A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness (level of pain control) and safety of the administration of 2 different dose levels of tapentadol (CG5503) compared with oxycodone and with placebo in subjects who have had a bunionectomy.

Detailed Description
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Patients undergoing bunionectomy 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, and less frequently, respiratory depression. Tapentadol (CG5503), a newly synthesized drug with an immediate release (IR) formulation, also acts as a centrally acting analgesic 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 2 dose levels of tapentadol (CG5503) IR compared to 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 is received), active- and placebo-controlled, parallel-group, multicenter study to evaluate treatment of the acute pain from bunionectomy. The study will include a blinded 72 hour inpatient (the patient will stay in the facility where the procedure is done) phase immediately following bunionectomy, during which patients will be treated with either 50- or 75-mg tapentadol (CG5503) IR, a placebo, or 10-mg oxycodone IR, and pain relief will be periodically assessed. Assessments of pain intensity (PI) and pain relief (PAR) are obtained using the numerical rating scale, and the patient global impression of change scale (PGIC) will measure overall patient status. 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 tapentadol (CG5503) and oxycodone. The study hypotheses are that at least one tapentadol (CG5503) IR dose will be different from placebo in controlling patients pain at 48 hours, followed by establishing that at least one tapentadol (CG5503) IR dose will be non-inferior compared with oxycodone IR (oxycodone IR is not clinically significantly better than a tapentadol (CG5503) IR dose). A comparison of the incidence rate of the adverse events of nausea and/or vomiting, and the incidence rate of the adverse event of constipation, between tapentadol (CG5503) IR and oxycodone IR will also be performed. Tapentadol (CG5503) IR 50 or 75 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 (acetaminophen is also allowed during the first 12 hours on Day 1, if needed for pain). All doses of study treatment will be taken with approximately 120 mL of water with or without 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 Tapentadol Immediate-Release Formulation in the Treatment of Acute Pain From Bunionectomy

Conditions
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Arthralgia, Bunion, Hallux Valgus, Pain

Intervention / Treatment
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* Drug: Tapentadol (CG5503)
* Drug: Tapentadol (CG5503)
* Drug: oxycodone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must undergo primary unilateral first metatarsal bunionectomy Pain intensity must be moderate to severe following removal of a continuous popliteal sciatic block Female patients must be postmenopausal, surgically sterile, or practicing an effective method of birth control if they are sexually active. 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 severe renal insufficiency Moderately or severely impaired hepatic function Currently treated with anticonvulsants, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), neuroleptics, or serotonin norepinephrine reuptake inhibitor (SNRI).

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: 004<br>placebo 1 capsule q4-6 hrs for 3 days | Drug: placebo<br>* 1 capsule q4-6 hrs for 3 days<br>|
| Active Comparator: 003<br>oxycodone 10mg capsule q4-6 hrs for 3 days | Drug: oxycodone<br>* 10mg capsule q4-6 hrs for 3 days<br>|
| Experimental: 001<br>Tapentadol (CG5503) 50mg capsule q4-6 hrs for 3 days | Drug: Tapentadol (CG5503)<br>* 50mg capsule q4-6 hrs for 3 days<br>|
| Experimental: 002<br>Tapentadol (CG5503) 75mg capsule q4-6 hrs for 3 days | Drug: Tapentadol (CG5503)<br>* 75mg capsule q4-6 hrs for 3 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. A positive difference between the mean SPID48 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Rescue Pain Medication Use. | The effect of tapentadol (CG5503) IR on the time to the first use of rescue pain medication. | 3 days | 
| The SPID at 12 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. A positive difference between the mean SPID12 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief. | 12 hours | 
| SPID at 24 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. A positive difference between the mean SPID24 for an active study drug and placebo would indicate a numerically larger analgesic effect for subjects dosed with active study drug than in the placebo group. A higher value in SPID indicates greater pain relief. | 24 hours | 
| Percentage of Patients Who Reported Very Much Improved or Much Improved From Baseline in Patient Global Impression of Change to Day 3 | Ordinal measure indicating change from the start of treatment (On a scale of 7 = Very much Worse to 1 = very much improved) to endpoint at Day 3 | Baseline and 3 days | 
| Total Pain Relief (TOTPAR)at 48 Hours | Total Pain Relief (TOTPAR48) was defined as the weighted sum over all pain relief scores(PAR) from 0.5 hour to Hour 48, with the actual time elapsed from the previous PAR observation as the weight. A higher value in TOTPAR indicates greater pain relief. | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute pain, bunionectomy, tapentadol