Spinal Disorder
Conditions
Brief summary
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
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.
Interventions
DRUGBuprenorphine
8weeks treatment with Norspan®(Buprenorphine)
Sponsors
Mundipharma Korea Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain Intensity* at Week 8 of Treatment With the Study Drug From Baseline | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain Intensity at 4 Week of Treatment With Study Srug From Baseline. | 4 weeks | 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. |
| Change in Quality of Life at 8 Week of Treatment With Study Drug From Baseline | 8 weeks | 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). |
| Change of EQ-VAS at 8 Weeks of Treatment With Study Drug From Baseline. | 8 week | EQ-5D Visual Analogue Scale (VAS) in rates the participant's overall health status using values from 0 (worst imaginable) to 100 (best imaginable). |
| Clinician Global Impression of Change(CGIC) | 8weeks | 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). |
| Patients Global Impression og Change(PGIC) | 8 week | 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). |
Countries
South Korea
Participant flow
Recruitment details
Duration of study: from 16 Oct. 2012 to 28 Jun 2013
Pre-assignment details
This study is single arm for Norspan(buprenorphine) patch. Treatment with NORSPAN will be started from 5 μg/h 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. judgement by considering any titration needed situation.
Participants by arm
| Arm | Count |
|---|---|
| Norspan Patch (Buprenorphine) Trade name is Norspan. Buprenorphine 5μg/h, 10 μg/h, 20 μg/h patches will be used (4 patches a box). Patch will be administered every 7th day.
Buprenorphine: 8weeks treatment with Norspan®(Buprenorphine) | 241 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 67 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Other | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 27 |
Baseline characteristics
| Characteristic | Norspan Patch (Buprenorphine) |
|---|---|
| Age, Customized Age | 63.51 years STANDARD_DEVIATION 11.53 |
| Region of Enrollment Korea, Republic of | 241 participants |
| Sex: Female, Male Female | 167 Participants |
| Sex: Female, Male Male | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 143 / 241 |
| serious Total, serious adverse events | 1 / 241 |
Outcome results
Primary
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.
Time frame: 8 weeks
Population: FAS set: 210. Missing values were imputed by LOCF FAS included the data obtained from all subjects who had at least one dose of the study drug and had data of at least one primary efficacy endpoint assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Change of Pain Intensity* at Week 8 of Treatment With the Study Drug From Baseline | -1.65 units on a scale | Standard Deviation 1.96 |
p-value: <0.0595% CI: [-10, 10]t-test, 2 sided
Secondary
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).
Time frame: 8 weeks
Population: FAS set: 210. Missing values were imputed by LOCF. Even though 210 subjects at Visit 1, baseline were assessed EQ-5D questionnaire, At visit 4(8weeks), 153 subjects were assessed EQ-5D questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Change in Quality of Life at 8 Week of Treatment With Study Drug From Baseline | 0.18 units on a scale | Standard Deviation 0.31 |
Secondary
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).
Time frame: 8 week
Population: FAS set: 210. Missing values were imputed by LOCF. Even though 210 subjects were assessed EQ-VAS at visit 1(baseline), 153 Subjects were assessed EQ-VAS at visit 4(8week)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Change of EQ-VAS at 8 Weeks of Treatment With Study Drug From Baseline. | 10.55 units on a scale | Standard Deviation 24.76 |
Secondary
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.
Time frame: 4 weeks
Population: FAS set: 210. Missing values were imputed LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Change of Pain Intensity at 4 Week of Treatment With Study Srug From Baseline. | -1.26 units on a scale | Standard Deviation 1.71 |
Secondary
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).
Time frame: 8weeks
Population: FAS set: 210. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Very much improved | 16 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Much improved | 63 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Minimally improved | 55 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | No change | 68 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Minimally worse | 8 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Much worse | 0 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Clinician Global Impression of Change(CGIC) | Very much worse | 0 participants |
Secondary
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).
Time frame: 8 week
Population: FAS set: 210. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Very much improved | 12 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Much improved | 60 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Minimally improved | 57 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | No change | 71 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Minimally worse | 10 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Much worse | 0 participants |
| Single Arm-Norspan Patch (Buprenorphine) | Patients Global Impression og Change(PGIC) | Very much worse | 0 participants |