SB-681323-Methotrexate Interaction Study

Inclusion Criteria: * Male or female. Females must be of non-child-bearing capacity * BMI 19 - 30 kg/m2 (inclusive) * Diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) * Negative urine drugs of abuse screen, breath alcohol tests, hepatitis B and C, and HIV tests. * Liver function tests within normal limits * Must be on a stable dose of methotrexate (2.5 - 25 mg/week) for \>8 weeks prior to enrolment and which will not be changed during the course of this study. * Must be on stable folate supplements for \>8 weeks prior to enrolment with normal red cell folate levels at enrollment. Exclusion Criteria: * History of alcohol \&/or drug abuse * Abnormal ECGs at screening * Liver disease, uncontrolled hypertension, diabetes mellitus, psoriasis, history of peptic ulcer disease * The patient is using glucocorticoid at doses \>10mg/day. * The patient is using sulphasalazine at a dose \>3g/day. * The patient is using hydroxychloroquine at a dose \>400mg/day. * The patient is on treatment regimen of DMARDs other than MTX plus one or both of sulphasalazine and hydrochloroquine (e.g. leflunomide) * The patient dose of NSAIDs, COX-2 inhibitors or glucocorticoids change at any time during 2 weeks prior to enrolment until the end of the clinical phase of the study