(CB-01-02/02) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Procedure: Blood sampling, endoscopyDrug: Placebo
- Registration Number
- NCT00679380
- Lead Sponsor
- Bausch Health Americas, Inc.
- Brief Summary
This will be a multicentre, randomised, double-blind, double-dummy, parallel group comparative study in patients with mild or moderate, active ulcerative colitis. The study will compare budesonide-MMX™ 6 mg and budesonide-MMX™ 9 mg tablets to placebo and to Entocort® 3 x 3 mg capsules, in four parallel groups of patients over an 8 week treatment period.
After the screening visit, patients will enter a washout period of 2 days, then they will be randomised to the following four treatment groups: budesonide-MMX™ tablets (6 mg), budesonide-MMX™ tablets (9 mg), Entocort® capsules (3 x 3 mg) and placebo (tablets and capsules), all administered once a day after breakfast. Hence, each patient will receive, in the morning after breakfast, either one budesonide-MMX™ 6 mg or budesonide MMX™ 9 mg tablet and 3 placebo Entocort® matching capsules, or three Entocort® 3 mg capsules and one placebo budesonide-MMX™ matching tablet, or one placebo budesonide-MMX™ matching tablet and three placebo Entocort® matching capsules.
- Detailed Description
Each patient will receive one of the following regimens in the morning after breakfast:
1. One budesonide MMX® 6 mg tablet plus three placebo Entocort enteric-coated (EC®) overencapsulated capsules, or
2. One budesonide MMX® 9 mg tablet plus three placebo Entocort EC® overencapsulated capsules, or
3. Three placebo Entocort EC® overencapsulated capsules plus one placebo budesonide MMX® tablet, or
4. Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet, daily for eight weeks.
Hence, each patient is to take four tablets/capsules per day of active or placebo study medication as per the randomization schedule. Placebo tablets of Budesonide MMX® and placebo overencapsulated capsules of Entocort EC® 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 If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 514
-
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.
-
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 anaemia, leucopaenia or granulocytopaenia.
- 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 tumour 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 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-humoural 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4: Placebo Blood sampling, endoscopy Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast. 1: budesonide-MMX® 6 mg Blood sampling, endoscopy One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast. 1: budesonide-MMX® 6 mg Budesonide MMX® 6 mg One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast. 2: budesonide-MMX® 9 mg Blood sampling, endoscopy One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast. 2: budesonide-MMX® 9 mg Budesonide MMX® 9 mg One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast. 3: Entocort EC® 3 mg Blood sampling, endoscopy Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast. 3: Entocort EC® 3 mg Entocort EC® 3 mg Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast. 4: Placebo Placebo Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.
- Primary Outcome Measures
Name Time Method Clinical and Endoscopic Remission. 8 weeks Clinical and endoscopic remission defined as an 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
Name Time Method Endoscopic Improvement. 8 weeks 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.Clinical Improvement. 8 weeks Clinical improvement, defined as a ≥ 3-point improvement in UCDAI from baseline to the end of Week 8.
Trial Locations
- Locations (71)
Centre for Digestive Diseases
🇦🇺Sydney, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,
🇦🇺Box Hill, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Monash Medical Centre
🇦🇺Melbourne, Australia
Imelda Hospital
🇧🇪Bonheiden, Belgium
East Viru Central Hospital
🇪🇪Kohtla-Jarve, Estonia
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
West Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
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