(CB-01-02/02) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Blood sampling, endoscopy; Budesonide MMX® 6 mg; Budesonide MMX® 9 mg; Entocort EC® 3 mg; Placebo
Intervention description: Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores; 6 mg/day, 6 mg tablets; 9 mg/day, 9 mg tablets; 9 mg/day, 3 mg tablets; Placebo
Intervention MeSH terms: Budesonide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 514.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Ulcerative colitis

Summary:

      This will be a multicentre, randomised, double-blind, double-dummy, parallel group
      comparative study in patients with mild or moderate, active ulcerative colitis. The study
      will compare budesonide-MMX™ 6 mg and budesonide-MMX™ 9 mg tablets to placebo and to
      Entocort® 3 x 3 mg capsules, in four parallel groups of patients over an 8 week treatment
      period.

      After the screening visit, patients will enter a washout period of 2 days, then they will be
      randomised to the following four treatment groups: budesonide-MMX™ tablets (6 mg),
      budesonide-MMX™ tablets (9 mg), Entocort® capsules (3 x 3 mg) and placebo (tablets and
      capsules), all administered once a day after breakfast. Hence, each patient will receive, in
      the morning after breakfast, either one budesonide-MMX™ 6 mg or budesonide MMX™ 9 mg tablet
      and 3 placebo Entocort® matching capsules, or three Entocort® 3 mg capsules and one placebo
      budesonide-MMX™ matching tablet, or one placebo budesonide-MMX™ matching tablet and three
      placebo Entocort® matching capsules.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients fulfilling the following criteria at the screening visit are eligible for
             participation in the study:

               -  Male and female patients, 18-75 years old, suffering from ulcerative colitis for
                  at least 6 months.

               -  Diagnosis of ulcerative colitis in active phase, of mild or moderate entity with
                  Ulcerative Colitis Disease Activity Index (UCDAI) ≥ 4 and ≤ 10 according to
                  Sutherland.

               -  All females of child-bearing potential must have a negative serum pregnancy test
                  immediately prior to enrollment. In addition, all females of child-bearing
                  potential must agree to be completely abstinent or be using an accepted form of
                  contraception throughout the entire study period. Accepted forms of contraception
                  are defined as those with a failure rate <1% when properly applied and include:
                  combination oral pill, some intra-uterine devices, and a sterilised partner in a
                  stable relationship. Female subjects must also not be actively breast-feeding
                  through the entire study period.

               -  Ability to comprehend the full nature and purpose of the study, including
                  possible risks and side effects.

               -  Ability to co-operate with the investigator and to comply with the requirements
                  of the entire study.

               -  Must be able to understand and voluntarily sign written informed consent prior to
                  inclusion in the study.

        Exclusion Criteria:

          -  Patients who meet any of the following criteria at screening visit are to be excluded
             from study participation:

               -  Patients with limited distal proctitis (from anal verge up to 15 cm above the
                  pectineal line).

               -  Patients with severe ulcerative colitis (UCDAI >10).

               -  Patients with infectious colitis.

               -  Evidence or history of toxic megacolon.

               -  Severe anaemia, leucopaenia or granulocytopaenia.

               -  Use of oral or rectal steroids in the last 4 weeks.

               -  Use of immuno-suppressive agents in the last 8 weeks before the study.

               -  Use of anti tumour necrosis factor alpha (anti-TNFα) agents in the last 3 months.

               -  Concomitant use of any rectal preparation.

               -  Concomitant use of antibiotics.

               -  Concurrent use of cytochrome P450 3A4 (CYP3A4) inducers or CYP3A4 inhibitors.

               -  Patients with verified, presumed or expected pregnancy or ongoing lactation.

               -  Patients with liver cirrhosis, or evident hepatic or renal disease or
                  insufficiency, and/or severe impairment of the bio-humoural parameters (i.e. 2 x
                  upper limit of normal for alanine aminotransferase (ALT), aspartate
                  aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) or creatinine).

               -  Patient with severe diseases in other organs and systems.

               -  Patients with local or systemic complications or other pathological states
                  requiring a therapy with corticosteroids and/or immuno-suppressive agents.

               -  Patients diagnosed with type 1 diabetes.

               -  Patients diagnosed with, or with a family history of, glaucoma.

               -  All patients with known hepatitis B, hepatitis C or with human immunodeficiency
                  virus (HIV), according to the local privacy policy.

               -  Participation in experimental therapeutic studies in the last 3 months. (Note:
                  patients who participated in observational only studies are not excluded).

               -  Any other medical condition that in the principal investigator's opinion would
                  make the administration of the study drug or study procedures hazardous to the
                  subject or obscure the interpretation of adverse events (AEs).