Compare the Efficacy and Safety of Norspan to Tramadol/Acetaminophen With Prolonged Postoperative Pain (PASSION)

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of buprenorphine transdermal system to tramadol/acetaminophen.

Official Title
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A Multicenter, Phase IV, Interventional Study to Compare the Efficacy and Safety of NORSPAN to Tramadol/Acetaminophen in Patients With Prolonged Postoperative Pain After Spinal Surgery (PASSION)

Conditions
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Pain

Intervention / Treatment
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* Drug: buprenorphine
* Drug: tramadol/acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Korean men and women aged 20 years or more Presence of pain associated with a spinal disease and lumbar fusion at 1-2 spinal segments (1-2 level lumbar fusion surgery) Moderate to severe pain of the NRS pain score ≥ 4 at Visit 1 (14 90 days after surgery, Baseline) (Amended 21Nov2013) Consent to participate in the study and voluntary signature on the informed consent form Exclusion Criteria: Women of childbearing potential, except for the following cases: A partner who is vasectomized or otherwise surgically sterile. Use of 2 contraception methods. Two methods include the combination of double-barrier contraception or barrier contraception and hormone contraception, and appropriate barrier methods are as follows: Diaphragm (female contraceptive device), condom, intrauterine (copper or hormone), sponge or spermicide. Hormonal contraceptives include all commercially available products containing estrogen and/or progesterone. Pregnant or breastfeeding women. Pregnant woman is defined as a woman after fertilization to late pregnancy with a positive result from the urine pregnancy test. History of hypersensitivity to buprenorphine, tramadol, APAP or excipients, and celecoxib Medical history of asthma, acute rhinitis, nasal polyp, vascular edema urticaria or allergic reaction to aspirin or other non-steroidal anti-inflammatory drugs(NSAIDs, COX-2) Hypersensitivity or intolerance to Domperidone Risk of gastrointestinal irritation such as gastrointestinal bleeding, mechanical ileus or perforation Genetic problem such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Severely impaired respiratory function or respiratory depression Current use of monoamine oxidase(MAO) inhibitors or the medication history within 2 weeks prior to study participation Convulsive disorder, head injury, shock, decreased level of consciousness of uncertain origin, intracranial lesion or increased intracranial pressure or severe hepatic impairment Biliary tract disorder Presence or suspected drug abuse history Medical history of opioid or drug dependence Current use of other CNS inhibitors or muscle relaxants that may result in dyspnea, hypotension, severe sedation or coma when used with the investigational product, opioid analgesics Use of strong opioids, buprenorphine or tramadol/APAP within 1 week prior to study participation (however, study participation is allowed for PRN prescription of PCA and strong opioids) Any condition representing a contraindication of application of buprenorphine, tramadol/APAP or celecoxib Major pain not attributable to a spinal disease Anticancer therapy that may affect pain assessment Clinically significant cardiovascular or renal dysfunction Postoperative complications Symptoms of acute pain after lumbar fusion or characteristic analgesic features showing rapidly changing needs for analgesics Current use of other investigational product at enrollment or within 30 days after administration of other investigational product

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: buprenorphine<br>Patch | Drug: buprenorphine<br>* Dosage and administration: This one patch should be attached every 7 days.<br>* Other names: Norspan patch;|
| Active Comparator: tramadol/acetaminophen<br>Oral tablet | Drug: tramadol/acetaminophen<br>* Amount of drug ingredients : Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug. Dosage and administration: Adjust dose depending on a patient's pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.<br>* Other names: Ultracet ER semi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment. | NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week6/ET minus mean score at Baseline. | baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration | NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week 2/ET minus mean score at Baseline. | 2 weeks | 
| Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose | EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions for 'Motor capability', 'Self-care', 'Daily activities', 'Pain/discomfort', 'Depression/anxiety' and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)). *EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents) EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by 1 means that the healthy condition and high quality of life. | Baseline and at 6 weeks | 
| Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS) | The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (score = 100) and 'Worst imaginable health state' (score = 0). Higher points were positive results and positive points of difference gap means improvement results. | Baseline and at 6weeks | 
| Clinical Global Impression of Change(CGIC) | The number of patients who choose the best opinion of overall satisfaction among Clinical Global Impression of Change Scale(CGIC) among 7 point scale. Missing data was imputed by LOCF. Scores measure from 1: Very much improved to 7:very much worse. | 6 weeks | 
| Patient Global Impressions of Change(PGIC) | In the PP set, Number of participants with categorical change in overall satisfaction. PGIC: a participant-rated instrument assessing change in participant's overall satisfaction from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse). | 6 weeks |