Osteoarthritis
Conditions
Keywords
Chronic pain, osteoarthritis, transdermal
Brief summary
The original objective of this study was to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (BTDS) 20 micrograms (mcg)/hour (h) in comparison to the buprenorphine transdermal system 5 mcg/h 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 or ibuprofen) will be provided to all subjects in addition to study drug. This study was terminated early due to administrative reasons with only 20% of the planned sample size; therefore, the primary objective was changed to focus on the safety evaluation.
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
Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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. * taking between 30-80 milligrams (mg) of oral morphine sulfate or equivalent/day, at least 4 days a week.
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 conditions in addition to osteoarthritis. Other protocol-specific exclusion/inclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Throughout BTDS exposure (Includes run-in period, double-blind phase and extension phase) | Safety assessments included monitoring and recording of all adverse events and serious adverse events (SAEs). |
Countries
United States
Participant flow
Recruitment details
07-Jan-2004 (First subject first visit); 09-Mar-2005 (last subject last visit of extension \[subjects went directly into the extension upon completion of the double-blind phase\]) at 42 sites in the United States (US).
Pre-assignment details
Adult subjects (≥ 40 years), with osteoarthritis (OA) of the hip, knee or spine for longer than 1 year, controlled on oral opioid therapy, who met the inclusion/exclusion criteria specified in the protocol. The open-label run-in period (N = 188) selected subjects who tolerated BTDS 20 mcg/h and showed stable pain control (N = 96 completed).
Participants by arm
| Arm | Count |
|---|---|
| Double-blind BTDS 5 Reference treatment: Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear | 47 |
| Double-blind BTDS 20 Test treatment: Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear | 49 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Phase | Administrative | 0 | 0 | 4 | 0 |
| Double-blind Phase | Adverse Event | 0 | 2 | 8 | 0 |
| Double-blind Phase | Lack of Efficacy | 0 | 9 | 1 | 0 |
| Double-blind Phase | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Extension Phase | Administrative | 0 | 0 | 0 | 29 |
| Extension Phase | Adverse Event | 0 | 0 | 0 | 8 |
| Extension Phase | Lack of Efficacy | 0 | 0 | 0 | 2 |
| Extension Phase | Lost to Follow-up | 0 | 0 | 0 | 3 |
| Extension Phase | Withdrawal by Subject | 0 | 0 | 0 | 6 |
| Open-label Run-in Period | Administrative | 10 | 0 | 0 | 0 |
| Open-label Run-in Period | Adverse Event | 33 | 0 | 0 | 0 |
| Open-label Run-in Period | Did not qualify | 1 | 0 | 0 | 0 |
| Open-label Run-in Period | Lack of Efficacy | 44 | 0 | 0 | 0 |
| Open-label Run-in Period | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Open-label Run-in Period | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-blind BTDS 5 | Double-blind BTDS 20 | Total |
|---|---|---|---|
| Age Continuous | 58.1 years STANDARD_DEVIATION 11.65 | 61.1 years STANDARD_DEVIATION 11.72 | 59.6 years STANDARD_DEVIATION 11.72 |
| Sex: Female, Male Female | 34 Participants | 28 Participants | 62 Participants |
| Sex: Female, Male Male | 13 Participants | 21 Participants | 34 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 | 17 / 47 | 22 / 49 | 52 / 188 | 101 / 188 |
| serious Total, serious adverse events | 1 / 47 | 1 / 49 | 2 / 188 | 6 / 188 |
Outcome results
Primary
The Number of Participants With Adverse Events (AEs) as a Measure of Safety.
Safety assessments included monitoring and recording of all adverse events and serious adverse events (SAEs).
Time frame: Throughout BTDS exposure (Includes run-in period, double-blind phase and extension phase)
Population: The safety population consists of all subjects who received at least 1 dose of study drug and had at least 1 safety assessment after the initial dose of BTDS in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind BTDS 5 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Deaths | 0 Participants |
| Double-blind BTDS 5 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Other Adverse Events in ≥ 4.5% of subjects | 17 Participants |
| Double-blind BTDS 5 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Serious adverse events | 1 Participants |
| Double-blind BTDS 20 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Deaths | 0 Participants |
| Double-blind BTDS 20 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Other Adverse Events in ≥ 4.5% of subjects | 22 Participants |
| Double-blind BTDS 20 | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Serious adverse events | 1 Participants |
| Run-in Period | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Serious adverse events | 2 Participants |
| Run-in Period | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Deaths | 0 Participants |
| Run-in Period | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Other Adverse Events in ≥ 4.5% of subjects | 52 Participants |
| Overall BTDS Exposure | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Deaths | 0 Participants |
| Overall BTDS Exposure | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Other Adverse Events in ≥ 4.5% of subjects | 101 Participants |
| Overall BTDS Exposure | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Serious adverse events | 6 Participants |