Intervention: Naproxen
Trial phase: Phase 2
ATC code: G02CC02 | M01AE02 | M01AE52 | M01AE56 | M02AA12
SMILES: COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 46
Group description: Naproxen: 500 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study
Eligibility criteria:
Inclusion Criteria:

Male and female participants between 18 and 75 years of age, inclusive
Have a documented history of rheumatoid arthritis (diagnosed according to American College of Rheumatology criteria)
Have painful rheumatoid arthritis with pain predominantly in the lower extremities (that is, hip, knees, ankles, and/or feet)
Have an evoked lower extremity pain intensity (ELEPI) score of 5 or higher on a numeric pain rating scale (NPRS) 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 during 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 participants, be surgically sterile or agree to use an appropriate method of contraception
For female participants of child bearing potential, be surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive deemed highly effective by the US Food and Drug Administration (FDA) through the completion of the study and have negative findings on a urine pregnancy test before administration of study medication (women who are postmenopausal [no menses for at least 2 years] are also eligible to participate)
Have a body weight of at least 45 kilograms (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 (OPI) 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 (that is, back, neck, fingers, wrists, elbows, and/or shoulders) above 7 on a numeric pain rating scale (NPRS) 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 evidence of symptomatic orthostatic hypotension
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