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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
White film coated round biconvex GSK2586184 200 mg tablets, administered 2 X twice daily. Tablet containing GSK2586184A, with the following excipients: microcrystalline cellulose, lactose, hypromellose, croscarmellose sodium, magnesium stearate and titanium dioxide.
GSK Investigational Site
Amsterdam, Netherlands
Safety and Tolerability of twice daily doses of GSK2586184
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.
Time frame: Up to Week 8
Safety as assessed by the collection of adverse events (AEs)
AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Time frame: Up to Week 8
Safety as assessed by laboratory parameters
Laboratory parameters include hematology, clinical chemistry, urinalysis Absolute values and changes over time of hematology, clinical chemistry, urinalysis will be assessed.
Time frame: Up to Week 8
Safety as assessed by vital sign measurement
Vital signs include systolic blood pressure, diastolic blood pressure, temperature, and heart rate.
Time frame: Up to Week 8
Safety as assessed by ECG rhythm.
Continuous monitoring of a subject' heart rate and rhythm by ECG.
Time frame: Up to Week 8
Efficacy of GSK2586184 in achieving clinical and endoscopic remission after 8 weeks of treatment
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.
Time frame: Up to Week 8
Efficacy of GSK2586184 in achieving symptomatic clinical remission after 8 weeks
Efficacy assessed by Mayo score for the proportion of subjects who achieve a score of 0 for both rectal bleeding and stool frequency.
Time frame: Up to Week 8
Efficacy of GSK2586184 in achieving clinical response
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
Time frame: Up to Week 8
Efficacy of GSK2586184 in achieving mucosal healing.
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).
Time frame: Up to Week 8
The effect of twice daily doses of GSK2586184 on health related quality of life (QoL) in UC patients.
Change from baseline of inflammatory bowel disease questionnaire (IBDQ) was assessed
Time frame: Up to Week 8
The effect of twice daily doses of GSK2586184 on serum C reactive protein (CRP) levels in UC patients
Change from baseline in mean serum CRP levels was assessed.
Time frame: Up to Week 8
The effect of twice daily doses of GSK2586184 on faecal calprotectin levels
Change from baseline of mean faecal calprotectin levels was assessed.
Time frame: Up to Week 8
The plasma pharmacokinetics of repeated, twice daily doses of GSK2586184
Plasma concentrations and derived pharmacokinetic parameters of GSK2586184 were assessed.
Time frame: Up to Week 8
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