Pain
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of buprenorphine transdermal system to tramadol/acetaminophen.
Interventions
DRUGbuprenorphine
Dosage and administration: This one patch should be attached every 7 days.
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.
Sponsors
Mundipharma Korea Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment. | baseline and 6 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration | 2 weeks | 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. |
| Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose | Baseline and at 6 weeks | 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. |
| Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS) | Baseline and at 6weeks | 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. |
| Clinical Global Impression of Change(CGIC) | 6 weeks | 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. |
| Patient Global Impressions of Change(PGIC) | 6 weeks | 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). |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine Patch
buprenorphine: Dosage and administration: This one patch should be attached every 7 days. | 69 |
| Tramadol/Acetaminophen Oral tablet
tramadol/acetaminophen: 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. | 65 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | Buprenorphine | Tramadol/Acetaminophen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 43 Participants | 27 Participants | 70 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 38 Participants | 64 Participants |
| Age, Continuous | 64.42 years STANDARD_DEVIATION 10.84 | 61.54 years STANDARD_DEVIATION 8.96 | 63.02 years STANDARD_DEVIATION 10.04 |
| Sex: Female, Male Female | 44 Participants | 29 Participants | 73 Participants |
| Sex: Female, Male Male | 25 Participants | 36 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 69 | 13 / 65 |
| serious Total, serious adverse events | 3 / 69 | 0 / 65 |
Outcome results
Primary
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.
Time frame: baseline and 6 weeks
Population: In the PP set, the change in the pain intensity score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment. | -2.32 Scores on a scale | Standard Deviation 1.96 |
| Tramadol/Acetaminophen | Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment. | -2.75 Scores on a scale | Standard Deviation 1.56 |
Comparison: In the Per protocol setp-value: 0.265897.5% CI: [-6, 3]t-test, 2 sided
Secondary
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.
Time frame: Baseline and at 6weeks
Population: In the PP set, the change in the your today health score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS) | 14.33 scores on a scale | Standard Deviation 20.34 |
| Tramadol/Acetaminophen | Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS) | 9.08 scores on a scale | Standard Deviation 19.63 |
Secondary
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.
Time frame: 2 weeks
Population: In the PP set, the reduction in the pain intensity score from Visit 1 (Baseline) to Week 2 of the investigational product administration was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration | -1.19 Scores on a scale | Standard Deviation 1.61 |
| Tramadol/Acetaminophen | Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration | -1.70 Scores on a scale | Standard Deviation 1.73 |
Secondary
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.
Time frame: Baseline and at 6 weeks
Population: In the PP set, the change in the quality of life (EQ-5D) total score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose | 0.09 EQ-5D Total score | Standard Deviation 0.19 |
| Tramadol/Acetaminophen | Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose | 0.21 EQ-5D Total score | Standard Deviation 0.22 |
Secondary
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.
Time frame: 6 weeks
Population: In the per protocol: Analyze the within-group change in the CGIC from Baseline (Week 0) to Week 6 of the investigational product administration by using a paired t-test, and analyze the between-group difference in the change of satisfaction by using a t-test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Clinical Global Impression of Change(CGIC) | 2.28 Scores on 1 to 7 point | Standard Deviation 1.21 |
| Tramadol/Acetaminophen | Clinical Global Impression of Change(CGIC) | 2.43 Scores on 1 to 7 point | Standard Deviation 1.01 |
Secondary
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).
Time frame: 6 weeks
Population: Per protocol set: Analyze the within-group change in the PGIC from Baseline (Week 0) to Week 6 by using a paired t-test, and analyze the between-group difference in the change of satisfaction by using a t-test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine | Patient Global Impressions of Change(PGIC) | 2.32 Scores on 1 to 7point | Standard Deviation 1.22 |
| Tramadol/Acetaminophen | Patient Global Impressions of Change(PGIC) | 2.45 Scores on 1 to 7point | Standard Deviation 0.93 |