participants
Number of Participants With Shift From Baseline in Hematology Parameters White blood cell count high	9 Participants	12 Participants	6 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Segmented neutrophils low	3 Participants	2 Participants	1 Participants
Number of Participants With Shift From Baseline in Hematology Parameters Segmented neutrophils high	22 Participants	20 Participants	20 Participants

SECONDARY outcome

Timeframe: Upto Week 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included total protein, phosphorous, albumin, sodium, potassium, chloride, calcium, glucose, gamma glutamyl transferase, total bilirubin, direct bilirubin, alkaline phosphatase, alanine amino transferase, aspartate amino transferase, blood urea nitrogen (BUN)/Urea, creatinine, uric acid, lactate dehydrogenase, bicarbonate, cholesterol and creatinine kinase. Assessments were carried out at Weeks 4, 8, 12, 20, 28, 36, 44, 52 and 56. The consolidated data for number of participants with shift from Baseline (change from Baseline) in clinical chemistry parameters characterized as high and low have been presented.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Total protein low	3 Participants	7 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Total protein high	0 Participants	1 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Phosphorous low	2 Participants	9 Participants	13 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Phosphorous high	8 Participants	3 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Albumin low	1 Participants	2 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Albumin high	4 Participants	4 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Sodium low	1 Participants	1 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Sodium high	0 Participants	1 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Potassium low	4 Participants	1 Participants	4 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Potassium high	4 Participants	0 Participants	4 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Chloride low	0 Participants	0 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Chloride high	9 Participants	8 Participants	11 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Calcium low	3 Participants	5 Participants	7 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Calcium high	2 Participants	2 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Glucose low	6 Participants	8 Participants	12 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Glucose high	13 Participants	16 Participants	10 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Gamma glutamyl transferase high	5 Participants	6 Participants	10 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Total bilirubin high	4 Participants	3 Participants	2 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Direct bilirubin high	1 Participants	1 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Alkaline phosphatase high	8 Participants	4 Participants	7 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Alanine amino transferase high	5 Participants	3 Participants	8 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Asparatate amino transferase high	9 Participants	2 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters BUN/Urea low	4 Participants	6 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters BUN/Urea high	1 Participants	0 Participants	2 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Creatinine low	6 Participants	8 Participants	12 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Creatinine high	1 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Uric acid low	3 Participants	3 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Uric acid high	0 Participants	1 Participants	4 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Bicarbonate low	21 Participants	16 Participants	18 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Lactate dehydrogenase high	1 Participants	1 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Cholesterol high	7 Participants	4 Participants	11 Participants
Number of Participants With Shift From Baseline in Clinical Chemistry Parameters Creatinine kinase high	7 Participants	4 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56.

Population: Safety Population. Only those participants available at the specified time points were analyzed

Liver function test parameter included total bilirubin. Assessments were carried out at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 2	0.7 micromoles per liter Standard Deviation 3.21	0.0 micromoles per liter Standard Deviation 2.09	-0.7 micromoles per liter Standard Deviation 2.48
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 4	0.7 micromoles per liter Standard Deviation 3.46	0.0 micromoles per liter Standard Deviation 2.33	-0.1 micromoles per liter Standard Deviation 2.24
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 6	0.9 micromoles per liter Standard Deviation 2.29	0.1 micromoles per liter Standard Deviation 2.60	-0.4 micromoles per liter Standard Deviation 2.95
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 8	1.0 micromoles per liter Standard Deviation 3.38	0.2 micromoles per liter Standard Deviation 2.49	0.0 micromoles per liter Standard Deviation 2.31
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 10	0.9 micromoles per liter Standard Deviation 3.46	0.5 micromoles per liter Standard Deviation 3.25	-0.1 micromoles per liter Standard Deviation 3.27
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 12	0.8 micromoles per liter Standard Deviation 2.70	0.2 micromoles per liter Standard Deviation 2.42	0.6 micromoles per liter Standard Deviation 3.33
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 16	0.8 micromoles per liter Standard Deviation 3.75	0.8 micromoles per liter Standard Deviation 2.99	-0.2 micromoles per liter Standard Deviation 2.00
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 20	1.4 micromoles per liter Standard Deviation 3.07	0.9 micromoles per liter Standard Deviation 3.25	0.4 micromoles per liter Standard Deviation 2.89
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 24	1.0 micromoles per liter Standard Deviation 3.26	0.8 micromoles per liter Standard Deviation 2.63	0.8 micromoles per liter Standard Deviation 4.27
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 28	0.8 micromoles per liter Standard Deviation 3.37	0.4 micromoles per liter Standard Deviation 2.08	0.2 micromoles per liter Standard Deviation 4.30
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 32	0.5 micromoles per liter Standard Deviation 2.37	0.2 micromoles per liter Standard Deviation 2.41	0.8 micromoles per liter Standard Deviation 5.70
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 36	0.4 micromoles per liter Standard Deviation 2.62	0.6 micromoles per liter Standard Deviation 3.09	0.5 micromoles per liter Standard Deviation 2.44
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 40	0.7 micromoles per liter Standard Deviation 2.52	-0.5 micromoles per liter Standard Deviation 2.67	0.7 micromoles per liter Standard Deviation 3.16
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 44	1.4 micromoles per liter Standard Deviation 2.79	0.0 micromoles per liter Standard Deviation 1.66	1.0 micromoles per liter Standard Deviation 6.44
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 48	1.0 micromoles per liter Standard Deviation 4.49	-1.4 micromoles per liter Standard Deviation 3.35	-1.5 micromoles per liter Standard Deviation 6.97
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 52	0.7 micromoles per liter Standard Deviation 4.81	0.6 micromoles per liter Standard Deviation 1.42	-1.7 micromoles per liter Standard Deviation 9.53
Change From Baseline in Liver Function Test Parameter Total Bilirubin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 and 56. Week 56	0.2 micromoles per liter Standard Deviation 3.69	1.4 micromoles per liter Standard Deviation 2.81	1.8 micromoles per liter Standard Deviation 3.47

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Liver function test parameter included albumin. Assessments were carried out at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 2	-0.3 grams per liter Standard Deviation 1.26	0.0 grams per liter Standard Deviation 2.51	-0.1 grams per liter Standard Deviation 1.35
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 4	0.7 grams per liter Standard Deviation 2.20	0.1 grams per liter Standard Deviation 2.39	-0.2 grams per liter Standard Deviation 2.30
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 6	-1.0 grams per liter Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	-1.0 grams per liter Standard Deviation 2.00	-0.6 grams per liter Standard Deviation 2.30
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 8	0.2 grams per liter Standard Deviation 2.44	0.3 grams per liter Standard Deviation 2.37	-0.6 grams per liter Standard Deviation 2.63
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 10	-2.0 grams per liter Standard Deviation 2.97	-1.5 grams per liter Standard Deviation 2.08	-1.4 grams per liter Standard Deviation 1.34
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 12	0.0 grams per liter Standard Deviation 2.48	0.0 grams per liter Standard Deviation 2.43	0.0 grams per liter Standard Deviation 2.70
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 16	-3.0 grams per liter Standard Deviation 2.65	-1.0 grams per liter Standard Deviation 3.00	-1.5 grams per liter Standard Deviation 2.52
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 20	0.4 grams per liter Standard Deviation 2.02	0.7 grams per liter Standard Deviation 2.78	0.0 grams per liter Standard Deviation 2.42
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 24	-0.2 grams per liter Standard Deviation 4.55	-2.3 grams per liter Standard Deviation 4.35	-4.0 grams per liter Standard Deviation 3.61
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 28	0.1 grams per liter Standard Deviation 2.06	0.1 grams per liter Standard Deviation 4.47	0.5 grams per liter Standard Deviation 2.89
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 32	—	-4.0 grams per liter Standard Deviation 4.36	—
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 36	-0.2 grams per liter Standard Deviation 2.78	0.7 grams per liter Standard Deviation 4.01	0.4 grams per liter Standard Deviation 2.79
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 40	0.5 grams per liter Standard Deviation 2.12	—	—
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 44	-0.2 grams per liter Standard Deviation 2.55	0.0 grams per liter Standard Deviation 2.69	0.4 grams per liter Standard Deviation 2.33
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 48	2.0 grams per liter Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	1.0 grams per liter Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.	1.0 grams per liter Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed.
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 52	-0.1 grams per liter Standard Deviation 2.14	-1.3 grams per liter Standard Deviation 1.94	1.9 grams per liter Standard Deviation 2.27
Change From Baseline in Liver Function Test Parameter Albumin at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Week 56	-1.0 grams per liter Standard Deviation 2.48	-0.5 grams per liter Standard Deviation 3.52	-0.2 grams per liter Standard Deviation 3.03

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Liver function test parameters included alanine amino transferase, aspartate amino transferase, alkaline phosphatase and gamma glutamyl transferase. Assessments were carried out at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 2	-1.0 units per liter Standard Deviation 14.70	0.3 units per liter Standard Deviation 5.88	0.2 units per liter Standard Deviation 6.27
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 24	-6.4 units per liter Standard Deviation 15.11	-3.0 units per liter Standard Deviation 19.17	2.6 units per liter Standard Deviation 7.95
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 28	-7.8 units per liter Standard Deviation 25.33	-4.3 units per liter Standard Deviation 17.17	1.3 units per liter Standard Deviation 6.56
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 32	-13.2 units per liter Standard Deviation 31.99	-9.0 units per liter Standard Deviation 31.31	6.5 units per liter Standard Deviation 13.53
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 4	0.2 units per liter Standard Deviation 8.93	-0.6 units per liter Standard Deviation 4.83	-0.1 units per liter Standard Deviation 6.94
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 6	0.4 units per liter Standard Deviation 11.92	1.1 units per liter Standard Deviation 6.66	0.3 units per liter Standard Deviation 7.35
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 8	0.0 units per liter Standard Deviation 9.46	-0.2 units per liter Standard Deviation 6.20	1.0 units per liter Standard Deviation 6.43
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 10	-2.1 units per liter Standard Deviation 8.15	-0.5 units per liter Standard Deviation 5.24	0.9 units per liter Standard Deviation 7.33
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 12	-2.7 units per liter Standard Deviation 8.60	-0.6 units per liter Standard Deviation 5.13	0.6 units per liter Standard Deviation 7.40
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 16	-1.4 units per liter Standard Deviation 9.00	0.5 units per liter Standard Deviation 7.69	0.4 units per liter Standard Deviation 4.98
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 20	-2.7 units per liter Standard Deviation 8.85	-0.4 units per liter Standard Deviation 7.07	1.4 units per liter Standard Deviation 4.59
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 24	-1.3 units per liter Standard Deviation 9.94	-0.2 units per liter Standard Deviation 6.25	2.3 units per liter Standard Deviation 6.19
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 28	-1.6 units per liter Standard Deviation 10.08	-0.2 units per liter Standard Deviation 5.91	0.3 units per liter Standard Deviation 5.12
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 32	-2.3 units per liter Standard Deviation 9.48	-0.8 units per liter Standard Deviation 6.81	11.1 units per liter Standard Deviation 35.32
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 36	-2.3 units per liter Standard Deviation 8.17	-0.6 units per liter Standard Deviation 7.46	5.4 units per liter Standard Deviation 10.74
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 40	-3.4 units per liter Standard Deviation 10.74	0.1 units per liter Standard Deviation 10.24	6.0 units per liter Standard Deviation 10.13
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 44	-3.2 units per liter Standard Deviation 13.37	-1.5 units per liter Standard Deviation 7.72	0.3 units per liter Standard Deviation 4.82
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 48	-3.8 units per liter Standard Deviation 13.98	-2.0 units per liter Standard Deviation 12.21	-0.6 units per liter Standard Deviation 6.52
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 52	-5.1 units per liter Standard Deviation 11.47	-1.2 units per liter Standard Deviation 11.41	-1.3 units per liter Standard Deviation 5.22
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alanine amino transferase at Week 56	-5.8 units per liter Standard Deviation 28.79	0.4 units per liter Standard Deviation 8.11	10.3 units per liter Standard Deviation 41.19
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 2	0.4 units per liter Standard Deviation 12.18	0.3 units per liter Standard Deviation 3.76	0.6 units per liter Standard Deviation 5.41
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 4	0.5 units per liter Standard Deviation 7.19	0.1 units per liter Standard Deviation 4.24	-0.2 units per liter Standard Deviation 5.45
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 6	1.2 units per liter Standard Deviation 9.18	0.8 units per liter Standard Deviation 3.99	-0.1 units per liter Standard Deviation 3.94
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 8	0.1 units per liter Standard Deviation 6.39	0.0 units per liter Standard Deviation 4.07	1.0 units per liter Standard Deviation 4.58
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 10	-0.7 units per liter Standard Deviation 5.17	0.6 units per liter Standard Deviation 3.94	0.8 units per liter Standard Deviation 4.18
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 12	0.4 units per liter Standard Deviation 8.38	0.5 units per liter Standard Deviation 5.97	1.1 units per liter Standard Deviation 6.11
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 16	0.0 units per liter Standard Deviation 7.57	1.5 units per liter Standard Deviation 5.29	0.4 units per liter Standard Deviation 4.24
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 20	-0.2 units per liter Standard Deviation 7.18	0.8 units per liter Standard Deviation 4.74	0.2 units per liter Standard Deviation 5.02
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 24	0.0 units per liter Standard Deviation 8.35	0.2 units per liter Standard Deviation 4.52	1.7 units per liter Standard Deviation 6.21
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 28	1.3 units per liter Standard Deviation 10.01	0.5 units per liter Standard Deviation 4.52	-0.9 units per liter Standard Deviation 4.42
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 32	-0.2 units per liter Standard Deviation 7.06	-0.6 units per liter Standard Deviation 6.67	4.9 units per liter Standard Deviation 17.50
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 36	0.0 units per liter Standard Deviation 8.17	0.3 units per liter Standard Deviation 4.36	3.3 units per liter Standard Deviation 7.00
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 40	-0.7 units per liter Standard Deviation 9.95	-0.5 units per liter Standard Deviation 3.66	3.8 units per liter Standard Deviation 8.43
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 44	-1.3 units per liter Standard Deviation 7.14	-0.8 units per liter Standard Deviation 5.03	-0.8 units per liter Standard Deviation 4.09
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 48	-0.1 units per liter Standard Deviation 11.65	-3.4 units per liter Standard Deviation 8.87	-0.4 units per liter Standard Deviation 6.32
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 52	-1.4 units per liter Standard Deviation 10.05	-0.9 units per liter Standard Deviation 3.98	-1.0 units per liter Standard Deviation 2.83
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Aspartate amino transferase at Week 56	-2.5 units per liter Standard Deviation 17.99	-0.3 units per liter Standard Deviation 4.13	5.4 units per liter Standard Deviation 20.70
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 2	-0.2 units per liter Standard Deviation 7.42	1.3 units per liter Standard Deviation 9.54	0.4 units per liter Standard Deviation 9.96
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 4	0.1 units per liter Standard Deviation 9.30	2.0 units per liter Standard Deviation 10.63	0.4 units per liter Standard Deviation 11.00
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 6	1.0 units per liter Standard Deviation 11.21	3.6 units per liter Standard Deviation 11.28	1.0 units per liter Standard Deviation 11.16
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 8	1.7 units per liter Standard Deviation 12.04	3.9 units per liter Standard Deviation 12.61	0.2 units per liter Standard Deviation 11.21
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 10	-1.4 units per liter Standard Deviation 10.54	5.6 units per liter Standard Deviation 12.55	2.8 units per liter Standard Deviation 12.93
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 12	1.2 units per liter Standard Deviation 10.99	5.6 units per liter Standard Deviation 14.85	2.4 units per liter Standard Deviation 11.38
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 16	1.5 units per liter Standard Deviation 13.71	7.2 units per liter Standard Deviation 13.16	3.4 units per liter Standard Deviation 13.23
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 20	3.7 units per liter Standard Deviation 13.70	9.3 units per liter Standard Deviation 16.74	2.0 units per liter Standard Deviation 12.80
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 24	1.9 units per liter Standard Deviation 13.77	9.2 units per liter Standard Deviation 17.74	3.4 units per liter Standard Deviation 11.00
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 28	1.9 units per liter Standard Deviation 16.62	12.2 units per liter Standard Deviation 16.71	-0.6 units per liter Standard Deviation 12.53
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 32	-1.0 units per liter Standard Deviation 16.55	10.5 units per liter Standard Deviation 19.52	4.3 units per liter Standard Deviation 9.63
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 36	2.3 units per liter Standard Deviation 18.43	9.4 units per liter Standard Deviation 16.98	6.3 units per liter Standard Deviation 13.11
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 40	1.5 units per liter Standard Deviation 18.60	6.5 units per liter Standard Deviation 6.71	-0.2 units per liter Standard Deviation 9.14
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 44	2.6 units per liter Standard Deviation 17.32	6.0 units per liter Standard Deviation 9.88	-3.6 units per liter Standard Deviation 8.31
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 48	10.6 units per liter Standard Deviation 23.54	1.1 units per liter Standard Deviation 19.93	-5.5 units per liter Standard Deviation 11.25
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 52	2.1 units per liter Standard Deviation 13.76	3.9 units per liter Standard Deviation 10.28	3.9 units per liter Standard Deviation 9.58
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Alkaline phosphatase at Week 56	3.5 units per liter Standard Deviation 12.84	3.8 units per liter Standard Deviation 14.98	4.9 units per liter Standard Deviation 8.29
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 2	-3.0 units per liter Standard Deviation 8.06	1.8 units per liter Standard Deviation 13.22	0.4 units per liter Standard Deviation 8.89
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 4	-4.2 units per liter Standard Deviation 9.86	-0.4 units per liter Standard Deviation 12.58	2.1 units per liter Standard Deviation 11.32
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 6	-5.0 units per liter Standard Deviation 15.47	1.7 units per liter Standard Deviation 13.10	1.9 units per liter Standard Deviation 10.50
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 8	-1.2 units per liter Standard Deviation 24.86	1.1 units per liter Standard Deviation 16.05	2.0 units per liter Standard Deviation 7.55
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 10	-6.2 units per liter Standard Deviation 11.03	0.7 units per liter Standard Deviation 14.38	2.2 units per liter Standard Deviation 6.71
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 12	-8.2 units per liter Standard Deviation 15.00	0.5 units per liter Standard Deviation 14.94	2.3 units per liter Standard Deviation 8.21
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 16	-3.4 units per liter Standard Deviation 19.57	-0.9 units per liter Standard Deviation 12.17	3.7 units per liter Standard Deviation 8.72
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 20	-6.5 units per liter Standard Deviation 17.94	-1.9 units per liter Standard Deviation 11.95	2.9 units per liter Standard Deviation 8.57
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 36	-9.0 units per liter Standard Deviation 27.65	-6.7 units per liter Standard Deviation 18.39	11.0 units per liter Standard Deviation 13.38
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 40	-11.7 units per liter Standard Deviation 21.56	-6.1 units per liter Standard Deviation 18.98	8.9 units per liter Standard Deviation 10.49
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 44	-7.4 units per liter Standard Deviation 15.82	-8.6 units per liter Standard Deviation 20.03	4.4 units per liter Standard Deviation 9.15
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 48	-4.4 units per liter Standard Deviation 9.80	-13.5 units per liter Standard Deviation 40.87	4.1 units per liter Standard Deviation 9.30
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 52	-10.4 units per liter Standard Deviation 19.75	0.0 units per liter Standard Deviation 11.64	8.3 units per liter Standard Deviation 10.40
Change From Baseline in Liver Function Test Parameter Alanine Amino Transferase, Aspartate Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56 Gamma glutamyl transferase at Week 56	-4.2 units per liter Standard Deviation 12.03	-3.4 units per liter Standard Deviation 13.50	0.8 units per liter Standard Deviation 21.68

SECONDARY outcome

Timeframe: Week 28 and 52

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

A 12 lead ECG was collected at Weeks 28 and 52. ECG abnormalities were characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS). A-NCS data for Week 28 and 52 have been presented.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules once daily.	GSK1605786A 500 mg BID n=76 Participants Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules BID.
Number of Participants With 12 Lead Electocardiogram (ECG) Abnormalities at Week 28 and 52 A-NCS, Week 28	5 Participants	7 Participants	4 Participants
Number of Participants With 12 Lead Electocardiogram (ECG) Abnormalities at Week 28 and 52 A-NCS, Week 52	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for change from Baseline in SF-36 v2 at Weeks 28 and 52 was not collected.

The SF-36v2 health survey is a self-administered, generic, 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health). SF-36 v2 items are scored such that a higher score indicates a better health state and better functioning. Data for change from Baseline in SF-36 v2 at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in European Quality of Life (EuroQol ) five dimensions questionnaire (EQ-5D) at Weeks 28 and 52 was not collected.

EQ-5D self-reported questionnaire is used to measure health-related quality of life by measuring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D questionnaire includes a visual analog scale (VAS) which records participants self-rated health status on a graduated (0-100) scale with higher scores indicating higher Health-Related Quality of Life (HRQoL). Data for Change from Baseline in EuroQol five dimensions questionnaire (EQ-5D) at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in Work productivity \& activity impairment - Crohn's disease (WPAI-CD) at Weeks 28 and 52 was not collected.

WPAI measures the effect of your CD on your ability to work and perform regular activities. 6-items assess impairment in work productivity and daily activity during the 7 days before the assessment. It measures the percentage of overall impairment in work productivity and daily activity due to CD. A WPAI score of 0% = no impairment and a score of 100% = total loss of work productivity or activity. An absolute change in WPAI score of 7% is considered the minimum clinically important difference (MCID). Data for change from Baseline in WPAI-CD at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 28 and 52

Population: ITT population. Following early termination of study CCX114157 data for Receipt of disability benefits at Weeks 28 and 52 was not collected.

Receipt of disability benefits (Yes/No) was to be recorded at Weeks 0, 28 and 52 and Early Withdrawal visit if applicable. Change from baseline in receipt of disability benefits was to be compared between participants in remission versus participants not in remission using a Wilcoxon rank sum test. Data for Receipt of disability benefits at Weeks 28 and 52 was not collected following early termination of this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in health-related resource utilization at Weeks 28 and 52 was not collected.

Healthcare related resource utilization was to include: Hospitalizations (all cause and Crohn's disease related), Length of stay, Surgical procedures (all cause and Crohn's disease related), Outpatient visits (all cause and Crohn's disease related ). The frequency of hospitalizations, surgical procedures and hospital out-patient visits were to be recorded at Weeks 28 and 52. The number and percentage of participants reporting all cause and Crohn's disease -related hospitalizations, surgeries, and hospital out-patient visits were to be summarized and compared between each GSK1605786A dose group and placebo using Fisher's exact test. Data for Change from Baseline in health-related resource utilization at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0 and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in C reactive protein (CRP) at Weeks 28 and 52 was not collected.

C-reactive protein (CRP) at was to be assessed at Weeks 4, 8, 12, 20, 28, 36, 44, 52 visit if applicable. Data for Change from Baseline in C reactive protein (CRP) at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 28 and 52

Population: ITT Population. Following early termination of study CCX114157 data for Change from Baseline in faecal calprotectin at Weeks 28 and 52 was not collected.

Stool sample for faecal calprotectin were to be collected at Weeks 28 and 52 visit if applicable. Data for Change from baseline in faecal calprotectin at Weeks 28 and 52 was not collected following early termination of this study. Baseline was defined as value at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

GSK1605786A 500 mg Once Daily

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

GSK1605786A 500 mg BID

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=76 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 milligram (mg) capsules once daily.	GSK1605786A 500 mg BID n=76 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules twice daily (BID).
Infections and infestations Lower respiratory tract infecion	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	0.00% 0/77 • Up to Week 56 Safety population was used for analysis.	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.
Infections and infestations Anal abscess	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	1.3% 1/77 • Up to Week 56 Safety population was used for analysis.	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.
Cardiac disorders Sinus tachycardia	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.	0.00% 0/77 • Up to Week 56 Safety population was used for analysis.	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Crohn's disease	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	1.3% 1/77 • Up to Week 56 Safety population was used for analysis.	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	0.00% 0/77 • Up to Week 56 Safety population was used for analysis.	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	1.3% 1/77 • Up to Week 56 Safety population was used for analysis.	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.

Other adverse events

Measure	Placebo n=76 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral matching placebo capsules to GSK1605786A 500 mg capsules.	GSK1605786A 500 mg Once Daily n=77 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 milligram (mg) capsules once daily.	GSK1605786A 500 mg BID n=76 participants at risk Eligible participants received 52 weeks randomized, double-blind treatment with oral GSK1605786A 500 mg capsules twice daily (BID).
Gastrointestinal disorders Crohn's disease	17.1% 13/76 • Up to Week 56 Safety population was used for analysis.	15.6% 12/77 • Up to Week 56 Safety population was used for analysis.	13.2% 10/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Abdominal pain	13.2% 10/76 • Up to Week 56 Safety population was used for analysis.	6.5% 5/77 • Up to Week 56 Safety population was used for analysis.	11.8% 9/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Diarrhoea	10.5% 8/76 • Up to Week 56 Safety population was used for analysis.	3.9% 3/77 • Up to Week 56 Safety population was used for analysis.	3.9% 3/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Nausea	7.9% 6/76 • Up to Week 56 Safety population was used for analysis.	1.3% 1/77 • Up to Week 56 Safety population was used for analysis.	7.9% 6/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Vomiting	5.3% 4/76 • Up to Week 56 Safety population was used for analysis.	2.6% 2/77 • Up to Week 56 Safety population was used for analysis.	3.9% 3/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Toothache	3.9% 3/76 • Up to Week 56 Safety population was used for analysis.	0.00% 0/77 • Up to Week 56 Safety population was used for analysis.	5.3% 4/76 • Up to Week 56 Safety population was used for analysis.
Gastrointestinal disorders Dyspepsia	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.	5.2% 4/77 • Up to Week 56 Safety population was used for analysis.	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.
Infections and infestations Nasopharyngitis	11.8% 9/76 • Up to Week 56 Safety population was used for analysis.	11.7% 9/77 • Up to Week 56 Safety population was used for analysis.	11.8% 9/76 • Up to Week 56 Safety population was used for analysis.
Infections and infestations Influenza	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.	5.2% 4/77 • Up to Week 56 Safety population was used for analysis.	2.6% 2/76 • Up to Week 56 Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 8/76 • Up to Week 56 Safety population was used for analysis.	7.8% 6/77 • Up to Week 56 Safety population was used for analysis.	5.3% 4/76 • Up to Week 56 Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Back pain	5.3% 4/76 • Up to Week 56 Safety population was used for analysis.	5.2% 4/77 • Up to Week 56 Safety population was used for analysis.	6.6% 5/76 • Up to Week 56 Safety population was used for analysis.
Nervous system disorders Headache	7.9% 6/76 • Up to Week 56 Safety population was used for analysis.	3.9% 3/77 • Up to Week 56 Safety population was used for analysis.	11.8% 9/76 • Up to Week 56 Safety population was used for analysis.
Skin and subcutaneous tissue disorders Rash	9.2% 7/76 • Up to Week 56 Safety population was used for analysis.	2.6% 2/77 • Up to Week 56 Safety population was used for analysis.	1.3% 1/76 • Up to Week 56 Safety population was used for analysis.
Blood and lymphatic system disorders Anaemia	0.00% 0/76 • Up to Week 56 Safety population was used for analysis.	2.6% 2/77 • Up to Week 56 Safety population was used for analysis.	5.3% 4/76 • Up to Week 56 Safety population was used for analysis.

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