Open-Label Extension Study of GSK1605786A

An Open-Label Extension Study to Assess the Safety of GSK1605786A in Subjects With Crohn's Disease

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01318993

Acronym

SHIELD-3

Enrollment

399

Registered

2011-03-21

Start date

2011-04-01

Completion date

2013-10-29

Last updated

2017-09-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Keywords

GSK1605786A; Inflammatory Bowel Disease; Crohn's disease; long-term treatment; quality of life; CCR9 antagonist

Brief summary

An open-label study to evaluate the safety and effectiveness of GSK1605786A 500 mg twice daily over 108 weeks in adult subjects with Crohn's disease. Subjects completing previous GSK-sponsored studies with GSK1605786A or subjects who withdraw early from Study CCX114157 (maintenance study of GSK1605786A) due to worsening of Crohn's disease requiring a treatment change may be eligible to participate. The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and receipt of disability.

Detailed description

This is a multi-centre, open-label extension study to assess the long-term safety, tolerability and effectiveness of GSK1605786A in subjects with Crohn's disease. Subjects will enter the study via one of three routes: 1. completion of the placebo-controlled induction study, CCX114151, without achieving clinical response (CDAI decrease of at least 100 points) or clinical remission (CDAI score less than 150) at Week 12 or completion of any other GSK-sponsored induction study as designated by the sponsor 2. completion of maintenance study CCX114157 at Week 52 3. withdrawal from maintenance study CCX114157 due to worsening of Crohn's disease and requiring a treatment change. The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and disability. It is estimated that approximately 800 subjects will be enrolled in total. All subjects will enter the study at baseline (Week 0) and commence oral treatment with GSK1605786A 500 mg twice daily. The study will be conducted for 108 weeks. Once the results of the induction study CCX114151 are known, the risk-to-benefit ratio will be re-assessed and the study duration may be amended. Study assessments for Crohn's disease will be performed every 12 weeks through Week 108. At week 12, the investigator will make a determination of whether the subject is receiving clinical benefit, and subjects who are not receiving clinical benefit must be withdrawn. More frequent blood draws are required for liver function testing only; every 2 weeks for the first 12 weeks, then every 4 weeks up to Week 52, and every 12 weeks after Week 60 for the duration of the study.

Interventions

DRUGGSK1605786A

500 milligrams twice daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Previous participation in a GSK-sponsored study with GSK1605786A * Written informed consent prior to any study-specific procedures * Female subjects: To be eligible, females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with less than 1% failure rate

Exclusion criteria

* If female, is pregnant, has a positive pregnancy test or is breast-feeding, or is planning to become pregnant * Subjects with known or suspected coeliac disease or a positive screening test for anti-tissue transglutaminase antibodies should have been excluded from enrolment into any induction study. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should be tested for anti-tissue transglutaminase antibodies and excluded or withdrawn from the study upon positive test result * Fixed symptomatic stenoses or strictures of small bowel or colon * Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period * Current sepsis or infections requiring intravenous antibiotic therapy greater than 2 weeks * Evidence of hepatic dysfunction or viral hepatitis * Subjects who have demonstrated safety or tolerability issues during participation in a previous study with GSK1605786A which, in the opinion of the investigator, was possibly related to study treatment and poses an unacceptable risk to the subject.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE)	Up to Week 112	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.

Secondary

Measure	Time frame	Description
Change From Baseline (Week 0) in Heart Rate (HR) Over Period	Baseline (week 0) and up to Week 112	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.
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Baseline (Week 0) and up to Week 112	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.
Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Baseline (Week 0) and up to Week 112	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.
Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT)	Baseline (Week 0) and up to Week 112	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.
Change From Baseline (Week 0) in Total Bilirubin	Baseline (Week 0) and up to Week 112	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.
Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period	Baseline (Week 0) and up to Week 112	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.
Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value	Baseline (week 0) and Weeks 24, 48, 72, 108, and 112 (4 weeks post treatment)	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.
Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks	Baseline (Week 0) and up to 108 weeks	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.
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	Baseline (Week 0) and up to 108 weeks	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.
Percentage of Participants Achieving Response (CDAI Decrease of at Least 100 Points From Baseline ([Week 0] of Prior Induction Study) in the Sub-population of Non-responders at Study Entry Over 112 Weeks	Baseline (Week 0) and up to 112 weeks	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.
Change From Baseline (Week 0) in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form Health Survey (SF-36) Version 2, EuroQol 5 Dimensional (EQ-5D), Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and Disability Over 112 Weeks	Baseline (Week 0) and up to 112 weeks	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.
Change From Baseline (Week 0) in Albumin	Baseline (Week 0) and up to Week 112	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.

Countries

Australia, Austria, Belgium, Bulgaria, Canada, Chile, Czechia, Denmark, Estonia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, New Zealand, Poland, Portugal, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States

Participant flow

Recruitment details

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.

Pre-assignment details

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

Participants by arm

Arm	Count
GSK1605786A 500 mg BID 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.	398
Total	398

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	53
Overall Study	Lack of Efficacy	121
Overall Study	Lost to Follow-up	4
Overall Study	Physician Decision	13
Overall Study	Protocol based stopping criteria	6
Overall Study	Protocol Violation	3
Overall Study	Study closed or terminated	174
Overall Study	Withdrawal by Subject	24

Baseline characteristics

Characteristic	GSK1605786A 500 mg BID
Age, Continuous	36.5 Years STANDARD_DEVIATION 11.99
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	38 Participants
Race (NIH/OMB) Black or African American	7 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	351 Participants
Sex: Female, Male Female	213 Participants
Sex: Female, Male Male	185 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 398
other Total, other adverse events	295 / 398
serious Total, serious adverse events	41 / 398

Outcome results

Primary

Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE)

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.

Time frame: Up to Week 112

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK1605786A 500 mg BID	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE)	Any AE	303 Participants
GSK1605786A 500 mg BID	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE)	Any SAE	41 Participants

Secondary

Change From Baseline (Week 0) in Albumin

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 84	41.9 Grams/Liter (G/L)	Standard Deviation 4.2
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 2	39.4 Grams/Liter (G/L)	Standard Deviation 5.68
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 4	39.8 Grams/Liter (G/L)	Standard Deviation 4.76
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 6	40.4 Grams/Liter (G/L)	Standard Deviation 4.88
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 8	40.0 Grams/Liter (G/L)	Standard Deviation 4.8
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 10	40.5 Grams/Liter (G/L)	Standard Deviation 4.94
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 12	40.3 Grams/Liter (G/L)	Standard Deviation 4.56
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 16	37.9 Grams/Liter (G/L)	Standard Deviation 5.4
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 20	42.2 Grams/Liter (G/L)	Standard Deviation 3.3
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 24	41.0 Grams/Liter (G/L)	Standard Deviation 4.28
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 28	40.1 Grams/Liter (G/L)	Standard Deviation 5.54
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 32	35.8 Grams/Liter (G/L)	Standard Deviation 8.01
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 36	41.4 Grams/Liter (G/L)	Standard Deviation 4.81
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 40	41.5 Grams/Liter (G/L)	Standard Deviation 3.02
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 44	41.0 Grams/Liter (G/L)	—
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 48	41.0 Grams/Liter (G/L)	Standard Deviation 5.22
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 52	41.3 Grams/Liter (G/L)	Standard Deviation 6.22
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 60	41.4 Grams/Liter (G/L)	Standard Deviation 4.38
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 72	42.0 Grams/Liter (G/L)	Standard Deviation 4.89
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 96	43.2 Grams/Liter (G/L)	Standard Deviation 2.28
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, Week 108	44.7 Grams/Liter (G/L)	Standard Deviation 3.72
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Albumin	Albumin, 4 week post treatment	40.6 Grams/Liter (G/L)	Standard Deviation 4.46

Secondary

Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT)

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 10.2
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 21.9
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 3.8
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 25.6
GSK1605786A 500 mg BID	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 25.6
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 26.5
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 18.8
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 31.5
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 23.5
GSK1605786A 500 mg BID	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 25.3
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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

Secondary

Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks

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.

Time frame: Baseline (Week 0) and up to 108 weeks

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	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 115.7
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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

Change From Baseline (Week 0) in Heart Rate (HR) Over Period

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.

Time frame: Baseline (week 0) and up to Week 112

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 4	1.3 beats per minute	Standard Deviation 10.92
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 8	0.1 beats per minute	Standard Deviation 11.41
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 12	0.8 beats per minute	Standard Deviation 11.93
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 24	-0.5 beats per minute	Standard Deviation 12.56
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 36	2.1 beats per minute	Standard Deviation 12.35
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 48	-1.2 beats per minute	Standard Deviation 13.16
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 60	0.4 beats per minute	Standard Deviation 12.85
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 72	-1.2 beats per minute	Standard Deviation 12.39
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 84	-0.7 beats per minute	Standard Deviation 15.44
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 96	-4.9 beats per minute	Standard Deviation 17.01
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Heart Rate (HR) Over Period	HR, Week 108	-7.7 beats per minute	Standard Deviation 12.83
GSK1605786A 500 mg BID	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

Change From Baseline (Week 0) in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form Health Survey (SF-36) Version 2, EuroQol 5 Dimensional (EQ-5D), Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and Disability Over 112 Weeks

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.

Time frame: 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.

Secondary

Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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 9.8
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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

Change From Baseline (Week 0) in Total Bilirubin

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 36	7.1 micromole/Liter	Standard Deviation 2.42
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 40	7.4 micromole/Liter	Standard Deviation 3.01
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 2	6.9 micromole/Liter	Standard Deviation 2.85
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 4	7.1 micromole/Liter	Standard Deviation 3.24
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 6	6.8 micromole/Liter	Standard Deviation 2.76
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 8	6.8 micromole/Liter	Standard Deviation 2.61
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 10	7.1 micromole/Liter	Standard Deviation 2.91
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 12	6.7 micromole/Liter	Standard Deviation 2.54
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 16	7.0 micromole/Liter	Standard Deviation 2.78
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 20	6.9 micromole/Liter	Standard Deviation 2.99
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 24	7.2 micromole/Liter	Standard Deviation 2.8
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 28	7.0 micromole/Liter	Standard Deviation 2.7
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 32	6.9 micromole/Liter	Standard Deviation 2.58
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 44	7.4 micromole/Liter	Standard Deviation 2.56
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 48	7.0 micromole/Liter	Standard Deviation 2.35
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 52	7.0 micromole/Liter	Standard Deviation 2.57
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 60	7.3 micromole/Liter	Standard Deviation 2.05
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 72	7.1 micromole/Liter	Standard Deviation 2.38
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 84	7.2 micromole/Liter	Standard Deviation 2.44
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 96	8.1 micromole/Liter	Standard Deviation 2.29
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, Week 108	7.0 micromole/Liter	Standard Deviation 1.79
GSK1605786A 500 mg BID	Change From Baseline (Week 0) in Total Bilirubin	TB, 4 week post treatment	8.4 micromole/Liter	Standard Deviation 4.11

Secondary

Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	TB, shift to normal or no change	391 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	ALT, shift to high	48 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Total Protein, shift to low	27 Participants
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Total Protein, shift to high	1 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Phosphorous, shift to low	85 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Phosphorous, shift to normal or no change	283 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Phosphorous, shift to high	30 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Albumin, shift to low	19 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Albumin, shift to normal or no change	373 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Albumin, shift to high	3 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Sodium, shift to low	18 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Sodium, shift to normal or no change	376 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Sodium, shift to high	1 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Potassium, shift to low	25 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Potassium, shift to normal or no change	360 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Potassium, shift to high	10 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Chloride, shift to low	3 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Chloride, shift to normal or no change	361 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Chloride, shift to high	31 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Calcium, shift to low	43 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Calcium, shift to normal or no change	340 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Calcium, shift to high	12 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Glucose, shift to low	54 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Glucose, shift to normal or no change	279 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Glucose, shift to high	66 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	GGT, shift to normal or no change	330 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	GGT, shift to high	67 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	TB, shift to high	6 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	DB, shift to normal or no change	397 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	DB, shift to high	0 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	ALP, shift to low	0 Participants
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	ALP, shift to high, n=370	14 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	ALT, shift to normal or no change	349 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	AST, shift to normal or no change	362 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	AST, shift to high	35 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	BUN/Urea, shift to low	44 Participants
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	BUN/Urea, shift to high	6 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Creatinine, shift to low	50 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Creatinine, shift to normal or no change	335 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Creatinine, shift to high	10 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Uric Acid, shift to low	21 Participants
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Uric Acid, shift to high	24 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Bicarbonate, shift to low	92 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Bicarbonate, shift to normal or no change	303 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Bicarbonate, shift to high	0 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	LDH, shift to normal or no change	386 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	LDH, shift to high	9 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Cholesterol, shift to normal or no change	330 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	Cholesterol, shift to high	65 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	CK, shift to normal or no change	357 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters	CK, shift to high	38 Participants

Secondary

Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters

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.

Time frame: Baseline (Week 0) and up to Week 112

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Eosinophils, shift to normal or no change	366 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Platelets, shift to low	2 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Platelets, shift to normal or no change	325 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Platelets, shift to high	67 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	NL, shift to low	5 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	NL, shift to normal or no change	284 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	NL, shift to high	106 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Lymphocytes, shift to low	99 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Lymphocytes, shift to normal or no change	292 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Lymphocytes, shift to high	4 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Monocytes, shift to low	0 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Monocytes, shift to normal or no change	372 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Monocytes, shift to high	23 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Eosinophils, shift to high	29 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Basophils, shift to normal or no change	395 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Basophils, shift to high	0 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hematocrit, shift to low	75 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hematocrit, shift to normal or no change	312 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hematocrit, shift to high	8 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Band cells, shift to normal or no change	5 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Band cells, shift to high	1 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	RBC Count, shift to low	62 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	RBC Count, shift to normal or no change	322 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	RBC Count, shift to high	11 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hemoglobin, shift to low	74 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hemoglobin, shift to normal or no change	320 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Hemoglobin, shift to high	1 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	WBC Count, shift to low	23 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	WBC Count, shift to normal or no change	289 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	WBC Count, shift to high	83 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Segmented (Seg) NL, shift to low	5 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Seg NL, shift to normal or no change	283 Participants
GSK1605786A 500 mg BID	Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters	Seg NL, shift to high	107 Participants

Secondary

Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value

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.

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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

Percentage of Participants Achieving Response (CDAI Decrease of at Least 100 Points From Baseline ([Week 0] of Prior Induction Study) in the Sub-population of Non-responders at Study Entry Over 112 Weeks

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.

Time frame: 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.

Secondary

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

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.

Time frame: Baseline (Week 0) and up to 108 weeks

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

Arm	Measure	Group	Value (NUMBER)
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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
GSK1605786A 500 mg BID	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

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Open-Label Extension Study of GSK1605786A

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE)

Change From Baseline (Week 0) in Albumin

Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT)

Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks

Change From Baseline (Week 0) in Heart Rate (HR) Over Period

Change From Baseline (Week 0) in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form Health Survey (SF-36) Version 2, EuroQol 5 Dimensional (EQ-5D), Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and Disability Over 112 Weeks

Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period

Change From Baseline (Week 0) in Total Bilirubin

Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters

Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters

Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value

Percentage of Participants Achieving Response (CDAI Decrease of at Least 100 Points From Baseline ([Week 0] of Prior Induction Study) in the Sub-population of Non-responders at Study Entry Over 112 Weeks

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