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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01036022
• Date of registration: 17/12/2009
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Effect of GSK1399686 in Patients With Mild to Moderately Active Ulcerative Colitis
• Scientific 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 Mild to Moderately Active Ulcerative Colitis
• Date of first enrolment: September 1, 2009
• Target sample size: 120
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01036022
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Belgium, Canada, Germany, Norway, Sweden

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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-a 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: GSK1399686

Primary Outcome(s)

Number of Participants With Abnormal Electrocardiography (ECG) Findings [Time Frame: Screening (Day -7 to -1), Week 2, 4 and 6]

Number of Participants With Clinical Chemistry Data Outside the Reference Range [Time Frame: Screening (Day -7 to -1), Day 1, Week 1, 2, 3, 4 and 6]

Number of Participants With Hematology Data Outside the Reference Range [Time Frame: Screening (Day -7 to -1), Day 1, Week 1, 2, 3, 4 and 6]

Number of Participants of Abnormal Urinalysis Dipstick Results [Time Frame: Screening (Day -7 to -1), Week 2, 4 and 6]

Number of Participants With Vital Sign Outside Range of Potential Clinical Importance (PCI) [Time Frame: Screening (Day -7 to -1), Week 2, 4 and 6]

Mean Concentration of GSK1399686 in Colon Biopsy Obtained Within 24 h After the Last Dose [Time Frame: Week 4]

Mean Treatment Effects on Basal Morning Cortisol and Adrenocorticotropic Hormone (ACTH) Stimulated Cortisol Levels at Week 4 in Comparison With Baseline [Time Frame: Baseline (Day 1, pre dose) and Week 4]

Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) [Time Frame: Up to Week 6]

Secondary Outcome(s)

Mean Fecal Calprotectin Levels Over Time [Time Frame: Up to Week 6]

Mean Fecal Lactoferrin Levels Over Time [Time Frame: Up to Week 6]

Pre-dose Trough Concentration at the End of the Dosing Interval (Ct) on Day 28 Derived From Observed Plasma Concentrations of GSK1399686 After Repeated Oral Dosing [Time Frame: Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)]

Mean Maximum Observed Concentration (Cmax) on Day 1 and Day 28 Derived From Observed Plasma Concentrations of GSK1399686 After Repeated Oral Dosing [Time Frame: Day 1 (1 hour, 2 hour, 3 hour post dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)]

Number of Participants With Clinical Response and Clinical Remission at Week 4 and Week 6 [Time Frame: Week 4 and Week 6]

Mean Simple Clinical Colitis Activity Index (SCCAI) Score [Time Frame: Up to Week 6]

Plasma Clearance Estimated Based on Population Pharmacokinetic Analysis of Healthy Volunteers (Historical Data) and Patient Data [Time Frame: Day 1 (1 hour, 2 hour, 3 hour post dose), Week 1 (anytime relative to the last dose), Week 2 (anytime relative to the last dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)]

Volume of Distribution Estimated Based on Population Pharmacokinetic Analysis of Healthy Volunteers (Historical Data) and Patient Data [Time Frame: Day 1 (1 hour, 2 hour, 3 hour post dose), Week 1 (anytime relative to the last dose), Week 2 (anytime relative to the last dose) and Day 28 (Week 4 at pre dose, 1 hour, 2 hour, 3 hour and 4 hour morning post dose)]

Median Time to Clinical Response and Clinical Remission [Time Frame: Up to Week 6]

Secondary ID(s)

111407

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/06/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01036022