A Study To Investigate The Safety And Efficacy Of CP- 690,550 In Patients With Moderate And Severe Ulcerative Colitis.

Study Overview
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Brief Summary
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The hypothesis of the study is that at least one dose of CP 690 550 is superior to placebo (inactive drug) in inducing remission in patients with moderate to severe ulcerative colitis.

Official Title
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A Randomized, Placebo Controlled, Double Blind, Parallel Group Multi-Center Study In Order To Investigate Safety And Efficacy Of CP- 690 550 In Subjects With Moderate To Severe Ulcerative Colitis.

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: CP- 690 550
* Drug: CP- 690 550
* Drug: CP- 690 550
* Drug: CP- 690 550
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be at least 18 years of age at screening Males and female patients with clinical diagnosis of ulcerative colitis ≥3 months prior to entry into the study. Male and female patients with active currently moderate to severe ulcerative colitis defined by Mayo score of ≥6 Patients with endoscopic sub-score of ≥2 on the Mayo score determined within 7 days of baseline. Exclusion Criteria: Diagnosis of Crohn's disease or diagnosis of indeterminate colitis Treatment naive subjects who have not had previous exposure to treatment for ulcerative colitis Patients that are currently receiving immunosuppressants, anti-TNFα therapy or interferon

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15 mg BID<br> | Drug: CP- 690 550<br>* Administration via oral route twice daily for the duration of treatment<br>|
| Experimental: 10 mg BID<br> | Drug: CP- 690 550<br>* Administration via oral route twice daily for the duration of treatment<br>|
| Experimental: 3 mg BID<br> | Drug: CP- 690 550<br>* Administration via oral route twice daily for the duration of treatment<br>|
| Experimental: 0.5 mg BID<br> | Drug: CP- 690 550<br>* Administration via oral route twice daily for the duration of treatment<br>|
| Placebo Comparator: Placebo<br> | Other: placebo<br>* Administration via oral route twice daily for the duration of treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response | Clinical response was defined as a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with accompanying decrease in subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy and physician global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission | Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mayo score:instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy and physician global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). | Week 8 | 
| Percentage of Participants With Endoscopic Response | Endoscopic response was defined as decrease from baseline in the findings of the flexible proctosigmoidoscopy subscore of the Mayo score at least 1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy and physician global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). | Week 8 | 
| Percentage of Participants With Endoscopic Remission | Endoscopic remission was defined as the findings of flexible proctosigmoidoscopy subscore of the Mayo score equals 0. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy and physician global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). | Week 8 | 
| Change From Baseline in Partial Mayo Score at Week 2, 4, 8 and 12 | Partial Mayo score was ranged from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores: stool frequency, rectal bleeding and physician's global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). | Baseline, Week 2, 4, 8, 12 | 
| Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | IBDQ: Psychometrically validated patient reported outcome (PRO) instrument for measuring disease-specific quality of life (QOL) in participants with IBD. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is sum of each item score, ranged from 32 to 224 with higher score indicates better QOL. Positive change in total score indicated improvement in QOL. | Baseline, Week 8 | 
| Change From Baseline in Level of C-Reactive Protein (CRP) at Week 4 and 8 | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 4, 8 | 
| Change From Baseline in Level of Fecal Calprotectin at Week 2, 4, 8 and 12 | Fecal calprotectin is an inflammatory marker for the gastrointestinal tract and considered as a measurement of neutrophil migration to the gastrointestinal tract. Higher values indicate more serious inflammation. | Baseline, Week 2, 4, 8, 12 | 
| Plasma Concentration of CP-690,550 | Summary statistics were calculated for each dose group using the nominal collection times and by setting concentration values below the lower limit of quantification (LLOQ) (LLOQ=0.1 nanogram per milliliter [ng/mL]) to zero. | 0.25, 0.5, 1, 2 hours post-dose on Day 1, 0 (pre-dose) and 1 hour post-dose on Week 2, Week 4, 0 (pre-dose), 0.25, 0.5, 1, 2 hours post-dose on Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment of ulcerative colitis; CP 690 550