Effect of GSK1399686 in Patients With Mild to Moderately... | NCT01036022

Description Module

Brief Summary

This study is the first-time-in-patient trial of GSK1399686, a novel locally-acting anti-inflammatory compound, aimed at obtaining initial information on the tolerability, safety, pharmacokinetics (including concentrations in colon mucosa) and anti-inflammatory activity of GSK1399686 upon oral dosing in patients with active ulcerative colitis.

The study is designed as a randomized, double-blind, double-dummy, placebo-controlled, sequential dose escalating trial, with an active control (ASACOL) group as internal control. Up to three cohorts (Cohorts 1-3), each consisting of approximately 20 patients with mild-moderately active ulcerative colitis not limited to the rectum, will be included, one for each dose level of GSK1399686 to be tested. Within a cohort, patients will be randomized in a 3:1:1 ratio to receive GSK1399686 (once daily over 4 weeks, followed by 2 weeks dosing with placebo), placebo, or ASACOL (t.i.d. for 6 weeks), respectively.

An interim analysis of fecal markers and disease activity data will be performed by the end of Cohort 3. Based upon results, the study may be stopped or continued by recruiting either Cohort 4 (if data on an additional dose level would be warranted to establish or clarify a dose-response relationship) or, in the case of a robust efficacy signal at any dose level previously studied, Cohort 5 (to expand the sample size for given dose level in order to evaluate the efficacy of GSK1399686). The number of patients and randomization allocation ratio may be altered in Cohort 5 and it may not include an active control arm. If Cohort 4 is initiated upon interim analysis, then a second interim analysis may be performed at the end of Cohort 4, to assess whether progression into Cohort 5 (as defined above) would be justifiable.

Label	Type	Description	Intervention Names
Group 2	Experimental	ASACOL 800mg t.i.d.	Drug: GSK1399686
Group 1	Experimental	GSK1399686 at 3-4 dose levels	Drug: GSK1399686
Group 3	Experimental	Placebo	Drug: GSK1399686

Name	Type	Description	Arm Group Labels	Other Names
GSK1399686	Drug	Each dose level of GSK1399686 will be subsequently tested in a cohort of approximately 20 patients, who will be randomized in a 3:1:1 ratio to receive GSK1399686 (once daily over 4 weeks, followed by 2 weeks dosing with placebo), placebo, or ASACOL (t.i.d. for 6 weeks), respectively.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE)	An AE is defined as any untoward medical occurrence in a 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, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5.	Up to Week 6
Number of Participants With Clinical Chemistry Data Outside the Reference Range	Normal reference range for clinical chemistry parameters include: alanine amino transferase (ALT) 0-41 international units per liter (IU/L); aspartate amino transferase (AST) 10 - 38 IU/L; alkaline phosphatase 40 - 129 IU/L; gamma glutamyl transferase (GGT) 10 - 66 IU/L; albumin 39 - 48 gram per liter (g/L); total protein 66 - 87 g/L; direct bilirubin 0 - 5.13 micromole per liter (µmol/L); total bilirubin 0 - 17.1 µmol/L; creatinine 61.88 - 106.08 µmol/L; uric acid 202.232 - 416.36 µmol/L; calcium 2.0958 - 2.42015 millimole per liter (mmol/L); cholesterol 2.8446 - 5.9478 mmol/L; chloride 98 - 106 mmol/L; glucose 2.2204 - 11.102 mmol/L; potassium 3.4 - 4.5 mmol/L; magnesium 0.6576 - 1.0686 mmol/L; sodium 0 - 2.26 mmol/L; urea/ blood urea nitrogen (BUN) 0 - 17.85 mmol/L. Number of participants with high and low values compared to the reference range is presented. Only those parameters for which at least one value outside the reference range was reported at any visit are summarized.	Screening (Day -7 to -1), Day 1, Week 1, 2, 3, 4 and 6
Number of Participants With Hematology Data Outside the Reference Range	Normal reference range for clinical chemistry parameters include: basophils 0 - 0.2 giga cells (GI)/L; eosinophils 0 - 0.4 GI/L; lymphocytes 1 - 4.8 GI/L; monocyte 0 - 0.8 GI/L; total neutrophils (total absolute neutrophils count) 1.8 - 7.7 GI/L; platelet count 150 - 400 GI/L; red blood cell count 4.5 - 5.9 GI/L; white blood cell count 3.9 - 10.6 GI/L; hemoglobin 135 - 175 g/L; hematocrit 0.41 - 0.53 ratio; mean corpuscle hemoglobin concentration 310 - 370 g/L; mean corpuscle hemoglobin 26 - 34 picogram (PG); mean corpuscle volume 80 - 100 femtoliter (FL); reticulocytes 0.05 - 0.1 trillion cells (TI)/L. Number of participants with high and low values compared to the reference range is presented. Only those parameters for which at least one value outside the reference range was reported at any visit are summarized.

Secondary Outcomes

Measure	Description	Time Frame
Mean Simple Clinical Colitis Activity Index (SCCAI) Score	SSCAI included composite score: bowel frequency during day on a scale of 0-3 defined as 0 was <= 3, 1= 4 to 6, 2= 7 to 9 and 3 was > 9, during night on a scale of 0-2 defined as 0= none, 1=1 to 3 and 2 was >=4, defecation urgency on a scale of 0-3 defined as 0=none, 1=hurry, 2=immediately and 3=incontinence, blood in stool on a scale of 0-3 defined as 0= none, 1= trace, 2= occasionally frank and 3= usually frank, general well being on a scale of 0-4 defined as 0=very well, 1= slightly below par, 2= poor, 3 = very poor and 4= terrible, extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis) on a scale of 0-1 defined as 0= absent, 1= present. The SCCAI score was calculated as a sum of scores for each individual component of the SCCAI. Minimum score 0, maximum score 19. Higher score implied worsening of symptoms. Participants were given a diary to score each component of SCCAI each morning. Average SCCAI scores over last 3 days were used for each Week.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female of non-childbearing potential between 18 and 65 years of age inclusive.
Presence of mild-to-moderately active ulcerative colitis spread beyond the rectum as evidenced by clinical signs and endoscopy.
UCDAI score 4-10 (inclusive) with rectal bleeding score ≥ 1, endoscopy score ≥ 1 and Physician's rating of disease activity < 3.
Body weight > or = to 50 kg and BMI within the range 18.5-29.9 kg/m2 (inclusive).
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

History of sensitivity to any component of study medications, history of hypersensitivity to ACTH, or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates patient's participation in the study.
History of renal sensitivity to 5-ASA or presence of nephritis, nephropathia or renal function impairment.
Presence or a history of asthma or presence or history of other serious allergic disorder.
Presence or history of chronic liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
Presence of significant hematologic disorder, or significant bleeding or immune system disorder.
QTcB or QTcF >450 msec; or QTc >480 msec in patients with Bundle Branch Block, based on an average QTc value of triplicate ECGs, if the first ECG showed an abnormal value.
Presence of a significant cardiac, pulmonary, metabolic or infectious disease or mental disorder that, in the opinion of the Investigator, represents an unacceptable safety risk for participation in this trial.
History of malignant neoplastic disease within the past 5 years other than localized basal cell skin cancer, squamous cell skin cancer or cancer in situ that has been resected.
History of regular alcohol consumption within 6 months of the study or presence of recreational drug abuse or dependence.
Presence of infectious colitis as evidenced by stool culture positive for enteric pathogens or positive Clostridium difficile cytotoxin assay.
Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
Bowel surgery within last 12 months.
Treatment with oral aminosalicylates at dose ≥ 2.4 g/day and/or with topical aminosalicylates at any dose within 2 weeks prior to Day 1 visit.
Treatment with systemic or topical corticosteroids within 4 weeks prior to Day 1 visit.
Treatment with TNF-α inhibitors or other biologics within 2 months prior to Day 1 visit.
Treatment with immunosuppressants (azathioprine or 6-mercaptopurine), if initiated within 3 months prior to Day 1 visit, or if changed in terms of drug or dose within 3 months prior to Day 1 visit.
Regular use of probiotic or prebiotic preparations, if initiated within 4 weeks prior to Day 1 visit.
Regular daily use of non-steroidal anti-inflammatory drugs (NSAIDs), except low dose aspirin (325 mg/day) for cardioprotection, within 7 days prior to Day 1 visit.
Treatment with medications known to be strong inducers of CYP3A4/5 (e.g. carbamezipine, phenobarbital, phenytoin, rifabutin, rifampin, troglitazone) or regular use of St. John's Wort within 14 days prior to Day 1 visit.
Treatment with medications known to be strong inhibitors of CYP3A4/5 (e.g. ketoconazole, itraconazole, fluconazole, mibefradil, clarithromycin, erythromycin, diltiazem, verapamil), or regular use of grapefruit juice within 7 days prior to Day 1 visit.
Treatment with medications known to be sensitive CYP3A4 substrates with a narrow therapeutic index (e.g. alfentanil, astemizole, cisapride, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine) within 7 days prior to Day 1 visit.
Participation in a clinical trial and treatment with an investigational product within the following time period prior to the Day 1 visit: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Prior enrolment in the present trial.

For Canadian sites only:
Patients with existing gastric or duodenal ulcers.
Patients with urinary tract obstruction

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Bonheiden		2820	Belgium
GSK Investigational Site

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
111407	Informed Consent Form	View IPD

ID	Title	Description
FG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules three times a day (TID) as directed by the investigator for Week 1 to Week 6. Topical 5-aminosalicylic acid (5-ASA) preparation was used as a rescue therapy.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG002	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG003	GSK1399686 100 mg	Participants were administered oral dose of GSK1399686 100 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 100 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG004	GSK1399686 300 mg	Participants were administered oral dose of GSK1399686 300 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 300 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG005	Asacol	Participants were administered oral dose of asacol at 400 mg or 800 mg taken as 1 or 2 capsules TID as directed by the investigator, depending on the 5-ASA dose received by the participants for Week 1 to Week 6. Blinding was maintained by administration of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

An AE is defined as any untoward medical occurrence in a 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, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5.

Intent-To-Treat (ITT) Population was defined as all participants who were randomized to treatment, who received at least one dose of study medication and who had at least one valid post dose assessment.

Posted

Number

Participants

Up to Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG002	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG003	GSK1399686 100 mg	Participants were administered oral dose of GSK1399686 100 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 100 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG004

Units	Counts
Participants	OG00015 OG00111 OG00212 OG003

Title

Denominators

Categories

Any AE

Title	Measurements
	OG00010 OG0017 OG0029 OG003

Primary

Number of Participants With Clinical Chemistry Data Outside the Reference Range

Normal reference range for clinical chemistry parameters include: alanine amino transferase (ALT) 0-41 international units per liter (IU/L); aspartate amino transferase (AST) 10 - 38 IU/L; alkaline phosphatase 40 - 129 IU/L; gamma glutamyl transferase (GGT) 10 - 66 IU/L; albumin 39 - 48 gram per liter (g/L); total protein 66 - 87 g/L; direct bilirubin 0 - 5.13 micromole per liter (µmol/L); total bilirubin 0 - 17.1 µmol/L; creatinine 61.88 - 106.08 µmol/L; uric acid 202.232 - 416.36 µmol/L; calcium 2.0958 - 2.42015 millimole per liter (mmol/L); cholesterol 2.8446 - 5.9478 mmol/L; chloride 98 - 106 mmol/L; glucose 2.2204 - 11.102 mmol/L; potassium 3.4 - 4.5 mmol/L; magnesium 0.6576 - 1.0686 mmol/L; sodium 0 - 2.26 mmol/L; urea/ blood urea nitrogen (BUN) 0 - 17.85 mmol/L. Number of participants with high and low values compared to the reference range is presented. Only those parameters for which at least one value outside the reference range was reported at any visit are summarized.

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

Posted

Number

Participants

Screening (Day -7 to -1), Day 1, Week 1, 2, 3, 4 and 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Primary

Number of Participants With Hematology Data Outside the Reference Range

Normal reference range for clinical chemistry parameters include: basophils 0 - 0.2 giga cells (GI)/L; eosinophils 0 - 0.4 GI/L; lymphocytes 1 - 4.8 GI/L; monocyte 0 - 0.8 GI/L; total neutrophils (total absolute neutrophils count) 1.8 - 7.7 GI/L; platelet count 150 - 400 GI/L; red blood cell count 4.5 - 5.9 GI/L; white blood cell count 3.9 - 10.6 GI/L; hemoglobin 135 - 175 g/L; hematocrit 0.41 - 0.53 ratio; mean corpuscle hemoglobin concentration 310 - 370 g/L; mean corpuscle hemoglobin 26 - 34 picogram (PG); mean corpuscle volume 80 - 100 femtoliter (FL); reticulocytes 0.05 - 0.1 trillion cells (TI)/L. Number of participants with high and low values compared to the reference range is presented. Only those parameters for which at least one value outside the reference range was reported at any visit are summarized.

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

Posted

Number

Participants

Screening (Day -7 to -1), Day 1, Week 1, 2, 3, 4 and 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg

Primary

Number of Participants of Abnormal Urinalysis Dipstick Results

The urinalysis parameters included urine occult blood, urine general, glucose, ketones and protein by dipstick analysis. The assessments were done on screening, Week 2, Week 4 and Week 6.The number of participants with results of 0, 0.3, 1, 1+, 1.5, 10, 2+, 3+, 30, 4+, 5+, 55, not rated (NR), positive (pos) and trace is presented.

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

Posted

Number

Participants

Screening (Day -7 to -1), Week 2, 4 and 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Primary

Number of Participants With Vital Sign Outside Range of Potential Clinical Importance (PCI)

Vital signs assessment included systolic blood pressure (SBP), Diastolic blood pressure (DBP) and heart rate (HR). Criteria for vital sign values meeting PCI included: SBP < 85 and > 160 millimeter of mercury (mmHg); DBP < 45 and > 100 mmHg and HR < 40 and > 110 beats per minute (bpm). The assessments were done on screening, Week 2, Week 4 and Week 6. The participants with values higher and lower than the PCI range is presented. Only those parameters for which at least one value of PCI was reported at any visit are summarized.

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

Posted

Number

Participants

Screening (Day -7 to -1), Week 2, 4 and 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Primary

Number of Participants With Abnormal Electrocardiography (ECG) Findings

Single 12-lead ECGs were obtained at each timepoint during the study using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, and QTc intervals. Criteria for ECG parameter values meeting PCI included absolute QTc interval >500 millisecond (msec); increase from Baseline QTc >60 msec; PR interval <110 and >220 msec; QRS interval <75 and >110 msec. Only those participants for whom at least one value of abnormal clinically significant or abnormal not clinically significant ECG findings were reported at any visit are summarized.

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

Posted

Number

Participants

Screening (Day -7 to -1), Week 2, 4 and 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Primary

Mean Treatment Effects on Basal Morning Cortisol and Adrenocorticotropic Hormone (ACTH) Stimulated Cortisol Levels at Week 4 in Comparison With Baseline

Treatment effects was assessed using a low-dose ACTH stimulation test which was performed on Day 1 pre dose (Baseline) and at Week 4 visit. A blood sample for plasma cortisol was taken immediately, before and 30 minutes after an intravenous injection of 1 microgram (μg). tetracosactide acetate, a synthetic peptide displaying the same physiological properties as ACTH. The change from morning basal cortisol was calculated for Day 1 pre-dose (ACTH1) and Week 4 (ACTH2) using the equation: ACTH1 = Day 1 post ACTH - Day 1 pre ACTH; ACTH2 = Week 4 post ACTH - Week 4 pre ACTH. The change from morning basal cortisol between Week 4 and Day 1 (ACTH effect) was calculated as : ACTH effect = ACTH2 - ACTH1. The difference in morning basal cortisol between Week 4 and Day 1 (ACTH morning) was calculated as:- ACTH morning = Week 4 pre ACTH - Day 1 pre ACTH. Adrenocorticol function was classed as normal if the change from post ACTH to pre ACTH (using ACTH1 and ACTH2) was >= 200 nanomoles per liter.

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

Posted

Least Squares Mean

Standard Error

Nanomoles per liter

Baseline (Day 1, pre dose) and Week 4

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Primary

Mean Concentration of GSK1399686 in Colon Biopsy Obtained Within 24 h After the Last Dose

The assessment was done on the samples collected from the sigmoid colon and from the rectum obtained within 24 hour after the last dose on Week 4 visit after endoscopic evaluation of respective area for determination of GSK1399686 concentration. Non-quantifiable (NQ) concentration values were imputed as 0.

Pharmacokinetic (PK) Population which was defined as the participants in the ITT Population for whom a PK sample was obtained and analysed. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Nanogram (ng)/mL

Week 4

ID	Title	Description
OG000	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Mean Simple Clinical Colitis Activity Index (SCCAI) Score

SSCAI included composite score: bowel frequency during day on a scale of 0-3 defined as 0 was <= 3, 1= 4 to 6, 2= 7 to 9 and 3 was > 9, during night on a scale of 0-2 defined as 0= none, 1=1 to 3 and 2 was >=4, defecation urgency on a scale of 0-3 defined as 0=none, 1=hurry, 2=immediately and 3=incontinence, blood in stool on a scale of 0-3 defined as 0= none, 1= trace, 2= occasionally frank and 3= usually frank, general well being on a scale of 0-4 defined as 0=very well, 1= slightly below par, 2= poor, 3 = very poor and 4= terrible, extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis) on a scale of 0-1 defined as 0= absent, 1= present. The SCCAI score was calculated as a sum of scores for each individual component of the SCCAI. Minimum score 0, maximum score 19. Higher score implied worsening of symptoms. Participants were given a diary to score each component of SCCAI each morning. Average SCCAI scores over last 3 days were used for each Week.

ITT Population. Only those participants available at the specified time points were analyzed. Analysis was done on OC data referred to data collected on the electronic case report form (eCRF) without any imputations added.

Posted

Least Squares Mean

Standard Error

Score on scale

Up to Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Number of Participants With Clinical Response and Clinical Remission at Week 4 and Week 6

Participants were defined as clinical responders if the average change from baseline total SCCAI score was <-2. (i.e. the post dose total SCCAI score was decreased by >2 points compared to the baseline total SCCAI score). Baseline was defined as the value on Day -1. The change from baseline total SCCAI score was derived by subtracting the baseline value (Day -1) from the individual post-dose values. Participants were defined as in clinical remission if the post dose total SCCAI score was <3 and baseline SCCAI score was not <3 (i.e . =>3).

ITT Population. Only those participants available at the specified time points were analyzed. Analysis was done on OC data referred to data collected on the eCRF without any imputations added.

Posted

Number

Participants

Week 4 and Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Median Time to Clinical Response and Clinical Remission

Time to clinical response was defined as the number of days between first dose of study medication and first day of at least 3 consecutive days with SCCAI score decreased for >2 points in comparison with baseline (Day -1 value). Time to clinical remission was defined as the number of days between the first dose of study medication and the first day of at least 3 consecutive days with SCCAI score < 3. Time to clinical response and remission was derived using daily diary data. Participants who did not meet the criteria for clinical response or clinical remission were censored at their last day on study medication.

ITT Population. Data is presented for the participants available at the time of assessment. Analysis was done on OC data referred to data collected on the eCRF without any imputations added.

Posted

Median

Full Range

Days

Up to Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Mean Fecal Calprotectin Levels Over Time

Fecal calprotectin, a non-invasive surrogate marker of inflammation in the small intestine, and levels of which was associated with mucosal healing. Calprotectin is a calcium and zinc-binding protein found in neutrophils, monocytes and macrophages. Calprotectin is produced in significant amounts by inflammatory cells. Fecal levels of this protein has been demonstrated to correlate with colorectal and intestinal inflammation. Calprotectin plays a regulatory role in the inflammatory process and used as a diagnostic biomarker. It was assessed from Week 1 to Week 6.

ITT Population. Only those participants available at the specified time points were analyzed. Analysis was done on OC data referred to data collected on the eCRF without any imputations added.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/g

Up to Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Mean Fecal Lactoferrin Levels Over Time

Fecal lactoferrin, a non-invasive surrogate marker of inflammation in the small intestine, and levels of which was associated with mucosal healing. Lactoferrin is an iron binding glycoprotein that is the major component of the secondary granules of polymorphonuclear neutrophils (but not monocytes and lymphocytes). Lactoferrin is produced in significant amounts by inflammatory cells. Fecal levels of this protein has been demonstrated to correlate with colorectal and intestinal inflammation. Lactoferrin plays an important role in the innate immunity as a bactericidal and used as a diagnostic biomarker. It was assessed from Week 1 to Week 6.

ITT Population. Only those participants available at the specified time points were analyzed. Analysis was done on OC data referred to data collected on the eCRF without any imputations added.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg/L

Up to Week 6

ID	Title	Description
OG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Mean Maximum Observed Concentration (Cmax) on Day 1 and Day 28 Derived From Observed Plasma Concentrations of GSK1399686 After Repeated Oral Dosing

Cmax was derived on Day 1 and Day 28 from observed plasma concentrations of GSK1399686 after repeated oral dosing. Blood samples were collected on Day 1 (1 hour, 2 hour, 3 hour post dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose).

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram (ng)/mL

Day 1 (1 hour, 2 hour, 3 hour post dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)

ID	Title	Description
OG000	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Pre-dose Trough Concentration at the End of the Dosing Interval (Cτ) on Day 28 Derived From Observed Plasma Concentrations of GSK1399686 After Repeated Oral Dosing

Cτ was derived on Day 28 from observed plasma concentrations of GSK1399686 after repeated oral dosing. Blood samples were collected on Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose).

PK Population. Data is presented for the participants available at the time of assessment.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)

ID	Title	Description
OG000	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.

Secondary

Plasma Clearance Estimated Based on Population Pharmacokinetic Analysis of Healthy Volunteers (Historical Data) and Patient Data

Clearance derived from plasma concentration-time data was planned to be combined with data from healthy volunteers from Phase I study to characterize the population pharmacokinetics of GSK1399686. However data for this outcome measure was not collected.

PK Population.

Posted

Day 1 (1 hour, 2 hour, 3 hour post dose), Week 1 (anytime relative to the last dose), Week 2 (anytime relative to the last dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)

ID	Title	Description
OG000	GSK1399686 10mg	Participants were administered oral dose of GSK1399686 10 mg QD in the morning for week 1 to week 4. Blinding was maintained by administration of matching placebo to asacol TID for week 1 to week 6 and matching placebo to GSK1399686 10 mg QD in the morning for week 5 to week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 30mg	Participants were administered oral dose of GSK1399686 30 mg QD in the morning for week 1 to week 4. Blinding was maintained by administration of matching placebo to asacol TID for week 1 to week 6 and matching placebo to GSK1399686 30 mg QD in the morning for week 5 to week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG002

Secondary

Volume of Distribution Estimated Based on Population Pharmacokinetic Analysis of Healthy Volunteers (Historical Data) and Patient Data

Volume of distribution derived from concentration-time data was planned to be combined with data from healthy volunteers from Phase I study to characterize the population pharmacokinetics of GSK1399686. However data for this outcome measure was not collected.

PK Population.

Posted

ID	Title	Description
OG000	GSK1399686 10mg	Participants were administered oral dose of GSK1399686 10 mg QD in the morning for week 1 to week 4. Blinding was maintained by administration of matching placebo to asacol TID for week 1 to week 6 and matching placebo to GSK1399686 10 mg QD in the morning for week 5 to week 6. Topical 5-ASA preparation was used as a rescue therapy.
OG001	GSK1399686 30mg	Participants were administered oral dose of GSK1399686 30 mg QD in the morning for week 1 to week 4. Blinding was maintained by administration of matching placebo to asacol TID for week 1 to week 6 and matching placebo to GSK1399686 30 mg QD in the morning for week 5 to week 6. Topical 5-ASA preparation was used as a rescue therapy.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants were administered oral dose of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1 capsule in the morning immediately before or within 1 hour after a meal, and matching placebo to asacol taken as 1 or 2 capsules TID as directed by the investigator for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	15	1	15	10	15
EG001	GSK1399686 10 mg	Participants were administered oral dose of GSK1399686 10 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 10 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	11	2	11	6	11
EG002	GSK1399686 30 mg	Participants were administered oral dose of GSK1399686 30 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 30 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	12	0	12	9	12
EG003	GSK1399686 100 mg	Participants were administered oral dose of GSK1399686 100 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 100 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	12	0	12	6	12
EG004	GSK1399686 300 mg	Participants were administered oral dose of GSK1399686 300 mg capsule once daily in the morning taken immediately before or within 1 hour after a meal for Week 1 to Week 4. Blinding was maintained by administration of matching placebo to asacol taken as 1 or 2 capsules as directed by the investigator TID for Week 1 to Week 6 and matching placebo to GSK1399686 300 mg once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 5 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	12	0	12	5	12
EG005	Asacol	Participants were administered oral dose of asacol at 400 mg or 800 mg taken as 1 or 2 capsules TID as directed by the investigator, depending on the 5-ASA dose received by the participants for Week 1 to Week 6. Blinding was maintained by administration of matching placebo to GSK1399686 (10 mg, 30 mg, 100 mg, 300 mg) once daily taken as 1capsule immediately before or within 1 hour after a meal in the morning for Week 1 to Week 6. Topical 5-ASA preparation was used as a rescue therapy.	16	1	16	12	16

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0004 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG0033 affected12 at risk EG0042 affected12 at risk EG0052 affected16 at risk
Influenza	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Bronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Cystitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected11 at risk EG0021 affected12 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Gastric disorder	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Regurgitation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0023 affected12 at risk EG003
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected11 at risk EG0020 affected12 at risk EG003
Malaise	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Chest discomfort	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Chills	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0022 affected12 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Photophobia	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Conjunctivitis	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Vision blurred	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Blood chloride increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Gamma- glutamyltransferase	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Serum ferritin decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Weight decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk EG0020 affected12 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0021 affected12 at risk EG003
Hot flush	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected11 at risk EG0020 affected12 at risk EG003

ID	Term
D003092	Colitis
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D015212	Inflammatory Bowel Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases