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

This study has been terminated.
(Slow enrollment)
Sponsor:
Collaborator:
Grünenthal GmbH
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00364533
First received: August 11, 2006
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Arthroplasty
Drug: Tapentadol IR (CG5503)
Drug: Placebo
Drug: Oxycodone HCL IR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Sum of Pain Intensity Difference Over 48 Hours (SPID48) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to First Rescue Pain Medication. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • The SPID at 12, 24, and 72 Hours Relative to First Dose. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 367
Study Start Date: October 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
004
Tapentadol IR (CG5503) Flexible Dose q4-6 hr Tapentadol IR 50 & 100 mg BID for 9 days
Drug: Tapentadol IR (CG5503)
Flexible Dose q4-6 hr Tapentadol IR 50 & 100 mg BID for 9 days

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT00364533

  Show 77 Study Locations
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Grünenthal GmbH
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00364533     History of Changes
Other Study ID Numbers: CR011221, R331333PAI3001, KF5503/31
Study First Received: August 11, 2006
Results First Received: December 19, 2008
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Arthralgia
Pain
Pain Assessment
Hip Replacement
Tapentadol

Additional relevant MeSH terms:
Acute Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014