• Evaluate the pharmacokinetics of ARRY-371797 in RA patients, and the potential interactions with MTX [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  
• Evaluate the effect of food on the pharmacokinetics of ARRY-371797 in RA patients in combination with MTX [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  

• Evaluate the safety of ARRY-371797 administered in RA patients concomitantly treated with stable doses of MTX [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  
• Evaluate the anti-inflammatory effects of two doses of ARRY-371797 compared to placebo over 28 days measured by the Patient's Assessment of Arthritis Pain (100 mm visual analog scale [VAS]) [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  
• Evaluate the bone resorption effects of two doses of ARRY-371797 compared to placebo over 28 days as measured by urinary N-Telopeptide Cross-Links (NTx) [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  
• Evaluate, at the discretion of Array BioPharma, additional PD biomarkers of inflammatory response to ARRY-371797 in combination with MTX [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
  

Inclusion Criteria:

• Diagnosed with RA at least 3 months prior to the Screening visit based upon the American College of Rheumatology (ACR) 1987 Revised Criteria,, fulfilling at least 4 of the following 7 criteria. The first 4 must have been present for at least 6 weeks:

  1. Morning stiffness in and around any joint for more than 1 hour;
  2. Soft tissue swelling of 3 or more joint areas;
  3. Swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints;
  4. Symmetrical joint swelling;
  5. Rheumatoid nodules;
  6. Serum rheumatoid factor positive;
  7. Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.
• On a stable weekly dose of MTX (10 - 25 mg/week inclusively; either oral or parenteral) for ≥ 6 weeks (calculated from Day 1) at the time of randomization and is willing to continue on this regimen for the duration of this study;
• On a stable dose of folate (≥ 5 mg weekly ) for ≥ 6 weeks at the time of randomization and is willing to continue on this regimen for the duration of this study;

• Minimum current level of disease activity characterized by:

  a. C-reactive protein (CRP) ≥ 0.8 mg/dL (8 mg/L)

• Meets the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II, or III

• Completed a 4-week washout period (calculated from Day -7) if treated with any of the following therapies:

  1. DMARDs - hydrochloroquine or chloroquine (plaquinil), auranofin (oral gold), injectable gold (aurothioglucose or aurothiomalate), sulfasalazine, or d-penicillamine;
  2. Immunosuppressive/Immunomodulatory therapies - azathioprine, cyclosporine, minocycline, or PROSORBA® device/column;
  3. Participation in another clinical trial within 4 weeks of screening;
  4. Other - herbal medications, immunization with any live virus vaccination (e.g., FluMist), intra-articular, intramuscular, or intravenous corticosteroids
• Completed washout period of any experimental therapy for RA (within or outside a clinical trial setting) within 8 weeks of screening unless reviewed and approved by the Sponsor;

• Patients may continue on stable background therapy for RA (doses should be stable for at least 6 weeks prior to the first dose of study drug, unless the patient stops due to documented disease improvement, with Sponsor approval), only if it is included in the following list:

  1. Non-investigational NSAIDs or COX-2 inhibitors;
  2. Low-dose oral corticosteroids (≤ 10 mg prednisone or equivalent per day);
  3. Opioid analgesics (≤ 30 mg oral morphine or equivalent per day)
  4. Acetaminophen (paracetamol) ≤ 2600 mg/day (2.6 g/day);
  5. Aspirin if taken for non-arthritic reasons (≤ 325 mg/day).

Exclusion Criteria:

• Diagnosis of any other inflammatory or non-inflammatory arthritis (e.g. spondyloarthritis; fibromyalgia, psoriatic arthritis, crystal-proven gout) that may interfere with disease activity assessments and/or clinically apparent osteoarthritis which would affect subsequent efficacy measures;

• Has received any of the following prior treatments:

  1. Within 4 weeks of first dose of study drug: anakinra (Kineret®), etanercept (Enbrel®);
  2. Within 8 weeks of first dose of study drug: infliximab (Remicade®), adalimumab (Humira®), leflunomide (Arava®);
  3. At any time: rituximab (Rituxan®), alemtuzab (CamPath®), any experimental B cell targeting agents;

• Presenting with any of the following:

  1. Any condition possibly affecting oral dug absorption (e.g., gastrectomy or clinically significant diabetic gastroenteropathy);
  2. Any clinically significant skin rash at Screening and/or within the past 3 months;
  3. A documented oral temperature ≥ 37.5˚C (99.5˚F) at Screening;
  4. An infection with human immunodeficiency virus (HIV) or hepatitis B or C at Screening;
  5. Any clinically significant active infection including herpes lesions;
  6. A confirmed screening QTc interval > 450 ms (either Bazett or Fredericia corrected will be assessed; if either one is > 450 ms the patient is not eligible).
• Requiring prohibited concomitant medications while on study, including potent CYP3A inhibitors, potent CYP3A inducers, DMARDs, and biologic response modifiers (BRMs)