(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
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Procedure: Blood sampling, endoscopy
Drug: budesonide-MMX® 6 mg
Drug: budesonide-MMX® 9 mg
Drug: Placebo
Drug: Asacol® 400 mg
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 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.

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 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.


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: 510
Study Start Date: June 2008
Study Completion Date: June 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores
Drug: Placebo
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.
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

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.

  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 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).
  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: NCT00679432

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

Publications:
Responsible Party: Salix Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00679432     History of Changes
Other Study ID Numbers: CB-01-02/01
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

Keywords provided by Salix Pharmaceuticals:
Ulcerative colitis

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

ClinicalTrials.gov processed this record on October 01, 2014