Inclusion criteria:

• No clinically significant disease as determined by history, physical examination and screening investigations.
• RA subjects on methotrexate (7.5mg - 25mg per week)
• Body weight >50 kg for males and >45 kg for females, who are not morbidly obese
• Diagnosis of RA
• Active disease defined as DAS28 = 4.0 and at least one MCP joint with either detectable vascularity or thickness
• Stable doses of DMARDs (Disease-modifying anti-rheumatic drugs, which must include methotrexate and can also include but is not restricted to sulphasalazine and hydroxychloroquine in any combination) for 8 weeks prior to enrolment
• Must be on stable folate supplements
• Subjects using NSAIDs or Cox-2 inhibitors must have been on stable doses for 2 weeks prior to screening
• LFT functions (ALT, AST, ALP) = 1.5 x ULN at screening and which have been stable on at least 2 occasions in the 7 months prior to screening
• Must provide signed and dated written informed consent prior to admission to the study
• Ability to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion criteria:

• Past or present disease, which as judged by the investigator, may affect the outcome of this study.
• Clinically significant abnormalities in safety laboratory analysis at screening
• Pregnant or nursing women
• Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined
• As a result of the medical interview, physical examination or screening investigations, the Physician Responsible considers the subject unfit for the study
• Taking >10mg/day oral glucocorticoids
• Currently receiving anti-rheumatic biological therapy
• Received their final dose of infliximab or adalimumab within 3 months of enrollment
• Received their final dose of etanercept or anakinra within 1 month of enrollment
• Has received an investigational drug or participated in any other NCE research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to enrol.ment
• Regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female.
• Has a screening QTc value of >430msec (males) or >450msec (females), PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements
• History of liver or renal disease in the 6 months prior to screening
• Current renal insufficiency (subject must have an estimated creatinine clearance less than50mL/min as estimated from the serum creatinine using the Cockroft-Gault formula
• Has donated a unit of blood within the previous month or intends to donate in the month after completing the study
• Has a history or drug or other allergy, which in the opinion of the physician responsible, contraindicates their participation
• History of, or risk factors for, HIV, Hepatitis B and Hepatitis C
• History of drug abuse