Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of Two Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate

The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) inhibitor, R935788 (R788), at a dose of 100 mg, orally, twice-a-day, and/or a dose of of 150 mg, orally, once-a-day is effective in the treatment of Rheumatoid Arthrits in patients who have had an inadequate clinical response to methotrexate.

Inclusion Criteria:

• Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
• Males and females, 18 years of age or older, with active RA for at least 6 months prior to Day 1 dosing.
• Patients must have been receiving weekly methotrexate doses (7.5-25 mg/week) for a minimum 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 dose for at least 6 weeks prior to Day 1 dosing.

• Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
• The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
• In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.

Exclusion Criteria:

• The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with 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 infectious disease;
  4. recent history (past 5 years prior to Day 1 dosing) of, or treatment for, a malignancy 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. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.

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