Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Placebo-Controlled Double-Blind Study to Evaluate the Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis
Brief Summary: The primary objective of the study is to determine the efficacy of Asacol™ 4.8 g/day (800 mg tablets) to induce clinical and endoscopic remission after 6 weeks of treatment compared to placebo in subjects with active ulcerative colitis (UC).


Options:
A: 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.
B: Inclusion Criteria:

(1) Male or non-pregnant, non-lactating females, 18 years of age or older. (2) Documented diagnosis of UC with disease extending at least 15 cm from the anal verge.

(3) Active UC defined by:

(a) modified UC-DAI score of 4-10 with (b) sigmoidoscopy component score ≥ 2 and (c) rectal bleeding component score ≥ 1 (4) Ability of subject to participate fully in all aspects of this clinical trial.

(5) Written informed consent must be obtained and documented.

Exclusion Criteria:

1. Severe UC defined by the following criteria:

   ³6 bloody stools daily with one or more of the following:
   1. oral temperature \> 37.8°C or \> 100.0°F
   2. pulse \> 90/min
   3. hemoglobin \< 10 g/dL
2. Previously failed treatment with a mesalazine dose of \> 2.0 g/day.
3. Current relapse lasting \> 6 weeks in the opinion of the investigator.
4. Treatment with 5-ASA at a dose of \>2.0g/day within 1 week prior to randomisation
5. Treatment with systemic or rectal steroids within 4 weeks prior to randomization.
6. Treatment with immunosuppressants within 6 weeks prior to randomization.
7. Treatment with infliximab or other biologics within 3 months prior to randomization.
8. Treatment with systemic antibiotics for UC within 7 days prior to randomization.
9. Treatment with probiotics within 7 days prior to randomization.
10. Treatment with anti-diarrheals within 7 days prior to randomization.
11. Treatment with nicotine patch within 7 days prior to randomization.
12. Received any investigational drug within 30 days prior to randomization.
13. History of colectomy or partial colectomy.
14. History of definite dysplasia in colonic biopsies.
15. Crohn's disease.
16. Known bleeding disorders.
17. Immediate or significant risk of toxic megacolon.
18. Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA.
19. Serum creatinine \> 1.5 times the upper limit of the normal range.
20. AST, ALT, total bilirubin or alkaline phosphatase \> 2 times the upper limit of the normal range.
21. Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study.
22. 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.
23. Stools positive for clostridium difficile.
24. Pregnant or lactating women.
25. Prior enrolment in the current study and had received study treatment.
C: Inclusion Criteria:

Patients will be included if they comply with the following inclusion criteria determined at baseline, prior to first drug administration:

* Aged over 18 years.
* Newly diagnosed or relapsing mild to moderate ulcerative colitis with disease extension beyond rectum (of at least 12-18 cm from the anorectal junction). All patients must have had at least one total colonoscopy in their disease history (within the previous 5 years).
* Disease activity will be assessed on the 15 days before inclusion and according to ulcerative colitis disease activity index (UC-DAI) score. The UC-DAI score will be from 3 to 8 (mild: 3-5 or moderate: 6-8).
* Men or non pregnant women.
* Women with childbearing potential must be using a contraceptive method judged effective by the investigator.
* Oral maintenance treatment with azathioprine or 6-mercaptopurine (taken for at least 6 months at stable dose and continued at the same dose throughout the study) is permitted.
* Informed consent given.

Exclusion Criteria:

The patients will not be included in the study if one of the following exclusion criteria is fulfilled at baseline, prior to first drug administration:

* Proctitis (less than 12-18 cm from the anorectal junction).
* Previous colonic surgery.
* Previously failed to respond to steroids within the previous year.
* Non-response to rectal 5-Amino Salicylic Acid (5-ASA) therapy or to oral 5-ASA therapy at a dose \> 3g/day for induction of remission within the previous year.
* Current relapse lasting more than 6 weeks (for patient recently diagnosed the period of 6 weeks runs from the endoscopic diagnosis)(from what patient says).
* Severe/fulminant ulcerative colitis.
* Evidence of other forms of inflammatory bowel disease or infectious disease.
* Allergy to aspirin or salicylate derivatives.
* The following treatment will be forbidden during the study (if present at selection, a wash-out will be necessary):
* Loperamide and other antidiarrheal agents, mucilages, antibiotics: 1 week wash-out.
* Oral steroids: 4 weeks wash-out.
* Rectal steroids: 2 weeks wash-out
* Repeated treatment (\> 3days of use) of non steroidal anti-inflammatory drugs (NSAID) oral or rectal route: 1 week wash-out (aspirin ≤ 325 mg/day used for cardioprotection is allowed).
* Sulfasalazine \> 4g/day or mesalazine or 4-ASA at a higher dose than what is permitted in the local formulary or standard care for maintenance treatment: 4 weeks wash-out
* Immunomodulating/suppressing drugs: 3 month for wash out (except for patients maintained on azathioprine or 6-mercaptopurine -see above).
* Known significant hepatic or renal function abnormalities.
* Moderate/severe abnormal renal, hepatic or blood count tests defined as: creatinine plasma value \> 1.5 x Upper Limit of Normal (ULN) or white blood cells \< 3500/mm˄3 or \> 15000/mm˄3 or Platelets \< 100000/mm˄3 or \> 800000/mm˄3 or aspartate aminotransferase/alanine Aminotransferase (ASAT/ALAT) \> 3 x ULN or Gamma glutamyl transpeptidase (GGT)/Alkaline Phosphatase's \> 3 x ULN (Primary Sclerosing Cholangitis is not an exclusion criteria).
* History or physical examination findings indicative of active alcohol or drug abuse,
* Pregnancy or breast-feeding,
* History of disease, including mental/emotional disorder, that might interfere with their participation in the study,
* Participation in another clinical study in the last 3 months.
* Inability to comply with the protocol requirements.
* Inability to fill in the diary cards.
D: 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.

Answer: B