(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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Procedure: Blood sampling, endoscopy; Drug: budesonide-MMX® 6 mg; Drug: budesonide-MMX® 9 mg; Drug: Asacol® 400 mg

Detailed Description

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 If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be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.

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • Santarus Clinical Investigational Site 6002
  • Toronto, Canada, M3N 2V7
    • Santarus Clinical Investigational Site 6006
  • British Columbia
    • Abbotsford, British Columbia, Canada, V2S 3N5
      • Santarus Clinical Investigational Site 6005
    • Vancouver, British Columbia, Canada, V5Z 1H2
      • Santarus Clinical Investigational Site 6000
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Santarus Clinical Investigational Site 6014
    • Victoria, British Columbia, Canada, V8R 1J8
      • Santarus Clinical Investigational Site 6008
  • Ontario
    • Richmond Hill, Ontario, Canada, L4B 3P8
      • Santarus Clinical Investigational Site 6004
    • Toronto, Ontario, Canada, M4N 3N5
      • Santarus Clinical Investigational Site 6017
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Santarus Clinical Investigational Site 6001
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Santarus Clinical Investigational Site 6016
• India
  • Andhra Pradesh, India
    • Santarus Clinical Investigational Site 9001
  • Andhra Pradesh, India
    • Santarus Clinical Investigational Site 9009
  • Andhra Pradesh, India
    • Santarus Clinical Investigational Site 9012
  • Andhra Pradesh, India
    • Santarus Clinical Investigational Site 9016
  • Assam, India
    • Santarus Clinical Investigational Site 9006
  • Gujarat, India
    • Santarus Clinical Investigational Site 9007
  • Karnataka, India
    • Santarus Clinical Investigational Site 9004
  • Karnataka, India
    • Santarus Clinical Investigational Site 9015
  • Kerala, India
    • Santarus Clinical Investigational Site 9003
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9002
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9008
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9010
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9011
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9013
  • Maharashtra, India
    • Santarus Clinical Investigational Site 9017
  • Rajasthan, India
    • Santarus Clinical Investigational Site 9018
  • Tamil Nadu, India
    • Santarus Clinical Investigational Site 9005
  • Uttar Pradesh, India
    • Santarus Clinical Investigational Site 9014
• Mexico
  • La Paz Baja California Sur
    • Colonia Centra, La Paz Baja California Sur, Mexico, 23000
      • Santarus Clinical Investigational Site 7000
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Santarus Clinical Investigational Site 5051
    • Mobile, Alabama, United States, 36606
      • Santarus Clinical Investigational Site 5102
    • Sylacauga, Alabama, United States, 35150
      • Santarus Clinical Investigational Site 5014
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Santarus Clinical Investigational Site 5088
  • California
    • Anaheim, California, United States, 92801
      • Santarus Clinical Investigational Site 5044
    • Encinitas, California, United States, 92024
      • Santarus Clinical Investigational Site 5099
    • Fremont, California, United States, 94536
      • Santarus Clinical Investigational Site 5075
    • Lakewood, California, United States, 90712
      • Santarus Clinical Investigational Site 5087
    • Los Angeles, California, United States, 90045
      • Santarus Clinical Investigational Site 5033
    • Palm Springs, California, United States, 92262
      • Santarus Clinical Investigational Site 5070
    • San Diego, California, United States, 92101
      • Santarus Clinical Investigational Site 5067
    • San Francisco, California, United States, 94117
      • Santarus Clinical Investigational Site 5028
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Santarus Clinical Investigational Site 5089
    • Hollywood, Florida, United States, 33021
      • Santarus Clinical Investigational Site 5041
    • New Smyrna Beach, Florida, United States, 32168
      • Santarus Clinical Investigational Site 5055
    • Port Orange, Florida, United States, 32127
      • Santarus Clinical Investigational Site 5074
    • Tampa, Florida, United States, 33607
      • Santarus Clinical Investigational Site 5032
    • Tampa, Florida, United States, 33613
      • Santarus Clinical Investigational Site 5009
    • West Palm Beach, Florida, United States, 33409
      • Santarus Clinical Investigational Site 5110
    • Winter Park, Florida, United States, 32789
      • Santarus Clinical Investigational Site 5047
    • Zephyrhills, Florida, United States, 33542
      • Santarus Clinical Investigational Site 5003
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Santarus Clinical Investigational Site 5016
    • Columbus, Georgia, United States, 31904
      • Santarus Clinical Investigational Site 5056
    • Savannah, Georgia, United States, 31406
      • Santarus Clinical Investigational Site 5103
  • Illinois
    • Addison, Illinois, United States, 60101
      • Santarus Clinical Investigational Site 5085
    • Evanston, Illinois, United States, 60201
      • Santarus Clinical Investigational Site 5068
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Santarus Clinical Investigational Site 5086
  • Iowa
    • Clive, Iowa, United States, 50325
      • Santarus Clinical Investigational Site 5053
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Santarus Clinical Investigational Site 5008
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Santarus Clinical Investigational Site 5090
    • Baltimore, Maryland, United States, 21229
      • Santarus Clinical Investigational Site 5025
    • Hollywood, Maryland, United States, 20636
      • Santarus Clinical Investigational Site 5092
    • Prince Frederick, Maryland, United States, 20678
      • Santarus Clinical Investigational Site 5077
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Santarus Clinical Investigational Site 5046
    • Brockton, Massachusetts, United States, 02301
      • Santarus Clinical Investigational Site 5115
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Santarus Clinical Investigational Site 5010
    • Troy, Michigan, United States, 48098
      • Santarus Clinical Investigational Site 5006
    • Wyoming, Michigan, United States, 49519
      • Santarus Clinical Investigational Site 5004
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Santarus Clinical Investigational Site 5105
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
      • Santarus Clinical Investigational Site 5094
    • Marlton, New Jersey, United States, 08053
      • Santarus Clinical Investigational Site 5005
    • Vineland, New Jersey, United States, 08360
      • Santarus Clinical Investigational Site 5024
  • New York
    • Great Neck, New York, United States, 11021
      • Santarus Clinical Investigational Site 5011
    • New York, New York, United States, 10016
      • Santarus Clinical Investigational Site 5101
    • Pittsford, New York, United States, 14534
      • Santarus Clinical Investigational Site 5020
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Santarus Clinical Investigational Site 5096
    • Huntersville, North Carolina, United States, 28078
      • Santarus Clinical Investigational Site 5058
    • New Bern, North Carolina, United States, 28562
      • Santarus Clinical Investigational Site 5091
    • Wilmington, North Carolina, United States, 28403
      • Santarus Clinical Investigational Site 5124
  • Ohio
    • Canton, Ohio, United States, 44701
      • Santarus Clinical Investigational Site 5118
    • Cincinnati, Ohio, United States, 45218
      • Santarus Clinical Investigational Site 5045
    • Dayton, Ohio, United States, 45440
      • Santarus Clinical Investigational Site 5078
    • Mentor, Ohio, United States, 44060
      • Santarus Clinical Investigational Site 5120
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Santarus Clinical Investigational Site 5066
    • Pottstown, Pennsylvania, United States, 19464
      • Santarus Clinical Investigational Site 5065
    • Sayre, Pennsylvania, United States, 18840
      • Santarus Clinical Investigational Site 5035
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Santarus Clinical Investigational Site 5107
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Santarus Clinical Investigational Site 5130
    • Kingsport, Tennessee, United States, 37660
      • Santarus Clinical Investigational Site 5095
  • Texas
    • Austin, Texas, United States, 78745
      • Santarus Clinical Investigational Site 5021
    • Houston, Texas, United States, 77034
      • Santarus Clinical Investigational Site 5076
    • Houston, Texas, United States, 77079
      • Santarus Clinical Investigational Site 5108
    • Houston, Texas, United States, 77090
      • Santarus Clinical Investigational Site 5019
    • Houston, Texas, United States, 77090
      • Santarus Clinical Investigational Site 5036
    • Irving, Texas, United States, 75061
      • Santarus Clinical Investigational Site 5063
    • Kingwood, Texas, United States, 77339
      • Santarus Clinical Investigational Site 5072
    • La Porte, Texas, United States, 77571
      • Santarus Clinical Investigational Site 5054
    • Lewisville, Texas, United States, 75057
      • Santarus Clinical Investigational Site 5030
    • Plano, Texas, United States, 75075
      • Santarus Clinical Investigational Site 5093
    • San Antonio, Texas, United States, 78229
      • Santarus Clinical Investigational Site 5049
    • San Antonio, Texas, United States, 78229
      • Santarus Clinical Investigational Site 5100
    • San Antonio, Texas, United States, 78258
      • Santarus Clinical Investigational Site 5079
    • Tomball, Texas, United States, 77375
      • Santarus Clinical Investigational Site 5098
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Santarus Clinical Investigational Site 5015
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • Santarus Clinical Investigational Site 5097
    • Norfolk, Virginia, United States, 23502
      • Santarus Clinical Investigational Site 5119

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 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.	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
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.	Drug: Placebo; Placebo; Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
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.	Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores; Drug: Asacol® 400 mg; 2400 mg/day, 400 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and Endoscopic Remission.	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement.	Clinical improvement, defined as a ≥ 3-point improvement in UCDAI from baseline to the end of Week 8.	8 weeks
Endoscopic Improvement	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.	8 weeks

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Bruce Eric Sands, Massachusetts General Hospital

Publications and helpful links

General Publications

• Sandborn WJ, Travis S, Moro L, Jones R, Gautille T, Bagin R, Huang M, Yeung P, Ballard ED 2nd. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012 Nov;143(5):1218-1226.e2. doi: 10.1053/j.gastro.2012.08.003. Epub 2012 Aug 11.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 14, 2008
• First Submitted That Met QC Criteria: May 15, 2008
• First Posted (Estimate): May 16, 2008

Study Record Updates

• Last Update Posted (Actual): December 10, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Ulcerative colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: CB-01-02/01