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.
Overview
- Phase
- Phase 1
- Intervention
- GSK2586184 400mg
- Conditions
- Colitis, Ulcerative
- Sponsor
- GlaxoSmithKline
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Safety as assessed by vital sign measurement
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- •Moderate to severely active UC at least 6 months prior to Screening confirmed by colonoscopy or sigmoidoscopy with video recording, and biopsy.
- •A Mayo score of 6 to 12 points and endoscopy sub score of 2 to 3 at screening, despite concurrent treatment with at least 1 of the following (oral corticosteroids or any oral 5-aminosalicylic acid (ASA) or both as defined below): Oral 5-ASA at a stable dose (\>=2.4grams (g)/day) for at least 4 weeks from first dose. Must remain on a stable dose until end of treatment, Stable oral corticosteroid dose (prednisone of \<=20 mg/day or equivalent) for at least 14 days prior to Baseline (must remain on a stable dose until end of treatment).
- •Otherwise healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
- •A female subject is eligible to participate if she is of: Non-childbearing potential defined as: pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.
- •In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milliinternational units (MlU)/milliliter (mL) and estradiol \<40 picograms (pg)/mL (\<147 picomole \[pmol\]/liter \[L\]) is confirmatory). Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status before study enrollment. For most forms of HRT, at least 2 to 4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- •Male subjects with female partners of child-bearing potential must agree to use acceptable contraception methods. This criterion must be followed during the study and for at least 2 weeks after their last dose.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria
- •Subjects with fulminant UC, or UC limited to rectum.
- •Subjects with previous colonic surgery, histological evidence of colonic dysplasia, or bowel stricture.
- •Subjects who have received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening endoscopy and during the remainder of Screening Period.
- •Unable to refrain from the use of the prohibited drugs before the stated time before first dose of study medication until completion of the follow-up visit.
- •A live vaccination within 4 weeks before the first dose of study medication, or a live vaccination planned during the course of the study (until completion of the follow-up visit).
- •A major organ transplant (e.g. heart, lung, kidney, liver) or haematopoietic stem cell/marrow transplant.
- •Significant unstable or uncontrolled acute or chronic disease unrelated to UC (i.e. cardiovascular including uncontrolled hypertension, hypercholesterolemia, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
- •A planned surgical procedure that, in the opinion of the investigator, makes the subject unsuitable for the study.
- •A history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
- •Acute or chronic infections, as follows: Known previous, active or latent infection with Mycobacterium Tuberculosis, Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria), Hospitalisation for treatment of infection within 60 days before first dose, Use of parenteral (IV or intramuscular) antibiotics (antibacterials, antivirals, antifungals, or antiparasitic agents) within 60 days before first dose, Serologic evidence of Hepatitis B (HB) infection based on the results of testing for HBsAg, anti-HBc antibody as follows: subjects positive for HBsAg are excluded; and subjects positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded, Positive test for Hepatitis C antibody confirmed on the same sample with a Hepatitis C third generation immunoassay or PCR. Subjects who are positive for Hepatitis C antibody, but negative when the Hepatitis C third generation immunoassay or PCR is performed on the same sample, will be eligible to participate, Subjects who are positive for Hepatitis C antibody and have a positive or indeterminate result when the Hepatitis C third generation immunoassay or PCR is performed on the same sample, will not be eligible to participate.
Arms & Interventions
GSK2586184
A total of 15 subjects to be administered 400 mg GSK2586184 Tablet (200 mg X 2) twice daily for up to 56 days
Intervention: GSK2586184 400mg
Outcomes
Primary Outcomes
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 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 ECG rhythm.
Time Frame: Up to Week 8
Continuous monitoring of a subject' heart rate and rhythm by ECG.
Secondary Outcomes
- The plasma pharmacokinetics of repeated, twice daily doses of GSK2586184(Up to Week 8)
- Efficacy of GSK2586184 in achieving clinical and endoscopic remission after 8 weeks of treatment(Up to Week 8)
- Efficacy of GSK2586184 in achieving clinical response(Up to Week 8)
- The effect of twice daily doses of GSK2586184 on health related quality of life (QoL) in UC patients.(Up to Week 8)
- The effect of twice daily doses of GSK2586184 on serum C reactive protein (CRP) levels in UC patients(Up to Week 8)
- The effect of twice daily doses of GSK2586184 on faecal calprotectin levels(Up to Week 8)
- Efficacy of GSK2586184 in achieving symptomatic clinical remission after 8 weeks(Up to Week 8)
- Efficacy of GSK2586184 in achieving mucosal healing.(Up to Week 8)