Efficacy and Safety of Budesonide MMX® vs. Budesonide CR for Induction of Remission in Microscopic Colitis

• Sponsor: University of Calgary (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05915104
• Collaborator: Ferring Pharmaceuticals (Industry)
• Enrollment: 80
• Arms: 2
• Anticipated Duration (Months): 40

Study Details

Study Description

Brief Summary

The purpose of this research study is to compare how well two formulations of budesonide (budesonide MMX [Cortiment] and budesonide CR [Entocort]) work for treating patients with microscopic colitis.

Condition or Disease	Intervention/Treatment	Phase
Microscopic Colitis	Drug: Budesonide MMX®; Drug: Budesonide controlled ileal release (CR) capsules	Phase 2

Detailed Description

After being informed of the study and potential risks, patients with symptomatically active microscopic colitis who provide written informed consent will undergo a 4-week screening period to determine their eligibility for the study. At week 0, eligible patients will be randomized in a single blind manner (patients will be aware, while investigators will be blinded) in a 1:1 ratio to budesonide MMX (9mg once daily) or budesonide CR (3mg three times daily). The total treatment duration will be for 8 weeks. The primary outcome will be clinical remission, defined by the Hjortswang criteria (daily average <3 loose/watery bowel movements per 24 hours in the week preceding the final assessment (loose/watery stool consistency will be measured using the Bristol Stool Chart (types 6 and 7)).

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This phase 2a trial is a prospective, randomized, single-blinded (investigator-blinded), active comparator clinical study. Eligible participants with active Microscopic Colitis will be randomized 1:1 to receive either budesonide MMX® or budesonide CR 9 mg daily for 8 weeks.This phase 2a trial is a prospective, randomized, single-blinded (investigator-blinded), active comparator clinical study. Eligible participants with active Microscopic Colitis will be randomized 1:1 to receive either budesonide MMX® or budesonide CR 9 mg daily for 8 weeks.
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: All qualified participants will be randomly assigned in a 1:1 ratio to receive budesonide MMX® or budesonide CR. Blocked randomization (block size of 8) will be stratified on disease subtype (collagenous colitis vs. lymphocytic colitis). Randomization will be conducted through the REDCap® clinical trials randomization module, which will generate a random, blinded allocation sequence that will be concealed to both investigators and participants. An independent pharmacist will prepare all treatment packages. Budesonide will be packaged into 4-week increments (two packages per 8-week treatment course). These treatment packages will be identical in appearance and size and labelled with a randomly generated study identification number. Investigators will not know the contents of each treatment package. At the randomization visit, eligible participants will be randomized and be given the corresponding treatment package. Participants will not be blinded to treatment.
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Budesonide MMX® vs. Budesonide CR for Induction of Remission in Microscopic Colitis: A Prospective, Randomized, Active Comparator Pilot Study
• Anticipated Study Start Date: Sep 1, 2023
• Anticipated Primary Completion Date: Sep 1, 2026
• Anticipated Study Completion Date: Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Budesonide MMX® Participant received 9 mg delayed and extended-release tablet, once daily, oral administration, for 8 weeks	Drug: Budesonide MMX®; 9 mg delayed and extended-release tablet once daily; Other Names: Cortiment®
Active Comparator: Budesonide controlled ileal release (CR) capsules Participant received three 3 mg capsules, daily oral administration, for 8 weeks	Drug: Budesonide controlled ileal release (CR) capsules; three 3 mg capsules daily oral administration for 8 weeks; Other Names: Entocort®

Outcome Measures

Primary Outcome Measures

1. Clinical remission [Week 8]

   Hjortswang criteria defines clinical remission as a daily average <3 loose/watery bowel movements per 24 hours in the week preceding the final assessment (loose/watery stool consistency will be measured using the Bristol Stool Chart (types 6 and 7)

Secondary Outcome Measures

1. Histologic remission [Week 8]

   <20 IELs/100 surface epithelial cells and subepithelial collagen band <10 micrometers in biopsy samples and a reduction in lamina propria inflammation

2. Histologic response [Week 8]

   50% reduction in IEL count or subepithelial collagen band thickness compared to baseline and/or a reduction in lamina propria inflammation

3. Clinical response [Week 8]

   50% reduction in average daily stool frequency for the week prior to final assessment compared to baseline

4. Patient-reported symptom improvement [Week 8]

   Change in the European Microscopic Colitis Activity Index (E-MCAI) and its component items, including stool frequency and consistency (stools per day, solid vs. loose stools, stools of each Bristol Stool chart consistency), stools at night, feeling of a need to pass more stools shortly after a bowel movement, urgency of defecation, leakage, and abdominal pain

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or non-pregnant, non-lactating females, 18-80 years old years of age

• Females of childbearing potential must be taking adequate contraceptive precautions (i.e., implants, injectables, hormonal intrauterine devices, combined hormonal contraceptives, having a vasectomized partner or total abstinence from heterosexual relations with no plans of becoming pregnant through insemination or in vitro fertilization) and have a negative urine pregnancy test prior to randomization.

• Active symptoms of MC defined by non-bloody, watery diarrhea or loose bowel movements for at least 12 weeks (for patients with newly diagnosed MC) or a history of clinical relapse for at least one week before randomization in patients with previously established MC, and with >=28 stools within 7 days preceding randomization, of which

=20 were watery/soft stools

• Colonoscopy or flexible sigmoidoscopy with histologically confirmed MC, defined by signs of inflammation of the lamina propria and either:

• lymphocytic colitis: ≥20 IELs/100 surface epithelial cells

• collagenous colitis: subepithelial collagen band >10 micrometers in diameter

• Ability of subject to participate fully in all aspects of this clinical trial

• Written informed consent must be obtained and documented

Exclusion Criteria:

• Evidence of infectious diarrhea (proved by stool culture or colonic biopsy), diarrhea due to other organic diseases of the gastrointestinal tract including Crohn's disease, ulcerative colitis, ischemic colitis, Celiac disease (ruled out by either duodenal biopsy or serum antibodies), radiation colitis, or polyps >2cm, suspicion of drug-induced MC

• History of partial or total colonic resection

• Previous exposure to >7 days of any budesonide formulation for treatment of MC

• Unwillingness to withhold protocol-proscribed medications during the trial

• Received any of: aminosalicylates, corticosteroids (other than budesonide), immunosuppressants (including thiopurines and methotrexate), bismuth subsalicylate, cholestyramine, biological treatments, or antibiotics (except for up to a 7-day course for conditions unrelated to microscopic colitis) within 8 weeks of randomization

• Use of loperamide or diphenoxylate/atropine as an anti-diarrheal agent is not permitted during the screening period

• Serious underlying disease other than MC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study, including a history of:

• Severe anaemia (haemoglobin < 90 g/L) or leukopenia (white blood cell count < 2.5 x 109 cells/L)

• Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus not on effective anti-viral therapy

• Active malignancy

• Cirrhosis or significant hepatic or renal insufficiency

• Poorly controlled type 1 or type 2 diabetes

• Glaucoma

• History of alcohol or drug abuse which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.

• Pregnant or lactating women

• Hypersensitivity to the active ingredient of budesonide MMX® or budesonide CR and excipients

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Calgary
• Ferring Pharmaceuticals

Investigators

• Principal Investigator: Christopher Ma, MD MPH, University of Calgary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Calgary
• ClinicalTrials.gov Identifier: NCT05915104
• Other Study ID Numbers: REB22-1240
• First Posted: Jun 22, 2023
• Last Update Posted: Jun 22, 2023
• Last Verified: Jun 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colitis; Colitis, Microscopic; Budesonide

Study Results

No Results Posted as of Jun 22, 2023