Please select the eligibility criteria that correspond to the clinical trial below.
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
Brief 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).


Options:
A: Inclusion Criteria:

* Documented history of ulcerative colitis that has been successfully maintained in remission for at least 3 months prior to study entry
* At least one flare in the past 18 months
* Utilizing a stable maintenance dose of oral Asacol of 1.6 g/day up to 2.4 g/day (stable dose is defined as the same dose for the past 3 months)
* Females must be postmenopausal or surgically sterile or have a negative urine pregnancy test and practice acceptable contraception

Exclusion Criteria:

* History of or current renal disease
* History of hepatic disease
* History of allergy or hypersensitivity to salicylates, aminosalicylates
* Treatment with immunomodulatory therapy, biologic therapy or corticosteroids within 90 days of screening
* Received any antidiarrheals, antispasmodics, or antibiotic within 1 month of screening
B: Induction phase - Main criteria for inclusion include:

1. Male or non-pregnant, non-lactating females, 18 years of age or older. Females of child bearing potential must have a negative serum pregnancy test prior to randomisation, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal \[defined as a minimum of one year since the last menstrual period\]).
2. Documented diagnosis of UC with disease extending at least 15 cm from the anal verge.
3. Active UC defined by:

   * a. Mayo score of ≥ 5
   * b. Sigmoidoscopy component score ≥ 2 confirmed by central review and
   * c. Rectal bleeding component score ≥ 1
4. Ability of the subject to participate fully in all aspects of this clinical trial.
5. Written informed consent must be obtained and documented.

Induction Phase - Main criteria for exclusion include:

Subjects who exhibit any of the following conditions are to be excluded from the study:

(1) Severe UC defined by the following criteria: 6 bloody stools daily with one or more of the following:

* a. oral temperature \> 37.8 degrees C or \> 100.0 degrees F
* b. pulse \> 90 beats/min
* c. haemoglobin \< 10 g/dL (2) Treatment with oral mesalamine at a dose of \> 2.4 g/day within 4 weeks prior to randomisation.

  (3) Treatment with topical therapy (mesalamine or corticosteroids) within 2 weeks prior to randomisation (4) Treatment with systemic or rectal steroids within 4 weeks prior to randomisation.

  (5) Treatment with immunosuppressants within 6 weeks prior to randomisation. (6) Treatment with infliximab or other biologics within 3 months prior to randomisation.

  (7) Treatment with antibiotics within 7 days prior to randomisation. (8) Treatment with probiotics within 7 days prior to randomisation. (9) Treatment with anti-diarrhoeal treatment within 7 days prior to randomisation.

  (10) Treatment with nicotine patch within 7 days prior to randomisation. (11) Received any investigational drug within 30 days prior to randomisation. (12) History of colectomy or partial colectomy. (13) History of definite dysplasia in colonic biopsies. (14) Crohn's disease. (15) Immediate or significant risk of toxic megacolon. (16) Known bleeding disorders. (17) Hypersensitivity to salicylates, aspirin, sulfasalazine or mesalazine. (18) Serum creatinine \> 1.5 times the upper limit of the normal range. (19) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin or alkaline phosphatase \> 2 times the upper limit of the normal range.

  (20) Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to fully participate in the study.

  (21) 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.

  (22) Stools positive for Clostridium difficile toxin. (23) Pregnant or lactating women. (24) Prior enrolment in the study.

OLE - Main criteria for inclusion include:

1. Attendance at the Week 8 visit and completion of disease activity assessments prior to enrolment in OLE at Week 12 (responders or remitters) or Week 8 (non-responders).
2. At least 75% compliance with study medication in the induction phase.

OLE - Main criteria for exclusion include:

(1) Withdrawal from the induction phase prior to the Week 8 visit.
C: Inclusion Criteria:

1. Understand and sign the informed consent form.
2. Have documented ulcerative colitis on the basis of usual diagnostic criteria including clinical symptoms and findings from endoscopy, radiology studies, and histology.
3. Have a Simple Clinical Colitis Activity Index (SCCAI)55 score below 3 with no category value greater than 1 (Table 5).
4. Three or fewer bowel movements per 24 hours at the time of enrollment.
5. No visible blood in their bowel movements in the three days prior to enrollment.
6. Have either been on a stable dose of mesalamine medication (oral, rectal or a combination of oral and rectal, including sulfasalazine) or on no mesalamine medications for at least 4 weeks prior to enrollment.
7. Have been on either a stable dose of azathioprine, 6-mercaptopurine, or methotrexate or on none of these medications for at least 8 weeks prior to enrollment.
8. Have experienced at least one flare of ulcerative colitis in the 2 years prior to enrollment. A flare is defined as an increase in stool frequency, bleeding, urgency and/or abdominal discomfort sufficient to warrant a change in medication dose or addition of a new medication.
9. Most recently measured serum creatinine level in the preceding year less than 1.5 mg/dL.

Exclusion Criteria:

1. Age less than 18
2. Inability to speak and read English
3. Presence of an ostomy or prior total or subtotal colectomy
4. Current corticosteroid use or use within the two weeks prior to enrollment
5. Remission for less than 4 weeks prior to enrollment
6. Previous intolerance to mesalamine at doses greater than the current dose.
7. Use of rectally administered mesalamine or steroids within the 2 weeks prior to enrollment.
8. Currently taking more than 3.0 gm/day of mesalamine (oral or rectal). If on oral and rectal mesalamine, the combined dose is more than 3.0 gm/day.
9. Use of anti-TNFα therapies within the 8 weeks prior to enrollment and/or intent to use anti-TNFα therapies as maintenance therapy in the coming 12 weeks.
10. Pregnant or breast feeding women.
11. Use of an experimental therapy for ulcerative colitis in the 8 weeks prior to enrollment.
12. Any condition that the investigator feels will make completion of the study unlikely.
13. Use of cyclosporine in the two weeks prior to enrollment.
14. Moderate or severe abdominal tenderness on examination at time of enrollment.
D: 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.

Answer: D