Conversion to Embeda With Rescue Trial

Study Overview
=================
Brief Summary
-----------------
The purpose of the research study is to find out if opioid dependent chronic pain patients who are judged by their physician to be eligible to change their current opioid medicine and to participate in this study can be successfully adjusted to a stable dose of EMBEDA (morphine sulfate and naltrexone hydrochloride). The study will also assess each patient's risk for prescription opioid abuse, misuse and diversion.

Detailed Description
-----------------
The decision to terminate the trial was based on a lack of study drug supply. The decision was not based on any safety concerns. The termination letter was sent on 11March2011.

Official Title
-----------------
A Multi-Center, Primary Care-Based, Open-Label Study to Assess the Success of Converting Opioid-Experienced Patients, With Chronic, Moderate to Severe Pain, to EMBEDA Using a Standardized Conversion Guide, and to Identify Behaviors Related to Prescription Opioid Abuse, Misuse, and Diversion

Conditions
-----------------
Chronic Disease, Pain

Intervention / Treatment
-----------------
* Drug: morphine sulfate and naltrexone hydrochloride (EMBEDA)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be able to read, speak and understand English Have chronic moderate to severe pain for at least 3 months Require around the clock opioid medication for the relief of pain Have been taking a daily opioid for at least 30 days prior to starting the study Be able to be safely switched to a different pain medication Be practicing acceptable birth control methods for female patients of childbearing potential Be willing to participate in the study and able to comply with study procedures Exclusion Criteria: Be currently diagnosed with or participating in and/or seeking treatment for opioid and/or alcohol abuse Be allergic or intolerant to morphine, morphine salts, naltrexone or other opioids Be currently taking tramadol and/or extended release morphine products Have respiratory depression Have acute or severe bronchial asthma or severe chronic obstructive pulmonary disease Have migraines as your main source of pain Have any form of bowel obstruction Be pregnant or breast feeding Have had 2 or more surgeries for low back pain Be planning a major surgery during the study Be staying in a hospital or nursing home Be planning to have steroid injections for your chronic pain during the study Have a life expectancy of less than 2 months

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

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

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

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

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: morphine sulfate and naltrexone hydrochloride (EMBEDA)<br> | Drug: morphine sulfate and naltrexone hydrochloride (EMBEDA)<br>* Capsules in dose strengths ranging from 20 to 100 mg morphine sulfate with 0.8 to 4 mg of naltrexone hydrochloride taken either once or twice daily with a starting dose calculated using the total daily dose of the current opioid being converted from until a stable dose is achieved or six weeks which ever comes first.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 
| Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase Stratified by Prior Opioid Therapy | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration to Titrate Participants to Stable Dose | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 
| Duration to Titrate Participants to Stable Dose Stratified by Prior Opioid Therapy | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 
| Number of Titration Steps to Achieve Stable Dose | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 
| Number of Titration Steps to Achieve Stable Dose Stratified by Prior Opioid Therapy | A dose was considered to be stable dose if it met all of the following criteria: dose was taken for at least 48 hours; investigator deemed the balance between an acceptable level of analgesia and/or function and tolerance of side effects had been achieved; and rescue medication use less than or equal to 2 doses per day. | Baseline through Week 6 | 
| Percentage of Participants With Rescue Medications Usage During Titration | Rescue pain medications were used for supplemental analgesia for breakthrough pain during titration phase. Morphine sulfate IR tablet (less than 20 percent of the total daily dose of EMBEDA per IR dose), ibuprofen (up to 400 milligram (mg)/dose; not to exceed 1200 mg/day), and acetaminophen (up to 1000 mg/dose, not to exceed 4000 mg/day) were used as rescue medications. | Baseline through Week 6 | 
| Change From Baseline in Brief Pain Inventory (BPI) at Visit 3 (First Visit After Successful Titration) | BPI is an 11-item self-report questionnaire: consist of 4 questions that assess pain intensity (worst, least, average, relief) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question answered on a scale range:0-10 (0%-100% for relief), '0=No pain/no relief/no interference and 10=Pain as bad as you can imagine/complete relief/ complete interference'.Measure can be scored by item, with lower scores being indicative of less pain or pain interference. | Baseline, Visit 3 (up to Week 6) | 
| Investigator's Level of Satisfaction With the EMBEDA Conversion Guide | The conversion assessment survey is a brief questionnaire using multiple choice options and numeric rating scale (NRS) with specified anchored responses ranging on a scale from 0-10 (0 = very dissatisfied, 5 = neutral, and 10=very satisfied) to assess the Investigator's level of satisfaction with the EMBEDA Conversion Guide. | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic pain, Embeda, opioid, moderate pain, severe pain, conversion, converting, switching, morphine, aberrant behavior, Pain (DT) + Chronic Disease (DT)