A Dose Ranging Study to Evaluate the Safety and Efficacy of GSK2586184 in Patients With Chronic Plaque Psoriasis

NCT ID: NCT01782664

Last Updated: 2017-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-01
• Study Completion Date: 2014-03-24

Brief Summary

A multi-centre, randomised, dose ranging study to evaluate the safety and clinical efficacy of GSK2586184 in patients with chronic plaque psoriasis.

There will be 2 study cohorts (Cohorts A and B). Cohort A is the main study cohort, and this part of the study will be randomised, double-blind and placebo-controlled. Fifty-six subjects will be randomised in Cohort A: 14 subjects in each treatment group: 100 mg, 200 mg or 400 mg GSK2586184, or placebo. Cohort B is an exploratory, open-label investigation of the effect of 400 mg GSK2586184 on inflammatory gene expression in the skin and whole blood, and GSK2586184 concentrations in the skin. A maximum of 8 subjects will be included, and all subjects will take 400 mg GSK2586184.

In both Cohorts A and B, study medication will be administered orally (as tablets), twice daily, for up to 12 weeks.

Each subject will have 7 out-patient visits: Screening; Baseline & Start of treatment; Week 2; Week 4; Week 8; Week 12; and Follow-up (Week 16)

Conditions

Psoriasis

Study Design

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

Study Groups

100 mg GSK2586184

Subjects will be randomized to 100 mg GSK2586184 twice daily for up to 84 days

Group Type: EXPERIMENTAL

100 mg GSK2586184

Intervention Type: DRUG

100 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

200 mg GSK2586184

Subjects will be randomized to 200 mg GSK2586184 twice daily for up to 84 days

Group Type: EXPERIMENTAL

200 mg GSK2586184

Intervention Type: DRUG

200 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

400 mg GSK2586184

Subjects will be randomized to 400 mg GSK2586184 twice daily for up to 84 days

Group Type: EXPERIMENTAL

400 mg GSK2586184

Intervention Type: DRUG

400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

Placebo

Subjects will be randomized to receive Placebo twice daily for up to 84 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets to be taken twice daily with food for up to 84 days.

400 mg GSK2586184 (Cohort B)

Subjects will take 400 mg GSK2586184 twice daily for up to 84 days

Group Type: EXPERIMENTAL

400 mg GSK2586184

Intervention Type: DRUG

400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

Interventions

100 mg GSK2586184

100 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

Intervention Type: DRUG

200 mg GSK2586184

200 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

Intervention Type: DRUG

400 mg GSK2586184

400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days.

Intervention Type: DRUG

Placebo

Placebo tablets to be taken twice daily with food for up to 84 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Otherwise healthy subjects with a diagnosis of moderate to severe plaque psoriasis defined by the following criteria:
• Diagnosed for at least 12 months before the first dose of study medication
• Psoriasis plaques cover >=10% of body surface area.
• PASI score of >=12, and PGA score of>=3, and suitable for systemic or light therapy.
• Male or female, between 18 and 75 years of age inclusive.
• Female subjects of childbearing potential must agree to avoid pregnancy and male subjects must agree to avoid female partners becoming pregnant.
• Subjects must agree to use ultra violet (UV) light protection.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria

• Unable to refrain from the use of the following prescription and non-prescription drugs from the following periods before the first dose of study medication until completion of the follow-up visit:
• 12 weeks: alefacept, ustekinumab, adalimumab, etanercept, infliximab, or certolizumab pegol
• 4 weeks or 5 half-lives, whichever is longer:
• systemic medications for other medical conditions that are known to affect psoriasis, including but not limited to oral corticosteroids, cyclosporine, methotrexate, lithium, and beta-adrenergic blockers
• 7 days or 5 half-lives, whichever is longer:
• statins and other OATP and BCRP sensitive substrates (e.g. rapaglinide)
• any agent known to be a substrate of MATE1 and MATE2-K, which undergoes significant renal secretion (e.g. cimetidine)
• 3 weeks or 5 half-lives, whichever is longer:
• any agent known to be a strong CYP3A4 inhibitor or inducer
• 2 weeks: topical therapies that are known to affect psoriasis, including but not limited to corticosteroids, retinoids, vitamin D derivatives, tar and anthralin
• Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis, and will be allowed if in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety.
• Phototherapy within 4 weeks before the first dose of study medication.
• 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 psoriasis (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 or active 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.
• Unable to refrain from the consumption of grapefruit or grapefruit juice from 3 weeks before the first dose of study medication until 2 weeks after the last dose of study medication.
• History of sensitivity to any components of the study medications, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates their participation.
• 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 sample with a Hepatitis C RIBA immunoblot assay or equivalent. Subjects who are positive for Hepatitis C antibody, but negative when the Hepatitis C RIBA immunoblot assay or equivalent test is performed will be eligible to participate. Subjects who are positive for Hepatitis C antibody and have a positive or indeterminate result when the Hepatitis C RIBA immunoblot assay or equivalent test is performed will not be eligible to participate.
• A positive test for HIV antibody.
• Pregnant females as determined by a positive serum hCG test at screening, or a positive urine hCG test pre-dose on Day 1.
• Lactating females.
• Haemoglobin <11 g/dL, haematocrit <30%, WBC count (absolute) <3 × 10^9/L, neutrophils <1.5 × 10^9/L, platelets <100 × 10^9/L, lymphocytes <1 x 10^9/L.
• Current or history of renal disease, or estimated creatinine clearance <60 mL/min/1.73m^2 or serum creatinine >1.5 ULN.
• Single QTc > 450 msec; or QTc > 480 msec in subjects with Bundle Branch Block.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• ALT > 2xULN; alkaline phosphatase and bilirubin ≥ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• The subject has participated in a clinical trial and has received an investigational product within 3 months before the first dose of study medication, or plans to take part in another clinical trial at the same time as participating in this clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 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

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Augsburg, Bavaria, Germany

GSK Investigational Site

Osnabrück, Lower Saxony, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Münster, North Rhine-Westphalia, Germany

GSK Investigational Site

Münster, North Rhine-Westphalia, Germany

GSK Investigational Site

Witten, North Rhine-Westphalia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Cardiff, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Salford, , United Kingdom

Countries

Germany; United Kingdom

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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

116679

Identifier Type: -

Identifier Source: org_study_id