Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

Exclusion Criteria

• •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• •Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
• •Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
• •Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
• •Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
• •Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
• •Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
• •Previous treatment with any cell depleting therapies, including investigational agents.
• •Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
• •Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
• •Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
• •Pregnant women or nursing (breast feeding) mothers.
• •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c \> 9.0%) or gastrointestinal (GI) disease.
• •Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
• •Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
• •History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
• •History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
• •History of alcohol, drug or chemical abuse within the 6 months prior to screening.
• •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• •Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• •Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).
• •For Magnetic Resonance Imaging (MRI) Only:
• •Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.
• •Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding \[eg, a metal worker, etc\]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.
• •Allergic or adverse reactions to gadolinium
• •Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease \[MDRD\] formula).