Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Controlled, Randomized, Double-blind, Multicenter Study, Comparing Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis
Brief Summary: * PHASE: II
* TYPE OF STUDY : With direct benefit
* DESCRIPTIVE: Multicenter, randomized, double-blind study
* INCLUSION CRITERIA: Steroid-dependent ulcerative colitis
* OBJECTIVES: To show superiority of methotrexate vs placebo in inducing steroid-free remission in steroid-dependent ulcerative colitis
* STUDY TREATMENTS: Methotrexate 1 intramuscular injection (25 mg) per week Placebo 1 intramuscular injection per week
* NUMBERS OF PATIENTS: 55 patients in each group, i.e. a total of 110 patients
* INCLUSION PERIOD: 24 months
* STUDY DURATION: 36 months
* EVALUATION CRITERIA: Remission without steroids, immunosuppressives and without colectomy at 16 weeks of treatment.


Options:
A: Inclusion Criteria:

* Subjects must have completed all assessments of SPD476-301 or SPD476-302 End of Study/Early Withdrawal Visit
* Subjects who did not achieve remission at the End of Study/Early Withdrawal Visits in Study 301 or 302 will be eligible to enter the Acute Phase; subjects who did achieve remission at the End of Study Visits in Study 301 or 302 will be eligible to enter directly into the Maintenance Phase
* Women of childbearing potential must use an acceptable contraceptive method while on study treatment

Exclusion Criteria:

* Subjects who withdrew from Study 301 or 302 before Study Visit 3, or who withdrew due to a possible or probably related severe adverse event or serious adverse event are not eligible to enter this study
B: Inclusion Criteria:

* UC diagnosed according to the Lennard-Jones criteria (Appendix 1) with endoscopic colorectal lesions, whatever their extension may be
* A Mayo Disease Activity Index £ 4, with no item \>1 for the clinical part of the score and from 0 to 2 for the endoscopic part at the time of inclusion
* Steroid-dependence defined by at least 1 unsuccessful attempt to stop systemic steroid therapy during the last 12 weeks. Steroid therapy might have been completely stopped if it has been restarted within the last 30 days
* To be receiving a treatment of prednisone at a dose between 10 and 40mg, stable for at least 2 weeks at the time of inclusion
* Under an adequate contraception for male or female subjects of childbearing potential

Exclusion Criteria:

* Indication to a colectomy.
* Alcoholism (more than 21 glasses per week for male subjects and 14 glasses per week for female subjects). 1 glass corresponds to 3 cl of strong alcohol, 10 cl glass of wine or a half pint of beer.
* Pregnant or breast-feeding female subjects.
* No efficacious contraception.
* NSAIDS or cotrimoxazole intake upon inclusion, or probenecid intake within 1 month prior to inclusion.
* Anti-TNFa treatment within 2 months prior to inclusion.
* Azathioprine, mercaptopurine, cyclosporin or thalidomide within 1 month prior to inclusion.
* Modification of mesalazine or olsalazine dosage within 1 month prior to inclusion.
* Chronic (broncho) pneumopathy.
* Renal failure (creatinaemia \> upper limit of normal laboratory values limit).
* Liver disease apart from primary sclerosing cholangitis.
* Unexplained rise higher than twice the normal level for transaminases, alkaline phosphatases and/or bilirubin.
* Folate level \< normal level.
* Past history of malignant condition (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers.
C: Inclusion Criteria:

* A positive histological diagnosis of UC ≥3 months prior to entry into the study. If a histological diagnosis is not available but all signs and symptoms suggest UC, the subject's eligibility should be discussed with Pfizer.
* Active UC as defined by a score of ≥6 on the Mayo score.
* An endoscopic (by flexible sigmoidoscopy) sub-score of ≥2 on the Mayo score determined within 7 days of first dosing.

Exclusion Criteria:

* Subjects with UC, which is confined to a proctitis on a flexible sigmoidoscopy.
* Subjects who have had surgery as a treatment for UC or are likely to require surgery within the duration of the study.
* Subjects displaying clinical signs of ischemic colitis.
D: Inclusion Criteria:

* Patients fulfilling the following criteria at the screening visit are eligible for participation in the study:

  * Male and female patients, 18-75 years old, suffering from ulcerative colitis for at least 6 months.
  * Diagnosis of ulcerative colitis in active phase, of mild or moderate entity with Ulcerative Colitis Disease Activity Index (UCDAI) ≥ 4 and ≤ 10 according to Sutherland.
  * All females of child-bearing potential must have a negative serum pregnancy test immediately prior to enrollment. In addition, all females of child-bearing potential must agree to be completely abstinent or be using an accepted form of contraception throughout the entire study period. Accepted forms of contraception are defined as those with a failure rate \<1% when properly applied and include: combination oral pill, some intra-uterine devices, and a sterilised partner in a stable relationship. Female subjects must also not be actively breast-feeding through the entire study period.
  * Ability to comprehend the full nature and purpose of the study, including possible risks and side effects.
  * Ability to co-operate with the investigator and to comply with the requirements of the entire study.
  * Must be able to understand and voluntarily sign written informed consent prior to inclusion in the study.

Exclusion Criteria:

* Patients who meet any of the following criteria at screening visit are to be excluded from study participation:

  * Patients with limited distal proctitis (from anal verge up to 15 cm above the pectineal line).
  * Patients with severe ulcerative colitis (UCDAI \>10).
  * Patients with infectious colitis.
  * Evidence or history of toxic megacolon.
  * Severe anemia, leucopenia or granulocytopenia.
  * Use of oral or rectal steroids in the last 4 weeks.
  * Use of immuno-suppressive agents in the last 8 weeks before the study.
  * Use of anti tumor necrosis factor alpha (anti-TNFα) agents in the last 3 months.
  * Concomitant use of any rectal preparation.
  * Concomitant use of antibiotics.
  * Concurrent use of cytochrome P450 3A4 (CYP3A4) inducers or CYP3A4 inhibitors.
  * Patients with intolerance to salicylates.
  * Patients with verified, presumed or expected pregnancy or ongoing lactation.
  * Patients with liver cirrhosis, or evident hepatic or renal disease or insufficiency, and/or severe impairment of the bio-humoral parameters (i.e. 2 x upper limit of normal for alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma glutamyl transpeptidase \[GGT\] or creatinine).
  * Patient with severe diseases in other organs and systems.
  * Patients with local or systemic complications or other pathological states requiring a therapy with corticosteroids and/or immuno-suppressive agents.
  * Patients diagnosed with type 1 diabetes.
  * Patients diagnosed with, or with a family history of, glaucoma.
  * All patients with known hepatitis B, hepatitis C or with human immunodeficiency virus (HIV), according to the local privacy policy.
  * Participation in experimental therapeutic studies in the last 3 months. (Note: patients who participated in observational only studies are not excluded).
  * 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 subject or obscure the interpretation of adverse events (AEs).

Answer: B