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

Efficacy and Safety of Budesonide MMX® vs. Budesonide CR for Induction of Remission in Microscopic Colitis: A Prospective, Randomized, Active Comparator Pilot Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Microscopic Colitis
• Intervention / Treatment: Drug: Budesonide MMX®; Drug: Budesonide controlled ileal release (CR) capsules

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christopher Ma, MD MPH; Phone Number: 403-592-5013; Email: christopher.ma@ucalgary.ca
• Study Contact Backup: Name: Katherine Buhler; Email: kaewert@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	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)	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histologic remission	<20 IELs/100 surface epithelial cells and subepithelial collagen band <10 micrometers in biopsy samples and a reduction in lamina propria inflammation	Week 8
Histologic response	50% reduction in IEL count or subepithelial collagen band thickness compared to baseline and/or a reduction in lamina propria inflammation	Week 8
Clinical response	50% reduction in average daily stool frequency for the week prior to final assessment compared to baseline	Week 8
Patient-reported symptom improvement	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	Week 8

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Ferring Pharmaceuticals
• Investigators: Principal Investigator: Christopher Ma, MD MPH, University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Colitis; Colitis, Microscopic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: REB22-1240

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified IPD may be shared upon completion of the study and with formal written request
• IPD Sharing Time Frame: Data will be available and stored for 15 years after the study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No