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

NCT ID: NCT01036022

Last Updated: 2017-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-15
• Study Completion Date: 2013-01-10

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.

Conditions

Colitis, Ulcerative

Keywords

mesalazine; ulcerative colitis; pharmacokinetics/dynamics; GSK1399686

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 2

ASACOL 800mg t.i.d.

Group Type: EXPERIMENTAL

GSK1399686

Intervention Type: DRUG

Each dose level of GSK1399686 will be subsequently tested in a cohort of approximately 20 patients, who 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.

Group 1

GSK1399686 at 3-4 dose levels

Group Type: EXPERIMENTAL

GSK1399686

Intervention Type: DRUG

Each dose level of GSK1399686 will be subsequently tested in a cohort of approximately 20 patients, who 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.

Group 3

Placebo

Group Type: EXPERIMENTAL

GSK1399686

Intervention Type: DRUG

Each dose level of GSK1399686 will be subsequently tested in a cohort of approximately 20 patients, who 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.

Interventions

GSK1399686

Each dose level of GSK1399686 will be subsequently tested in a cohort of approximately 20 patients, who 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Bonheiden, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Kingston, Ontario, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Vaughan, Ontario, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Münster, North Rhine-Westphalia, Germany

GSK Investigational Site

Ludwigshafen am Rhein, Rhineland-Palatinate, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Kiel, Schleswig-Holstein, Germany

GSK Investigational Site

Jena, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Lørenskog, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Tønsberg, , Norway

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Lund, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Stockholm, , Sweden

Countries

Belgium; Canada; Germany; Norway; Sweden

Study Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Document Type: Dataset Specification

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Clinical Study Report

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

111407

Identifier Type: -

Identifier Source: org_study_id