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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-Blind, Double-Dummy, Placebo- and Active-Controlled Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Inflammatory Effects of GSK1399686 in Patients With M

Brief Summary:

This study is the first-time-in-patient trial of GSK1399686, a novel locally-acting anti-inflammatory compound, aimed at obtaining initial information on the tolerability, safety, pharmacokinetics (including concentrations in colon mucosa) and anti-inflammatory activity of GSK1399686 upon oral dosing in patients with active ulcerative colitis.

The study is designed as a randomized, double-blind, double-dummy, placebo-controlled, sequential dose escalating trial, with an active control (ASACOL) group as internal control. Up to three cohorts (Cohorts 1-3), each consisting of approximately 20 patients with mild-moderately active ulcerative colitis not limited to the rectum, will be included, one for each dose level of GSK1399686 to be tested. Within a cohort, patients will be randomized in a 3:1:1 ratio to receive GSK1399686 (once daily over 4 weeks, followed by 2 weeks dosing with placebo), placebo, or ASACOL (t.i.d. for 6 weeks), respectively.

An interim analysis of fecal markers and disease activity data will be performed by the end of Cohort 3. Based upon results, the study may be stopped or continued by recruiting either Cohort 4 (if data on an additional dose level would be warranted to establish or clarify a dose-response relationship) or, in the case of a robust efficacy signal at any dose level previously studied, Cohort 5 (to expand the sample size for given dose level in order to evaluate the efficacy of GSK1399686). The number of patients and randomization allocation ratio may be altered in Cohort 5 and it may not include an active control arm. If Cohort 4 is initiated upon interim analysis, then a second interim analysis may be performed at the end of Cohort 4, to assess whether progression into Cohort 5 (as defined above) would be justifiable.


Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Safety and tolerability as determined by: Adverse events (AEs); effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings; and effects on basal morning cortisol [ Time Frame: 4 weeks ]
  • Concentration of GSK1399686 in colon biopsy obtained within 24 hours after the last dose [ Time Frame: 4 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Simple Clinical Colitis Activity Index (SCCAI) score over time [ Time Frame: 6 weeks ]
  • Clinical response rate (proportion of patients with SCCAI score decreased for > 2 points in comparison with baseline) at Week 4 and Week 6 [ Time Frame: 6 weeks ]
  • Time to clinical response (defined as the number of days between the first dose of study medication and the first day of at least 3 consecutive days with SCCAI score decreased for > 2 points in comparison with baseline). [ Time Frame: 4 weeks ]
  • Clinical remission rate (proportion of patients with SCCAI score < 3) at Week 4 and Week 6 [ Time Frame: 6 weeks ]
  • Time to clinical remission, defined as the number of days between the first dose of study medication and the first day of at least 3 consecutive days with SCCAI score < 3 [ Time Frame: 4 weeks ]
  • Fecal calprotectin and fecal lactoferrin levels over time [ Time Frame: 6 weeks ]
  • PK parameters for GSK1399686 derived from observed plasma concentrations of GSK1399686 after repeated oral dosing [ Time Frame: 4 weeks ]


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: December 17, 2009
Date Started: September 2009
Date Completion:
Last Updated: September 24, 2015
Last Verified: August 2013