Clinical trial NCT00679432: (CB-01-02/01) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2008-05-16
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be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

Primary outcomes:
measure: Clinical and Endoscopic Remission.
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical Improvement.
timeFrame: 8 weeks
measure: Endoscopic Improvement
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Santarus Clinical Investigational Site 5051
state: Alabama
city: Mobile
country: United States
facility: Santarus Clinical Investigational Site 5102
state: Alabama
city: Sylacauga
country: United States
facility: Santarus Clinical Investigational Site 5014
state: Alabama
city: Tucson
country: United States
facility: Santarus Clinical Investigational Site 5088
state: Arizona
city: Anaheim
country: United States
facility: Santarus Clinical Investigational Site 5044
state: California
city: Encinitas
country: United States
facility: Santarus Clinical Investigational Site 5099
state: California
city: Fremont
country: United States
facility: Santarus Clinical Investigational Site 5075
state: California
city: Lakewood
country: United States
facility: Santarus Clinical Investigational Site 5087
state: California
city: Los Angeles
country: United States
facility: Santarus Clinical Investigational Site 5033
state: California
city: Palm Springs
country: United States
facility: Santarus Clinical Investigational Site 5070
state: California
city: San Diego
country: United States
facility: Santarus Clinical Investigational Site 5067
state: California
city: San Francisco
country: United States
facility: Santarus Clinical Investigational Site 5028
state: California
city: Boynton Beach
country: United States
facility: Santarus Clinical Investigational Site 5089
state: Florida
city: Hollywood
country: United States
facility: Santarus Clinical Investigational Site 5041
state: Florida
city: New Smyrna Beach
country: United States
facility: Santarus Clinical Investigational Site 5055
state: Florida
city: Port Orange
country: United States
facility: Santarus Clinical Investigational Site 5074
state: Florida
city: Tampa
country: United States
facility: Santarus Clinical Investigational Site 5032
state: Florida
city: Tampa
country: United States
facility: Santarus Clinical Investigational Site 5009
state: Florida
city: West Palm Beach
country: United States
facility: Santarus Clinical Investigational Site 5110
state: Florida
city: Winter Park
country: United States
facility: Santarus Clinical Investigational Site 5047
state: Florida
city: Zephyrhills
country: United States
facility: Santarus Clinical Investigational Site 5003
state: Florida
city: Atlanta
country: United States
facility: Santarus Clinical Investigational Site 5016
state: Georgia
city: Columbus
country: United States
facility: Santarus Clinical Investigational Site 5056
state: Georgia
city: Savannah
country: United States
facility: Santarus Clinical Investigational Site 5103
state: Georgia
city: Addison
country: United States
facility: Santarus Clinical Investigational Site 5085
state: Illinois
city: Evanston
country: United States
facility: Santarus Clinical Investigational Site 5068
state: Illinois
city: Bloomington
country: United States
facility: Santarus Clinical Investigational Site 5086
state: Indiana
city: Clive
country: United States
facility: Santarus Clinical Investigational Site 5053
state: Iowa
city: Metairie
country: United States
facility: Santarus Clinical Investigational Site 5008
state: Louisiana
city: Annapolis
country: United States
facility: Santarus Clinical Investigational Site 5090
state: Maryland
city: Baltimore
country: United States
facility: Santarus Clinical Investigational Site 5025
state: Maryland
city: Hollywood
country: United States
facility: Santarus Clinical Investigational Site 5092
state: Maryland
city: Prince Frederick
country: United States
facility: Santarus Clinical Investigational Site 5077
state: Maryland
city: Boston
country: United States
facility: Santarus Clinical Investigational Site 5046
state: Massachusetts
city: Brockton
country: United States
facility: Santarus Clinical Investigational Site 5115
state: Massachusetts
city: Chesterfield
country: United States
facility: Santarus Clinical Investigational Site 5010
state: Michigan
city: Troy
country: United States
facility: Santarus Clinical Investigational Site 5006
state: Michigan
city: Wyoming
country: United States
facility: Santarus Clinical Investigational Site 5004
state: Michigan
city: Saint Louis
country: United States
facility: Santarus Clinical Investigational Site 5105
state: Missouri
city: Egg Harbor Township
country: United States
facility: Santarus Clinical Investigational Site 5094
state: New Jersey
city: Marlton
country: United States
facility: Santarus Clinical Investigational Site 5005
state: New Jersey
city: Vineland
country: United States
facility: Santarus Clinical Investigational Site 5024
state: New Jersey
city: Great Neck
country: United States
facility: Santarus Clinical Investigational Site 5011
state: New York
city: New York
country: United States
facility: Santarus Clinical Investigational Site 5101
state: New York
city: Pittsford
country: United States
facility: Santarus Clinical Investigational Site 5020
state: New York
city: Fayetteville
country: United States
facility: Santarus Clinical Investigational Site 5096
state: North Carolina
city: Huntersville
country: United States
facility: Santarus Clinical Investigational Site 5058
state: North Carolina
city: New Bern
country: United States
facility: Santarus Clinical Investigational Site 5091
state: North Carolina
city: Wilmington
country: United States
facility: Santarus Clinical Investigational Site 5124
state: North Carolina
city: Canton
country: United States
facility: Santarus Clinical Investigational Site 5118
state: Ohio
city: Cincinnati
country: United States
facility: Santarus Clinical Investigational Site 5045
state: Ohio
city: Dayton
country: United States
facility: Santarus Clinical Investigational Site 5078
state: Ohio
city: Mentor
country: United States
facility: Santarus Clinical Investigational Site 5120
state: Ohio
city: Duncansville
country: United States
facility: Santarus Clinical Investigational Site 5066
state: Pennsylvania
city: Pottstown
country: United States
facility: Santarus Clinical Investigational Site 5065
state: Pennsylvania
city: Sayre
country: United States
facility: Santarus Clinical Investigational Site 5035
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Santarus Clinical Investigational Site 5107
state: South Dakota
city: Jackson
country: United States
facility: Santarus Clinical Investigational Site 5130
state: Tennessee
city: Kingsport
country: United States
facility: Santarus Clinical Investigational Site 5095
state: Tennessee
city: Austin
country: United States
facility: Santarus Clinical Investigational Site 5021
state: Texas
city: Houston
country: United States
facility: Santarus Clinical Investigational Site 5076
state: Texas
city: Houston
country: United States
facility: Santarus Clinical Investigational Site 5108
state: Texas
city: Houston
country: United States
facility: Santarus Clinical Investigational Site 5019
state: Texas
city: Houston
country: United States
facility: Santarus Clinical Investigational Site 5036
state: Texas
city: Irving
country: United States
facility: Santarus Clinical Investigational Site 5063
state: Texas
city: Kingwood
country: United States
facility: Santarus Clinical Investigational Site 5072
state: Texas
city: La Porte
country: United States
facility: Santarus Clinical Investigational Site 5054
state: Texas
city: Lewisville
country: United States
facility: Santarus Clinical Investigational Site 5030
state: Texas
city: Plano
country: United States
facility: Santarus Clinical Investigational Site 5093
state: Texas
city: San Antonio
country: United States
facility: Santarus Clinical Investigational Site 5049
state: Texas
city: San Antonio
country: United States
facility: Santarus Clinical Investigational Site 5100
state: Texas
city: San Antonio
country: United States
facility: Santarus Clinical Investigational Site 5079
state: Texas
city: Tomball
country: United States
facility: Santarus Clinical Investigational Site 5098
state: Texas
city: Salt Lake City
country: United States
facility: Santarus Clinical Investigational Site 5015
state: Utah
city: Christiansburg
country: United States
facility: Santarus Clinical Investigational Site 5097
state: Virginia
city: Norfolk
country: United States
facility: Santarus Clinical Investigational Site 5119
state: Virginia
city: Abbotsford
country: Canada
facility: Santarus Clinical Investigational Site 6005
state: British Columbia
city: Vancouver
country: Canada
facility: Santarus Clinical Investigational Site 6000
state: British Columbia
city: Vancouver
country: Canada
facility: Santarus Clinical Investigational Site 6014
state: British Columbia
city: Victoria
country: Canada
facility: Santarus Clinical Investigational Site 6008
state: British Columbia
city: Richmond Hill
country: Canada
facility: Santarus Clinical Investigational Site 6004
state: Ontario
city: Toronto
country: Canada
facility: Santarus Clinical Investigational Site 6017
state: Ontario
city: Montreal
country: Canada
facility: Santarus Clinical Investigational Site 6001
state: Quebec
city: Saskatoon
country: Canada
facility: Santarus Clinical Investigational Site 6016
state: Saskatchewan
city: Quebec
country: Canada
facility: Santarus Clinical Investigational Site 6002
city: Toronto
country: Canada
facility: Santarus Clinical Investigational Site 6006
city: Andhra Pradesh
country: India
facility: Santarus Clinical Investigational Site 9001
city: Andhra Pradesh
country: India
facility: Santarus Clinical Investigational Site 9009
city: Andhra Pradesh
country: India
facility: Santarus Clinical Investigational Site 9012
city: Andhra Pradesh
country: India
facility: Santarus Clinical Investigational Site 9016
city: Assam
country: India
facility: Santarus Clinical Investigational Site 9006
city: Gujarat
country: India
facility: Santarus Clinical Investigational Site 9007
city: Karnataka
country: India
facility: Santarus Clinical Investigational Site 9004
city: Karnataka
country: India
facility: Santarus Clinical Investigational Site 9015
city: Kerala
country: India
facility: Santarus Clinical Investigational Site 9003
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9002
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9008
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9010
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9011
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9013
city: Maharashtra
country: India
facility: Santarus Clinical Investigational Site 9017
city: Rajasthan
country: India
facility: Santarus Clinical Investigational Site 9018
city: Tamil Nadu
country: India
facility: Santarus Clinical Investigational Site 9005
city: Uttar Pradesh
country: India
facility: Santarus Clinical Investigational Site 9014
city: Colonia Centra
country: Mexico
facility: Santarus Clinical Investigational Site 7000
state: La Paz Baja California Sur
Study officials:
affiliation: Massachusetts General Hospital
name: Bruce Eric Sands
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.