(CB-01-02/01) 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:
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00679432
First received: May 14, 2008
Last updated: July 3, 2014
Last verified: July 2014

May 14, 2008
July 3, 2014
June 2008
May 2010   (final data collection date for primary outcome measure)
Clinical and Endoscopic Remission. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Clinical and endoscopic remission defined as a 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.
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 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00679432 on ClinicalTrials.gov Archive Site
  • 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.

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 and in the Inflammatory Bowel Disease-Quality of Life questionnaire [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
(CB-01-02/01) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis
Efficacy and Safety of New Oral Budesonide-MMX™ (CB-01-02) 6 mg and 9 mg Extended Release Tablet Formulations in Patients With Mild or Moderate, Active Ulcerative Colitis. A Multicenter, Randomized, Double-blind, Double Dummy Comparative Study Versus Placebo, With an Additional Reference Arm Evaluating Asacol® 2400 mg.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Ulcerative Colitis
  • 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
Sandborn WJ, Travis S, Moro L, Jones R, Gautille T, Bagin R, Huang M, Yeung P, Ballard ED 2nd. Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012 Nov;143(5):1218-26.e1-2. doi: 10.1053/j.gastro.2012.08.003. Epub 2012 Aug 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
510
June 2010
May 2010   (final data collection date for primary outcome measure)

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 cytochrome P450 3A4 (CYP3A4) inducers or CYP3A4 inhibitors.
    • 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 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).
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Mexico,   India
 
NCT00679432
CB-01-02/01
No
Salix Pharmaceuticals
Salix Pharmaceuticals
Not Provided
Principal Investigator: Bruce Eric Sands Massachusetts General Hospital
Salix Pharmaceuticals
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP