Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis

Inclusion Criteria:

• Patients must give written informed consent by signing an IRB/EC-approved InformedConsent Form (ICF) prior to admission to this study.

• Males and females, 18 years of age or older, with active RA for at least 6 monthsprior to Day 1 dosing.

• Patients must have been receiving weekly methotrexate doses (7.5-25 mg/week) for aminimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose,with no change in route, for the previous 6 weeks prior to Day 1 dosing.

`Patients must be receiving a folic or folinic acid supplementation at a stable dosefor at least 6 weeks prior to Day 1 dosing.

• Females of childbearing potential must be fully informed of the potential for R788 toadversely affect the fetus and, if sexually active, must agree to use a wellestablished method of birth control during the study (oral contraceptive, mechanicalbarrier, long acting hormonal agent). These patients must not be lactating and musthave a negative urine pregnancy test at the time of randomization and at eachlaboratory determination.

• The patient must otherwise be in good health as determined by the Investigator on thebasis of medical history, physical examination, and laboratory screening tests duringthe screening period. See exclusion criteria for specific exclusions.

• In the Investigator's opinion, the patient has the ability to understand the nature ofthe study and any hazards of participation, and to communicate satisfactorily with theInvestigator and to participate in, and to comply with, the requirements of the entireprotocol.

Exclusion Criteria:

• The patient has a history of, or a concurrent, clinically significant illness, medicalcondition (other than arthritis) or laboratory abnormality that, in the Investigator'sopinion, could affect the conduct of the study. Specifically, excluded are patientswith the following:

1. uncontrolled or poorly controlled hypertension;

2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder)or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);

3. recent (within past 2 months prior to Day 1 dosing) serious surgery or infectiousdisease;

4. recent history (past 5 years prior to Day 1 dosing) of, or treatment for, amalignancy other than nonmelanomatous skin cancer, or any history of lymphoma;

5. Hepatitis B ;

6. Hepatitis C ;

7. interstitial pneumonitis or active pulmonary infection on chest x-ray;

8. Tuberculosis (TB): the TB skin test should be negative.

9. known laboratory abnormalities.

• The patient has a history of substance abuse, drug addiction or alcoholism. Patientsmay consume up to 4 units of alcohol per week; however, alcohol should be avoided inthe 72 hours prior to lab assessments. Patients who cannot reliably comply with thisshould be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilledspirits= 1.5 oz or 44 mL.

• The patient has been treated previously treated with R788 under a different protocol.