Low Back Pain
Conditions
Keywords
Chronic pain, opioid, transdermal, Moderate to severe chronic low back pain
Brief summary
The objective of this study is to determine the analgesic efficacy and safety of Buprenorphine Transdermal System (BTDS) 10 and 20 compared to placebo in opioid-naïve subjects with moderate to severe chronic low back pain. The double-blind treatment intervention duration is 12 weeks, during which time supplemental analgesic medication (immediate-release oxycodone for the first 6 days post-randomization and acetaminophen or ibuprofen for the remainder of the double-blind phase) 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 settings for the relief of moderate to severe pain. BTDS is a transdermal system formulation that is designed to deliver a consistent and a steady dose of buprenorphine over a 7-day period with limited blood concentration fluctuation.
Interventions
Buprenorphine transdermal system 10 or 20 mcg/h worn for 7 days
DRUGPlacebo
transdermal system (placebo) worn for 7 days
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with moderate to severe chronic low back pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to screening, * Subjects treated within the 14 days prior to screening with nonopioid therapy only, or with therapy including opioids at a dose of \<5 mg oxycodone (or equivalent) per day, * Subjects whose low back pain is not adequately controlled with non-opioid analgesic medication and who the Investigator feels are appropriate candidates for around-the-clock opioid therapy
Exclusion criteria
* Subjects who had a surgical procedure directed towards the source of back pain within 6 months of screening or planned during the study conduct period, * Subjects who are allergic to buprenorphine or who had a history of allergies to other opioids, * Subjects who have allergies or other contraindications to transdermal delivery systems or patch adhesives. Other protocol-specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Prerandomization phase consisted of a 6-10 day screening period and a <27 day open-label run-in period; and a 12-week double-blind phase. | Pain was assessed on an 11-point numerical scale ranging from 0 = no pain to 10 = pain as bad as you can imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Medications Taken During Weeks 2 Through 12 of the Double-blind Phase | weeks 2-12 | Nonopioid supplemental analgesic tablets were sponsor-supplied acetaminophen or ibuprofen. |
| The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Weeks 4, 8, 12 of double-blind phase | The MOS Sleep Scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of and optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 and Questions 2 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
Study dates: 27-Jun-2007 (first patient first visit) to 24-Jul-2008 (last patient last visit), at 86 medical/research sites in the USA.
Pre-assignment details
The open-label run-in period (N = 1024 started) was designed to select subjects for randomization in the double-blind phase who met both tolerability and responsiveness criteria for either BTDS 10 or 20 (an enriched design).
Participants by arm
| Arm | Count |
|---|---|
| Double-blind BTDS Buprenorphine transdermal patch 10 mcg/h or 20 mcg/h applied for 7-day wear during the 12-week double-blind phase | 256 |
| Double-blind Placebo TDS Matching placebo TDS 10 or 20 mcg/h applied for 7-day wear during the 12-week double-blind phase | 283 |
| Total | 539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Phase | Administrative | 0 | 6 | 6 |
| Double-blind Phase | Adverse Event | 0 | 40 | 20 |
| Double-blind Phase | Lack of Efficacy | 0 | 22 | 36 |
| Double-blind Phase | Lost to Follow-up | 0 | 8 | 11 |
| Double-blind Phase | Withdrawal by Subject | 0 | 10 | 11 |
| Open-label Run-in Period | Administrative | 40 | 0 | 0 |
| Open-label Run-in Period | Adverse Event | 239 | 0 | 0 |
| Open-label Run-in Period | Confirmed or suspected diversion | 3 | 0 | 0 |
| Open-label Run-in Period | Lack of Efficacy | 143 | 0 | 0 |
| Open-label Run-in Period | Lost to Follow-up | 21 | 0 | 0 |
| Open-label Run-in Period | Withdrawal by Subject | 37 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-blind BTDS | Double-blind Placebo TDS | Total |
|---|---|---|---|
| Age Continuous | 48.9 years STANDARD_DEVIATION 12.5 | 50.1 years STANDARD_DEVIATION 13.31 | 49.5 years STANDARD_DEVIATION 12.93 |
| Sex: Female, Male Female | 133 Participants | 163 Participants | 296 Participants |
| Sex: Female, Male Male | 123 Participants | 120 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 256 | 63 / 283 | 437 / 1,024 |
| serious Total, serious adverse events | 3 / 256 | 2 / 283 | 4 / 1,024 |
Outcome results
Primary
Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase.
Pain was assessed on an 11-point numerical scale ranging from 0 = no pain to 10 = pain as bad as you can imagine.
Time frame: Prerandomization phase consisted of a 6-10 day screening period and a <27 day open-label run-in period; and a 12-week double-blind phase.
Population: The full analysis population (FAP) (N = 541) \[539\] consisted of subjects who were randomized and received at least 1 dose of the double-blind study drug. (Two subjects did not have safety data.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind BTDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Screening | 7.24 Units on a scale | Standard Deviation 1.263 |
| Double-blind BTDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Prerandomization | 2.57 Units on a scale | Standard Deviation 1.283 |
| Double-blind BTDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Week 12 - Primary outcome | 3.83 Units on a scale | Standard Deviation 2.738 |
| Double-blind Placebo TDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Screening | 7.17 Units on a scale | Standard Deviation 1.223 |
| Double-blind Placebo TDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Prerandomization | 2.56 Units on a scale | Standard Deviation 1.207 |
| Double-blind Placebo TDS | Average Pain Over the Last 24 Hours Scores at Week 12 of the Double-blind Phase. | Week 12 - Primary outcome | 4.38 Units on a scale | Standard Deviation 2.69 |
Comparison: Missing average pain over the last 24 hours scores after treatment discontinuation were imputed using BOCF for adverse event-related withdrawals and LOCF for withdrawals due to other reasons.p-value: 0.010495% CI: [-1.02, -0.14]Mixed Models Analysis
Secondary
The Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Medications Taken During Weeks 2 Through 12 of the Double-blind Phase
Nonopioid supplemental analgesic tablets were sponsor-supplied acetaminophen or ibuprofen.
Time frame: weeks 2-12
Population: Subjects in the full analysis population who took at least one dose of supplemental analgesic medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind BTDS | The Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Medications Taken During Weeks 2 Through 12 of the Double-blind Phase | 0.620 tablets | Standard Error 0.0658 |
| Double-blind Placebo TDS | The Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Medications Taken During Weeks 2 Through 12 of the Double-blind Phase | 0.743 tablets | Standard Error 0.0574 |
p-value: 0.158695% CI: [-0.296, 0.048]ANCOVA
Secondary
The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase
The MOS Sleep Scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of and optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 and Questions 2 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 double-blind phase
Population: The full analysis population (FAP) (N = 541) consisted of subjects who were randomized and received at least 1 dose of the double-blind study drug. 2 subjects did not have safety data (N = 539).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind BTDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 4 | 32.84 Units on a scale | Standard Deviation 25.552 |
| Double-blind BTDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 8 | 35.63 Units on a scale | Standard Deviation 26.276 |
| Double-blind BTDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 12 | 34.97 Units on a scale | Standard Deviation 26.871 |
| Double-blind Placebo TDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 4 | 41.20 Units on a scale | Standard Deviation 26.813 |
| Double-blind Placebo TDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 8 | 39.87 Units on a scale | Standard Deviation 26.362 |
| Double-blind Placebo TDS | The Sleep Disturbance Subscale in the Medical Outcome Study (MOS) Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 12 | 40.42 Units on a scale | Standard Deviation 26.675 |
Comparison: The primary comparison between groups was based on estimates and contrasts for the weeks 4, 8, and 12 mean values.p-value: 0.006295% CI: [-7.55, -1.25]Mixed Models Analysis