Randomized Placebo-Controlled Trial of Budesonide Multi-Matrix System (MMX®) 9 Milligrams (mg) in Participants With Ulcerative Colitis Currently on a 5-Aminosalicylic Acid (5-ASA)
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Budesonide MMX®; Placebo; 5-ASA
Intervention description: Oral tablet taken daily in the morning after breakfast.; Matching budesonide MMX placebo oral tablet taken daily in the morning after breakfast.; Acceptable oral 5-ASA medications to be received during the study include:
Asacol®, Asacol® HD, Lialda®, Pentasa® (generic: mesalamine), minimum daily dose ≥2.4 grams (g)
Azulfidine® (generic: sulfasalazine), minimum daily dose ≥4.0 g
Dipentum® (generic: olsalazine), minimum daily dose ≥2.0 g
Colazal®, Colazide® (generic: balsalazide), minimum daily dose ≥6.75 g
Intervention MeSH terms: Budesonide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 510.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Ulcerative Colitis

Summary:

      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
      participants with active mild or moderate ulcerative colitis (UC).
    

Eligibility 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 an ulcerative colitis disease activity index (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 (for
             example, 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 centimeters [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*upper limit of normal [ULN] for alanine
             aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, or ≥2*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/deciliter [dL] hemoglobin), leukopenia (<2.5*10^9 white blood
             cells [WBC]/liter [L]), or granulocytopenia (<1.2*10^9 cells/L).

         17. Participants 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
             [that is, 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 (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:
             participants 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 participant
             or obscure the interpretation of adverse events (AEs) by the appropriate independent
             ethics committee/institutional review board.