Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-blind, Double-dummy, Randomised, Multicentre, Comparative Study of the Efficacy and Tolerability of Once Daily 3.0 g Mesalazine Granules Versus Three Times Daily 1.0 g Mesalazine Granules in Patients With Active Ulcerative Colitis
Brief Summary: To proof the therapeutic equivalence of once daily (OD) versus three times daily (TID) dosing of total 3.0 g mesalazine granules in patients with active ulcerative colitis


Options:
A: 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).
B: Inclusion Criteria:

1. Signed informed consent,
2. Men or women aged 18 to 75 years,
3. Active ulcerative colitis, except proctitis limited to 15 cm ab ano, confirmed by endoscopy and histology,
4. Established disease (presence of blood or mucus in the stools) or new diagnosis (bloody stools occurring at least during 14 days prior to baseline visit),
5. Clinical Activity Index (CAI) \>= 6 and Endoscopical Index (EI) \>= 4,
6. Women of child-bearing potential, if heterosexually active, have to apply a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptive method, some intrauterine devices (IUDs), sexual abstinence, or vasectomised partner. The investigator is responsible for determining whether the subject has adequate birth control for study participation.

Exclusion Criteria:

1. Crohn's disease, indeterminate colitis, ischaemic colitis, radiation colitis, microscopic colitis (i.e., collagenous colitis and lymphocytic colitis),
2. Toxic megacolon,
3. Baseline stool positive for germs causing bowel disease,
4. Diarrhoea as a result of the presence of other symptomatic organic disease(s) of the gastrointestinal tract,
5. Active peptic ulcer disease,
6. Haemorrhagic diathesis,
7. Asthma, diabetes mellitus, infection, osteoporosis, glaucoma, cataract, or cardiovascular disease if careful medical monitoring is not ensured,
8. Severe co-morbidity substantially reducing life expectancy,
9. Active colorectal cancer or a history of colorectal cancer,
10. Active malignancy other than colorectal cancer or treatment with anticancer drugs during the last 5 years. Patients with a history of cancer other than colorectal cancer and at least five years of uneventful follow up and no signs of recurrence may be eligible,
11. Immunosuppressants within 3 months and/or corticosteroids (oral, intravenous \[IV\] or topical rectal) within 4 weeks prior to baseline,
12. Current relapse occurred under maintenance treatment with \> 2.4 g mesalazine per day,
13. Abnormal renal function (Serum Cystatin C \> upper limit of normal \[ULN\]),
14. Abnormal hepatic function (ALT, AST or AP \>= 2 x ULN) or liver cirrhosis,
15. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile, or to any of the other constituents of the study drugs,
16. Doubt about the patient's cooperation, e.g., because of addiction to alcohol or drugs,
17. Existing or intended pregnancy or breast-feeding,
18. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.
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: Inclusion Criteria (main):

* Active ulcerative colitis except proctitis, i.e. inflammation minimal 15cm ab ano, confirmed by endoscopy and histology
* Established or new diagnosis
* Disease activity at baseline: Clinical Activity Index (CAI) \>4 and Endoscopic Index (EI) \>= 4

Exclusion Criteria (main):

* Crohn's disease
* Toxic megacolon
* Present or past colorectal cancer
* Symptomatic gastrointestinal disease
* Serious secondary disease(s)
* Baseline stool positive for germs causing bowel disease
* Immunosuppressants within 3 months and/or corticosteroids within 1 month prior to baseline
* Current relapse occurred under maintenance treatment with \>2g/day mesalazine
* Serum creatinine \>= 1.2x upper limit of normal (ULN) and creatinine clearance \< 60 ml/min per 1.73 m2
* Serum transaminase (ALT and/or AST), and/or alkaline phosphatase \>= 2x ULN

Answer: D