Trial Outcomes & Findings for Open-Label Extension Study of GSK1605786A (NCT NCT01318993)

NCT ID: NCT01318993

Last Updated: 2017-09-14

Results Overview

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 SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. The Safety population consisted of all participants who enrolled in the study except those who did not take \>=1 dose of investigational product.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 399 participants
• Primary outcome timeframe: Up to Week 112
• Results posted on: 2017-09-14

Participant Flow

Participants were eligible to enter the study if they completed the placebo-controlled induction study CCX114151; completed the maintenance study CCX114157 at Week 52; or withdrew from the maintenance study CCX114157. A total of such 800 participants were planned to be enrolled.

All participants entered the study at a Baseline visit, Week 0, and received GSK1605786A 500 milligrams (mg), twice daily (BID) for 216 weeks.

Participant milestones

Measure	GSK1605786A Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Overall Study STARTED	398
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	398

Reasons for withdrawal

Measure	GSK1605786A Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Overall Study Adverse Event	53
Overall Study Lack of Efficacy	121
Overall Study Protocol Violation	3
Overall Study Protocol based stopping criteria	6
Overall Study Study closed or terminated	174
Overall Study Lost to Follow-up	4
Overall Study Physician Decision	13
Overall Study Withdrawal by Subject	24

Baseline Characteristics

Open-Label Extension Study of GSK1605786A

Baseline characteristics by cohort

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Age, Continuous	36.5 Years STANDARD_DEVIATION 11.99 • n=5 Participants
Sex: Female, Male Female	213 Participants n=5 Participants
Sex: Female, Male Male	185 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	38 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants
Race (NIH/OMB) White	351 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 112

Population: Safety Population

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 SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. The Safety population consisted of all participants who enrolled in the study except those who did not take >=1 dose of investigational product.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) Any AE	303 Participants
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) Any SAE	41 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

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

The SBP and DBP values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Baseline value was recorded at Week 0. Change from Baseline measurements in SBP and DBP were assessed at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 4	-0.4 millimeters of mercury (mmHg) Standard Deviation 11.39
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 8	-0.4 millimeters of mercury (mmHg) Standard Deviation 11.46
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 12	-0.9 millimeters of mercury (mmHg) Standard Deviation 13.12
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 24	1.0 millimeters of mercury (mmHg) Standard Deviation 12.69
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 36	1.3 millimeters of mercury (mmHg) Standard Deviation 12.64
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 48	-0.5 millimeters of mercury (mmHg) Standard Deviation 13.22
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 60	1.5 millimeters of mercury (mmHg) Standard Deviation 13.00
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 72	-0.1 millimeters of mercury (mmHg) Standard Deviation 13.15
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 84	5.4 millimeters of mercury (mmHg) Standard Deviation 18.65
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 96	-5.4 millimeters of mercury (mmHg) Standard Deviation 10.72
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, Week 108	2.2 millimeters of mercury (mmHg) Standard Deviation 13.44
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period SBP, 4 week post treatment	0.5 millimeters of mercury (mmHg) Standard Deviation 13.56
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 4	0.1 millimeters of mercury (mmHg) Standard Deviation 8.58
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 8	0.1 millimeters of mercury (mmHg) Standard Deviation 8.18
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 12	0.2 millimeters of mercury (mmHg) Standard Deviation 9.21
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 24	0.1 millimeters of mercury (mmHg) Standard Deviation 10.17
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 36	1.0 millimeters of mercury (mmHg) Standard Deviation 9.80
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 48	0.0 millimeters of mercury (mmHg) Standard Deviation 9.02
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 60	1.2 millimeters of mercury (mmHg) Standard Deviation 10.59
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 72	0.0 millimeters of mercury (mmHg) Standard Deviation 10.03
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 84	4.4 millimeters of mercury (mmHg) Standard Deviation 11.00
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 96	-1.8 millimeters of mercury (mmHg) Standard Deviation 9.33
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, Week 108, n=6	1.3 millimeters of mercury (mmHg) Standard Deviation 9.52
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period DBP, 4 week post treatment	0.1 millimeters of mercury (mmHg) Standard Deviation 9.91

SECONDARY outcome

Timeframe: Baseline (week 0) and up to Week 112

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

The HR values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline in HR was assessed at Week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 4	1.3 beats per minute Standard Deviation 10.92
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 8	0.1 beats per minute Standard Deviation 11.41
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 12	0.8 beats per minute Standard Deviation 11.93
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 24	-0.5 beats per minute Standard Deviation 12.56
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 36	2.1 beats per minute Standard Deviation 12.35
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 48	-1.2 beats per minute Standard Deviation 13.16
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 60	0.4 beats per minute Standard Deviation 12.85
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 72	-1.2 beats per minute Standard Deviation 12.39
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 84	-0.7 beats per minute Standard Deviation 15.44
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 96	-4.9 beats per minute Standard Deviation 17.01
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, Week 108	-7.7 beats per minute Standard Deviation 12.83
Change From Baseline (Week 0) in Heart Rate (HR) Over Period HR, 4 week post treatment	-0.8 beats per minute Standard Deviation 12.89

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

Population: Safety Population. Only the participants available at the time of analysis were included.

Hematology parameters measured included platelets, neutrophils (NL), lymphocytes, monocytes, eosinophils, basophils, hematocrit, band cells, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count, and segmented (seg) NL. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated hematology parameters data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, shift to high) until 4 weeks post treatment are presented.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters WBC Count, shift to normal or no change	289 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters RBC Count, shift to low	62 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters RBC Count, shift to normal or no change	322 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters RBC Count, shift to high	11 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hemoglobin, shift to low	74 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hemoglobin, shift to normal or no change	320 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hemoglobin, shift to high	1 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters WBC Count, shift to low	23 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Platelets, shift to low	2 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Platelets, shift to normal or no change	325 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Platelets, shift to high	67 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters NL, shift to low	5 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters NL, shift to normal or no change	284 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters NL, shift to high	106 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Lymphocytes, shift to low	99 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Lymphocytes, shift to normal or no change	292 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Lymphocytes, shift to high	4 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Monocytes, shift to low	0 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Monocytes, shift to normal or no change	372 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Monocytes, shift to high	23 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Eosinophils, shift to normal or no change	366 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Eosinophils, shift to high	29 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Basophils, shift to normal or no change	395 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Basophils, shift to high	0 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hematocrit, shift to low	75 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hematocrit, shift to normal or no change	312 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Hematocrit, shift to high	8 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Band cells, shift to normal or no change	5 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Band cells, shift to high	1 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters WBC Count, shift to high	83 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Segmented (Seg) NL, shift to low	5 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Seg NL, shift to normal or no change	283 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters Seg NL, shift to high	107 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

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

Clinical chemistry parameters included platelets, total protein, phosphorous, albumin, sodium, potassium, chloride, calcium, glucose, gamma-glutamyl transferase, total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/urea, creatinine, uric acid, bicarbonate, lactate dehydrogenase, cholesterol, alkaline phosphatase (ALP), gamma glutamyl transferases (GGT), and creatine kinase. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated clinical chemistry parameters' data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, or shift to high) until 4 weeks post-treatment are presented.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Total Protein, shift to low	27 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Total Protein, shift to normal or no change	367 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Total Protein, shift to high	1 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Phosphorous, shift to low	85 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Phosphorous, shift to normal or no change	283 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Phosphorous, shift to high	30 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Albumin, shift to low	19 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Albumin, shift to normal or no change	373 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Albumin, shift to high	3 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Sodium, shift to low	18 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Sodium, shift to normal or no change	376 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Sodium, shift to high	1 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Potassium, shift to low	25 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Potassium, shift to normal or no change	360 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Potassium, shift to high	10 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Chloride, shift to low	3 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Chloride, shift to normal or no change	361 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Chloride, shift to high	31 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Calcium, shift to low	43 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Calcium, shift to normal or no change	340 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Calcium, shift to high	12 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Glucose, shift to low	54 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Glucose, shift to normal or no change	279 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Glucose, shift to high	66 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters GGT, shift to normal or no change	330 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters GGT, shift to high	67 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters TB, shift to normal or no change	391 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters TB, shift to high	6 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters DB, shift to normal or no change	397 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters DB, shift to high	0 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters ALP, shift to low	0 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters ALP, shift to normal or no change, n=397	357 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters ALP, shift to high, n=370	14 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters ALT, shift to normal or no change	349 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters ALT, shift to high	48 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters AST, shift to normal or no change	362 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters AST, shift to high	35 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters BUN/Urea, shift to low	44 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters BUN/Urea, shift to normal or no change	345 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters BUN/Urea, shift to high	6 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Creatinine, shift to low	50 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Creatinine, shift to normal or no change	335 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Creatinine, shift to high	10 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Uric Acid, shift to low	21 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Uric Acid, shift to normal or no change	350 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Uric Acid, shift to high	24 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Bicarbonate, shift to low	92 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Bicarbonate, shift to normal or no change	303 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Bicarbonate, shift to high	0 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters LDH, shift to normal or no change	386 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters LDH, shift to high	9 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Cholesterol, shift to normal or no change	330 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters Cholesterol, shift to high	65 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters CK, shift to normal or no change	357 Participants
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters CK, shift to high	38 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

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

Changes in Baseline in ALP, ALT, AST, and GGT were assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 96	34.1 International Unit per Liter (IU/L) Standard Deviation 29.97
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 108	24.5 International Unit per Liter (IU/L) Standard Deviation 11.62
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, 4 week post treatment	31.7 International Unit per Liter (IU/L) Standard Deviation 30.19
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 44	17.4 International Unit per Liter (IU/L) Standard Deviation 12.77
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 24	17.8 International Unit per Liter (IU/L) Standard Deviation 7.92
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 84	33.7 International Unit per Liter (IU/L) Standard Deviation 28.66
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 2	15.2 International Unit per Liter (IU/L) Standard Deviation 11.33
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 4	19.3 International Unit per Liter (IU/L) Standard Deviation 43.93
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 6	17.0 International Unit per Liter (IU/L) Standard Deviation 18.98
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 8	17.0 International Unit per Liter (IU/L) Standard Deviation 23.94
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 10	16.1 International Unit per Liter (IU/L) Standard Deviation 16.17
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 12	16.7 International Unit per Liter (IU/L) Standard Deviation 17.07
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 16	16.2 International Unit per Liter (IU/L) Standard Deviation 13.77
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 20	17.9 International Unit per Liter (IU/L) Standard Deviation 32.94
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 24	15.2 International Unit per Liter (IU/L) Standard Deviation 10.77
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 28	17.1 International Unit per Liter (IU/L) Standard Deviation 20.11
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 32	15.7 International Unit per Liter (IU/L) Standard Deviation 12.25
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 36	15.8 International Unit per Liter (IU/L) Standard Deviation 10.74
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 40	16.6 International Unit per Liter (IU/L) Standard Deviation 11.49
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 48	15.0 International Unit per Liter (IU/L) Standard Deviation 7.61
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 52	14.7 International Unit per Liter (IU/L) Standard Deviation 7.74
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 60	16.0 International Unit per Liter (IU/L) Standard Deviation 10.20
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 72	15.1 International Unit per Liter (IU/L) Standard Deviation 6.55
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 84	15.4 International Unit per Liter (IU/L) Standard Deviation 7.11
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 96	16.8 International Unit per Liter (IU/L) Standard Deviation 6.03
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, Week 108	15.7 International Unit per Liter (IU/L) Standard Deviation 7.69
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALT, 4 week post treatment	18.9 International Unit per Liter (IU/L) Standard Deviation 22.52
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 2	16.9 International Unit per Liter (IU/L) Standard Deviation 6.87
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 4	18.6 International Unit per Liter (IU/L) Standard Deviation 19.31
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 6	17.6 International Unit per Liter (IU/L) Standard Deviation 9.56
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 8	17.7 International Unit per Liter (IU/L) Standard Deviation 14.11
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 10	17.4 International Unit per Liter (IU/L) Standard Deviation 9.51
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 12	19.2 International Unit per Liter (IU/L) Standard Deviation 25.75
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 16	17.8 International Unit per Liter (IU/L) Standard Deviation 8.76
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 20	19.4 International Unit per Liter (IU/L) Standard Deviation 21.90
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 28	18.6 International Unit per Liter (IU/L) Standard Deviation 12.59
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 32	18.1 International Unit per Liter (IU/L) Standard Deviation 8.55
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 36	18.4 International Unit per Liter (IU/L) Standard Deviation 8.01
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 40	18.4 International Unit per Liter (IU/L) Standard Deviation 7.68
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 44	18.7 International Unit per Liter (IU/L) Standard Deviation 8.66
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 48	17.6 International Unit per Liter (IU/L) Standard Deviation 6.11
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 52	17.1 International Unit per Liter (IU/L) Standard Deviation 5.71
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 60	18.4 International Unit per Liter (IU/L) Standard Deviation 6.07
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 72	17.2 International Unit per Liter (IU/L) Standard Deviation 3.80
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 84	18.2 International Unit per Liter (IU/L) Standard Deviation 4.96
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 96	19.7 International Unit per Liter (IU/L) Standard Deviation 5.92
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, Week 108	18.2 International Unit per Liter (IU/L) Standard Deviation 4.22
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) AST, 4 week post treatment	19.6 International Unit per Liter (IU/L) Standard Deviation 13.82
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 2	81.1 International Unit per Liter (IU/L) Standard Deviation 26.52
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 4	82.3 International Unit per Liter (IU/L) Standard Deviation 27.61
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 6	82.0 International Unit per Liter (IU/L) Standard Deviation 27.46
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 8	81.3 International Unit per Liter (IU/L) Standard Deviation 25.60
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 10	81.3 International Unit per Liter (IU/L) Standard Deviation 25.60
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 12	81.1 International Unit per Liter (IU/L) Standard Deviation 26.31
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 16	80.8 International Unit per Liter (IU/L) Standard Deviation 26.50
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 20	80.8 International Unit per Liter (IU/L) Standard Deviation 22.68
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 24	83.4 International Unit per Liter (IU/L) Standard Deviation 23.51
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 28	83.3 International Unit per Liter (IU/L) Standard Deviation 25.45
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 32	84.5 International Unit per Liter (IU/L) Standard Deviation 25.03
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 36	83.8 International Unit per Liter (IU/L) Standard Deviation 24.89
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 40	82.8 International Unit per Liter (IU/L) Standard Deviation 22.31
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 44	81.5 International Unit per Liter (IU/L) Standard Deviation 20.35
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 48	81.5 International Unit per Liter (IU/L) Standard Deviation 25.02
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 52	79.0 International Unit per Liter (IU/L) Standard Deviation 18.80
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 60	78.9 International Unit per Liter (IU/L) Standard Deviation 20.55
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 72	78.1 International Unit per Liter (IU/L) Standard Deviation 19.76
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 84	78.4 International Unit per Liter (IU/L) Standard Deviation 21.76
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 96	78.2 International Unit per Liter (IU/L) Standard Deviation 20.67
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, Week 108	81.5 International Unit per Liter (IU/L) Standard Deviation 19.64
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) ALP, 4 week post treatment	82.7 International Unit per Liter (IU/L) Standard Deviation 31.50
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 2	31.2 International Unit per Liter (IU/L) Standard Deviation 23.61
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 4	34.0 International Unit per Liter (IU/L) Standard Deviation 32.84
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 6	32.9 International Unit per Liter (IU/L) Standard Deviation 28.44
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 8	32.6 International Unit per Liter (IU/L) Standard Deviation 24.78
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 10	31.7 International Unit per Liter (IU/L) Standard Deviation 26.63
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 12	33.0 International Unit per Liter (IU/L) Standard Deviation 29.49
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 16	32.3 International Unit per Liter (IU/L) Standard Deviation 28.17
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 20	32.3 International Unit per Liter (IU/L) Standard Deviation 26.99
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 24	33.5 International Unit per Liter (IU/L) Standard Deviation 30.74
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 28	35.2 International Unit per Liter (IU/L) Standard Deviation 34.85
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 32	35.1 International Unit per Liter (IU/L) Standard Deviation 31.75
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 36	34.0 International Unit per Liter (IU/L) Standard Deviation 29.18
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 40	34.2 International Unit per Liter (IU/L) Standard Deviation 29.22
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 44	30.9 International Unit per Liter (IU/L) Standard Deviation 19.33
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 48	31.6 International Unit per Liter (IU/L) Standard Deviation 29.92
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 52	29.3 International Unit per Liter (IU/L) Standard Deviation 18.45
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 60	32.6 International Unit per Liter (IU/L) Standard Deviation 23.50
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) GGT, Week 72	32.2 International Unit per Liter (IU/L) Standard Deviation 25.30

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

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

Changes from Baseline (Week 0) in total bilirubin (TB) was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in Total Bilirubin TB, Week 2	6.9 micromole/Liter Standard Deviation 2.85
Change From Baseline (Week 0) in Total Bilirubin TB, Week 4	7.1 micromole/Liter Standard Deviation 3.24
Change From Baseline (Week 0) in Total Bilirubin TB, Week 6	6.8 micromole/Liter Standard Deviation 2.76
Change From Baseline (Week 0) in Total Bilirubin TB, Week 8	6.8 micromole/Liter Standard Deviation 2.61
Change From Baseline (Week 0) in Total Bilirubin TB, Week 10	7.1 micromole/Liter Standard Deviation 2.91
Change From Baseline (Week 0) in Total Bilirubin TB, Week 12	6.7 micromole/Liter Standard Deviation 2.54
Change From Baseline (Week 0) in Total Bilirubin TB, Week 16	7.0 micromole/Liter Standard Deviation 2.78
Change From Baseline (Week 0) in Total Bilirubin TB, Week 20	6.9 micromole/Liter Standard Deviation 2.99
Change From Baseline (Week 0) in Total Bilirubin TB, Week 24	7.2 micromole/Liter Standard Deviation 2.80
Change From Baseline (Week 0) in Total Bilirubin TB, Week 28	7.0 micromole/Liter Standard Deviation 2.70
Change From Baseline (Week 0) in Total Bilirubin TB, Week 32	6.9 micromole/Liter Standard Deviation 2.58
Change From Baseline (Week 0) in Total Bilirubin TB, Week 36	7.1 micromole/Liter Standard Deviation 2.42
Change From Baseline (Week 0) in Total Bilirubin TB, Week 40	7.4 micromole/Liter Standard Deviation 3.01
Change From Baseline (Week 0) in Total Bilirubin TB, Week 44	7.4 micromole/Liter Standard Deviation 2.56
Change From Baseline (Week 0) in Total Bilirubin TB, Week 48	7.0 micromole/Liter Standard Deviation 2.35
Change From Baseline (Week 0) in Total Bilirubin TB, Week 52	7.0 micromole/Liter Standard Deviation 2.57
Change From Baseline (Week 0) in Total Bilirubin TB, Week 60	7.3 micromole/Liter Standard Deviation 2.05
Change From Baseline (Week 0) in Total Bilirubin TB, Week 72	7.1 micromole/Liter Standard Deviation 2.38
Change From Baseline (Week 0) in Total Bilirubin TB, Week 84	7.2 micromole/Liter Standard Deviation 2.44
Change From Baseline (Week 0) in Total Bilirubin TB, Week 96	8.1 micromole/Liter Standard Deviation 2.29
Change From Baseline (Week 0) in Total Bilirubin TB, Week 108	7.0 micromole/Liter Standard Deviation 1.79
Change From Baseline (Week 0) in Total Bilirubin TB, 4 week post treatment	8.4 micromole/Liter Standard Deviation 4.11

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to Week 112

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

Change from Baseline in albumin was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post treatment. The last value on or prior to the treatment start date (Week 0) was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in Albumin Albumin, Week 2	39.4 Grams/Liter (G/L) Standard Deviation 5.68
Change From Baseline (Week 0) in Albumin Albumin, Week 4	39.8 Grams/Liter (G/L) Standard Deviation 4.76
Change From Baseline (Week 0) in Albumin Albumin, Week 6	40.4 Grams/Liter (G/L) Standard Deviation 4.88
Change From Baseline (Week 0) in Albumin Albumin, Week 8	40.0 Grams/Liter (G/L) Standard Deviation 4.80
Change From Baseline (Week 0) in Albumin Albumin, Week 10	40.5 Grams/Liter (G/L) Standard Deviation 4.94
Change From Baseline (Week 0) in Albumin Albumin, Week 12	40.3 Grams/Liter (G/L) Standard Deviation 4.56
Change From Baseline (Week 0) in Albumin Albumin, Week 16	37.9 Grams/Liter (G/L) Standard Deviation 5.40
Change From Baseline (Week 0) in Albumin Albumin, Week 20	42.2 Grams/Liter (G/L) Standard Deviation 3.30
Change From Baseline (Week 0) in Albumin Albumin, Week 24	41.0 Grams/Liter (G/L) Standard Deviation 4.28
Change From Baseline (Week 0) in Albumin Albumin, Week 28	40.1 Grams/Liter (G/L) Standard Deviation 5.54
Change From Baseline (Week 0) in Albumin Albumin, Week 32	35.8 Grams/Liter (G/L) Standard Deviation 8.01
Change From Baseline (Week 0) in Albumin Albumin, Week 36	41.4 Grams/Liter (G/L) Standard Deviation 4.81
Change From Baseline (Week 0) in Albumin Albumin, Week 40	41.5 Grams/Liter (G/L) Standard Deviation 3.02
Change From Baseline (Week 0) in Albumin Albumin, Week 44	41.0 Grams/Liter (G/L) Standard Deviation NA SD could not be calculated since only 1 participant was analyzed.
Change From Baseline (Week 0) in Albumin Albumin, Week 48	41.0 Grams/Liter (G/L) Standard Deviation 5.22
Change From Baseline (Week 0) in Albumin Albumin, Week 52	41.3 Grams/Liter (G/L) Standard Deviation 6.22
Change From Baseline (Week 0) in Albumin Albumin, Week 60	41.4 Grams/Liter (G/L) Standard Deviation 4.38
Change From Baseline (Week 0) in Albumin Albumin, Week 72	42.0 Grams/Liter (G/L) Standard Deviation 4.89
Change From Baseline (Week 0) in Albumin Albumin, Week 84	41.9 Grams/Liter (G/L) Standard Deviation 4.20
Change From Baseline (Week 0) in Albumin Albumin, Week 96	43.2 Grams/Liter (G/L) Standard Deviation 2.28
Change From Baseline (Week 0) in Albumin Albumin, Week 108	44.7 Grams/Liter (G/L) Standard Deviation 3.72
Change From Baseline (Week 0) in Albumin Albumin, 4 week post treatment	40.6 Grams/Liter (G/L) Standard Deviation 4.46

SECONDARY outcome

Timeframe: Baseline (week 0) and Weeks 24, 48, 72, 108, and 112 (4 weeks post treatment)

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

QTc is the corrected QT interval as measured by the electrocardiogram (ECG). ECG parameters including the change from Baseline in the QTc interval values QTcF and QTcB were summarised. The QTcF is Fridericia's formula and defined as the QT interval/cubed root of the R-R interval. The QTcB is the Bazett's formula defined as the QT/squared root of the R-R interval. The number of participants with change from Baseline in the QTcF and QTcB intervals of >30, 30 to <60 and >=60 milliseconds were assessed at Week 24, 48, 72, 108, and Week 112. The last value on or prior to the treatment start date was considered the Baseline value (Week 0). Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 24,<30, n=70	66 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 24, 30-<60, n=70	3 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 24, >=60, n=70	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 48,<30, n=35	34 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 48, 30-<60, n=35	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 48, >=60, n=35	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 72,<30, n=17	15 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 72, 30-<60, n=17	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 72, >=60, n=17	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 108,<30, n=3	3 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 108, 30-<60, n=3	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 108, >=60, n=3	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, 4 Weeks Post Treatment, <30, n=96	89 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, 4 Weeks Post Treatment, 30-<60, n=96	6 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, 4 Weeks Post Treatment, >=60, n=96	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 24,<30, n=23	22 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 24, 30-<60, n=23	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 24, >=60, n=23	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 48,<30, n=13	13 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 48, 30-<60, n=13	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcB, Week 48, >=60, n=13	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 72,<30, n=7	7 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 72, 30-<60, n=7	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 72, >=60, n=7	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 108,<30, n=2	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 108, 30-<60, n=2	1 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, Week 108, >=60, n=2	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, 4 Weeks Post Treatment, <30, n=32	32 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, 4 Weeks Post Treatment, 30-<60, n=32	0 Participants
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value QTcF, 4 Weeks Post Treatment, >=60, n=32	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to 108 weeks

Population: Safety population. Only the participants available at the time of assessment were analyzed.

The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant,investigator entries, standardized weight determination, and Hematocrit values received from the central laboratory. The Baseline CDAI score was recorded pre-dose on Week 0. Change from Baseline is the value at indicated time point minus the Baseline value. Remissions are defined as participants with CDAI score of < 150 points. No imputation for missing data was performed. The assessment was based on questionnaire like number of liquid stool in past 7 days, abdominal pain, other symptoms, antidiarrheal use, abdominal mass, anemia, and body weight. The total score is summation of all individual sub-scores. CDAI scoring scale ranges from 0-500 and 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.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 12	-76.0 Scores on a scale Standard Deviation 92.79
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 24	-89.2 Scores on a scale Standard Deviation 102.87
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 36	-103.6 Scores on a scale Standard Deviation 113.63
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 48	-116.6 Scores on a scale Standard Deviation 109.42
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 60	-121.3 Scores on a scale Standard Deviation 111.29
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 72	-110.4 Scores on a scale Standard Deviation 104.18
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 84	-121.4 Scores on a scale Standard Deviation 115.70
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 96	-91.0 Scores on a scale Standard Deviation 80.00
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks Week 108	-50.7 Scores on a scale Standard Deviation 19.86

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to 108 weeks

Population: Safety population. Only the participants available at the time of assessment were analyzed.

The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant and investigator entries and standardized weight determination. Haematocrit values received from the central laboratory on the day of the visit were to be utilized for calculation of the CDAI scores. The Baseline (Week 0) CDAI score was defined as the last evaluation prior to or on the date the first dose of investigational product is taken. The CDAI score was measured over 108 weeks although it was planned to be measured till 112 weeks. Remissions are defined as subjects with CDAI score of < 150 points. Percentages are based on the number of subjects with observed data. No imputation for missing data was performed. Combined data for participants with remission at Baseline and without remission at Baseline has been presented.

Outcome measures

Measure	GSK1605786A 500 mg BID n=398 Participants Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 0	8.5 Participants Interval 5.8 to 11.3
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 12	35.0 Participants Interval 28.9 to 41.2
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 24	41.2 Participants Interval 33.4 to 49.0
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 36	52.6 Participants Interval 42.6 to 62.5
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 48	54.4 Participants Interval 42.6 to 66.2
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 60	53.7 Participants Interval 38.4 to 68.9
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 72	51.9 Participants Interval 33.0 to 70.7
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 84	55.6 Participants Interval 32.6 to 78.5
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 96	66.7 Participants Interval 35.9 to 97.5
Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks Week 108	33.3 Participants Interval 0.0 to 86.7

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to 112 weeks

Population: ITT population was planned to be analyzed for this study.However, this outcome measure was not analyzed due to termination of study and no data was collected for this outcome measure.

The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant and investigator entries and standardized weight determination. Haematocrit values received from the central laboratory on the day of the visit were to be utilized for calculation of the CDAI scores. The Baseline (Week 0) CDAI score was defined as the last evaluation prior to or on the date the first dose of investigational product was taken. Remissions are defined as subjects with CDAI score of < 150 points. Percentages are based on the number of subjects with observed data. No imputation for missing data was performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 0) and up to 112 weeks

Population: ITT population was planned to be analyzed for this study. However, this outcome measure was not analyzed due to termination of study and no data was collected for this outcome measure.

IBDQ, SF-36, EQ-5D, WPAI-CD, and disability scores were all health outcome related scores that were based on assessment of participants based on different questionnaire. Each scoring scale had different range and participants were planned to be rated separately based on each scale.

Outcome measures

Outcome data not reported

Adverse Events

GSK1605786A

Serious events: 41 serious events

Other events: 295 other events

Deaths: 0 deaths

Serious adverse events

Measure	GSK1605786A n=398 participants at risk Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Gastrointestinal disorders Crohn's disease	2.0% 8/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Anal fistula	0.50% 2/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Small intestinal obstruction	0.50% 2/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain upper	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Gastrointestinal stenosis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Intestinal obstruction	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Intestinal perforation	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Large intestinal stenosis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Pancreatitis acute	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Subileus	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Anal abscess	0.75% 3/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Gastroenteritis	0.50% 2/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Abdominal abscess	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Appendicitis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Campylobacter gastroenteritis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Cellulitis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Gastroenteritis viral	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Lobar pneumonia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Pyelonephritis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Shigella infection	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Metabolism and nutrition disorders Dehydration	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Metabolism and nutrition disorders Hypokalaemia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Metabolism and nutrition disorders Hypomagnesaemia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Metabolism and nutrition disorders Malnutrition	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Nervous system disorders Dizziness	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Nervous system disorders Multiple sclerosis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Nervous system disorders Myoclonus	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Injury, poisoning and procedural complications Incisional hernia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Injury, poisoning and procedural complications Postoperative ileus	0.75% 3/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Investigations Liver function test abnormal	0.50% 2/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Arthralgia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Fistula	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Blood and lymphatic system disorders Iron deficiency anaemia	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Endocrine disorders Adrenal insufficiency	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
General disorders Drug ineffective	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Psychiatric disorders Anxiety	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Reproductive system and breast disorders Bartholinitis	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Vascular disorders Intermittent claudication	0.25% 1/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.

Other adverse events

Measure	GSK1605786A n=398 participants at risk Eligible participants received oral GSK1605786A 500 mg BID for 216 weeks and were followed-up till 220 weeks. The participants who prematurely discontinued the study were followed by for last 4 weeks after receiving the last dose of the study drug.
Nervous system disorders Headache	10.6% 42/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Abdominal Pain	12.3% 49/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Crohn's Disease	12.3% 49/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Nausea	6.5% 26/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Diarrhea	6.0% 24/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Gastrointestinal disorders Dyspepsia	5.0% 20/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 20/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
Infections and infestations Nasopharyngitis	16.6% 66/398 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks). On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.

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