Clinical trial NCT00364533: 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
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Arthroplasty
Keywords: Arthralgia
Pain
Pain Assessment
Hip Replacement
Tapentadol
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Grünenthal GmbH
First posted: 2006-08-15
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: Sum of Pain Intensity Difference Over 48 Hours (SPID48)
timeFrame: 48 hours
Secondary outcomes:
measure: Time to First Rescue Pain Medication.
timeFrame: 3 days
measure: The SPID at 12, 24, and 72 Hours Relative to First Dose.
timeFrame: 3 days
Other outcomes:
Locations:
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state: Kansas
city: Baltimore
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city: Boston
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state: Massachusetts
city: Royal Oak
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state: Michigan
city: Albany
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state: New York
city: Mineola
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state: New York
city: Charlotte
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state: North Carolina
city: Oklahoma City
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city: Philadelphia
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state: Pennsylvania
city: Sewickley
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city: Nashville
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city: Dallas
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city: Lubbock
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city: Plano
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city: Murray
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state: Utah
city: Weston
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state: Wisconsin
city: Aalst
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Halifax
country: Canada
state: Nova Scotia
city: Burlington
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Oshawa
country: Canada
state: Ontario
city: Scarborough
country: Canada
state: Ontario
city: Thunder Bay
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: London
country: Canada
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Hamilton
country: New Zealand
city: Cadiz N/A
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Borås
country: Sweden
city: Hässleholm
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Aberdeen
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Great Yarmouth
country: United Kingdom
city: London
country: United Kingdom
city: Middlesex
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: