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

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

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.

Study Overview

• Status: Terminated
• Conditions: Arthroplasty
• Intervention / Treatment: Drug: Placebo; Drug: Oxycodone HCL IR; Drug: Tapentadol IR (CG5503); Drug: Tapentadol IR (CG5503)

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.

• Study Type: Interventional
• Enrollment (Actual): 367
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
  • Genk, Belgium
  • Gent, Belgium
  • Leuven, Belgium
• Canada
  • London, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • Burlington, Ontario, Canada
    • Newmarket, Ontario, Canada
    • Oshawa, Ontario, Canada
    • Scarborough, Ontario, Canada
    • Thunder Bay, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• Finland
  • Helsinki, Finland
  • Tampere, Finland
  • Turku, Finland
• New Zealand
  • Hamilton, New Zealand
• Spain
  • Cadiz N/A, Spain
  • Madrid, Spain
  • Valencia, Spain
• Sweden
  • Borås, Sweden
  • Hässleholm, Sweden
  • Uppsala, Sweden
  • Örebro, Sweden
• United Kingdom
  • Aberdeen, United Kingdom
  • Birmingham, United Kingdom
  • Edinburgh, United Kingdom
  • Great Yarmouth, United Kingdom
  • London, United Kingdom
  • Middlesex, United Kingdom
  • Sheffield, United Kingdom
  • Wigan, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Mobile, Alabama, United States
    • Sheffield, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • Arkansas
    • Fort Smith, Arkansas, United States
    • Little Rock, Arkansas, United States
  • California
    • Anaheim, California, United States
    • Arcadia, California, United States
    • Glendale, California, United States
    • Laguna Hills, California, United States
    • Sacramento, California, United States
    • San Francisco, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Connecticut
    • Farmington, Connecticut, United States
  • Florida
    • Boynton Beach, Florida, United States
    • Deland, Florida, United States
    • Fort Lauderdale, Florida, United States
    • Hollywood, Florida, United States
    • Miami, Florida, United States
    • Plantation, Florida, United States
    • Port Orange, Florida, United States
    • Tamarac, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • Peoria, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Kansas
    • Topeka, Kansas, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Royal Oak, Michigan, United States
  • New York
    • Albany, New York, United States
    • Mineola, New York, United States
  • North Carolina
    • Charlotte, North Carolina, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Sewickley, Pennsylvania, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Austin, Texas, United States
    • Dallas, Texas, United States
    • Grapevine, Texas, United States
    • Houston, Texas, United States
    • Lubbock, Texas, United States
    • Plano, Texas, United States
  • Utah
    • Murray, Utah, United States
  • Wisconsin
    • Weston, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 003; Placebo Fixed Dose Matching placebo for 3 days	Drug: Placebo; Fixed Dose Matching placebo for 3 days
Active Comparator: 002; Oxycodone HCL IR Fixed Dose 10 mg BID for 3 days	Drug: Oxycodone HCL IR; Fixed Dose 10 mg BID for 3 days
Experimental: 001; Tapentadol IR (CG5503) Fixed Dose 50, 75, & 100 mg BID for 3 days	Drug: Tapentadol IR (CG5503); Fixed Dose 50, 75, & 100 mg BID for 3 days; Drug: Tapentadol IR (CG5503); Flexible Dose q4-6 hr Tapentadol IR 50 & 100 mg BID for 9 days
Other: 004; Tapentadol IR (CG5503) Flexible Dose q4-6 hr Tapentadol IR 50 & 100 mg BID for 9 days	Drug: Tapentadol IR (CG5503); Fixed Dose 50, 75, & 100 mg BID for 3 days; Drug: Tapentadol IR (CG5503); Flexible Dose q4-6 hr Tapentadol IR 50 & 100 mg BID for 9 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Difference Over 48 Hours (SPID48)	The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (48 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Rescue Pain Medication.		3 days
The SPID at 12, 24, and 72 Hours Relative to First Dose.	The SPID score incorporates the cumulative analgesic effects of tapentadol IR on pain intensity over an extended period (12 to 72 hours) allowing for an evaluation of multiple doses of drug, even when dosing frequency may vary. Scoring is derived from the Numerical Rating Scale (NRS) from 0 = No pain to 11 = Pain as bad as you can imagine.	3 days

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Grünenthal GmbH

Publications and helpful links

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: August 11, 2006
• First Submitted That Met QC Criteria: August 11, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Estimate): April 21, 2014
• Last Update Submitted That Met QC Criteria: April 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Arthralgia; Hip Replacement; Tapentadol; Pain Assessment
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Oxycodone; Tapentadol
• Other Study ID Numbers: CR011221; R331333PAI3001 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.); KF5503/31 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)