Budesonide Capsules Versus Mesalazine Granules in Active Ulcerative Colitis (UC)

Double-blind, Double-dummy, Randomised, Multi-centre, Comparative Phase III Clinical Study on the Efficacy and Tolerability of an 8 Week Oral Treatment With 9 mg Budesonide or 3 g Mesalazine in Patients With Active Ulcerative Colitis

The purpose of this study is to prove the therapeutic equivalence and safety of once-daily 9 mg budesonide versus 3 g mesalazine in a 8-week treatment in patients with active ulcerative colitis.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: budesonide; Drug: mesalazine

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Amberg, Germany, 92224
    • Klinikum St. Marien

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent,
2. Men or women aged 18 to 75 years,
3. Active ulcerative colitis, except proctitis limited to 15 cm ab ano, confirmed by endoscopy and histology,
4. Established disease (presence of blood or mucus in the stools) or new diagnosis (bloody stools occurring at least during 14 days prior to baseline visit),
5. Clinical Activity Index (CAI) >= 6 and Endoscopical Index (EI) >= 4,
6. Women of child-bearing potential, if heterosexually active, have to apply a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptive method, some intrauterine devices (IUDs), sexual abstinence, or vasectomised partner. The investigator is responsible for determining whether the subject has adequate birth control for study participation.

Exclusion Criteria:

1. Crohn's disease, indeterminate colitis, ischaemic colitis, radiation colitis, microscopic colitis (i.e., collagenous colitis and lymphocytic colitis),
2. Toxic megacolon,
3. Baseline stool positive for germs causing bowel disease,
4. Diarrhoea as a result of the presence of other symptomatic organic disease(s) of the gastrointestinal tract,
5. Active peptic ulcer disease,
6. Haemorrhagic diathesis,
7. Asthma, diabetes mellitus, infection, osteoporosis, glaucoma, cataract, or cardiovascular disease if careful medical monitoring is not ensured,
8. Severe co-morbidity substantially reducing life expectancy,
9. Active colorectal cancer or a history of colorectal cancer,
10. Active malignancy other than colorectal cancer or treatment with anticancer drugs during the last 5 years. Patients with a history of cancer other than colorectal cancer and at least five years of uneventful follow up and no signs of recurrence may be eligible,
11. Immunosuppressants within 3 months and/or corticosteroids (oral, intravenous [IV] or topical rectal) within 4 weeks prior to baseline,
12. Current relapse occurred under maintenance treatment with > 2.4 g mesalazine per day,
13. Abnormal renal function (Serum Cystatin C > upper limit of normal [ULN]),
14. Abnormal hepatic function (ALT, AST or AP >= 2 x ULN) or liver cirrhosis,
15. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile, or to any of the other constituents of the study drugs,
16. Doubt about the patient's cooperation, e.g., because of addiction to alcohol or drugs,
17. Existing or intended pregnancy or breast-feeding,
18. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; 9mg budesonide OD	Drug: budesonide; 3x 3mg budesonide capsules once daily; Other Names: Budenofalk 3mg capsules
Active Comparator: B; 3g mesalazine OD	Drug: mesalazine; 3x 1000mg mesalazine onc daily; Other Names: Salofalk 1000mg granules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of clinical remission (defined by CAI <= 4, with stool frequency and rectal bleeding subscores of ´0´) at week 8 (LOCF)	week 8 (LOCF)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to first resolution of clinical symptoms	within 8 weeks
CAI in the course of the study	week 0, 2, 4, 6, 8
Disease Activity Index (DAI)in the course of the study	week 0 and 8 (LOCF)
Endoscopical Index (EI)in the course of the study	week 0 and 8 (LOCF)

Collaborators and Investigators

• Sponsor: Dr. Falk Pharma GmbH
• Investigators: Study Director: Ralph Mueller, Dr, Dr. Falk Pharma GmbH

Publications and helpful links

General Publications

• Gross V, Bunganic I, Belousova EA, Mikhailova TL, Kupcinskas L, Kiudelis G, Tulassay Z, Gabalec L, Dorofeyev AE, Derova J, Dilger K, Greinwald R, Mueller R; International BUC-57 Study Group. 3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial. J Crohns Colitis. 2011 Apr;5(2):129-38. doi: 10.1016/j.crohns.2010.11.006. Epub 2010 Dec 14.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: September 3, 2008
• First Submitted That Met QC Criteria: September 3, 2008
• First Posted (Estimate): September 4, 2008

Study Record Updates

• Last Update Posted (Estimate): June 26, 2012
• Last Update Submitted That Met QC Criteria: June 25, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: ulcerative colitis; budesonide; mesalamine; mesalazine; 5-ASA
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide; Mesalamine
• Other Study ID Numbers: BUC-57/UCA; 2006-005377-22 (EudraCT Number)