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

This study has been completed.
Sponsor:
Collaborator:
Cosmo Technologies Ltd
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00679380
First received: May 14, 2008
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Procedure: Blood sampling, endoscopy
Drug: Budesonide MMX® 6 mg
Drug: Budesonide MMX® 9 mg
Drug: Entocort EC® 3 mg
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Salix Pharmaceuticals:

Primary Outcome Measures:
  • Clinical and Endoscopic Remission. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Clinical and endoscopic remission defined as an Ulcerative Colitis Disease Activity Index (UCDAI) score ≤ 1, with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance and with a ≥ 1 point reduction in the endoscopic index score.


Secondary Outcome Measures:
  • Clinical Improvement. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Clinical improvement, defined as a ≥ 3-point improvement in UCDAI from baseline to the end of Week 8.

  • Endoscopic Improvement. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    Greater or equal to a 1 point improvement in the mucosal appearance subscore of the UCDAI, from baseline to week 8.

    As per the hierarchical testing procedure for secondary endpoints, because clinical improvement was not statistically significant in the ITT population, formal statistical comparisons for endoscopic improvement between the 2 budesonide MMX groups and placebo were not conducted.



Enrollment: 514
Study Start Date: June 2008
Study Completion Date: April 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: budesonide-MMX® 6 mg
One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
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
Experimental: 2: budesonide-MMX® 9 mg
One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
Procedure: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
Drug: Budesonide MMX® 9 mg
9 mg/day, 9 mg tablets
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.
Procedure: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
Drug: Entocort EC® 3 mg
9 mg/day, 3 mg tablets
Placebo Comparator: 4: Placebo
Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.
Procedure: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
Drug: Placebo
Placebo

Detailed Description:

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 enteric-coated (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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679380

  Show 71 Study Locations
Sponsors and Collaborators
Salix Pharmaceuticals
Cosmo Technologies Ltd
Investigators
Principal Investigator: Simon Travis Oxford University Hospitals NHS Trust
  More Information

No publications provided by Salix Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Salix Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00679380     History of Changes
Other Study ID Numbers: CB-01-02/02
Study First Received: May 14, 2008
Results First Received: April 25, 2014
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Salix Pharmaceuticals:
Ulcerative colitis

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
Budesonide
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014