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

Condition(s) targeted: Rheumatoid Arthritis

Intervention: ADL5859 (Drug); naproxen (Drug); Placebo (Drug); ADL5859 (Drug); Lactose monohydrate, NF (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Adolor Corporation

Official(s) and/or principal investigator(s):
Bruce Berger, MD, Study Director, Affiliation: Adolor Corporation

Overall contact:
Bruce Berger, MD, Phone: 484-595-1911, Email: bberger@adolor.com

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.

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

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

Primary outcome: 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.

Secondary outcome:

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.

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

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;

Part A: the average difference between baseline and postdose evoked lower extremity pain over the 4 hours after dosing

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;

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;

Part A: Proportion of subjects able to walk on a treadmill for their target treadmill walking time; subject's global evaluation of study medication

Part B (multiple-dose comparison with placebo): average daily lower extremity pain intensity scores for Weeks 1 and 2

Part B: Average daily overall pain intensity scores at Week 1 and Week 2 visits and over the 2 week period

Part B: Proportion of subjects using rescue medication; mean dose of rescue medication for Weeks 1 and 2 and over the 2 week period

Part B: Subject's global evaluation of study medication at Week 1 and Week 2 visits

Reports of adverse events, and changes in the results of: clinical laboratory tests, vital signs and ECGs

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

Bruce Berger, MD, Phone: 484-595-1911, Email: bberger@adolor.com

New England Research Associates, Trumbull, Connecticut 06611, United States; Recruiting
Jennifer Molnar, Phone: 203-374-9816, Email: jen.molnar@neresearch.org
Jeannette Charles, Phone: 203-374-9816, Email: j.charles@neresearch.org
Geoffrey Gladstein, MD, Principal Investigator

Covance Clinical Research Unit Inc., Daytona Beach, Florida 32117, United States; Recruiting
Yvette Taylor, Phone: 386-274-4177, Ext: 315, Email: Yvette.Taylor@covance.com
Frank H Farmer, MD, Principal Investigator

The Center for Rheumatology and Bone Research, Wheaton, Maryland 20901, United States; Recruiting
Megan Bishop, Phone: 301-942-6610, Email: mbishop@arapc.com
Herbert SB Baraf, MD, Principal Investigator

Heartland Clinical Research, Inc., Omaha, Nebraska 68134, United States; Recruiting
Heather VanAckeren, Phone: 402-502-9364, Email: Heather@heartlandcr.com
Tracie Wesson, Phone: 402-502-9364, Email: Tracie@heartlandcr.com
Talha Shamim, MD, Principal Investigator

Advanced Biomedical Research of America, Las Vegas, Nevada 89123, United States; Recruiting
Adrian Bratu, Phone: 702-898-2088, Email: abratrials@prodigy.net
Vrijendra Kumar, MD, Principal Investigator

Winthrop University Hospital, Clinical Trials Center, Mineola, New York 11501, United States; Recruiting
Rob Kirshoff, Phone: 516-663-9582, Email: rkirshoff@winthrop.org
Elena Crespo, Phone: 516-663-9582, Email: ecrespo@winthrop.org
Gary Rosenblum, DO, Principal Investigator

University Hospitals Case Medical Center, Division of Rheumatology, Rheumatology Clinical Research Unit, Beachwood, Ohio 44122, United States; Recruiting
Mary Lesko, Phone: 216-591-1443, Email: mary.lesko@uhhospitals.org
Nora G Singer, MD, Principal Investigator
Roland Moskowitz, MD, Sub-Investigator

Altoona Center for Clinical Research, Duncansville, Pennsylvania 16635-8406, United States; Recruiting
Lisa Riley, Phone: 814-693-0300, Email: accr@atlanticbb.net
Alan Kivitz, MD, Principal Investigator

Adolor Corporation home web page address

Starting date: October 2007
Ending date: December 2008
Last updated: July 14, 2008