Clinical Trial: Safety and Tolerability Study of GSK2586184 in Patients With Moderate to Severely Active Ulcerative Colitis.

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: An Open Label, Experimental Medicine Investigation of the Safety and Tolerability of 400 mg b.i.d. GSK2586184 in Patients With Moderate to Severely Active Ulcerative Colitis

Brief Summary: This is an open label exploratory study to investigate the safety of 400 milligram (mg ) twice a day (b.i.d.) GSK2586184 in patients with moderate to severe, active ulcerative colitis (UC). Study medication will be administered orally (as tablets), twice daily, for up to 8 weeks (56 days). Study medication will be taken with food. Each subject will have 6 out-patient visits: Screening (Day -30 to -1); Baseline and Start of treatment (Day 1); Week 2 (Day 14); Week 4 (Day 28); Week 8 (Day 56); and Follow-up (Week 12; Day 84). Visit windows for weeks 2, 4 and 8 will be + 2 days. The primary objective of this study is to assess the safety and tolerability of GSK2586184. The primary endpoints to measure safety are laboratory tests (including haematology, clinical chemistry and serum creatinine), vital signs, 12-lead electrocardiogram (ECG), physical examination, and adverse event reporting. These are standard measurements to evaluate safety.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Safety and Tolerability of twice daily doses of GSK2586184 [ Time Frame: Up to Week 8 ]
    Safety and tolerability, as determined by laboratory tests (including haematology, clinical chemistry and serum creatinine) vital signs, 12-lead Electrocardiogram (ECG), physical examination, and adverse event reporting.
  • Safety as assessed by the collection of adverse events (AEs) [ Time Frame: Up to Week 8 ]
    AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
  • Safety as assessed by laboratory parameters [ Time Frame: Up to Week 8 ]
    Laboratory parameters include hematology, clinical chemistry, urinalysis Absolute values and changes over time of hematology, clinical chemistry, urinalysis will be assessed.
  • Safety as assessed by vital sign measurement [ Time Frame: Up to Week 8 ]
    Vital signs include systolic blood pressure, diastolic blood pressure, temperature, and heart rate.
  • Safety as assessed by ECG rhythm. [ Time Frame: Up to Week 8 ]
    Continuous monitoring of a subject' heart rate and rhythm by ECG.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Efficacy of GSK2586184 in achieving clinical and endoscopic remission after 8 weeks of treatment [ Time Frame: Up to Week 8 ]
    Efficacy assessed by total Mayo score of 2 points or lower, with no individual sub score exceeding 1 point, and reduction in endoscopic mucosal appearance score of >= 1.
  • Efficacy of GSK2586184 in achieving symptomatic clinical remission after 8 weeks [ Time Frame: Up to Week 8 ]
    Efficacy assessed by Mayo score for the proportion of subjects who achieve a score of 0 for both rectal bleeding and stool frequency.
  • Efficacy of GSK2586184 in achieving clinical response [ Time Frame: Up to Week 8 ]
    Efficacy assessed by Mayo score for the proportion of subjects of subjects who achieve a decrease from baseline in total Mayo score of >=3 points, with an accompanying decrease in the sub score for rectal bleeding of at least 1 point or an absolute sub score for rectal bleeding
  • Efficacy of GSK2586184 in achieving mucosal healing. [ Time Frame: Up to Week 8 ]
    Efficacy assessed by proportion of subjects who achieve an absolute sub score for endoscopy of 0 or 1, at week 8. And change from baseline of mucosal appearance determined by ulcerative colitis endoscopic index of severity (UCEIS).
  • The effect of twice daily doses of GSK2586184 on health related quality of life (QoL) in UC patients. [ Time Frame: Up to Week 8 ]
    Change from baseline of inflammatory bowel disease questionnaire (IBDQ) was assessed
  • The effect of twice daily doses of GSK2586184 on serum C reactive protein (CRP) levels in UC patients [ Time Frame: Up to Week 8 ]
    Change from baseline in mean serum CRP levels was assessed.
  • The effect of twice daily doses of GSK2586184 on faecal calprotectin levels [ Time Frame: Up to Week 8 ]
    Change from baseline of mean faecal calprotectin levels was assessed.
  • The plasma pharmacokinetics of repeated, twice daily doses of GSK2586184 [ Time Frame: Up to Week 8 ]
    Plasma concentrations and derived pharmacokinetic parameters of GSK2586184 were assessed.


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: November 27, 2013
Date Started: December 20, 2013
Date Completion:
Last Updated: May 9, 2017
Last Verified: May 2017