Osteoarthritis
Conditions
Keywords
Osteoarthritis, opioid, transdermal
Brief summary
The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (20 mg) in comparison to the buprenorphine transdermal system (5 mg) and oxycodone immediate release in subjects with moderate to severe osteoarthritis pain currently treated with oral opioids. The double-blind treatment intervention duration is 12 weeks during which time supplemental analgesic medication (acetaminophen, ibuprofen, immediate release oxycodone) will be provided to all subjects in addition to study drug.
Detailed description
Buprenorphine is a synthetic opioid analgesic with over twenty-five 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 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
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Osteoarthritis of the hip, knee, or spine for 1 year or longer, confirmed by radiographic evidence within the last 2 years. * Good pain control while on a stable dose of an opioid analgesic for osteoarthritis.
Exclusion criteria
* Not currently taking and tolerating opioids. * 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 osteoarthritis. Other protocol-specific exclusion/inclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Weeks 4, 8, and 12 of the double-blind phase | The average pain over the last 24 hours score was collected using an 11-point numerical scale ranging from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. This variable was obtained at each clinic visit during the double-blind phase of the study (postrandomization weeks 1, 2, 4, 8, and 12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Daily Number of Supplemental Analgesic Medication Tablets | Double-blind phase (84 days) | The mean daily number of supplemental analgesic medication tablets included sponsor-supplied ibuprofen, acetaminophen, or OxyIR®. |
| The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Weeks 4, 8 and 12 of the double-blind phase | The WOMAC (Version LK 3.1) measures symptoms and physical functioning of patients with OA of the hip and knee. It contains 24 items (5 pain, 2 stiffness, 17 physical function) and takes less than 5 minutes to complete. The WOMAC physical function subscale has 17 items coded as 0 to 4 (best to worst), which are summed, giving a range of 0 to 68 (best to worst). |
| The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | 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 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: 02-Apr-2004 (first subject first visit) to 18 Jul-2005 (last subject last visit); 15-Jun-2005 (first site notified of study termination). The study took place in 82 medical/research sites in the US; 59 sites randomized at least 1 subject.
Pre-assignment details
Men and women aged 40 years or older with OA of the hip, knee, or spine, on 30 to 80 mg/day morphine sulfate (MSO4) or equivalent, with or without nonopioid analgesic medication. (652 subjects entered the run-in period; 418 completed.) Subjects were eligible to enter the double-blind phase if they tolerated BTDS 20 and achieved stable analgesia.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind BTDS 5 Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear | 136 |
| Double-blind BTDS 20 Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear | 149 |
| Double-blind Oxycodone Immediate-Release Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours). | 133 |
| Total | 418 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Phase | Administrative | 0 | 26 | 37 | 33 |
| Double-blind Phase | Adverse Event | 0 | 10 | 19 | 18 |
| Double-blind Phase | Lack of Efficacy | 0 | 17 | 6 | 10 |
| Double-blind Phase | Lost to Follow-up | 0 | 0 | 2 | 2 |
| Double-blind Phase | Withdrawal by Subject | 0 | 6 | 8 | 7 |
| Open-label Run-in Period | Administrative | 42 | 0 | 0 | 0 |
| Open-label Run-in Period | Adverse Event | 74 | 0 | 0 | 0 |
| Open-label Run-in Period | Did not qualify | 5 | 0 | 0 | 0 |
| Open-label Run-in Period | Lack of Efficacy | 102 | 0 | 0 | 0 |
| Open-label Run-in Period | Lost to Follow-up | 5 | 0 | 0 | 0 |
| Open-label Run-in Period | Withdrawal by Subject | 6 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-blind BTDS 5 | Double-blind BTDS 20 | Double-blind Oxycodone Immediate-Release | Total |
|---|---|---|---|---|
| Age Continuous | 58.7 years STANDARD_DEVIATION 10.71 | 57.9 years STANDARD_DEVIATION 9.45 | 58.1 years STANDARD_DEVIATION 10.36 | 58.3 years STANDARD_DEVIATION 10.15 |
| Sex: Female, Male Female | 101 Participants | 116 Participants | 94 Participants | 311 Participants |
| Sex: Female, Male Male | 35 Participants | 33 Participants | 39 Participants | 107 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 | 30 / 136 | 70 / 149 | 56 / 133 | 187 / 652 |
| serious Total, serious adverse events | 3 / 136 | 7 / 149 | 7 / 133 | 8 / 652 |
Outcome results
Primary
Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase.
The average pain over the last 24 hours score was collected using an 11-point numerical scale ranging from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. This variable was obtained at each clinic visit during the double-blind phase of the study (postrandomization weeks 1, 2, 4, 8, and 12).
Time frame: Weeks 4, 8, and 12 of the double-blind phase
Population: Full Analysis Population (N = 418) 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 Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 8 | 3.78 Units on a scale | Standard Error 0.239 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 4 | 4.21 Units on a scale | Standard Error 0.219 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Screening | 6.60 Units on a scale | Standard Error 0.116 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Prerandomization | 3.25 Units on a scale | Standard Error 0.114 |
| Double-blind BTDS 5 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 12 | 3.67 Units on a scale | Standard Error 0.246 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Screening | 6.58 Units on a scale | Standard Error 0.103 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Prerandomization | 3.02 Units on a scale | Standard Error 0.093 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 4 | 3.57 Units on a scale | Standard Error 0.195 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 8 | 3.37 Units on a scale | Standard Error 0.19 |
| Double-blind BTDS 20 | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 12 | 3.56 Units on a scale | Standard Error 0.23 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 12 | 3.37 Units on a scale | Standard Error 0.232 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 8 | 3.59 Units on a scale | Standard Error 0.217 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Screening | 6.44 Units on a scale | Standard Error 0.117 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Week 4 | 3.45 Units on a scale | Standard Error 0.209 |
| Double-blind Oxycodone Immediate-Release | Average Pain Over the Last 24 Hours Scores at Weeks 4, 8, and 12 of the Double-blind Phase. | Prerandomization | 3.03 Units on a scale | Standard Error 0.099 |
p-value: 0.12695% CI: [-0.8562, 0.1054]Mixed Models Analysis
p-value: 0.1495% CI: [-0.8455, 0.1189]Mixed Models Analysis
Secondary
The Mean Daily Number of Supplemental Analgesic Medication Tablets
The mean daily number of supplemental analgesic medication tablets included sponsor-supplied ibuprofen, acetaminophen, or OxyIR®.
Time frame: Double-blind phase (84 days)
Population: Full Analysis Population (N = 418) 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 Mean Daily Number of Supplemental Analgesic Medication Tablets | Prerandomization | 2.0 Tablets | Standard Error 0.19 |
| Double-blind BTDS 5 | The Mean Daily Number of Supplemental Analgesic Medication Tablets | Double-blind | 3.3 Tablets | Standard Error 0.26 |
| Double-blind BTDS 20 | The Mean Daily Number of Supplemental Analgesic Medication Tablets | Prerandomization | 1.7 Tablets | Standard Error 0.13 |
| Double-blind BTDS 20 | The Mean Daily Number of Supplemental Analgesic Medication Tablets | Double-blind | 2.3 Tablets | Standard Error 0.19 |
| Double-blind Oxycodone Immediate-Release | The Mean Daily Number of Supplemental Analgesic Medication Tablets | Prerandomization | 1.6 Tablets | Standard Error 0.13 |
| Double-blind Oxycodone Immediate-Release | The Mean Daily Number of Supplemental Analgesic Medication Tablets | Double-blind | 2.3 Tablets | Standard Error 0.22 |
p-value: 0.00795% CI: [-1.47, -0.2]ANCOVA
p-value: 0.01195% CI: [-1.47, -0.17]ANCOVA
Secondary
The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase
The WOMAC (Version LK 3.1) measures symptoms and physical functioning of patients with OA of the hip and knee. It contains 24 items (5 pain, 2 stiffness, 17 physical function) and takes less than 5 minutes to complete. The WOMAC physical function subscale has 17 items coded as 0 to 4 (best to worst), which are summed, giving a range of 0 to 68 (best to worst).
Time frame: Weeks 4, 8 and 12 of the double-blind phase
Population: Full Analysis Population (N = 418) 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 Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 8 | 28.70 Units on a scale | Standard Error 1.364 |
| Double-blind BTDS 5 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 4 | 30.60 Units on a scale | Standard Error 1.187 |
| Double-blind BTDS 5 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Screening | 36.88 Units on a scale | Standard Error 1.093 |
| Double-blind BTDS 5 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Prerandomization | 25.96 Units on a scale | Standard Error 0.993 |
| Double-blind BTDS 5 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 12 | 29.68 Units on a scale | Standard Error 1.5 |
| Double-blind BTDS 20 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 4 | 28.34 Units on a scale | Standard Error 1.025 |
| Double-blind BTDS 20 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Screening | 37.69 Units on a scale | Standard Error 0.93 |
| Double-blind BTDS 20 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Prerandomization | 24.19 Units on a scale | Standard Error 0.947 |
| Double-blind BTDS 20 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 8 | 28.34 Units on a scale | Standard Error 1.199 |
| Double-blind BTDS 20 | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 12 | 29.35 Units on a scale | Standard Error 1.253 |
| Double-blind Oxycodone Immediate-Release | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 12 | 27.25 Units on a scale | Standard Error 1.651 |
| Double-blind Oxycodone Immediate-Release | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 8 | 26.59 Units on a scale | Standard Error 1.405 |
| Double-blind Oxycodone Immediate-Release | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Screening | 36.81 Units on a scale | Standard Error 1.043 |
| Double-blind Oxycodone Immediate-Release | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Week 4 | 26.65 Units on a scale | Standard Error 1.253 |
| Double-blind Oxycodone Immediate-Release | The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase | Prerandomization | 24.42 Units on a scale | Standard Error 0.93 |
p-value: 0.70795% CI: [-3.0054, 2.0397]Mixed Models Analysis
p-value: 0.18795% CI: [-4.4459, 0.8706]Mixed Models Analysis
Secondary
The Sleep Disturbance Subscale in The Medical Outcomes (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 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, and 12 of the Double-blind Phase
Population: Full Analysis Population (N = 418) 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 Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 8 | 35.95 Units on a scale | Standard Error 2.791 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 4 | 39.23 Units on a scale | Standard Error 2.144 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Screening | 51.91 Units on a scale | Standard Error 2.139 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Prerandomization | 34.64 Units on a scale | Standard Error 1.95 |
| Double-blind BTDS 5 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 12 | 39.13 Units on a scale | Standard Error 3.089 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 4 | 32.40 Units on a scale | Standard Error 1.941 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Screening | 55.28 Units on a scale | Standard Error 2.035 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Prerandomization | 28.65 Units on a scale | Standard Error 1.782 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 8 | 31.71 Units on a scale | Standard Error 2.473 |
| Double-blind BTDS 20 | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 12 | 32.95 Units on a scale | Standard Error 2.819 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 12 | 36.32 Units on a scale | Standard Error 3.29 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 8 | 34.13 Units on a scale | Standard Error 2.746 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Screening | 55.74 Units on a scale | Standard Error 2.197 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Week 4 | 35.72 Units on a scale | Standard Error 2.298 |
| Double-blind Oxycodone Immediate-Release | The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase | Prerandomization | 33.03 Units on a scale | Standard Error 1.926 |
p-value: 0.68595% CI: [-5.6177, 3.693]Mixed Models Analysis
p-value: 0.44395% CI: [-6.4415, 2.8255]Mixed Models Analysis