A Study to Evaluate the Effectiveness and Safety of Tapentadol(CG5503) in the Treatment of Acute Pain After Hip Replacement Surgery Compared With Oxycodone and Placebo Followed by a Voluntary Open-Label Extension For Safety

Condition(s) targeted: Arthralgia.; Pain Assessment; Arthroplasty; Replacement, Hip

Intervention: CG5503;tapentadol (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Official(s) and/or principal investigator(s):
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

The purpose of this study is to test in patients who have had hip replacement surgery the effectiveness (level of pain control) and the safety of 3 different dose levels of CG5503 compared with placebo and with 10-mg oxycodone during the 72-hour double-blind period and to assess the safety of the drug for 9 days after patients completed the double blind period.

Official title: A Randomized, Double-Blind, Active- and Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Multiple Doses of CG5503 Immediate Release Formulation in the Treatment of Acute Pain From Total Hip Replacement Surgery Followed by a Voluntary Open-Label Extension

Study design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The primary efficacy outcome for this study is SPID48 (i.e., the sum of pain intensity difference over 48 hours relative to the first dose). SPID will be evaluated over 12, 24, 48, and 72 hours after the first dose of study drug is taken.

Secondary outcome: Secondary effectiveness outcomes include, among others, the effect of CG5503 IR on the time to the need for the first rescue pain medication during the double-blind treatment period, and the SPID at 12, 24, and 72 hours relative to first dose.

Detailed description: Patients undergoing hip replacement often experience moderate to severe acute pain post-surgery. Normally such pain is controlled when patients receive repeated doses of opioid analgesics. However, opioid therapy is commonly associated with side effects such as nausea, vomiting, sedation, constipation, addiction, tolerance, and respiratory depression. CG5503, a newly synthesized drug also acts as a centrally acting pain reliever but has a dual mode of action. The aim of this study is to investigate the effectiveness (level of pain control) and safety (side effects) of 3 dose levels of CG5503, in an immediate release, (IR) formulation, compared with no drug (placebo) or one dose level of oxycodone (an opioid commonly used to treat post-surgical pain). This study is a randomized, double-blind (neither investigator nor patient will know which treatment was received), active- and placebo-controlled, parallel-group, multicenter study to evaluate the treatment of acute pain from hip replacement surgery. The study will include a blinded 72 hour in-patient phase immediately following hip replacement surgery, during which patients will be treated with either 50-, 75-, or 100-mg CG5503 base IR, a placebo, or 10-mg oxycodone, and pain relief will be periodically assessed. Following this phase, patients wishing to continue treatment with CG5503 IR may enter an outpatient voluntary nonrandomized, open-label extension phase for 9 days during which they will receive 50- or 100-mg CG5503 IR. Assessments of pain relief include the pain intensity numeric rating scale (PI), pain relief numeric rating scale (PAR) and patient global impression of change scale (PGIC). Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Venous blood samples will be collected for the determination of serum concentrations of CG5503 and oxycodone. The null hypothesis for the study is that efficacy results for all CG5503 IR dosage groups are equal to placebo based on the mean sum of pain intensity difference at 48 hours. The alternative study hypothesis is that at least 1 dose strength of CG5503 will be different from placebo in controlling pain at 48 hours.

CG5503 base IR 50, or 75, or 100 mg, or oxycodone 10 mg, or placebo, 1 capsule taken by mouth every 4 to 6 hours during the 72 hour postsurgery phase of the study (one extra dose is allowed, if needed for pain); and CG5503, 50 mg base capsules, 1 to 2 tablets taken by mouth every 4 to 6 hours for up to 9 days during the open label portion of the study. All doses of study treatment will be taken with approximately 120 mL of water with or with food.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Scheduled to undergo standard primary (first-time) one-sided total hip replacement

surgery due to degenerative joint disease (arthritis), not due to some inflammatory process, (eg. infection)

- Baseline pain intensity >= 4 on an 11-point (0 to 10) Pain Intensity rating scale,

rated within 30 minutes before randomization

- Women must be postmenopausal, surgically sterile, or practicing or agree to practice

an effective method of birth control throughout the study

Exclusion Criteria:

- Patients will be excluded from the study if they have a history of seizure disorder or

epilepsy

- History of malignancy within the past 2 years before starting the study

- History of alcohol or drug abuse

- Evidence of active infections that may spread to other areas of the body

- Clinical laboratory values reflecting moderate or severe kidney insufficiency

- Currently treated with anticonvulsants, monoamine oxidase inhibitors, tricyclic

antidepressants, neuroleptics, or selective norepinephrine reuptake inhibitor (SNRI), (selective serotonin reuptake inhibitor [SSRI] treatments are allowed if taken for at least 30 days before the screening period of the study at an unchanged dose)

Gent 9000, Belgium

Leuven 3000, Belgium

Aalst B-9300, Belgium

Genk 3600, Belgium

Tampere 33101, Finland

Helsinki 00280, Finland

Helsinki 00029, Finland

Turku 20700, Finland

Madrid 28007, Spain

Cadiz N/A 11009, Spain

Madrid 28805, Spain

Valencia 46014, Spain

Örebro 701 85, Sweden

Borås 501 82, Sweden

Hässleholm 281 25, Sweden

Uppsala 751 85, Sweden

Wrightington Hospital, Wigan Appley Bridge WN6 9EW, United Kingdom

Aberdeen Royal Hospital NHS Trust, Aberdeen AB25 2ZN, United Kingdom

St Bartholomew's Hospital, London EC1A 7BE, United Kingdom

James Paget Hospital, Great Yarmouth NR31 6LA, United Kingdom

Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom

Edinburgh University, Edinburgh EH16 4SA, United Kingdom

Hamilton, United Kingdom

Royal National Orthopaedic Hospital, Middlesex HA7 4LP, United Kingdom

Northern General Hospital, Sheffield S5 7AU, United Kingdom

Sheffield, Alabama 35660, United States

Birmingham, Alabama 35209, United States

Birmingham, Alabama 35235, United States

Mobile, Alabama 36695, United States

Mobile, Alabama 36608, United States

Phoenix, Arizona 85023, United States

Fort Smith, Arkansas 72901, United States

Little Rock, Arkansas 72205, United States

Arcadia, California 91007, United States

San Francisco, California 94143, United States

Glendale, California 91206, United States

Laguna Hills, California 92653, United States

Sacramento, California 95817, United States

Anaheim, California 92801, United States

Denver, Colorado 80012, United States

Farmington, Connecticut 06032, United States

Tamarac, Florida 33321, United States

Port Orange, Florida 32127, United States

Boynton Beach, Florida 33437, United States

Deland, Florida 32720, United States

Plantation, Florida 33324, United States

Miami, Florida 33145, United States

Hollywood, Florida 33021, United States

Fort Lauderdale, Florida 33334, United States

Decatur, Georgia 30033, United States

Chicago, Illinois 60612, United States

Peoria, Illinois 61614, United States

Indianapolis, Indiana 46278, United States

Topeka, Kansas 66604, United States

Baltimore, Maryland 21215, United States

Baltimore, Maryland 21229, United States

Boston, Massachusetts 02115, United States

Royal Oak, Michigan 48073, United States

Mineola, New York 11501, United States

Albany, New York 12208, United States

Charlotte, North Carolina 28207, United States

Halifax, Nova Scotia B3H 3A7, Canada

Oklahoma City, Oklahoma 73119, United States

Scarborough, Ontario M1E 5E9, Canada

Newmarket, Ontario L3Y 5G8, Canada

Thunder Bay, Ontario P7B 7C7, Canada

Burlington, Ontario L7R 2J2, Canada

Oshawa, Ontario L1G 2B9, Canada

Toronto, Ontario M5T 2S8, Canada

Sewickley, Pennsylvania 15143, United States

Philadelphia, Pennsylvania 19107, United States

Philadelphia, Pennsylvania 19140, United States

Montreal, Quebec H3G-1A4, Canada

Nashville, Tennessee 37232, United States

Lubbock, Texas 79410, United States

Lubbock, Texas 79403, United States

Lubbock, Texas 79430, United States

Houston, Texas 77024, United States

Plano, Texas 75093, United States

Austin, Texas 78705, United States

Dallas, Texas 75231, United States

Grapevine, Texas 76051, United States

Houston, Texas 77030, United States

Murray, Utah 84107, United States

Weston, Wisconsin 54476, United States

Starting date: August 2006
Last updated: March 28, 2008