(CB-01-02/01)Randomized Placebo Controlled Trial of Budesonide-MMX™ (CB-01-02) 6 mg and 9 mg in Patients With Ulcerative Colitis

The purpose of this study is to compare Budesonide MMX™ 6 mg and Budesonide MMX™ 9 mg tablets to placebo and to Asacol 6x 400 mg tablets over an 8-week treatment period to determine if Budesonide MMX™ is effective in the treatment of ulcerative colitis.

Each patient will receive one of the following regimens in the morning after breakfast:

1. one budesonide-MMX™ 6 mg tablet plus two placebo Asacol® over encapsulated tablets, or
2. one budesonide-MMX™ 9 mg tablet plus two placebo Asacol® over encapsulated tablets, or
3. two placebo Asacol® over encapsulated tablets plus one placebo budesonide tablet, or
4. two Asacol® 400 mg over encapsulated tablets plus one placebo budesonide tablet, daily for 8 weeks.

Each patient will also receive on each day after the midday meal and after the evening meal either:

• two Asacol® 400 mg over-encapsulated tablets (Group 4), or
• the equivalent placebo Asacol® over-encapsulated tablets, (Groups 1, 2 and 3)

Hence, each patient is to take seven tablets per day of active or placebo study medication as per the randomization schedule. Placebo tablets of budesonide-MMX™ and placebo over-encapsulated tablets of Asacol® will be used to maintain the study blind using a double-dummy technique.

During the study, five visits to the clinical center are scheduled: one at Screening and three in the double-blind treatment period (Day 1, Day 14, Day 28 and Day 56). A safety follow up visit will take place about 2 weeks after the final study visit. If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be conducted.

• Procedure: Blood sampling, endoscopy
  Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
• Drug: budesonide-MMX® 6 mg
  6 mg/day, 6 mg tablets
• Drug: budesonide-MMX® 9 mg
  9 mg/day, 9 mg tablets
• Drug: Placebo
  Placebo
• Drug: Asacol® 400 mg
  2400 mg/day, 400 mg tablets

• Experimental: 1: budesonide-MMX® 6 mg
  One budesonide-MMX® 6 mg plus two placebo Asacol® overencapsulated tablets daily in the morning after breakfast and two placebo Asacol® overencapsulated tablets daily after the mid-day meal and the evening meal for eight weeks.
  Interventions:

  • Procedure: Blood sampling, endoscopy
  • Drug: budesonide-MMX® 6 mg
• Experimental: 2: budesonide-MMX® 9 mg
  One budesonide-MMX® 9 mg plus two placebo Asacol® overencapsulated tablets daily in the morning after breakfast and two placebo Asacol® overencapsulated tablets daily after the mid-day meal and the evening meal for eight weeks.
  Interventions:

  • Procedure: Blood sampling, endoscopy
  • Drug: budesonide-MMX® 9 mg
• Placebo Comparator: 3: Placebo
  Two placebo Asacol® overencapsulated tablets plus one placebo Budesonide MMX® tablet daily in the morning after breakfast and two placebo Asacol® overencapsulated tablets daily after the mid-day meal and the evening meal for eight weeks.
  Interventions:

  • Procedure: Blood sampling, endoscopy
  • Drug: Placebo
• Active Comparator: 4: Asacol® 400 mg
  Two Asacol® 400 mg overencapsulated tablets plus one placebo budesonide MMX® tablet daily in the morning after breakfast and two Asacol® 400 mg overencapsulated tablets daily after the mid-day meal and the evening meal for eight weeks.
  Interventions:

  • Procedure: Blood sampling, endoscopy
  • Drug: Asacol® 400 mg

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 anemia, leucopenia or granulocytopenia.
  • 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 tumor necrosis factor alpha (anti-TNFα) agents in the last 3 months.
  • Concomitant use of any rectal preparation.
  • Concomitant use of antibiotics.
  • Concurrent use of CYP3A4 inducers or CYP3A4 inhibitors. See Section 4.2, Table 5 for complete list.
  • Patients with intolerance to salicylates.
  • 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-humoral parameters (i.e. 2 x upper limit of normal for ALT, AST, 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).