Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Active-Controlled, Double-Blind and Open Label Extensions Study to Evaluate the Efficacy, Long-Term Safety and Tolerability of TP05 3.2g/Day for the Treatment of Active Ulcerative Colitis
Brief Summary: The purpose of this research study was to compare the medication TP05 to the medication Asacol™ for the treatment of ulcerative colitis (UC) and to assess the safety and tolerability of TP05. This study investigated whether TP05 is as good as (non-inferior to) Asacol™(1).

(1)The trademark Asacol™ is registered in over 55 countries as Asacol™ and as Octasa™, Fivasa™, Lixacol™, Asacolon™ in the United Kingdom, France, Spain and Ireland, respectively. The rights to Asacol, including the rights to the trademark, are owned by Tillotts Pharma AG in various countries except for the following: Switzerland, USA, United Kingdom, Canada, Italy, Belgium, the Netherlands and Luxembourg.


Options:
A: 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
B: 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.
C: 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.
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: D