Study Evaluating the Analgesic Efficacy and Safety of ADL5859 in Participants With Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: ADL5859; Naproxen; Placebo; ADL5859; Placebo
Intervention MeSH terms: Naproxen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Rheumatoid arthritis; arthritis

Summary:

      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.
    

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