The Safety and Efficacy of the Buprenorphine Transdermal System (BTDS) in Subjects With Chronic Back Pain.

Study Overview
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Brief Summary
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The objective of this study is to assess the safety of the buprenorphine transdermal system (5, 10, and 20) in comparison to placebo transdermal system and immediate release oxycodone/ acetaminophen in subjects with chronic back pain. The double-blind treatment intervention duration is 84 days during which time supplemental analgesic medication (non-steroidal anti-inflammatory drugs) will be allowed for all subjects in addition to study drug.

Detailed Description
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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.

Official Title
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A Comparative Study of Buprenorphine TDS, Oxycodone/ Acetaminophen Tablets Qid and Placebo in Patients With Chronic Back Pain

Conditions
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Back Pain

Intervention / Treatment
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* Drug: Buprenorphine transdermal patch
* Drug: Placebo oxycodone/acetaminophen tablets
* Drug: OXY/APAP
* Drug: Placebo transdermal patch (TDS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical evidence of stable, chronic (>2 months) back pain related to intervertebral disc disease, nerve root entrapment, spondylolithesis, and osteoarthritis or other, similar nonmalignant conditions. unacceptable pain control despite currently taking a nonsteroidal anti-inflammatory drug considered at a therapeutic and/or tolerated dose or, subjects currently taking </=2 short-acting opioid doses per day, or subjects taking 3-12 short-acting opioid doses per day. Exclusion Criteria: receiving opioids at an average daily dose of >90 mg of oral morphine equivalents or receiving more than 12 tablets per day of short-acting opioid-containing products. scheduled to have surgery (including dental) involving the use of preoperative or postoperative analgesics or anesthetics during the study period. Other protocol-specific exclusion/inclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo oxycodone (OXY)/acetaminophen (APAP) tablets and placebo transdermal patch (TDS) 5, 10, or 20 | Drug: Placebo oxycodone/acetaminophen tablets<br>* Placebo oxycodone/acetaminophen tablets; 1, 2, or 3 tablets taken four times/day.<br>Drug: Placebo transdermal patch (TDS)<br>* Placebo transdermal patch 5, 10, or 20 applied transdermally for 7-day wear<br>|
| Active Comparator: OXY/APAP<br>5 mg oxycodone/325 mg acetaminophen tablets | Drug: OXY/APAP<br>* 5 mg oxycodone / 325 mg acetaminophen tablets; 1, 2, or 3 tablets taken four times/day.<br>|
| Experimental: BTDS<br>Buprenorphine transdermal patch 5, 10, or 20 mcg/hour | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 5, 10, or 20 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain on the Average, Mean Change From Baseline Days 21-84 (Last Observation Carried Forward [LOCF]) | Subjects were asked, Please rate your pain by circling the one number (0-10) that best describes your pain on the average since your last visit. 0 = no pain and 10 = pain as bad as you can imagine it. | On baseline day 1 and days 21, 30, 45, 60, 75, and 84, and, if applicable, at early termination. | 
| Pain Right Now, Mean Change From Baseline, Days 21-84 (LOCF) | Subjects were asked, Please rate your pain by circling the one number (0-10) that tells how much pain you have right now. Subjects rated their answers on a 0-10 ordinal scale from 0 = No pain to 10 = Pain as bad as you can imagine it. Pain right now is presented as the LSmean [change from baseline] (SE). | Assessed at baseline day 1 and days 21, 30, 45, 60, 75, and 84, and, if applicable, at early termination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Functioning Scale of the Medical Outcomes Survey (MOS) 36 Item Short-Form Health Survey (SF-36): Mean Percent ± Standard Error of the Mean (SEM) at Day 84 (LOCF) | The Medical Outcomes Survey (MOS) Short-Form-36 Health Survey (SF-36) assesses 8 categories of functionality through 36 individual questions. Physical Functioning is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. The mean scores were analyzed. | Day 84, or, if applicable, at early termination | 
| Physical Role Scale (MOS SF-36): Mean Percent ± SEM at Day 84(LOCF) | The Medical Outcomes Survey Short-Form-36 health survey assesses 8 categories of functionality through 36 individual questions. Physical Role is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. The mean scores were analyzed. | Day 84 | 
| Bodily Pain (MOS SF-36): Mean Percent at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. Bodily Pain is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. The mean scores were analyzed. | Day 84 | 
| General Health (MOS SF-36): Mean Percent ± SEM at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. General Health is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at clinic. The mean scores were analyzed. | Day 84 | 
| Vitality (MOS SF-36): Mean Percent ± SEM at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. Vitality is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. The mean scores were analyzed. | Day 84 | 
| Social Functioning (MOS SF-36): Mean Percent ± SEM at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. Social Functioning is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. | Day 84 | 
| Emotional Role (MOS SF-36): Mean Percent ± SEM at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. Emotional Role is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. | Day 84 | 
| Mental Health (MOS SF-36):Mean Percent ± SEM at Day 84 (LOCF) | The MOS Short-Form Health Survey assesses 8 categories of functionality through 36 individual questions. Mental Health is 1 of the 8 categories. Its transformed score, scaled from 0% to 100%, is used. A higher score represents a better subject condition. The survey was completed by the subject at the clinic. | Day 84 | 
| Therapeutic Response - Investigator: Mean ± SEM (Day 84)(LOCF) | The therapeutic response was rated by the investigator. The assessment was completed by the investigator using a 0-3 ordinal scale from 0 = No response to 3 = Marked response. | Day 84 | 
| Therapeutic Response - Subject: Mean ± SEM (Day 84) (LOCF) | The therapeutic response was rated by the subject. The assessment was completed by the subject using a 0-3 ordinal scale from 0 = No response to 3 = Marked response. | Day 84 | 
| Subject Comparison to Prestudy Analgesic: Mean ± SEM (Day 84)(LOCF) | The subject compared study drug treatment to prestudy analgesic. The assessment was completed by the subject using a 0-2 ordinal scale from 0 = Worse than prestudy medicine to 2 = Better than prestudy medicine. | Day 84 | 
| Subject Satisfaction: Mean ± SEM (Day 84)(LOCF) | The subject assessed satisfaction with study drug. The assessment was completed by the subject using a 0-3 ordinal scale from 0 = No response to 3 = Marked response. | Day 84 | 
| Time to Stable Pain Management | For each subject, time to stable pain management is defined as the first (post-baseline) time during the titration period when his/her diary pain was 4 or less (or at least 2 points lower than baseline) for 3 consecutive daily records or the pain on the average (at the day 7 or day 21 visit) was 4 or less (or at least 2 points lower than baseline). | Start of study to day 21. | 
| The Time to Discontinuation Due to Lack of Efficacy | Dropouts due to various reasons were summarized by counts and percentage. Cox proportional hazards regression was used to assess the treatment differences in time to dropout due to lack of efficacy. Clinically important covariates (including gender, age, race, weight, baseline pain, and previous opioid use) were incorporated into the model when statistically significant at P< .10, using a backward elimination procedure. | Time after dosing to dropout due to lack of efficacy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic back pain, opioid, transdermal