Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Chronic Nonmalignant Pain

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (5, 10 and 20) in comparison to matching placebo transdermal system in subjects with chronic nonmalignant pain syndromes currently controlled by oral opioids. The double-blind treatment intervention duration is 2 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.

Official Title
-----------------
An Open-label Run-in, Followed by a Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Show the Effectiveness of Buprenorphine Transdermal System in Management of Patients With Chronic Nonmalignant Pain Syndromes

Conditions
-----------------
Chronic Non-malignant Pain

Intervention / Treatment
-----------------
* Drug: Buprenorphine transdermal patch
* Drug: Placebo to match BTDS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 2 month's history of nonmalignant pain, currently in stable pain control on opioid therapy. Good, very good or excellent pain control on current opioid therapy. Willing and able to use a telephone interactive voice response service. Exclusion Criteria: Currently receiving daily morphine or oxycodone monotherapy. Scheduled for surgery of the disease site (eg, major joint replacement surgery), or any other major surgery, which would fall within the study period. Other protocol-specific exclusion/inclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BTDS (5, 10 or 20)<br>Buprenorphine transdermal patch | Drug: Buprenorphine transdermal patch<br>* Buprenorphine transdermal patch 5, 10 or 20 mcg/h applied for 7-day wear.<br>* Other names: Butrans™;|
| Placebo Comparator: Placebo to match BTDS<br>Placebo to match buprenorphine transdermal patch | Drug: Placebo to match BTDS<br>* Placebo to match buprenorphine transdermal patch applied for 7-day wear.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects With Ineffective Treatment During the Double-blind Evaluation Phase. | Ineffective treatment was defined as: Subject took >1 gram of acetaminophen in a 24-hour period, or Subject required a change in transdermal patch (TDS) dose, or Subject had difficulty in keeping the TDS on, or Subject discontinued due to ineffective treatment (but did not meet any of the above criteria). Note: some subjects may have had multiple reasons for ineffective treatment and are counted under each category. Therefore the sum of subjects across all criteria for ineffective treatment is greater than the total number of subjects with ineffective treatment. | Double-blind phase (14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (Days) From the Initial Dose of Study Drug in the Double-blind Evaluation Phase to Ineffective Treatment | The time of ineffective treatment was calculated as the earliest of the following: The date the subject first took >1 gram of acetaminophen, The visit date when ineffective treatment was first determined, or The date the last patch was removed. | 14 days | 
| The Number of Subjects Who Had Ineffective Treatment or Who Discontinued Due to Reasons Other Than Ineffective Treatment in the Double-blind Phase | Note: The total numbers of Subjects w/ineffective treatment or who discont'd for placebo and BTDS are 1 less because there were reasons other than lack of efficacy that made up this total: adverse event, death, lost to follow- up, protocol violation, and other. Example for placebo 89+5=94; however, 93 is indicated for the total because there is 1 subject in the placebo group who was counted under ineffective treatment and discontinued due to reasons other than lack of efficacy. The same is true for 1 subject in BTDS. | 14 days | 
| The Amount of Rescue Medication Used for Pain (Average Daily Number of Acetaminophen Tablets). | The average daily acetaminophen (Panadol) use (1 tablet = 500 mg) during the double-blind phase was compared between the treatment groups using ANCOVA methodology with terms for country and treatment. The average escape medication used in the last 4 days prior to randomization was included as a covariate. | 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic pain, opioid, transdermal, Butrans™ [BTDS]