Crohn's Disease
Conditions
Keywords
Crohn's disease, capsule, GSK1605786A, quality of life, inflammatory bowel disease, oral therapy
Brief summary
This is a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A as compared to placebo over 12 weeks in adult subjects with moderately-to-severely active Crohn's disease. Efficacy will be assessed by proportion of subjects achieving response, defined as a decrease in Crohn's Disease Activity Index (CDAI) score of at least 100 points (clinical response). Clinical remission (CDAI score less than 150 points) will be evaluated as a key secondary endpoint. Safety will be assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram (ECG). Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form-36 version 2 (SF-36v2), EQ-5D and Work Productivity and Activity Impairment-CD (WPAI-CD) and receipt of disability.
Detailed description
This is a multi-centre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of two oral doses of GSK1605786A (500 mg once daily, 500 mg twice daily) as compared to placebo in the induction of clinical response over a 12-week treatment period in subjects with moderately-to-severely active Crohn's disease. Secondary objectives will include assessment of the safety and evaluation of the efficacy in induction of remission. The study is planned to randomise approximately 600 subjects (200 subjects/group) with active Crohn's disease, diagnosed for at least 4 months with a documented history of disease in the small and/or large intestine, and characterised by a Crohn's Disease Activity Index (CDAI) score between 220 to and 450, inclusive. Subjects must have reported an inadequate response or intolerance to Crohn's disease treatment with corticosteroids or immunosuppressants. Inclusion of subjects who received prior treatment with a biologic anti-tumour necrosis factor (TNF) agent will be limited to approximately 50% of the study population. All subjects are required to have a diagnosis with identification of anatomic location of Crohn's disease, which has been established by visualisation of the gastrointestinal tract within 12 months of screening. Subjects who have not had a visualisation of the gastrointestinal tract within 12 months are required to undergo an endoscopic assessment during the screening period. Subjects will be required to have evidence of current active inflammation at the time of randomisation either by endoscopy or by inflammatory biomarkers \[elevated C-reactive protein (CRP) greater than the upper limit of normal (ULN) plus a positive faecal calprotectin test\]. Subjects who do not meet the requirements based on inflammatory biomarker test results will be required to qualify based on endoscopic assessment during screening. Subjects will be allowed to participate in the study while continuing on stable doses of agents typically used to treat Crohn's disease. Following the screening period, subjects will be randomised at baseline to receive blinded treatment with one of two doses of GSK1605786A (500 mg once daily or twice daily) or placebo for 12 weeks. Response and remission endpoints, using the CDAI, will be evaluated at Weeks 4, 8 and 12.
Interventions
DRUGGSK1605786A
500 mg twice daily, administered orally for 12 weeks
DRUGPlacebo
Placebo capsules, administered orally for 12 weeks
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects aged 18 years or older * Written informed consent * Diagnosis of Crohn's disease for greater than 4 months duration with small bowel and/or colonic involvement * Confirmation of Crohn's disease established by visualisation of the gastrointestinal tract within the 12 months prior to screening or by screening endoscopy at study entry * History of inadequate response and/or intolerance/adverse event leading to discontinuation of either corticosteroids or immunosuppressants * Moderately-to-severely active disease characterised by a CDAI score between 220 and 450, inclusive, at Baseline * Confirmation of current active Crohn's disease by screening endoscopy or inflammatory biomarkers \[elevated C-reactive protein (greater than upper limit of normal) plus positive test for faecal calprotectin\] at Screening * Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn's disease * Demonstrated ability to comply with Crohn's disease symptom recording using the interactive voice response system * Females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with a failure rate of less than 1% for the duration of this study
Exclusion criteria
* If female: pregnant, has a positive pregnancy test or is breast-feeding * Diagnosis of coeliac disease, follow a gluten-free diet to manage symptoms, or positive test for coeliac disease * Diagnosis of ulcerative or indeterminate colitis * Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period * Bowel surgery, other than appendectomy, within 12 weeks prior to screen and/or has surgery planned or deemed likely for Crohn's disease during the study period * Extensive colonic resection, subtotal or total colectomy * Presence of ileostomies, colostomies or rectal pouches * Known fixed symptomatic stenoses * History of more than 3 small bowel resections or diagnosis of short bowel syndrome * Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication * Use of prohibited medications, including enteral feeding or elemental diet, within their specified time frames 1. Biologic use: Use of any biologic (tumour necrosis factor inhibitor or natalizumab) within 8 weeks prior to screening 2. Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to screening 3. Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to screening 4. Intravenous antibiotic use: Use of intravenous antibiotics for Crohn's disease within 4 weeks prior to screening 5. Use of rectal treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to screening 6. Use of tube or enteral feeding, elemental diet, or parenteral alimentation within 2 weeks prior to screening 7. Leukocytapheresis or granulocytapheresis within 2 weeks prior to screening * Positive immunoassay for Clostridium difficile * Known human immunodeficiency virus (HIV) infection * Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening * Immunisation with a live vaccine within 4 weeks of screening, with the exception of influenza vaccine * Active or latent tuberculosis infection * Current sepsis or infections requiring intravenous antibiotic therapy for more than 2 weeks * Evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH) * Positive test for Hepatitis B or Hepatitis C antibody at screening * Corrected QT interval of ECG (electrocardiogram) greater than or equal to 450 milliseconds * Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study * History or evidence of adenomatous colonic polyps that have not been removed * History of evidence of colonic mucosal dysplasia * Current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or any cancer in situ that has been resected) * Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B) * Medical history of sensitivity to any of the components of GSK1605786A * Use of any investigational product within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12 | Week 12 | CDAI is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. CDAI score was calculated based on the data collected in the diary card. The total CDAI score ranged from 0 to approximately 600, where higher scores indicate more severe disease. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI response at Week 12 was presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12 | At Week 8 and 12 | Responders were defined as participants with CDAI decrease from baseline of \>= 100 points. CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI decrease from baseline of \>=100 points was presented. |
| Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12 | Week 8 and 12 | Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission defined as a CDAI score of less than 150 points at other time points was presented. |
| Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8 | Week 8 | CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of Participants with a clinical response CDAI decrease from baseline of \>=100 points at Week 8 was presented. |
| Percentage of Participants With CDAI Remission at Week 12 | Week 12 | CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. Participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission at Week 12 was presented. |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Baseline (Week 0), Week 8 and Week 12 | The IBDQ is a 32-item IBD-specific health related quality of life instrument evaluating general activities of daily living, intestinal function, social performance, personal interactions, and emotional status. Each item response was graded from 1 to 7 for each area evaluated. A higher score indicated better function in that area. Total IBDQ score was obtained by summing up scores for all 32 questions. Total IBDQ score ranged from 32 to 224. A higher score indicated better quality of life and lower score indicated worse quality of life. Day 1 assessment was considered as Baseline. Change from Baseline was calculated by subtracting value at Baseline from value at Weeks 8 and 12. |
| Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | Up to Week 12 | Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. |
| Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8 | Week 8 | Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants achieving clinical remission with CDAI \<150 points at Week 8 was presented. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Slovakia, South Africa, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 608 participants with moderately-to-severely active Crohn's disease were enrolled in this study. The study was conducted at 162 centres in 23 countries, with sites in North America, Europe, Israel, South Africa, Japan, Australia, Korea and New Zealand. Study duration was from 20 December 2010 to 11 July 2013.
Pre-assignment details
Of the total 1205 participants screened, 597 were screen failures and 608 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible participants were randomized at baseline (Week 0) to receive matching placebo orally for 12 weeks treatment period. | 203 |
| GSK1605786A 500 mg Once Daily Eligible participants were randomized at baseline (Week 0) to receive GSK1605786A 500 mg once daily hard gelatin capsules orally for 12 weeks treatment period. | 203 |
| GSK1605786A 500 mg Twice Daily Eligible participants were randomized at baseline (Week 0) to receive GSK1605786A 500 mg twice daily hard gelatin capsules orally for 12 weeks treatment period. | 202 |
| Total | 608 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 26 | 25 | 20 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 8 | 20 | 12 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 |
| Overall Study | Protocol Defined Stopping criteria | 1 | 2 | 6 |
| Overall Study | Protocol Violation | 2 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 8 | 6 |
Baseline characteristics
| Characteristic | Placebo | GSK1605786A 500 mg Once Daily | GSK1605786A 500 mg Twice Daily | Total |
|---|---|---|---|---|
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 12.62 | 37.0 Years STANDARD_DEVIATION 12.6 | 35.9 Years STANDARD_DEVIATION 12.51 | 36.3 Years STANDARD_DEVIATION 12.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 21 Participants | 17 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 177 Participants | 177 Participants | 179 Participants | 533 Participants |
| Sex: Female, Male Female | 103 Participants | 130 Participants | 106 Participants | 339 Participants |
| Sex: Female, Male Male | 100 Participants | 73 Participants | 96 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 202 | 0 / 202 | 1 / 201 |
| other Total, other adverse events | 77 / 202 | 82 / 202 | 100 / 201 |
| serious Total, serious adverse events | 18 / 202 | 12 / 202 | 12 / 201 |
Outcome results
Primary
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12
CDAI is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. CDAI score was calculated based on the data collected in the diary card. The total CDAI score ranged from 0 to approximately 600, where higher scores indicate more severe disease. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI response at Week 12 was presented.
Time frame: Week 12
Population: The intent to treat population comprised of all participants randomized to double-blind treatment for 12 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12 | 25.1 Percentage of participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12 | 27.6 Percentage of participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12 | 27.2 Percentage of participants |
Comparison: comparison of Placebo and GSK1605786A 500 mg once dailyp-value: 0.54695% CI: [-6.1, 11]Mantel Haenszel
Comparison: comparison of Placebo and GSK1605786A 500 mg twice dailyp-value: 0.64895% CI: [-6.5, 10.7]Mantel Haenszel
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12
The IBDQ is a 32-item IBD-specific health related quality of life instrument evaluating general activities of daily living, intestinal function, social performance, personal interactions, and emotional status. Each item response was graded from 1 to 7 for each area evaluated. A higher score indicated better function in that area. Total IBDQ score was obtained by summing up scores for all 32 questions. Total IBDQ score ranged from 32 to 224. A higher score indicated better quality of life and lower score indicated worse quality of life. Day 1 assessment was considered as Baseline. Change from Baseline was calculated by subtracting value at Baseline from value at Weeks 8 and 12.
Time frame: Baseline (Week 0), Week 8 and Week 12
Population: Intent to treat population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 8 | 13.18 Score on scale | Standard Error 1.728 |
| Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 12 | 13.00 Score on scale | Standard Error 1.889 |
| GSK1605786A 500 mg Once Daily | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 8 | 12.06 Score on scale | Standard Error 1.704 |
| GSK1605786A 500 mg Once Daily | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 12 | 12.66 Score on scale | Standard Error 1.863 |
| GSK1605786A 500 mg Twice Daily | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 8 | 16.55 Score on scale | Standard Error 1.757 |
| GSK1605786A 500 mg Twice Daily | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12 | Week 12 | 14.86 Score on scale | Standard Error 1.921 |
Comparison: Week 8p-value: 0.64295% CI: [-5.89, 3.64]ANCOVA
Comparison: Week 12p-value: 0.89895% CI: [-5.55, 4.87]ANCOVA
Comparison: Week 8p-value: 0.17395% CI: [-1.48, 8.21]ANCOVA
Comparison: Week 12p-value: 0.49395% CI: [-3.45, 7.15]ANCOVA
Secondary
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)
Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time frame: Up to Week 12
Population: The Safety population comprised of all participants in the intent to treat population except those who did not take at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 141 Participants |
| Placebo | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 18 Participants |
| GSK1605786A 500 mg Once Daily | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 148 Participants |
| GSK1605786A 500 mg Once Daily | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 12 Participants |
| GSK1605786A 500 mg Twice Daily | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 157 Participants |
| GSK1605786A 500 mg Twice Daily | Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 12 Participants |
Secondary
Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8
Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants achieving clinical remission with CDAI \<150 points at Week 8 was presented.
Time frame: Week 8
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8 | 12.3 Percentage of participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8 | 10.3 Percentage of participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8 | 9.9 Percentage of participants |
p-value: 0.54195% CI: [-8.1, 4.2]Mantel Haenszel
p-value: 0.4395% CI: [-8.5, 3.7]Mantel Haenszel
Secondary
Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12
Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission defined as a CDAI score of less than 150 points at other time points was presented.
Time frame: Week 8 and 12
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12 | 7.9 Percentage of participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12 | 7.9 Percentage of participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12 | 6.9 Percentage of participants |
p-value: 0.98595% CI: [-5.2, 5.2]Mantel Haenszel
p-value: 0.70995% CI: [-6.1, 4.1]Mantel Haenszel
Secondary
Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12
Responders were defined as participants with CDAI decrease from baseline of \>= 100 points. CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI decrease from baseline of \>=100 points was presented.
Time frame: At Week 8 and 12
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12 | 15.8 Percentage of participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12 | 18.7 Percentage of participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12 | 19.3 Percentage of participants |
p-value: 0.41595% CI: [-4.4, 10.3]Mantel Haenszel
p-value: 0.35495% CI: [-3.9, 10.9]Mantel Haenszel
Secondary
Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8
CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of Participants with a clinical response CDAI decrease from baseline of \>=100 points at Week 8 was presented.
Time frame: Week 8
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8 | 24.1 Percentage of Participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8 | 26.1 Percentage of Participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8 | 24.8 Percentage of Participants |
p-value: 0.63395% CI: [-6.5, 10.4]Mantel Haenszel
p-value: 0.88995% CI: [-7.8, 9]Mantel Haenszel
Secondary
Percentage of Participants With CDAI Remission at Week 12
CDAI is a recognized scoring system to categorize disease severity with scores of \>= 220 to \<= 450 describing the moderately-to-severely active population. Clinical remission is defined as a CDAI score \< 150 points if baseline CDAI is \>= 150. If baseline CDAI is \<150, the participant was not considered in remission. Participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission at Week 12 was presented.
Time frame: Week 12
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With CDAI Remission at Week 12 | 15.3 Percentage of participants |
| GSK1605786A 500 mg Once Daily | Percentage of Participants With CDAI Remission at Week 12 | 13.3 Percentage of participants |
| GSK1605786A 500 mg Twice Daily | Percentage of Participants With CDAI Remission at Week 12 | 12.9 Percentage of participants |
p-value: 0.59295% CI: [-8.8, 4.8]Mantel Haenszel
p-value: 0.47595% CI: [-9.2, 4.4]Mantel Haenszel