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 Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Arthroplasty

Intervention / Treatment
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* Drug: Tapentadol IR (CG5503)
* Drug: Placebo
* Drug: Oxycodone HCL IR
* Drug: Tapentadol IR (CG5503)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthralgia, Pain, Pain Assessment, Hip Replacement, Tapentadol