Official Title: “Efficacy and Safety of Oral Budesonide-MMX™ (CB-01-02) 6 mg and 9 mg Extended Release Tablets in Patients With Mild or Moderate Active Ulcerative Colitis. A Multicentre, Randomised, Double-Blind, Double-Dummy, Comparative Study Versus Placebo With an Additional Reference Arm Evaluating Entocort®EC”

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Study Primary Completion Date: February 2010

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

1. One budesonide MMX® 6 mg tablet plus three placebo Entocort EC® overencapsulated capsules, or

2. One budesonide MMX® 9 mg tablet plus three placebo Entocort EC® overencapsulated capsules, or

3. Three placebo Entocort EC® overencapsulated capsules plus one placebo budesonide MMX® tablet, or

4. Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet, daily for eight weeks.

Hence, each patient is to take four tablets/capsules per day of active or placebo study medication as per the randomization schedule. Placebo tablets of Budesonide MMX® and placebo overencapsulated capsules of Entocort EC® 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.

Intervention(s) in this Clinical Trial

• 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: Entocort EC® 3 mg
  • 9 mg/day, 3 mg tablets
• Drug: Placebo
  • Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1: budesonide-MMX® 6 mg
  • One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
• Experimental: 2: budesonide-MMX® 9 mg
  • One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
• Active Comparator: 3: Entocort EC® 3 mg
  • Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast.
• Placebo Comparator: 4: Placebo
  • Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.

Primary Measures

• To evaluate the clinical efficacy and safety of budesonide-MMX™ (CB-01-02) 6 mg and 9 mg oral tablets in patients with active mild or moderate ulcerative colitis, when administered for 8 weeks, and compared to placebo
  • Time Frame: 8 weeks
    Safety Issue?: Yes

Secondary Measures

• Efficacy & safety of oral budesonide-MMX 6 mg and 9 mg compared to 3 times daily Asacol®. To evaluate the improvement in rectal bleeding,endoscopic, histological, bio humoral parameters.
  • Time Frame: 8 weeks
    Safety Issue?: Yes

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 CYP3A4 inducers or CYP3A4 inhibitors. See Section 4.2, Table 5 for complete list.
• 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 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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Santarus

Overall Clinical Trial Officials and Contacts

Simon Travis Principal Investigator John Radcliffe Hospital  

Information obtained from ClinicalTrials.gov on September 02, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00679380

Study ID Number: CB-01-02/02

ClinicalTrials.gov Identifier: NCT00679380

Health Authority: United States: Food and Drug Administration