Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

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 week 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.