Clinical trial NCT00626275: Study Evaluating the Analgesic Efficacy and Safety of ADL5859 in Participants With Rheumatoid Arthritis
Official title: A Phase 2a Randomized, Placebo- and Active-Controlled, Single-Dose, 3-Period, Crossover Study Followed by a Randomized, Placebo-Controlled, 14-Day, Parallel-Group Study Evaluating the Analgesic Efficacy and Safety of ADL5859 in Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
arthritis
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2008-02-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing
timeFrame: Baseline through 6 hours post dose
measure: Part B: The Mean of Daily Average "Now" Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period
timeFrame: Baseline through 2 Weeks
Secondary outcomes:
measure: Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain
timeFrame: Baseline up to 12 hours post dose
measure: Part B: Mean Daily LEPI Scores for Weeks 1 and 2
timeFrame: Baseline through Week 1 and Week 1 through Week 2
measure: Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain
timeFrame: Baseline, 6 and 12 hours post dose
measure: Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing
timeFrame: Baseline, 4 hours post dose
measure: Part A: Mean Peak Difference in ELEPI According to the NPRS Scale
timeFrame: Baseline, Up to 6 hours post dose
measure: Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores
timeFrame: Up to 2, 4, and 6 hours post dosing
measure: Part B: Participants' Global Evaluation of Study Medication
timeFrame: Up to Week 1 and Week 2
measure: Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2
timeFrame: Week 1 and Week 2
measure: Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period
timeFrame: Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2
measure: Part B: Percentage of Participants Using Rescue Medication
timeFrame: Baseline through Week 2
measure: Part A: Participant's Global Evaluation of Study Medication
timeFrame: 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A
Other outcomes:
Locations:
city: Trumbull
country: United States
facility: New England Research Associates
state: Connecticut
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit Inc.
state: Florida
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Omaha
country: United States
facility: Heartland Clinical Research, Inc.
state: Nebraska
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Mineola
country: United States
facility: Winthrop University Hospital, Clinical Trials Center
state: New York
city: Beachwood
country: United States
facility: University Hospitals Case Medical Center, Division of Rheumatology, Rheumatology Clinical Research Unit
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Bruce Berger, MD
role: STUDY_DIRECTOR
References: