Randomized Placebo Controlled Trial of Budesonide Multi-Matrix System (MMX®) 9 mg in Patients With Ulcerative Colitis Currently on a 5-Aminosalicylic Acid (5-ASA).

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01532648
First received: December 13, 2011
Last updated: March 27, 2014
Last verified: December 2013
  Purpose

This study is to compare the efficacy and safety of budesonide MMX 9 mg versus placebo as add-on therapy to an existing oral 5-ASA regimen for the induction of remission in patients with active, mild or moderate ulcerative colitis (UC).


Condition Intervention Phase
Ulcerative Colitis
Drug: Budesonide
Drug: Placebo
Procedure: Procedure/Surgery: Blood sampling, endoscopy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Salix Pharmaceuticals:

Primary Outcome Measures:
  • The induction of Clinical remission in patients with active, mild or moderate ulcerative colitis (UC) after 8 weeks of study therapy. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare the percentages of patients who achieve Clinical Response in the two treatment groups. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Compare the percentages of patients who achieve ulcerative colitis disease activity index (UCDAI) remission in the two treatment groups. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Compare the percentages of patients who achieve Endoscopic Remission in the two treatment groups. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Compare the percentages of patients who achieve Histologic Healing in the two treatment groups. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Compare the percentages of patients who experience Treatment Failures in the two treatment groups. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Compare the effects of the two treatment groups on the irritable bowel disease quality of life (IBD-QoL), c-reactive protein (CRP), and fecal calprotectin. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 509
Study Start Date: February 2012
Study Completion Date: November 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Budesonide
Budesonide MMX 9 mg (one tablet)
Drug: Budesonide
One budesonide-MMX® 9 mg tablet plus current oral 5-aminosalicylic acid (5-ASA) regimen daily in the morning after breakfast.
Procedure: Procedure/Surgery: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores.
Placebo Comparator: Placebo
Placebo (tablet indistinguishable from budesonide MMX 9 mg tablet)
Drug: Placebo
One tablet indistinguishable from budesonide MMX 9 mg tablet plus current oral 5-aminosalicylic acid (5-ASA) regimen daily in the morning after breakfast.
Procedure: Procedure/Surgery: Blood sampling, endoscopy
Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores.

Detailed Description:

Eligible patients will be randomized to one of the following two treatment arms:

  1. Budesonide MMX 9 mg (one tablet)
  2. Placebo (tablet indistinguishable from budesonide MMX 9 mg tablet)

The assigned study drug will be taken as a single oral tablet each morning after breakfast. In addition to the study drug, all patients will continue their existing background oral 5-ASA regimen during the treatment period.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 75 years, inclusive.
  2. Established diagnosis of UC, based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
  3. Active mild or moderate UC with a UCDAI score ≥ 4 and ≤ 10, with a mucosal appearance score of ≥ 1, and physician's rating of disease activity of 1 or 2.
  4. Experiencing active UC (flare) despite a therapeutic dose of an oral 5-ASA (e.g., mesalamine ≥ 2.4 g/day for ≥ 6 weeks prior to randomization, or equivalent). At screening, photographic evidence of active UC based on mucosal appearance must be obtained.
  5. Women of childbearing potential or men of reproductive potential must be willing to use an acceptable form of contraception. .
  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 an informed consent prior to any study procedures.

Exclusion Criteria:

  1. Limited distal proctitis (from anal verge to 15 cm above the pectineal line).
  2. Severe UC (UCDAI > 10 or physician global assessment [PGA] > 2), or non-active UC (UCDAI < 4).
  3. Infectious colitis or any recent history of infectious colitis (within 30 days of Screening).
  4. Active malignancy or carcinoma in situ within the last 5 years (treated non-melanoma skin cancers are not exclusionary).
  5. 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. Crohn's disease or indeterminate colitis.
  8. Known hypersensitivity to budesonide or any ingredients of the budesonide MMX tablets
  9. Active tuberculosis or other active systemic or local bacterial, fungal, or viral infection
  10. 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 alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, or ≥ 2 x ULN for creatinine). Elevations in bilirubin due to benign conditions such as Gilbert's syndrome are not exclusionary.
  11. Severe diseases in other organs or systems.
  12. Local or systemic complications or other pathological states requiring therapy with corticosteroids and/or immunosuppressive agents.
  13. Type 1 diabetes.
  14. Glaucoma, or with a family history of glaucoma in first degree relatives.
  15. Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), according to the local privacy policy.
  16. 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 budesonide MMX treatment.
  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-TNFα) agents or other biologic therapies within the last 3 months prior to randomization.
  23. Participation in experimental therapeutic studies within 30 days of randomization (or within the last 3 months if in an anti-TNFα 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 interpretation of adverse events (AEs) by the appropriate independent ethics committee/institutional review board.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01532648

  Show 114 Study Locations
Sponsors and Collaborators
Salix Pharmaceuticals
Investigators
Principal Investigator: David Rubin, MD University of Chicago
  More Information

No publications provided

Responsible Party: Salix Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01532648     History of Changes
Other Study ID Numbers: C2011-0401
Study First Received: December 13, 2011
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Bulgaria: Ministry of Health

Keywords provided by Salix Pharmaceuticals:
Ulcerative Colitis

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Aminosalicylic Acid
Budesonide
Mesalamine
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on August 19, 2014