Osteoarthritis
Conditions
Keywords
Chronic pain, opioid, transdermal, osteoarthritis
Brief summary
The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (BTDS) (5, 10 and 20) in comparison to placebo transdermal system in subjects with moderate to severe osteoarthritis pain of the hip and knee currently treated with oral opioids. The double-blind treatment intervention duration is 4 weeks during which time supplemental analgesic medication (acetaminophen) 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
Buprenorphine transdermal patch 5, 10 or 20 mcg/h applied for 7-day wear.
DRUGPlacebo
Placebo to match BTDS 5, 10, or 20 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 75 Years
Healthy volunteers
No
Inclusion criteria
* clinical diagnosis of chronic osteoarthritis of the hip or knee for 1 year or longer. * an average pain due to osteoarthritis of moderate, moderately-severe, or severe for the 14 days prior to enrollment.
Exclusion criteria
* ingest opioid analgesics on a daily basis. * ingest \>2500 milligrams (mg) acetaminophen on a daily basis. * require \<20 mg or \>80 mg of morphine (or opioid equivalents) per day for control of their osteoarthritis pain. Other protocol-specific exclusion/inclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time (Days) From First Administration of Double-blind Treatment to the Development of Inadequate Analgesia at the Primary Osteoarthritis Pain Site. | Double-blind phase ( 28 days): reaching inadequate analgesia on any 2 days of the 7-day dosing periods | Inadequate analgesia: * average pain over the last 24 hours score for pain at primary osteoarthritis (OA) site ≥ 5 on any 2 days of any 7-day dosing period, on a scale from 0 - 10 (0 = no pain to 10 = pain as bad as you can imagine)or; * \>1000 mg/day acetaminophen for pain at primary OA site for ≥ 2 days in any 7-day dosing period, or; * ingested nonstudy opioid analgesic medication for pain at primary OA site. Score: lowest score = shortest time to inadequate analgesia; highest score = longest time to inadequate analgesia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Maximum Pain Right Now Score for the Primary Osteoarthritis (OA) Pain Site | 7 days of the last dosing period of the double-blind phase, or the last 7-day dosing period prior to emergence of inadequate analgesia or discontinuation from the double-blind phase. | The daily maximum 'pain right now' score for the primary OA pain site was calculated over the last 7-day dosing period in the double-blind phase or the last 7-day dosing period prior to emergence of inadequate analgesia or discontinuation from the double-blind phase. Collected prior to ingestion of acetaminophen. Pain right now scale score for primary OA site on a scale from 0-10 (where 0= no pain and 10= worst pain you can imagine). |
Countries
United States
Participant flow
Recruitment details
25-Apr-2003 (first patient first visit) to 01-Jun-2004 (last patient last visit). This study was conducted at 41 medical/research sites in the United States.
Pre-assignment details
529 subjects began the run-in period with buprenorphine transdermal system (BTDS) 5 and their dose was titrated to BTDS 10 or 20 to achieve effective pain control. Subjects meeting criteria for adequate analgesia within 21 days were randomized into the double-blind phase (the number of subjects \[N\] = 328 completed run-in period).
Participants by arm
| Arm | Count |
|---|---|
| Double-blind Placebo Reference treatment in the double-blind phase. Placebo transdermal patches matched the BTDS patches applied for 7-day wear. | 162 |
| Double-blind BTDS Test treatment in the double-blind phase. Buprenorphine transdermal patches 5, 10, or 20 applied for 7-day wear. | 164 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 2 | 3 |
| Overall Study | Adverse Event | 1 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Double-blind Placebo | Double-blind BTDS | Total |
|---|---|---|---|
| Age Continuous | 61.2 years STANDARD_DEVIATION 9.64 | 60.4 years STANDARD_DEVIATION 9.28 | 60.8 years STANDARD_DEVIATION 9.45 |
| Sex: Female, Male Female | 106 Participants | 113 Participants | 219 Participants |
| Sex: Female, Male Male | 56 Participants | 51 Participants | 107 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 | 15 / 162 | 28 / 164 | 229 / 529 |
| serious Total, serious adverse events | 0 / 162 | 1 / 164 | 6 / 529 |
Outcome results
Primary
The Time (Days) From First Administration of Double-blind Treatment to the Development of Inadequate Analgesia at the Primary Osteoarthritis Pain Site.
Inadequate analgesia: * average pain over the last 24 hours score for pain at primary osteoarthritis (OA) site ≥ 5 on any 2 days of any 7-day dosing period, on a scale from 0 - 10 (0 = no pain to 10 = pain as bad as you can imagine)or; * \>1000 mg/day acetaminophen for pain at primary OA site for ≥ 2 days in any 7-day dosing period, or; * ingested nonstudy opioid analgesic medication for pain at primary OA site. Score: lowest score = shortest time to inadequate analgesia; highest score = longest time to inadequate analgesia.
Time frame: Double-blind phase ( 28 days): reaching inadequate analgesia on any 2 days of the 7-day dosing periods
Population: The Full Analysis Population (N = 326) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug and had at least 1 primary efficacy observation during the double-blind phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | The Time (Days) From First Administration of Double-blind Treatment to the Development of Inadequate Analgesia at the Primary Osteoarthritis Pain Site. | 12.3 days | Standard Error 0.77 |
| Double-blind BTDS | The Time (Days) From First Administration of Double-blind Treatment to the Development of Inadequate Analgesia at the Primary Osteoarthritis Pain Site. | 17.2 days | Standard Error 0.89 |
p-value: 0.0026Kaplan-Meier estimate mean
Secondary
Daily Maximum Pain Right Now Score for the Primary Osteoarthritis (OA) Pain Site
The daily maximum 'pain right now' score for the primary OA pain site was calculated over the last 7-day dosing period in the double-blind phase or the last 7-day dosing period prior to emergence of inadequate analgesia or discontinuation from the double-blind phase. Collected prior to ingestion of acetaminophen. Pain right now scale score for primary OA site on a scale from 0-10 (where 0= no pain and 10= worst pain you can imagine).
Time frame: 7 days of the last dosing period of the double-blind phase, or the last 7-day dosing period prior to emergence of inadequate analgesia or discontinuation from the double-blind phase.
Population: Full Analysis Population (N = 326) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug and had at least 1 primary efficacy observation during the double-blind phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | Daily Maximum Pain Right Now Score for the Primary Osteoarthritis (OA) Pain Site | 3.8 units on a scale | Standard Error 0.15 |
| Double-blind BTDS | Daily Maximum Pain Right Now Score for the Primary Osteoarthritis (OA) Pain Site | 3.2 units on a scale | Standard Error 0.14 |