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

NCT00626275 | Completed Phase 2 Results

• 1 other identifier: 33CL232
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 8

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; arthritis

Outcome Measures

Primary Outcomes (2)

• 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

  Approximately 1 hour before baseline and again approximately 45 minutes before the 2-, 4-, and 6-hour time points, participants rested for 45 minutes, then they started the treadmill walk at 15 minutes before baseline and at the 2-, 4-, and 6-hour time points. After the treadmill walk, participants were asked to rate their lower extremity pain on an 11 point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. The average difference between baseline and 6 hours post dose evoked lower-extremity pain intensity scores (AELEPID-6) is presented for each treatment group. Difference = predose (baseline) NPRS score - NPRS score 6 hours post dose. Least square (LS) means and standard errors (SE) were calculated from an analysis-of-covariance (ANCOVA) model with fixed effects for sequence, treatment, period, predose evoked lower extremity pain intensity as a covariate, and a random effect for participant nested within sequence.

  Baseline through 6 hours post dose

• Part B: The Mean of Daily Average "Now" Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period

  Participants assessed their "Now" LEPI 3 times each day (morning, midday, and evening at approximately 10 AM, 2 PM, and 8 PM) and before taking any rescue medication. At each time point, participants were asked to rate their lower extremity pain on an 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. LS means and SE were calculated from an analysis-of-covariance model with effect for treatment and baseline "Now" LEPI (before dosing for Treatment Period 1 of Part A) as a covariate. Participants with no postbaseline assessments were excluded from the baseline summary.

  Baseline through 2 Weeks

Secondary Outcomes (11)

• Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain

  Baseline up to 12 hours post dose

• Part B: Mean Daily LEPI Scores for Weeks 1 and 2

  Baseline through Week 1 and Week 1 through Week 2

• Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain

  Baseline, 6 and 12 hours post dose

• Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing

  Baseline, 4 hours post dose

• Part A: Mean Peak Difference in ELEPI According to the NPRS Scale

  Baseline, Up to 6 hours post dose

Study Arms (5)

ADL5859 -- 200 mg (Part A)

EXPERIMENTAL

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

Drug: ADL5859

Naproxen -- 500 mg (Part A)

ACTIVE COMPARATOR

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

Drug: Naproxen

Placebo (Part A)

PLACEBO COMPARATOR

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

Drug: Placebo

ADL5859 - 100 mg (Part B)

EXPERIMENTAL

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

Drug: ADL5859

Placebo (Part B)

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

ADL5859 DRUG

Also known as: ADL-5859

ADL5859 -- 200 mg (Part A)

Naproxen DRUG

Also known as: Naprosyn

Naproxen -- 500 mg (Part A)

Placebo DRUG

Also known as: Lactose Monohydrate National Formulary (NF)

Placebo (Part A)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (8)

New England Research Associates

Trumbull, Connecticut, 06611, United States

Location

Covance Clinical Research Unit Inc.

Daytona Beach, Florida, 32117, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20901, United States

Location

Heartland Clinical Research, Inc.

Omaha, Nebraska, 68134, United States

Location

Advanced Biomedical Research of America

Las Vegas, Nevada, 89123, United States

Location

Winthrop University Hospital, Clinical Trials Center

Mineola, New York, 11501, United States

Location

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

Beachwood, Ohio, 44122, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635-8406, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis

Interventions

N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide; Naproxen

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: Cubist Pharmaceuticals

1.781.860.8660

Study Officials

• Bruce Berger, MD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2008
• First Posted: February 29, 2008
• Study Start: October 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: July 1, 2015
• Results First Posted: July 1, 2015

Record last verified: 2015-06

Locations

US (8)