The purpose of this study is to determine if GSK706769 can maintain clinical remission
established by Enbrel after withdrawal of Enbrel in rheumatoid arthritis patients.
Minimum age: 18 Years.
Maximum age: N/A.
- 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
- 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
- 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
- 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
- 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
- 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.