• Part A (single-dose crossover): pain intensity score for overall pain, for lower extremity pain, & for evoked (by treadmill walking) lower extremity pain at each scheduled time point. [ Time Frame: 2, 4, or 6 hours ] [ Designated as safety issue: No ]
• Part B (multiple-dose comparison with placebo): average daily LEPI scores for Weeks 1 & 2; average daily overall pain intensity scores at Week 1 and Week 2 visits and over the 2 week period; proportion of subjects using rescue [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
• Part A: Pain intensity difference between baseline and the value at each scheduled time point for overall pain, for lower extremity pain, and for evoked lower extremity pain; [ Time Frame: 2, 4, or 6 hours ] [ Designated as safety issue: No ]
• Part A: the average difference between baseline and postdose evoked lower extremity pain over the 4 hours after dosing [ Time Frame: 4 hours post dosing ] [ Designated as safety issue: No ]
• Part A: peak evoked lower extremity pain; average difference between baseline and postdose lower extremity pain intensity at rest over the 6 hours after dosing; [ Time Frame: 6 hours post dosing ] [ Designated as safety issue: No ]
• Part A: percentage of subjects in each treatment group achieving a 25%, 50%, or 75% reduction in evoked lower extremity pain intensity scores at 2, 4, or 6 hours; [ Time Frame: 2, 4, or 6 hours post dosing ] [ Designated as safety issue: No ]
• Part A: Proportion of subjects able to walk on a treadmill for their target treadmill walking time; subject's global evaluation of study medication [ Time Frame: Week 1 and Week 2 study visits ] [ Designated as safety issue: No ]
• Part B (multiple-dose comparison with placebo): average daily lower extremity pain intensity scores for Weeks 1 and 2 [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
• Part B: Average daily overall pain intensity scores at Week 1 and Week 2 visits and over the 2 week period [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
• Part B: Proportion of subjects using rescue medication; mean dose of rescue medication for Weeks 1 and 2 and over the 2 week period [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
• Part B: Subject's global evaluation of study medication at Week 1 and Week 2 visits [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
• Reports of adverse events, and changes in the results of: clinical laboratory tests, vital signs and ECGs [ Time Frame: Trial duration ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate the effectiveness of ADL5859 in relieving pain associated with rheumatoid arthritis (RA) compared with placebo and naproxen (similar to Aleve®). A second objective is to see whether the effect of ADL5859 differs after a single dose compared with multiple doses. The study drug, ADL5859, has not been previously tested in patients with RA; it is anticipated to provide pain relief in RA because it demonstrated effectiveness in animal studies.

• Drug: ADL5859
• Drug: naproxen
• Drug: Placebo
• Drug: Lactose monohydrate, NF

• Experimental: ADL5859
• Active Comparator: 500 mg naproxen
• Placebo Comparator: Lactose monohydrate, NF

Inclusion Criteria:

• Male and female subjects between 18 and 75 years of age, inclusive
• Have a documented history of rheumatoid arthritis (diagnosed according to American College of Rheumatology criteria) for at least 6 months before study entry
• Have painful rheumatoid arthritis with pain predominantly in the lower extremities (ie, hip, knees, ankles, and/or feet)
• Have a lower extremity pain intensity score of 5 or higher on a pain rating scale completed on Day 1 of Part A before dosing (after resting for 45 minutes and then walking for at least 10 minutes on a treadmill)and then have a minimum ELEPI score of 4 on other visits in Part A
• If receiving disease modifying antirheumatic drugs, have a stable dose regimen for at least 30 days before study entry (90 days before study entry for biologic therapy)
• If biologic therapy has been recently discontinued, Enbrel™ or Orencia™ must have been discontinued at least 30 days before study entry, and Humira™, Remicade™, and Rituxan™ must have been discontinued at least 60 days before study entry
• For male subjects, be surgically sterile or agree to use an appropriate method of contraception
• For female subjects of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the FDA
• Have a body weight of at least 45 kg
• Be able to understand and comply with the protocol requirements (such as repeated treadmill walking and diary completion via the interactive voice response system), instructions, and protocol specified restrictions.

Exclusion Criteria:

• Have an overall pain intensity score equal to 10 at screening or before the first dose of study medication in Part A
• Have a pain intensity score for the upper body (ie, back, neck, fingers, wrists, elbows, and/or shoulders) above 7 on a pain rating scale before study medication administration
• Have a history of headache requiring prescription treatment within 6 months of study entry
• Have significant renal disease (as indicated by blood urea nitrogen or serum creatinine ≥ 2 times the upper limit of normal) or have significant hepatic disease (as indicated by liver function test results ≥ 2 times the upper limit of normal)
• Have low blood pressure symptoms when going from a sitting position to standing
• Have a history of a seizure disorder, including febrile seizures
• Have, as determined by the investigator or the sponsor's medical monitor, a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other conditions that would affect study participation
• Are taking cytochrome P450 (CYP) 3A4/5 or P glycoprotein (P gp) transporter inhibitors
• Have taken oral steroids within 30 days of study entry or intra articular steroids within 60 days of study entry (inhaled or topical steroids or stable oral dose ≤ 10 mg is permitted)
• Have a history or presence of allergy or intolerance to nonsteroidal anti inflammatory drugs or acetaminophen, or have a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study
• Have a history of alcoholism or drug addiction or abuse within 5 years before the scheduled administration of study medication
• Have participated in a trial of any investigational medication within 30 days before study drug administration