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Health Condition(s) or Problem
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Crohn's Disease
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Lay Summary
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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.
(from ClinicalTrials.gov)
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Who can enter the trial
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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 in
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Who cannot enter the trial
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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 in
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What will happen
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Drug; GSK1605786A; 500 mg twice daily, administered orally for 12 weeks; GSK1605786A 500mg twice daily; Drug; GSK1605786A; 500 mg once daily, administered orally for 12 weeks; GSK1605786A 500mg once daily; Drug; Placebo; Placebo capsules, administered orally for 12 weeks; Placebo
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Primary aim
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Proportion of subjects achieving clinical response
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Secondary Aim
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Proportion of subjects in clinical remission; 12 weeks; No; Proportion of subjects in clinical remission, defined as a CDAI score of less than 150 points at Week 12; Proportion of subjects achieving clinical response at other time points; 8 and 12 weeks; No; Proportion of subjects achieving clinical response, defined as at least a 100 point decrease from baseline in Crohn's Disease Activity Index (CDAI) score; Proportion of subjects in clinical remission at other time points; 8 and 12 weeks; No; Proportion of subjects in clinical remission defined as a CDAI score of less than 150 points at other time points; Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score; 12 weeks; No; Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12; Incidence of adverse events or serious adverse events; 12 weeks; No; Incidence of adverse events or serious adverse events by treatment group
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Participant Information Sheet
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Sorry, not currently available
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Website
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Sorry, not currently available
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Recruitment Status
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Not Recruiting
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Nation
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England, Scotland
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Location
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Harrow, Birmingham, Bristol, Edinburgh, Manchester, Newcastle upon Tyne, Oxford, Salford
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