Study Evaluating the Analgesic Efficacy and Safety of ADL5859 in Participants With Rheumatoid Arthritis

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: ADL5859; Drug: Naproxen

Study type: Interventional

Funder types: Industry

Identifiers

NCT00626275

33CL232

Details and patient eligibility

About

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.

Full description

This Phase 2a study was conducted in 2 parts. Part A was a randomized, single-dose, double-blind, placebo- and active-controlled, 3-way crossover phase during which participants were administered study medication in the clinical facility. Part B was a 14-day, randomized, double-blind, placebo-controlled, parallel-group, multiple-dose phase in which participants self-administered study medication at home.

Enrollment: 46 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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46 participants in 5 patient groups, including a placebo group

ADL5859 -- 200 mg (Part A)

Experimental group

Description:

ADL5859: 200 milligrams (mg), capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study

Treatment:

Drug: ADL5859

Drug: ADL5859

Naproxen -- 500 mg (Part A)

Active Comparator group

Description:

Naproxen: 500 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study

Treatment:

Drug: Naproxen

Placebo (Part A)

Placebo Comparator group

Description:

Matching placebo, capsules, administered orally, as a single dose during 1 of 3 Treatment Periods in Part A of the study

Treatment:

Drug: Placebo

Drug: Placebo

ADL5859 - 100 mg (Part B)

Experimental group

Description:

ADL5859: 100 mg, capsules, administered orally, twice daily (BID) for 2 weeks during Part B of the study

Treatment:

Drug: ADL5859

Drug: ADL5859

Placebo (Part B)

Placebo Comparator group

Description:

Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study

Treatment:

Drug: Placebo

Drug: Placebo