(CB-01-02/04) Extension Study of Budesonide Multi-Matrix System (MMX) 6 mg in Maintenance Of Remission In Patients With Ulcerative Colitis.

Study Overview
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Brief Summary
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Randomized, double-blind, comparative study versus placebo performed in patients from studies CB-01-02/01 (NCT00679432), CB-01-02/02 (NCT00679380), or CB-01-02/06 (NCT01100112) who achieved ulcerative colitis disease activity index (UCDAI) remission after 8 weeks of treatment. Patients in remission at the End of Study visit will be given the opportunity to enter the 12-month Maintenance Phase study outlined in this protocol (CB-01-02/04). The End of Study visit in studies 01, 02, and 06 will be set as the Visit 1 (Day 0) of this study. There will be no interruption of study treatment between the parent studies and this study. It is planned that approximately 150 patients will be enrolled in the study. Patients will be randomly assigned to two groups to receive either budesonide MMX 6 mg or placebo irrespective of the treatment assigned in studies 01, 02, or 06. Treatments will be administered once a day after breakfast for a maximum of 12 months or up to the occurrence of the first clinical relapse, where clinical relapse is defined as combined recurrence of rectal bleeding and stool frequency ≥ 1-2 stools/day above normal for the patient (score ≥ 1 in both UCDAI items). During the study, patients will be assessed for safety and efficacy at Visit 1 and after 1, 3, 6, 9, and 12 months of treatment. Patients will be contacted by telephone on a monthly basis for safety assessment. In case of occurrence of symptoms suggestive of clinical relapse, patients will attend an unscheduled visit at any time during the study.

Official Title
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Randomised, Double-Blind, Multi-Centre, 12 Month Extension Study to Evaluate the Safety And Efficacy of Daily Budesonide MMX 6 mg Versus Placebo in the Maintenance of Remission in Subjects With Ulcerative Colitis.

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Budesonide MMX 6 mg Tablet
* Drug: Placebo Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfilling the following criteria are eligible for participation in the study: Male and female patients, 18-75 years old, who are able to understand and voluntarily provide written informed consent. Patients in UCDAI remission defined as a UCDAI score ≤ 1 point with a score of 0 for rectal bleeding and stool frequency, and a ≥ 1 point reduction from baseline in the endoscopy score without any sign of mucosal friability (score 0 for mucosal appearance). Patients who have completed all End of Study assessments for the CB-01-02/01, CB-01-02/02 and CB-01-02/06 studies. Females of child-bearing potential must have had a serum pregnancy test performed at the End of Study visit of the parent studies and must use an acceptable contraceptive method throughout the study treatment period. Exclusion Criteria: Patients who meet any of the following criteria at screening visit are to be excluded from study participation: Subjects who have withdrawn from studies CB-01-02/01, CB 01 02/02 or CB-01-02/06. Subjects who did not achieve induction of remission according to the primary endpoint definition in studies CB-01-02/01, CB 01 02/02 or CB-01-02/06 (i.e. clinical remission defined as a UCDAI score ≤ 1 point with a score of 0 for rectal bleeding and stool frequency, and ≥ 1 point reduction from baseline in the endoscopy score without any sign of mucosal friability [score 0 for mucosal appearance]). Subjects with bone density lower than normal by age and sex (T-score lower than -1) as assessed via dual energy X-ray absorptiometry (DXA) scans.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Budesonide MMX® 6 mg<br>One Budesonide-MMX® 6 mg tablet self-administered by the patients with a glass of water, in the morning after breakfast. | Drug: Budesonide MMX 6 mg Tablet<br>* Budesonide MMX 6 mg Tablet once daily.<br>|
| Placebo Comparator: 2: Placebo<br>One placebo tablet self-administered by the patients with a glass of water, in the morning after breakfast. | Drug: Placebo Tablet<br>* Placebo Tablet once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission | Clinical remission was defined as the combined absence of recurrence of rectal bleeding and absence of increased stool frequency. | 1, 3, 6, 9, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Relapse | Clinical relapse was defined as the recurrence of rectal bleeding and/or an abnormal stool frequency [≥ 1-2 stools/day above normal for the participant. Clinical remission/relapse status was based on participant diary entries prior to each scheduled visit. | 12 months | 
| Percentage of Participants With Endoscopic Relapse | Endoscopic relapse was defined as an increase of ≥ 2 points in the Endoscopic Index score from the value calculated at baseline. The score is comprised of four components (granulated scattering reflected light, vascular pattern, vulnerability of mucosa, and mucosal damage). Scores range from 0 to 12, and higher scores indicate more severe (worse) endoscopic findings. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis