Effect of GSK1399686 in Patients With Mild to Moderately Active Ulcerative Colitis

This is an interventional treatment trial for Colitis, Ulcerative focused on measuring mesalazine, ulcerative colitis, pharmacokinetics/dynamics, GSK1399686 Read More

Inclusion Criteria:

1. Male or female of non-childbearing potential between 18 and 65 years of age inclusive.
2. Presence of mild-to-moderately active ulcerative colitis spread beyond the rectum as evidenced by clinical signs and endoscopy.
3. UCDAI score 4-10 (inclusive) with rectal bleeding score ≥ 1, endoscopy score ≥ 1 and Physician's rating of disease activity < 3.
4. Body weight > or = to 50 kg and BMI within the range 18.5-29.9 kg/m2 (inclusive).
5. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

1. History of sensitivity to any component of study medications, history of hypersensitivity to ACTH, or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates patient's participation in the study.
2. History of renal sensitivity to 5-ASA or presence of nephritis, nephropathia or renal function impairment.
3. Presence or a history of asthma or presence or history of other serious allergic disorder.
4. Presence or history of chronic liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
5. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
6. Presence of significant hematologic disorder, or significant bleeding or immune system disorder.
7. QTcB or QTcF >450 msec; or QTc >480 msec in patients with Bundle Branch Block, based on an average QTc value of triplicate ECGs, if the first ECG showed an abnormal value.
8. Presence of a significant cardiac, pulmonary, metabolic or infectious disease or mental disorder that, in the opinion of the Investigator, represents an unacceptable safety risk for participation in this trial.
9. History of malignant neoplastic disease within the past 5 years other than localized basal cell skin cancer, squamous cell skin cancer or cancer in situ that has been resected.
10. History of regular alcohol consumption within 6 months of the study or presence of recreational drug abuse or dependence.
11. Presence of infectious colitis as evidenced by stool culture positive for enteric pathogens or positive Clostridium difficile cytotoxin assay.
12. Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
13. Bowel surgery within last 12 months.
14. Treatment with oral aminosalicylates at dose ≥ 2.4 g/day and/or with topical aminosalicylates at any dose within 2 weeks prior to Day 1 visit.
15. Treatment with systemic or topical corticosteroids within 4 weeks prior to Day 1 visit.
16. Treatment with TNF-α inhibitors or other biologics within 2 months prior to Day 1 visit.
17. Treatment with immunosuppressants (azathioprine or 6-mercaptopurine), if initiated within 3 months prior to Day 1 visit, or if changed in terms of drug or dose within 3 months prior to Day 1 visit.
18. Regular use of probiotic or prebiotic preparations, if initiated within 4 weeks prior to Day 1 visit.
19. Regular daily use of non-steroidal anti-inflammatory drugs (NSAIDs), except low dose aspirin (325 mg/day) for cardioprotection, within 7 days prior to Day 1 visit.
20. Treatment with medications known to be strong inducers of CYP3A4/5 (e.g. carbamezipine, phenobarbital, phenytoin, rifabutin, rifampin, troglitazone) or regular use of St. John's Wort within 14 days prior to Day 1 visit.
21. Treatment with medications known to be strong inhibitors of CYP3A4/5 (e.g. ketoconazole, itraconazole, fluconazole, mibefradil, clarithromycin, erythromycin, diltiazem, verapamil), or regular use of grapefruit juice within 7 days prior to Day 1 visit.
22. Treatment with medications known to be sensitive CYP3A4 substrates with a narrow therapeutic index (e.g. alfentanil, astemizole, cisapride, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine) within 7 days prior to Day 1 visit.
23. Participation in a clinical trial and treatment with an investigational product within the following time period prior to the Day 1 visit: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

24. Prior enrolment in the present trial.

    For Canadian sites only:

25. Patients with existing gastric or duodenal ulcers.
26. Patients with urinary tract obstruction