A Study to Investigate the Ability of GSK706769 to Maintain Clinical Remission After Withdrawal of Enbrel in Rheumatoid Arthritis Patients

• Male or female over 18 years of age, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time Female subjects must agree to use contraception until 4 days post-last dose.
• Body weight greater than or equal to 50 kg and BMI within the range 19 - 32 kg/m2.
• The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) and has been treated with an anti TNF-alpha agent for \< 2 years.
• The subject is taking Enbrel for at least 6 months prior to enrollment.
• The subject is willing to stop taking Enbrel for 56 days.
• The subject is in clinical remission, defined as DAS28 less than or equal to 2.6 and has been for the preceding 6 months.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
• AST and ALT \< 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Exclusion Criteria:

• The subject is using oral prednisolone at doses > 10mg/day.
• The subject's NSAID or glucocorticoid dosing regimen has changed during the 4 weeks prior to randomisation.
• The subject's receiving DMARDs other than Enbrel and methotrexate.
• The subject's current methotrexate regimen has changed significantly (i.e. likely to impact disease activity during the study period) within the 3 months prior to dosing e.g. changes in dose of greater than 2.5mg.
• Use of CYP3A4 inhibitors/inducers within 14 days prior to dosing and CYP3A4 substrates with a narrow therapeutic index within 7 days prior to dosing.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Absolute neutrophil count \< 1500/ul.
• History of sensitivity to the study medication, or components thereof or a history of drug or other allergy that contraindicates their participation.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug screen, unless the subject is receiving a prescribed medication that could give a positive in the drug screen and prior to the screen being sent the medication has been discussed and pre-approved by the medical monitor.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined by the protocol.
• The subject has an acute infection or a history of repeated or chronic infections.
• The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that in the opinion of the investigator and/or medical monitor, places the subject at an unacceptable risk as a participant in this trial.
• Subjects with autoimmune hemolytic anemia or G6PD deficiency.
• Malignancy in the past 2 years, except for adequately treated non-invasive cancers of the skin.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Consumption of grapefruit, grapefruit juice or grapefruit hybrids within 7 days prior to the first dose of study medication.