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

This study has been completed.
Sponsor:
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00626275
First received: February 22, 2008
Last updated: December 4, 2008
Last verified: October 2008
  Purpose

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. The study drug, ADL5859, has not been previously tested in patients with RA; it is anticipated to provide pain relief in RA because it demonstrated effectiveness in animal studies.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: ADL5859
Drug: naproxen
Drug: Placebo
Drug: Lactose monohydrate, NF
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 ADL 5859 in Subjects With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • Part A (single-dose crossover part): Average difference between baseline and postdose lower extremity pain intensity (LEPI) over 6 hours after repeated treadmill walking. Part B: mean daily LEPI score over 2 weeks. [ Time Frame: 6 hours post dosing and 3xdaily IVRS calls during 2 wks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A (single-dose crossover): pain intensity score for overall pain, for lower extremity pain, & for evoked (by treadmill walking) lower extremity pain at each scheduled time point. [ Time Frame: 2, 4, or 6 hours ] [ Designated as safety issue: No ]
  • Part B (multiple-dose comparison with placebo): average daily LEPI scores for Weeks 1 & 2; average daily overall pain intensity scores at Week 1 and Week 2 visits and over the 2 week period; proportion of subjects using rescue [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Part A: Pain intensity difference between baseline and the value at each scheduled time point for overall pain, for lower extremity pain, and for evoked lower extremity pain; [ Time Frame: 2, 4, or 6 hours ] [ Designated as safety issue: No ]
  • Part A: the average difference between baseline and postdose evoked lower extremity pain over the 4 hours after dosing [ Time Frame: 4 hours post dosing ] [ Designated as safety issue: No ]
  • Part A: peak evoked lower extremity pain; average difference between baseline and postdose lower extremity pain intensity at rest over the 6 hours after dosing; [ Time Frame: 6 hours post dosing ] [ Designated as safety issue: No ]
  • Part A: percentage of subjects in each treatment group achieving a 25%, 50%, or 75% reduction in evoked lower extremity pain intensity scores at 2, 4, or 6 hours; [ Time Frame: 2, 4, or 6 hours post dosing ] [ Designated as safety issue: No ]
  • Part A: Proportion of subjects able to walk on a treadmill for their target treadmill walking time; subject's global evaluation of study medication [ Time Frame: Week 1 and Week 2 study visits ] [ Designated as safety issue: No ]
  • Part B (multiple-dose comparison with placebo): average daily lower extremity pain intensity scores for Weeks 1 and 2 [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Part B: Average daily overall pain intensity scores at Week 1 and Week 2 visits and over the 2 week period [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Part B: Proportion of subjects using rescue medication; mean dose of rescue medication for Weeks 1 and 2 and over the 2 week period [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Part B: Subject's global evaluation of study medication at Week 1 and Week 2 visits [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • Reports of adverse events, and changes in the results of: clinical laboratory tests, vital signs and ECGs [ Time Frame: Trial duration ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: October 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1
ADL5859
Drug: ADL5859
Four 50-mg ADL5859 opaque, Swedish Orange, capsules (No. 0) as single dose
Other Name: ADL-5859
Active Comparator: A2
500 mg naproxen
Drug: naproxen
Two 250-mg naproxen capsules [each placed in an opaque, Swedish Orange capsule (No. 0) with lactose monohydrate, NF]AND two matching placebo capsules containing lactose monohydrate, NF
Other Name: Naprosyn
Placebo Comparator: A3
Lactose monohydrate, NF
Drug: Placebo
Four opaque, Swedish Orange, capsules (no.0), each containing lactose monohydrate,NF
Other Names:
  • placebo
  • lactose
Experimental: B1
ADL5859
Drug: ADL5859
Two 50-mg ADL5859 opaque, Swedish Orange, capsules (no.0) twice daily for 14 days
Other Name: ADL-5859
Placebo Comparator: B2
Lactose monohydrate, NF
Drug: Lactose monohydrate, NF
Two Opaque, Swedish Orange, No.0 capsules containing lactose monohydrate, NF, twice daily
Other Name: lactose

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects between 18 and 75 years of age, inclusive
  • Have a documented history of rheumatoid arthritis (diagnosed according to American College of Rheumatology criteria) for at least 6 months before study entry
  • Have painful rheumatoid arthritis with pain predominantly in the lower extremities (ie, hip, knees, ankles, and/or feet)
  • Have a lower extremity pain intensity score of 5 or higher on a pain rating scale 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 in 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 subjects, be surgically sterile or agree to use an appropriate method of contraception
  • For female subjects of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the FDA
  • Have a body weight of at least 45 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 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 (ie, back, neck, fingers, wrists, elbows, and/or shoulders) above 7 on a pain rating scale 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 low blood pressure symptoms when going from a sitting position to standing
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626275

Locations
United States, Connecticut
New England Research Associates
Trumbull, Connecticut, United States, 06611
United States, Florida
Covance Clinical Research Unit Inc.
Daytona Beach, Florida, United States, 32117
United States, Maryland
The Center for Rheumatology and Bone Research
Wheaton, Maryland, United States, 20901
United States, Nebraska
Heartland Clinical Research, Inc.
Omaha, Nebraska, United States, 68134
United States, Nevada
Advanced Biomedical Research of America
Las Vegas, Nevada, United States, 89123
United States, New York
Winthrop University Hospital, Clinical Trials Center
Mineola, New York, United States, 11501
United States, Ohio
University Hospitals Case Medical Center, Division of Rheumatology, Rheumatology Clinical Research Unit
Beachwood, Ohio, United States, 44122
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635-8406
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Bruce Berger, MD Cubist Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Bruce Berger, MD, Adolor Corporation
ClinicalTrials.gov Identifier: NCT00626275     History of Changes
Other Study ID Numbers: 33CL232
Study First Received: February 22, 2008
Last Updated: December 4, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
Rheumatoid arthritis
arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Analgesics
Naproxen
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014