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

NCT ID: NCT00626275

Last Updated: 2015-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2008-09-30

Brief 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.

Detailed 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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ADL5859 -- 200 mg (Part A)

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

Group Type: EXPERIMENTAL

ADL5859

Intervention Type: DRUG

Naproxen -- 500 mg (Part A)

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

Group Type: ACTIVE_COMPARATOR

Naproxen

Intervention Type: DRUG

Placebo (Part A)

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

ADL5859 - 100 mg (Part B)

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

Group Type: EXPERIMENTAL

ADL5859

Intervention Type: DRUG

Placebo (Part B)

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

ADL5859

Intervention Type: DRUG

Naproxen

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

ADL5859

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

ADL-5859; Naprosyn; Lactose Monohydrate National Formulary (NF); ADL-5859; Lactose Monohydrate NF

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce Berger, MD

Role: STUDY_DIRECTOR

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

Locations

New England Research Associates

Trumbull, Connecticut, United States

Covance Clinical Research Unit Inc.

Daytona Beach, Florida, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Heartland Clinical Research, Inc.

Omaha, Nebraska, United States

Advanced Biomedical Research of America

Las Vegas, Nevada, United States

Winthrop University Hospital, Clinical Trials Center

Mineola, New York, United States

University Hospitals Case Medical Center, Division of Rheumatology, Rheumatology Clinical Research Unit

Beachwood, Ohio, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Countries

United States

Other Identifiers

33CL232

Identifier Type: -

Identifier Source: org_study_id