An 8 week study to compare budesonide MMX 9 mg versus placebo in patients with mild to moderate ulcerative colitis who experience a flare of their disease while taking an existing 5 aminosalicylic acid.

• Register: EUCTR
• Last refreshed on: 6 January 2014
• Main ID: EUCTR2011-005115-82-LT
• Date of registration: 24/05/2012
• Prospective Registration: Yes
• Primary sponsor: Santarus, Inc.
• Public title: An 8 week study to compare budesonide MMX 9 mg versus placebo in patients with mild to moderate ulcerative colitis who experience a flare of their disease while taking an existing 5 aminosalicylic acid.
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Budesonide MMX® 9 mg Extended-release Tablets as Add-on Therapy in Patients with Active, Mild or Moderate Ulcerative Colitis not Adequately Controlled on a Background Oral 5-ASA Regimen
• Date of first enrolment: 12/09/2012
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005115-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Canada, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Ukraine, United States

Contacts

• Name: Michael Huang, MD, Medical Director
• Affiliation: Santarus, Inc.

• Name: Michael Huang, MD, Medical Director
• Affiliation: Santarus, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Patients with diagnosed UC fulfilling the following criteria at Screening are eligible for participation in the study:
1. Age 18 to 75 years, inclusive
2. Established diagnosis of UC, based on clinical history, exclusion of infectious causes (e.g., enteric bacterial infection, Clostridium difficile, parasites, ova, etc.), characteristic endoscopic findings, and histopathology results from biopsies.
3. UC of mild or moderate severity with an Ulcerative Colitis Disease Activity Index (UCDAI) score = 4 and = 10 according to Sutherland, with a mucosal appearance subscore of = 1 and a physician’s rating of disease activity of 1 or 2.
4. Currently experiencing active UC (flare) despite taking a therapeutic dose of an oral 5-ASA (e.g., mesalamine = 2.4 g/day, or equivalent dose of another 5-ASA for a minimum of 6 weeks prior to randomization. At screening, photographic evidence of active UC based on mucosal appearance must be obtained from the flexible sigmoidoscopy procedure.
5. Women of childbearing potential, or men of reproductive potential, must be willing to use an acceptable form of contraception. Acceptable forms of contraception are defined as those with a failure rate < 1% when properly applied and include: a combination oral pill, some intra-uterine devices, and a sterilized partner in a stable relationship. Female patients must not be actively breast-feeding through the entire study period.
6. Able to comprehend the full nature and purpose of the study, including possible risks and side effects, and also able to comply with all requirements of the study. Must be able to understand and voluntarily sign a written informed consent prior to any study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
Patients who meet any of the following criteria at Screening are to be excluded from study participation:
1. Patients with limited distal proctitis (from anal verge up to 15 cm above the pectineal line).
2. Patients with severe UC (UCDAI > 10 or PGA > 2), or patients not currently in an active phase or flare (defined in this study as a UCDAI score < 4).
3. Patients with infectious colitis (based on positive microbiologic tests, Clostridium difficile toxin, or ova and parasites per the central laboratory) or any recent history of infectious colitis (within 30 days of Screening).
4. Patients with a history of active malignancy or carcinoma in situ within the last 5 years (excised or treated non-melanoma skin cancers are not exclusionary).
5. Patients with an active ulcer or bleeding disorder that may affect evaluation of blood in the stool.
6. Evidence or history of toxic megacolon or bowel resection.
7. Patients with Crohn’s disease or indeterminate colitis.
8. Patients with a known hypersensitivity to budesonide or any of the ingredients of the budesonide MMX tablets
9. Patients with active tuberculosis or any other active systemic or local bacterial, fungal, or viral infection.
10. Patients with liver cirrhosis, evident hepatic or renal disease or insufficiency, or significant impairment of the biohumoral parameters (= 2.5 x upper limit of normal [ULN] for ALT, AST, GGT, or = 2 x ULN for creatinine). Elevations in bilirubin due to benign conditions such as Gilbert’s syndrome are not exclusionary.
11. Patients with severe diseases in other organs or systems.
12. Patients with local or systemic complications or other pathological states requiring therapy with corticosteroids and/or immunosuppressive agents.
13. Patients diagnosed with type 1 diabetes.
14.Patients diagnosed as having glaucoma, or with a family history of glaucoma in first degree relatives.
15. Patients with known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), according to the local privacy policy.
16. Patients with severe anemia (< 9 g/dL hemoglobin), leukopenia (< 2.5 x 109 white blood cells [WBC]/L), or granulocytopenia (< 1.2 x 109 cells/L).
17. Patients with a history of pancolitis (disease that extends to the hepatic flexure or beyond) for = 8 years or left-sided colitis (disease confined to the left colon [i.e., distal to the splenic flexure]) = 15 years who have not yet completed a surveillance colonoscopy for dysplasia/colorectal cancer screening within the past year.
18. Prior treatment with budesonide MMX.
19. Use of oral corticosteroids including other budesonide formulations within the last 4 weeks prior to randomization.
20. Use of any rectal 5-ASA or corticosteroid formulations within the last 2 weeks prior to randomization.
21. Use of immunosuppressive agents within the last 8 weeks prior to randomization.
22. Use of anti-tumor necrosis factor-alpha (anti-TNFa) agents or other biologic therapies within the last 3 months prior to randomization.
23. Participation in experimental therapeutic studies within the last 30 days prior to randomization (or within the last 3 months if in an anti-TNFa or biologic agent study). Note: patients who participated in observational-only studies (and who did not receive study therapy) are not excluded.
24. 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 patient, or obscure the

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 15.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: Budesonide-MMX®
Pharmaceutical Form: Film coated gastro-resistant tablet
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9-
Pharmaceutical form of the placebo: Film coated gastro-resistant tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the efficacy of budesonide MMX 9 mg and placebo as add-on therapy to an existing oral 5-ASA regimen for the induction of UCDAI remission in patients with active, mild or moderate UC.

Primary end point(s): The primary efficacy endpoint is UCDAI (clinical and endoscopic) remission at Day 56, defined as a total UCDAI score (according to the Sutherland index of = 1, with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance.

Secondary Objective: -To compare the efficacy of budesonide MMX 9 mg and placebo as add-on therapy to an existing oral 5-ASA regimen for the induction of clinical remission in patients with active, mild or moderate UC.
-To compare the efficacy of budesonide MMX 9 mg and placebo as add-on therapy to an existing oral 5-ASA regimen for the induction of endoscopic remission in patients with active, mild or moderate UC.
- To compare the time to onset of clinical remission in the two treatment groups.
- To compare the percentages of patients who achieve clinical improvement in the two treatment groups.
- To compare the percentages of patients who achieve histologic healing in the two treatment groups.
-To compare the percentages of treatment failures in the two treatment groups.
- To evaluate the effects of budesonide MMX 9 mg on the inflammatory bowel disease-quality of life (IBD-QoL) questionnaire, CRP, and fecal calprotectin when compared to placebo.

Timepoint(s) of evaluation of this end point: Day 56

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 56

Secondary end point(s): Secondary efficacy endpoints are as follows:
• Clinical remission at Day 56, defined as a score of 0 for rectal bleeding and 0 for stool frequency from the UCDAI
• Endoscopic remission at Day 56, defined as a score of 0 from the mucosal appearance subscore from the UCDAI

Secondary ID(s)

2011-005115-82-HU

C2011-0401

Source(s) of Monetary Support

Santarus Inc.