Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-blind, Randomised, Placebo and Mesalazine Controlled Phase II Study to Explore the Safety and Activity of Dersalazine in Patients With Mild to Moderate Active Colitis
Brief Summary: The purpose of the study is to obtain a first clinical assessment of the safety of dersalazine sodium in ulcerative colitis patients with mild to moderate disease.


Options:
A: Inclusion Criteria:

* Age 18 to 65 inclusive
* Male, non-child-bearing female or fertile female with appropriate contraception.
* Mild to moderate confirmed active ulcerative colitis
* Able and willing to give informed consent

Exclusion Criteria:

* Colitis of other cause
* Pregnancy, inadequate contraception for fertile female patients
* Liver or kidney disease, unstable cardiovascular disease, coagulation disorder.
* Other significant medical condition that preclude participation at investigator criteria
* Allergy or hypersensitivity to salicylates
* Previous or concomitant treatment for ulcerative colitis interfering with safety or activity assessments
B: 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).
C: 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.
D: 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.

Answer: A