This study is an exploratory study to evaluate the effectiveness, safety and tolerability of three concentrations of GW786034 ointment following treatment to small areas of stable psoriatic plaques. Dosing will proceed using a microplaque approach, where small volumes of ointment will be applied under full occlusion to representative psoriatic plaques. The effectiveness of topical GW786034 treatments and controls will be explored using visual intensity assessments in addition to dermal imaging and histological surrogates of disease activity.

Inclusion criteria:

• Stable (2-3 months) chronic plaque psoriasis covering greater than 5% body surface area (as determined by PASI palm method).
• Other than having chronic plaque psoriasis, subject is health and ambulatory.
• Women will be eligible to enter the study if they are of non-child-bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile).
• Must have at least two clinically similar lesions with the following characteristics as deemed by the dermatologist: Moderate to severe in elevation (thickness), erythema, and scaling (with a total score of at least 6 for each target lesion, when assessed using a 0-4 PASI score). Located on the trunk, buttocks, thighs or upper arms. Are of a sufficient size that will allow the application of three occlusive patches.

Exclusion criteria:

• Guttate, erythrodermic, or pustular psoriasis.
• Psoriasis is spontaneously improving.
• Have had psoriasis that was unresponsive to adequately dosed (> 10 weeks) cyclosporine.
• Any systemic disorder or active skin disease (other than psoriasis) or subjects who present with scars, moles, tattoos, body piercings, sunburn in the test area.
• History of congestive heart failure (NYHA Class 3 or 4), myocardial infarction, coronary artery bypass graft, percutaneous transluminal balloon angioplasty, cerebrovascular accident, chronic or intermittent oedema.
• Blood pressure of greater than 150mmHg systolic and /or 95mmHg diastolic following triplicate measurements taken 5 minutes apart.
• Presence of unstable or severe angina or coronary insufficiency.
• Uncontrolled bacterial, viral, or fungal infection.
• Congenital or acquired immunodeficiency.
• History of malignancy within the last five years, except for surgically cured skin carcinoma or cervical dysplasia (CIN I-II).
• An unwillingness of male subjects to use a condom/spermicide in addition to having their female partner use another form of contraception if the woman could become pregnant from the time of the first dose of study medication until 5 half-lives of the drug have elapsed following removal of the last dose of study medication.
• An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of first dose of study medication until five half-lives or 5 days (whichever is longer) following removal of the last dose of study medication.
• Prolonged exposure to the sun (or tanning beds) during the study.
• Systemic anti-psoriasis therapy, including but not limited to: acitretin, cyclosporine, isotretinoin, infliximab, entercept, alefacept, oral steroids and psoralen during the 4 weeks prior to the first dose of study medication and throughout the study.
• Concomitant use of phototherapy or photochemotherapy.
• Concomitant use of lithium, antimalarials, interferons.
• Systemic beta-blockers are permitted provided the dose is stable for four weeks before baseline and remains stable throughout the study.
• Concomitant use of anti-arthritis therapies with known propensity for hepatotoxicity (i.e. diclofenac, gold, D-penicillamine, leflunomide).
• Use of topical or intralesional treatments for psoriasis (e.g. mid- or high-potency topical corticosteroids) within 2 weeks prior to Day 1 and throughout the study, except for class VI or VII topical steroid treatments (Desonide, or 2.5% hydrocortisone) which will be allowed on the face.
• Concomitant use of non-drug therapies (i.e. herbal products or alternative therapies) for psoriasis.