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

Ulcerative Colitis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00679432
• Other study ID #: CB-01-02/01
• Status: Completed
• Phase: Phase 3
• Start date: June 2008
• Est. completion date: June 2010

Study information

• Verified date: November 2019
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 510
• Est. completion date: June 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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-TNFa) 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).

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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
• budesonide-MMX® 9 mg
9 mg/day, 9 mg tablets
• Placebo
Placebo
• Asacol® 400 mg
2400 mg/day, 400 mg tablets

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Countries where clinical trial is conducted

United States,  Canada,  India,  Mexico, 

References & Publications (1)

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. Gastro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical Improvement.	Clinical improvement, defined as a = 3-point improvement in UCDAI from baseline to the end of Week 8.	8 weeks
Secondary	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