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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2008

Intervention(s) in this Clinical Trial

• Drug: ADL5859
  • Four 50-mg ADL5859 opaque, Swedish Orange, capsules (No. 0) as single dose
• 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
• Drug: Placebo
  • Four opaque, Swedish Orange, capsules (no.0), each containing lactose monohydrate,NF
• Drug: ADL5859
  • Two 50-mg ADL5859 opaque, Swedish Orange, capsules (no.0) twice daily for 14 days
• Drug: Lactose monohydrate, NF
  • Two Opaque, Swedish Orange, No.0 capsules containing lactose monohydrate, NF, twice daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A1
  • ADL5859
• Active Comparator: A2
  • 500 mg naproxen
• Placebo Comparator: A3
  • Lactose monohydrate, NF
• Experimental: B1
  • ADL5859
• Placebo Comparator: B2
  • Lactose monohydrate, NF

Primary 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
    Safety Issue?: No

Secondary 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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    Safety Issue?: No
• Reports of adverse events, and changes in the results of: clinical laboratory tests, vital signs and ECGs
  • Time Frame: Trial duration
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Adolor Corporation

Overall Clinical Trial Officials and Contacts

Bruce Berger, MD Study Director Adolor Corporation  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00626275

Study ID Number: 33CL232

ClinicalTrials.gov Identifier: NCT00626275

Health Authority: United States: Food and Drug Administration

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