Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-centre Double Blind Randomised Placebo-controlled Study of the Use of Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis
Brief Summary: Ulcerative Colitis (UC) is a life-long incurable disease with remissions and exacerbations. Inflammation confined to the rectum occurs in a quarter of patients and can be extremely hard to treat. Many medications have been tried in order to control the inflammation, but they do not always work. One of the newer medications is the immunosuppressing medication, tacrolimus that has been shown to be effective in UC when taken orally. Unfortunately, the oral use of this medication can have numerous serious side effects. In order to overcome these side effects, the use of topical rectal tacrolimus has been examined. Pilot studies in ulcerative proctitis (inflammation confined to the rectum) resistant to conventional therapies have demonstrated a clinical remission in 75% of patients and although the medication was well absorbed through the lining of the bowel, the levels in the blood were very low and no serious side effects were reported. The findings suggest that this preparation is indeed effective for inflammation in the distal bowel and that the method of administration reduces side effects. Further work, however, now needs to be undertaken to validate the original findings.


Options:
A: Inclusion Criteria:

* Subject must be at least 18 years of age.
* Males and females with a documented diagnosis of UC at least 4 months prior to entry into the study.
* Subjects with moderately to severely active UC based on Mayo score criteria.
* Subjects must have failed or be intolerant of at least one of the following treatments for UC:

  * Corticosteroids (oral or intravenous).
  * Azathioprine or 6 mercaptopurine (6 MP).
  * Anti TNF therapy.

Exclusion Criteria:

* Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease.
* Subjects with disease limited to distal 15 cm.
* Subjects without previous treatment for UC (ie, treatment naïve).
* Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
B: Inclusion Criteria:

* Has a clinical diagnosis of Ulcerative Colitis (UC) at least 3 months before Screening
* Has moderately to severely active UC, defined as a Baseline (Week 0) Mayo score of 6 to 12, including a Screening endoscopy subscore of the Mayo score greater than or equal to (\>=) 2 as determined by a central reading of the video endoscopy
* Have failed biologic therapy, that is, have received treatment with 1 or more tumour necrosis factor (TNF) antagonists or vedolizumab at a dose approved for the treatment of UC, and have a documented history of failure to respond to or tolerate such treatment; OR Be naïve to biologic therapy (TNF antagonists or vedolizumab) or have received biologic therapy but have not demonstrated a history of failure to respond to, or tolerate, a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following: a. Inadequate response to or failure to tolerate current treatment with oral corticosteroids or immunomodulators (6-mercaptopurine \[6-MP\] or azathioprine \[AZA\]) OR b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) OR c. History of corticosteroid dependence (that is, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
* Before the first administration of study agent, the following conditions must be met: vedolizumab must have been discontinued for at least 4 months and anti-tumor necrosis factors (TNFs) for at least 8 weeks

Exclusion Criteria:

* Has severe extensive colitis and is at imminent risk of colectomy
* Has UC limited to the rectum only or to \< 20 centimeters (cm) of the colon
* Presence of a stoma or history of a fistula
* Participants with history of extensive colonic resection (for example, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity
* Participants with history of colonic mucosal dysplasia. Participants will not be excluded from the study because of a pathology finding of "indefinite dysplasia with reactive atypia''
C: Inclusion Criteria:

1. Is able to provide informed consent.
2. Is over the age of 18 years
3. Has a diagnosis of ulcerative colitis of over 3 months duration that was confirmed by a specialist gastroenterologist
4. Has inflammation limited to 25cm proximal to the anal verge
5. Has failed to achieve remission with, or be intolerant of, the use of conventional therapy defined as oral and/or rectal 5-Aminosalicylates, and/or oral and rectal steroids
6. Has symptoms of active UC with a Mayo score of between 6 and12
7. Medications:

   1. Oral 5-Aminosalicylates: If taking an oral 5-Aminosalicylates the patient has used them continuously for 4 weeks and has been on a stable dose for 2 weeks prior to the screening visit.
   2. Oral Corticosteroids: If taking oral corticosteroids the patient has used them continuously for 4 weeks and has been on a stable dose for 2 weeks prior to the screening visit at a dose of ≤30mg.
   3. Oral Azathioprine/6MP or Methotrexate: If taking one of these medications the patient has used them for a minimum of 12 weeks and has been on a stable dose for 4 weeks prior to screening.
   4. Rectal Preparations; 5-Aminosalicylates and corticosteroids: All rectal preparations have been ceased at least one day prior to Week 0.
8. Has a normal serum potassium levels defined as 3.4-5mmol/L.
9. Has normal renal function defined as a Glomerular Filtration Rate (GFR) \>60ml/min.
10. Willing to participate in the study and comply with the proceedings by signing a written informed consent.
11. Free of any clinically significant disease, other than ulcerative colitis, that would interfere with the study's evaluations.
12. Subjects can understand and is able to adhere to the dosing and visit schedules; Agrees to record symptom severity scores, medication times, adverse events and concomitant medications accurately and consistently.

Exclusion Criteria:

1. Has Crohn's disease.
2. Has colitis extending more than 25cm from the anal verge.
3. Has a known hypersensitivity/allergic reaction to tacrolimus.
4. Is pregnant or is breast-feeding.
5. Has unstable, or poorly controlled, hypertension.
6. Has an abnormal serum potassium level defined as outside the range of 3.4-5mmol/L.
7. Has chronic renal failure defined as a Glomerular Filtration Rate \<60 ml/min.
8. Is currently using a potassium-sparing diuretic agent.
9. Has received a trial medication within 12 weeks of screening.
10. Has documented HIV infection.
11. Has a known malignancy, a pre-malignant lesion, or any history of malignancy within the past 5 years (excluding squamous and/or basal cell carcinomas).
12. Presence of alcoholism, alcoholic liver disease, or other chronic liver disease.
13. Has known dementia and the inability to understand the trial requirements.
D: Inclusion Criteria:

* Subject must be at least 18 years of age.
* Males and females with a documented diagnosis of UC at least 4 months prior to entry into the study.
* Subjects with moderately to severely active UC based on Mayo score criteria.
* Subjects must have failed or be intolerant of at least one of the following treatments for UC:

  * Corticosteroids (oral or intravenous).
  * Azathioprine or 6 mercaptopurine (6 MP).
  * Anti TNF-alpha therapy.

Exclusion Criteria:

* Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease.
* Subjects with disease limited to distal 15 cm.
* Subjects without previous treatment for UC (ie, treatment naïve).
* Subjects displaying clinical signs of fulminant colitis or toxic megacolon.

Answer: C