An Interventional Study to Assess the Efficacy and Safety of Buprenorphine in Korean Patients With Spinal Disorders

Study Overview
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Brief Summary
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The purpose of this study is to assess the pain reduction rate after 8 weeks treatment of NORSPAN® from baseline. And secondary purpose are: pain reduction rate after 4 weeks treatment from baseline(week 0) the EQ-5D, the pain and sleep questionnaire, physician's overall satisfaction subject's overall satisfaction, and safety

Detailed Description
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Upon providing written informed consent, subject will be screened in the study and assessment will be performed at that time such as safety laboratory assessments, physical examination, vital sign, medical history taking, 24 hours pain intensity score, EQ-5D, pain and sleep questionnaire, physician's overall satisfaction and subject's overall satisfaction. If patient is eligible in inclusion/exclusion criteria at the time of visit 1, the patient will receive treatment with NORSPAN®. Treatment with NORSPAN® will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision.

Official Title
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A Multicenter, Phase IV, Interventional Study to Assess the Efficacy and Safety of NORSPAN® (Buprenorphine) in Korean Patients With Spinal Disorders (NOBLE)

Conditions
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Spinal Disorder

Intervention / Treatment
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* Drug: Buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 years old or above male or female Korean patients Patients who have spinal disorders related pain Patients who had been treated with weak opioids and/or NSAIDs before study participation Patients who have moderate to severe pain intensity Naïve patients for Buprenorphine (Naïve patient are defined as those who had not been treated with Buprenorphine for 90 days) Patients who signed a written informed consent form Exclusion Criteria: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: women whose partners have been sterilized by vasectomy or other means using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test Patients with known hypersensitivity to buprenorphine or to any of the excipients Patients with severely impaired respiratory function or respiratory depression status Patients concurrently receiving MAOIs or who have received MAOIs within the previous two weeks Patients with convulsive disorders, head injury, shock, a reduced level of consciousness of uncertain origin, intracranial lesions or increased intracranial pressure, or in patients with severe hepatic impairment Patients with biliary tract disorders Patients known to have, or suspected of having a history of drug abuse Patients with history of opioid or drug dependence Patients who are concurrently taking other CNS depressants or muscle relaxants that may cause respiratory depression, hypotension, profound sedation or potentially result in coma. Patients who are taking Buprenorphine or strong opioid. Any situation where Buprenorphine is contraindicated Major surgery within 1 month prior to screening or planned surgery Mainly pain originated other than spinal disorders disease Non-malignant patients or cancer patients who are receiving any oncology treatment that could affect the measure of pain control With a disability that may prevent the patient from completing all study requirements and in particular, interfere with 24hrs pain intensity score Clinically significant impairment of cardiovascular, respiratory and renal function Patient who needs acute dose titration or whose pain intensity fluctuate significantly in a short period according to investigator's judgment Having used other investigational drugs at the time of enrollment, or within 30 days of enrollment

Ages Eligible for Study
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Minimum Age: 20 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm-Norspan patch (Buprenorphine)<br>This trial is single arm with Norspan patch. Treatment with NORSPAN Ò will be started from 5 μg/h (1 patch a week) for 2 weeks, and proper titration (up-titration) will be allowed at visit 2(wk 2) and at visit 3(wk 4) according to the investigator's decision. The up-titration will be considered by investigator's judgement as follows; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average NRS(Numeric Rating Scale), if the NRS was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication). | Drug: Buprenorphine<br>* 8weeks treatment with Norspan®(Buprenorphine)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain Intensity* at Week 8 of Treatment With the Study Drug From Baseline | NRS-Pain scale assessed the severity of a subject's lower back pain on a scale of 0 (No pain) and 10 (Worst possible pain). NRS-Pain scale: Change = mean score at Week 8/ET minus mean score at Baseline. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain Intensity at 4 Week of Treatment With Study Srug From Baseline. | NRS-Pain scale assessed the severity of a subject's lower back pain on a scale of 0 (No pain) and 10 (Worst possible pain). NRS-Pain scale: Change = mean score at Week 4/ET minus mean score at Baseline. | 4 weeks | 
| Change in Quality of Life at 8 Week of Treatment With Study Drug From Baseline | The Euroqol Health Survey (EQ-5D, 3-level) was completed on five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression) to measure health-related quality of life on a scale from 0-1. A higher score indicates better quality of life. EQ-5D score = 1 - 0.081 - (relevant score by level for the relevant item)-0.269 (only if there is at least one level 3). Table of scores by level for EQ-5D items mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.236). | 8 weeks | 
| Change of EQ-VAS at 8 Weeks of Treatment With Study Drug From Baseline. | EQ-5D Visual Analogue Scale (VAS) in rates the participant's overall health status using values from 0 (worst imaginable) to 100 (best imaginable). | 8 week | 
| Clinician Global Impression of Change(CGIC) | Number of clinician with categorical change in overall status. CGIC: a clinician-rated instrument assessing change in clinician's overall status from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse). | 8weeks | 
| Patients Global Impression og Change(PGIC) | Number of clinician with categorical change in overall status. PGIC: a participant-rated instrument assessing change in patient's overall status from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse). | 8 week |