Back Pain Lower Back Chronic
Conditions
Keywords
Low back pain, opioid, transdermal, Butrans
Brief summary
The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (BTDS) 20 in comparison to the buprenorphine transdermal system (BTDS) 5 and oxycodone immediate-release in subjects with moderate to severe low back pain currently treated with oral opioids. The double-blind treatment intervention duration is 12 weeks during which time supplemental analgesic medication (acetaminophen, ibuprofen) will be provided to all subjects in addition to study drug.
Detailed description
Buprenorphine is a synthetic opioid analgesic with over 25 years of international clinical experience indicating it to be safe and effective in a variety of therapeutic situations for the relief of moderate to severe pain.
Interventions
DRUGBuprenorphine
Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear.
Oxycodone HCl immediate-release 40 mg (two 5-mg capsules every 6 hours).
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* low back pain for 3 months or longer, confirmed by radiographic evidence. * receiving a stable dose of an opioid analgesic for low back pain.
Exclusion criteria
* taking more than 80 mg per day of oral morphine sulfate or equivalent within 30 days of enrollment. * requiring frequent analgesic therapy for chronic condition(s), in addition to low back pain. Other protocol-specific exclusion/inclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Last 24 hours score at weeks 4, 8, 12 of the double-blind phase | Subjects were evaluated during the double-blind phase for average pain over the last 24 hours prior to the study visits. Pain scale is 11 points (0 = no pain to 10 = pain as bad as you can imagine) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Number of Supplemental Analgesic Tablets | Double-blind phase (84 days) | The mean daily number of tablets of supplemental analgesic medications used during the double-blind phase |
| Oswestry Disability Index (ODI) Score (V 2.0) | Weeks 4, 8, 12 | The ODI (version 2) is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0 = good to 5 = worse). (Note: A higher score represents greater disability.) |
| The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Weeks 4, 8, 12 of the double-blind phase | The MOS-Sleep Scale consists of 12 individual items: (4 sleep disturbance, 2 sleep adequacy, 1 quantity/ optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath). Question 1 is scored on a scale of 1 to 5 and Questions 3 to 12 are scored on a scale of 1 to 6. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7 and 8, and ranges from 0 to 100, where higher scores indicate greater sleep disturbance. |
Countries
United States
Participant flow
Recruitment details
The study began with first patient first visit (FPFV) on 25-Feb-2004 to last patient last visit (LPLV) on 23-Sep-2005, at 75 medical/research sites in the United States.
Pre-assignment details
Prerandomization: screening period \[Prospective assessment: subjects were assessed to ensure compliance with all inclusion/exclusion criteria\]. Opioid taper segment: assessed the severity of the subject's low back pain upon analgesic medication discontinuation. Open-label run-in period: identified subjects whose pain was controlled with BTDS 20.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind BTDS 5 Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear | 221 |
| Double-blind BTDS 20 Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear | 219 |
| Double-blind Oxycodone Immediate-Release Oxycodone HCl immediate-release 40 mg (two 5-mg capsules every 6 hours). | 220 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 9 | 6 | 14 |
| Overall Study | Adverse Event | 14 | 29 | 16 |
| Overall Study | Lack of Efficacy | 52 | 25 | 16 |
| Overall Study | Lost to Follow-up | 7 | 6 | 10 |
| Overall Study | Withdrawal by Subject | 11 | 7 | 5 |
Baseline characteristics
| Characteristic | Double-blind BTDS 5 | Double-blind BTDS 20 | Double-blind Oxycodone Immediate-Release | Total |
|---|---|---|---|---|
| Age Continuous | 50.2 years STANDARD_DEVIATION 12.88 | 50.4 years STANDARD_DEVIATION 11.93 | 49.5 years STANDARD_DEVIATION 12.37 | 50.0 years STANDARD_DEVIATION 12.39 |
| Sex: Female, Male Female | 101 Participants | 113 Participants | 100 Participants | 314 Participants |
| Sex: Female, Male Male | 120 Participants | 106 Participants | 120 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 54 / 221 | 118 / 219 | 93 / 220 | 389 / 1,160 |
| serious Total, serious adverse events | 6 / 221 | 7 / 219 | 9 / 220 | 10 / 1,160 |
Outcome results
Primary
Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12.
Subjects were evaluated during the double-blind phase for average pain over the last 24 hours prior to the study visits. Pain scale is 11 points (0 = no pain to 10 = pain as bad as you can imagine)
Time frame: Last 24 hours score at weeks 4, 8, 12 of the double-blind phase
Population: Full Analysis Population (N = 660) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 8 | 3.83 units on a scale | Standard Error 0.162 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 4 | 3.79 units on a scale | Standard Error 0.149 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Screening | 6.36 units on a scale | Standard Error 0.075 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Prerandomization | 2.84 units on a scale | Standard Error 0.075 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 12 | 4.02 units on a scale | Standard Error 0.179 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 4 | 3.40 units on a scale | Standard Error 0.128 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Screening | 6.46 units on a scale | Standard Error 0.084 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Prerandomization | 2.91 units on a scale | Standard Error 0.075 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 8 | 3.35 units on a scale | Standard Error 0.14 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 12 | 3.35 units on a scale | Standard Error 0.139 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 12 | 3.26 units on a scale | Standard Error 0.152 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 8 | 3.24 units on a scale | Standard Error 0.145 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Screening | 6.46 units on a scale | Standard Error 0.079 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Week 4 | 3.14 units on a scale | Standard Error 0.125 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12. | Prerandomization | 2.74 units on a scale | Standard Error 0.074 |
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: <0.00195% CI: [-0.99, -0.35]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: <0.00195% CI: [-1.07, -0.44]Mixed Models Analysis
Secondary
Mean Daily Number of Supplemental Analgesic Tablets
The mean daily number of tablets of supplemental analgesic medications used during the double-blind phase
Time frame: Double-blind phase (84 days)
Population: Full Analysis Population (N = 660) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind BTDS 5 | Mean Daily Number of Supplemental Analgesic Tablets | 3.8 tablets | Standard Error 0.12 |
| Double-blind BTDS 20 | Mean Daily Number of Supplemental Analgesic Tablets | 3.3 tablets | Standard Error 0.13 |
| Double-blind Oxycodone Immediate-Release | Mean Daily Number of Supplemental Analgesic Tablets | 3.5 tablets | Standard Error 0.13 |
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: 0.00695% CI: [-0.9, -0.13]ANCOVA
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: 0.15895% CI: [-0.7, 0.09]ANCOVA
Secondary
Oswestry Disability Index (ODI) Score (V 2.0)
The ODI (version 2) is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0 = good to 5 = worse). (Note: A higher score represents greater disability.)
Time frame: Weeks 4, 8, 12
Population: Full Analysis Population (N = 660) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind BTDS 5 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 8 | 35.69 units on a scale | Standard Error 1.245 |
| Double-blind BTDS 5 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 4 | 34.80 units on a scale | Standard Error 1.066 |
| Double-blind BTDS 5 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 12 | 36.30 units on a scale | Standard Error 1.392 |
| Double-blind BTDS 20 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 8 | 34.27 units on a scale | Standard Error 1.094 |
| Double-blind BTDS 20 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 4 | 33.04 units on a scale | Standard Error 1.019 |
| Double-blind BTDS 20 | Oswestry Disability Index (ODI) Score (V 2.0) | Week 12 | 33.06 units on a scale | Standard Error 1.231 |
| Double-blind Oxycodone Immediate-Release | Oswestry Disability Index (ODI) Score (V 2.0) | Week 4 | 30.79 units on a scale | Standard Error 1.124 |
| Double-blind Oxycodone Immediate-Release | Oswestry Disability Index (ODI) Score (V 2.0) | Week 12 | 32.96 units on a scale | Standard Error 1.243 |
| Double-blind Oxycodone Immediate-Release | Oswestry Disability Index (ODI) Score (V 2.0) | Week 8 | 31.64 units on a scale | Standard Error 1.165 |
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: 0.06595% CI: [-3.55, 0.11]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: 0.03195% CI: [-3.79, -0.18]Mixed Models Analysis
Secondary
The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12.
The MOS-Sleep Scale consists of 12 individual items: (4 sleep disturbance, 2 sleep adequacy, 1 quantity/ optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath). Question 1 is scored on a scale of 1 to 5 and Questions 3 to 12 are scored on a scale of 1 to 6. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7 and 8, and ranges from 0 to 100, where higher scores indicate greater sleep disturbance.
Time frame: Weeks 4, 8, 12 of the double-blind phase
Population: Full Analysis Population (N = 660) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 8 | 42.28 units on a scale | Standard Error 2.264 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 4 | 40.67 units on a scale | Standard Error 2.025 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 12 | 40.85 units on a scale | Standard Error 2.376 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 8 | 35.69 units on a scale | Standard Error 1.721 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 4 | 34.65 units on a scale | Standard Error 1.607 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 12 | 33.65 units on a scale | Standard Error 1.941 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 4 | 38.10 units on a scale | Standard Error 1.788 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 12 | 41.60 units on a scale | Standard Error 2.205 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in the MOS-Sleep Scale at Weeks 4, 8, and 12. | Week 8 | 39.17 units on a scale | Standard Error 1.924 |
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that the BTDS 20 arm was different from the BTDS 5 arm.p-value: <0.00195% CI: [-9.64, -2.82]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between BTDS 20 or oxycodone HCl immediate-release 40 mg with respect to BTDS 5. The alternative hypothesis was that BTDS 20 arm was different from the BTDS 5 arm.p-value: 0.12195% CI: [-6.01, 0.7]Mixed Models Analysis