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

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