ConvERT: Conversion to Embeda With Rescue Trial

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01179191
• Collaborator: (none)
• Enrollment: 684
• Locations: 166
• Arm: 1
• Duration (Months): 8
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Disease; Pain	Drug: morphine sulfate and naltrexone hydrochloride (EMBEDA)	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 684 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: morphine sulfate and naltrexone hydrochloride (EMBEDA)	Drug: morphine sulfate and naltrexone hydrochloride (EMBEDA); 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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase [Baseline through Week 6]

   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.

2. Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase Stratified by Prior Opioid Therapy [Baseline through Week 6]

   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.

Secondary Outcome Measures

1. Duration to Titrate Participants to Stable Dose [Baseline through Week 6]

   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.

2. Duration to Titrate Participants to Stable Dose Stratified by Prior Opioid Therapy [Baseline through Week 6]

   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.

3. Number of Titration Steps to Achieve Stable Dose [Baseline through Week 6]

   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.

4. Number of Titration Steps to Achieve Stable Dose Stratified by Prior Opioid Therapy [Baseline through Week 6]

   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.

5. Percentage of Participants With Rescue Medications Usage During Titration [Baseline through Week 6]

   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.

6. Change From Baseline in Brief Pain Inventory (BPI) at Visit 3 (First Visit After Successful Titration) [Baseline, Visit 3 (up to Week 6)]

   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.

7. Investigator's Level of Satisfaction With the EMBEDA Conversion Guide [Week 6]

   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.

Other Outcome Measures

1. Number of Participants With Aberrant Behaviors [Day 5]

   Current Opioid Misuse Measure (COMM) is a 17-item self-administered test used to monitor aberrant behavior in participants on opioid therapy. Aberrant behaviors assessed using a 5-point scale [0 = 'never' and 4 = 'very often']. Score range 0-68. Scores greater than or equal to 9 indicated the presence of aberrant behaviors.

2. Number of Participants With Abnormal Urine Drug Test Results [Baseline, Visit 3 (up to Week 6)]

   Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy [3, 4-methylenedioxyamphetamine (MDMA)], cocaine, phencyclidine (PCP) and marijuana [tetrahydrocannabinol (THC)]. Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.

3. Number of Participants With Urine Drug Test Results Positive for Unaccounted Opioids [Visit 3 (up to Week 6)]

   Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy (3, 4-MDMA), cocaine, PCP and marijuana (THC). Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.

4. Number of Participants With Urine Drug Test Results Positive for Illicit Substances [Baseline, Visit 3 (up to Week 6)]

   Urine samples collected were screened using immunoassay techniques for following types of drugs:opioids,barbiturates,benzodiazepines,amphetamines,ecstasy(3,4MDMA),cocaine,PCP,marijuana (THC).Quantitative, confirmatory urine drug testing performed for positive results using gas chromatography or high-pressure liquid chromatography for following analytes: morphine,oxycodone,oxymorphone,hydrocodone,hydromorphone,fentanyl,methadone,benzodiazepines,amphetamines,cocaine,THC,PCP,MDMA. Illicit substances were drugs of categories:marijuana (THC) metabolite,cocaine metabolite,PCP,amphetamine.

5. Number of Participants With Greater Than or Equal to One Urine Drug Test Results Negative for Expected Opioid [Baseline, Visit 3 (up to Week 6)]

   Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy (3, 4-MDMA), cocaine, PCP and marijuana (THC). Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Adamsville Family Medicine	Adamsville	Alabama	United States	35005
2	Office of David McLain	Birmingham	Alabama	United States	35209
3	Monte Sano Clinical Research, LLC	Huntsville	Alabama	United States	35801
4	Tennessee Valley Pain Consultants Properties, LLC	Huntsville	Alabama	United States	35801
5	Sunbelt Research Group, LLC	Mobile	Alabama	United States	36693
6	Office of Vaughn H. Mancha, Jr., PC	Montgomery	Alabama	United States	36117
7	Dedicated Clinical Research	Goodyear	Arizona	United States	85395
8	Dedicated Clinical Research, Inc	Phoenix	Arizona	United States	85020
9	Redpoint Research	Phoenix	Arizona	United States	85029
10	Anasazi Internal Medicine, PC	Phoenix	Arizona	United States	85032
11	Cochise Clinical Research	Sierra Vista	Arizona	United States	85635
12	Premiere Phamaceutical Research, LLC	Tempe	Arizona	United States	85282
13	Quality of Life Medical and Research Center, LLC	Tucson	Arizona	United States	85712
14	Ouachita Regional Pain Management	Hot Springs	Arkansas	United States	71913
15	NEA Baptist Clinic	Jonesboro	Arkansas	United States	72401
16	Hollis Family Medical Clinic, PLC	Paragould	Arkansas	United States	72450
17	CSI Clinical Trials	Costa Mesa	California	United States	92626
18	Global Wellness Medical Corporation	Foothill Ranch	California	United States	92610
19	Chrishard Medical Group	Inglewood	California	United States	90301
20	Triwest Research Associates LLC	La Mesa	California	United States	91942
21	Pacific Coast Pain Management Center	Laguna Hills	California	United States	92637
22	Valerius Medical Group and Research Center of Greater Long Beach, Inc.	Long Beach	California	United States	90806
23	LA Pain & Wellness Institute	Los Angeles	California	United States	90017
24	Samaritan Center for Medical Research	Los Gatos	California	United States	95032
25	Newport Beach Clinical Research Associates, Inc.	Newport Beach	California	United States	92663
26	Bayview Research Group, LLC	Paramount	California	United States	90723
27	Pasadena Rehabilitation Institute	Pasadena	California	United States	91105
28	Quality Control Research, Inc.	Roseville	California	United States	95661
29	Northern California Research	Sacramento	California	United States	95821
30	Quality Control Research, Inc.	Sacramento	California	United States	95842
31	Rancho Santa Fe Medical Group, Inc.	San Marcos	California	United States	92078
32	Probe Clinical Research Corporation	Santa Ana	California	United States	92701
33	Trinity Clinical Trials	Santa Ana	California	United States	92701
34	Facility Medical Center	Upland	California	United States	91786
35	Bayview Research Group, LLC	Valley Village	California	United States	91607
36	Rocky Mountain Internal Medicine, PC	Aurora	Colorado	United States	80012
37	Clinicos, LLC	Colorado Springs	Colorado	United States	80904
38	Saint Luke's Medical Clinic, LLC	Fort Collins	Colorado	United States	80525
39	ProHealth Physicians PC	Manchester	Connecticut	United States	06040
40	Milford Physician Services, PC	Milford	Connecticut	United States	06460
41	Orthopedic Research Institute, LLC	Boynton Beach	Florida	United States	33472
42	Florida Research & Testing, LLC	Clearwater	Florida	United States	33755
43	Omega Research Consultants, LLC	Debary	Florida	United States	32713
44	Omega Research Consultants, LLC	DeBary	Florida	United States	32746
45	West Florida Medical Associate, PA	Dunnellon	Florida	United States	34432
46	International Research Associates, LLC	Hialeah	Florida	United States	33012
47	Palm Springs Research Institute, Inc	Hialeah	Florida	United States	33012
48	FPA Clinical Research, LLC	Kissimmee	Florida	United States	34741
49	Clinical Research of Central Florida, Inc.	Lakeland	Florida	United States	33810
50	NextPhase Clinical Trials, Inc.	Miami Beach	Florida	United States	33140
51	Community Research Foundation, Inc.	Miami	Florida	United States	33155
52	New Horizon Research Center, Inc.	Miami	Florida	United States	33175
53	Harmony Clinical Research, Inc.	North Miami Beach	Florida	United States	33162
54	Office of Laszlo J. Mate, MD, PA	North Palm Beach	Florida	United States	33408
55	Office of Richard E. Promin, MD, PA	Ocala	Florida	United States	34474
56	Advent Clinical Research Centers, Inc.	Pinellas Park	Florida	United States	33781
57	Pain Management Strategies, Inc.	Pompano Beach	Florida	United States	33064
58	Sarasota Pain Medicine Research, LLC	Sarasota	Florida	United States	34238
59	Stedman Clinical Trials, LLC	Tampa	Florida	United States	33613
60	Clinical Research Center, LLC	Wellington	Florida	United States	33414
61	Perimeter Institute for Clinical Research, Inc.	Atlanta	Georgia	United States	30338
62	Medical Research and Health Education Foundation, Inc.	Columbus	Georgia	United States	31909
63	Ialum Clinical Research, LLC	Decatur	Georgia	United States	30032
64	Ialum Clinical Research, LLC	Stone Mountain	Georgia	United States	30088
65	Herman Clinical Research, LLC	Suwanee	Georgia	United States	30024
66	Centers for Pain Management	Tifton	Georgia	United States	31794
67	Chicago Clinical Research Institute Inc.	Chicago	Illinois	United States	60616
68	Creve Coeur Family Practice	Creve Coeur	Illinois	United States	61610
69	Office of Rebecca Knight, MD	Peoria	Illinois	United States	61614
70	Josephson Wallack Munshower Neurology P.C.	Indianapolis	Indiana	United States	46237
71	Laporte County Institute for Clinical Research Inc.	Michigan City	Indiana	United States	46360
72	McKinley Research, LLC	Mishawaka	Indiana	United States	46545
73	Accelovance, Inc.	South Bend	Indiana	United States	46601
74	Des Moines Orthopaedic Surgeons, PC	West Des Moines	Iowa	United States	50266
75	The Pain Treatment Center of the Bluegrass	Lexington	Kentucky	United States	40503
76	Healing Options	Louisville	Kentucky	United States	40223
77	Four Rivers Clinical Research, Inc.	Paducah	Kentucky	United States	42003
78	Lakewood Family Practice	Russell Springs	Kentucky	United States	42642
79	Diseasebusters, LLC	College Park	Maryland	United States	20740
80	Office of Steven C. Miller, MD	Pikesville	Maryland	United States	21208
81	Beacon Clinical Research, LLC	Brockton	Massachusetts	United States	02301
82	Ronald J. Rapoport, MD, PC	Fall River	Massachusetts	United States	02720
83	Boston Paincare Center, Inc.	Waltham	Massachusetts	United States	02154
84	Clarkston Medical Group, PC	Clarkston	Michigan	United States	48346
85	Apex Medical Research, AMR, Inc.	Flint	Michigan	United States	48504
86	East Michigan Medical Associates	Flint	Michigan	United States	48507
87	PCM Medical Services, PC	Lansing	Michigan	United States	48910
88	Remedica LLC	Rochester	Michigan	United States	48307
89	Michigan Lifestyle Change and Health Center, PC	Sterling	Michigan	United States	48314
90	MAPS Applied Research Center, Inc.	Edina	Minnesota	United States	55435
91	MAPS Applied Research Center, Inc.	Shakopee	Minnesota	United States	55379
92	Anesthesia and Pain Control Services	Biloxi	Mississippi	United States	39531
93	CRC of Jackson, LLC	Jackson	Mississippi	United States	39202
94	Midsouth Anesthesia Consultants, PLLC	Southhaven	Mississippi	United States	38671
95	Patterson Medical Clinic, Inc.	Florissant	Missouri	United States	63031
96	Quality Clinical Research Inc.	Florissant	Missouri	United States	63033
97	Primary Care Medicine, PC	Jefferson City	Missouri	United States	65109
98	The Reiter Foundation, Inc.	Anaconda	Montana	United States	59711
99	Medical Pain Relief Clinic	Omaha	Nebraska	United States	68114
100	Omaha Clinical Research, PC	Omaha	Nebraska	United States	68116
101	Atco Medical Associates, PC	Atco	New Jersey	United States	08004
102	Office of John V. Bernard, MD	Belvidere	New Jersey	United States	07823
103	Central Jersey Medical Research Center, Inc.	Elizabeth	New Jersey	United States	07202
104	Center for Pain Management	Hackensack	New Jersey	United States	07601
105	Advocare Heights Primary Care	Haddon Heights	New Jersey	United States	08035
106	NJ Heart, LLC	Linden	New Jersey	United States	07036
107	Spine and Pain Centers, PA	Shrewsbury	New Jersey	United States	07702
108	Premier Research, Inc.	Trenton	New Jersey	United States	08611
109	Adirondack Medical Research Center	Glens Falls	New York	United States	12801
110	Long Island Gastrointestinal Research Group LLP	Great Neck	New York	United States	11023
111	Drug Trials America, Inc.	Hartsdale	New York	United States	10530
112	Office of Roger Kasendorf, DO	Long Beach	New York	United States	11561
113	Family Health Medical Services PLLC	Mayville	New York	United States	14757
114	New York Spine & Wellness Center	North Syracuse	New York	United States	13212
115	North American Partners in Pain Management, LLP	Valley Stream	New York	United States	11580
116	Carolina Clinical Research and Consulting, LLC	Asheboro	North Carolina	United States	27203
117	Carolina Clinical Research and Consulting, LLC	Asheboro	North Carolina	United States	27205
118	Joint and Muscle Research Institute, Inc.	Charlotte	North Carolina	United States	28204
119	Catawba Valley Internal Medicine	Hickory	North Carolina	United States	28602
120	Profen Research Network at ECMA	Jacksonville	North Carolina	United States	28546
121	The Center For Clinical Research, LLC	Winston-Salem	North Carolina	United States	27103
122	Medical Frontiers, LLC	Carlisle	Ohio	United States	45005
123	Valley Medical Research	Centerville	Ohio	United States	45459
124	Hightop Medical Research Center	Cincinnati	Ohio	United States	45224
125	Sentral Clinical Research Services	Cincinnati	Ohio	United States	45236
126	Delaware Smith Clinic Research	Delaware	Ohio	United States	43015
127	Medical Frontiers, LLC	Franklin	Ohio	United States	45005
128	Jeffrey J. Haggenjos, DO, Inc.	New Lexington	Ohio	United States	43764
129	Whole Family Medical Care LLC	Perrysburg	Ohio	United States	43551
130	Office of Jocelyn F. Shimek, DO	Salem	Ohio	United States	44460
131	Office of James Lassiter	Tiffin	Ohio	United States	44883
132	Health Research Institute, LLC	Oklahoma City	Oklahoma	United States	73109
133	Office of Siavash Nael, MD, Inc.	Oklahoma City	Oklahoma	United States	73109
134	Associates of Medicine/John D. Williams, MD, PLLC	Stillwater	Oklahoma	United States	74074
135	Portland Rheumatology Clinic, LLC	Lake Oswego	Oregon	United States	97035
136	Office of Joseph E. Yankee, DO, PC	Milwaukie	Oregon	United States	97222
137	Pennsylvania Pain Specialists, PC	Allentown	Pennsylvania	United States	18102
138	Ware Medical Associates, PC	Aston	Pennsylvania	United States	19014
139	Altoona Center for Clinical Research, PC	Duncansville	Pennsylvania	United States	16635
140	Kandra, Fierer, Kuskin Associates, Ltd.	Harrisburg	Pennsylvania	United States	17112
141	Onuorah Umeh, M.D. P.C	Philadelphia	Pennsylvania	United States	19104
142	Founders Research Corporation	Philadelphia	Pennsylvania	United States	19152
143	Progressive Pain Solutions, LLC	Wind Gap	Pennsylvania	United States	18091
144	Hartwell Research Group, LLC	Anderson	South Carolina	United States	29621
145	Low Country Rheumatology, PA	Charleston	South Carolina	United States	29406
146	Pharmacorp Clinical Trials, Inc.	Charleston	South Carolina	United States	29412
147	Internal Medicine of Greer Research LLC	Greer	South Carolina	United States	29650
148	Clinical Research Authority, LLC	Murrells Inlet	South Carolina	United States	29576
149	Trident Institute of Medical Research, LLC	North Charleston	South Carolina	United States	29406
150	Low Country Pain Center, LLC	Orangeburg	South Carolina	United States	29118
151	Brown Clinic, PLLP	Watertown	South Dakota	United States	57201
152	Chattanooga Medical Research, LLC	Chattanooga	Tennessee	United States	37404
153	Comprehensive Pain Specialists	Hendersonville	Tennessee	United States	37075
154	Corsicana Medical Research, PLLC	Corsicana	Texas	United States	75110
155	DCT - Genesis Neighborhood Research, LLC	Dallas	Texas	United States	75254
156	Southwest Urgent Care Center	El Paso	Texas	United States	79902
157	Westbury Medical Clinic	Houston	Texas	United States	77005
158	Accurate Clinical Research, Inc.	Houston	Texas	United States	77034
159	Medstar Clinical Research	Houston	Texas	United States	77083
160	Texas Medical Research Associates, LLC	San Antonio	Texas	United States	78238
161	Hillcrest Family Health Center, Division of Clinical Research	Waco	Texas	United States	76710
162	Hillcrest Family Health Center	Waco	Texas	United States	76710
163	Progressive Clinical Research, LLC	Bountiful	Utah	United States	84010
164	Sentara Medical Group, NDC Medical Center	Norfolk	Virginia	United States	23502
165	Washington Center for Pain Management PLLC	Edmonds	Washington	United States	98026
166	Pain Care, PLLC	Huntington	West Virginia	United States	25701

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01179191
• Other Study ID Numbers: ALO-01-10-4003; B4541001
• First Posted: Aug 11, 2010
• Last Update Posted: Oct 11, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Pfizer: chronic pain; Embeda; opioid; moderate pain; severe pain; conversion; converting; switching; morphine; aberrant behavior; Pain (DT) + Chronic Disease (DT)
• Additional relevant MeSH terms: Chronic Disease; Naltrexone; Morphine

Study Results

Participant Flow

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Period Title: Titration Phase (up to 6 Weeks)
STARTED	684
COMPLETED	351
NOT COMPLETED	333
Period Title: Titration Phase (up to 6 Weeks)
STARTED	351
COMPLETED	234
NOT COMPLETED	117

Baseline Characteristics

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Overall Participants	684
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.77 (12.34)
Sex: Female, Male (Count of Participants)
Female	378 55.3%
Male	306 44.7%
Brief Pain Inventory (BPI) (Units on a scale) [Mean (Standard Deviation) ]
Average Pain (n = 636)	6.27 (1.79)
Worst Pain (n = 636)	7.95 (1.64)
Least Pain (n = 642)	4.63 (2.27)
Relief (n = 639)	53.36 (22.72)
General Activity (n = 643)	7.01 (2.33)
Mood (n = 642)	6.31 (2.73)
Walking Ability (n = 641)	6.48 (2.78)
Normal Work (n = 637)	7.21 (2.48)
Relationships with Others (n = 644)	5.41 (3.08)
Sleep (n = 642)	6.80 (2.74)
Enjoyment of Life (n = 640)	7.03 (2.64)
Investigator(Ir) Compared to Participant(Pa)-Derived Risk Level Assessment of Misuse,Abuse,Diversion (Number) [Number]
Abuse: Low(Ir)/ Low(Pa) (n= 6)	6 0.9%
Abuse: Low(Ir)/ Moderate (Mod)(Pa) (n= 6)	0 0%
Abuse: Low(Ir)/ High(Pa) (n= 6)	0 0%
Abuse: Mod(Ir)/ Low(Pa) (n= 1)	1 0.1%
Abuse: Mod(Ir)/ Mod(Pa) (n= 1)	0 0%
Abuse: Mod(Ir)/ High(Pa) (n= 1)	0 0%
Abuse: High(Ir)/ Low(Pa) (n= 1)	0 0%
Abuse: High(Ir)/ Mod(Pa) (n= 1)	1 0.1%
Abuse: High(Ir)/ High(Pa) (n= 1)	0 0%
Misuse General: Low(Ir)/ Low(Pa) (n= 127)	118 17.3%
Misuse General: Low(Ir)/ Mod(Pa) (n= 127)	9 1.3%
Misuse General: Low(Ir)/ High(Pa) (n= 127)	0 0%
Misuse General: Mod(Ir)/ Low(Pa) (n= 24)	22 3.2%
Misuse General: Mod(Ir)/ Mod(Pa) (n= 24)	2 0.3%
Misuse General: Mod(Ir)/ High(Pa) (n= 24)	0 0%
Misuse General: High(Ir)/ Low(Pa) (n= 3)	2 0.3%
Misuse General: High(Ir)/ Mod(Pa) (n= 3)	1 0.1%
Misuse General: High(Ir)/ High(Pa) (n= 3)	0 0%
Misuse Pseudoaddiction: Low(Ir)/ Low(Pa) (n= 227)	208 30.4%
Misuse Pseudoaddiction: Low(Ir)/ Mod(Pa) (n= 227)	18 2.6%
Misuse Pseudoaddiction: Low(Ir)/ High(Pa) (n= 227)	1 0.1%
Misuse Pseudoaddiction: Mod(Ir)/ Low(Pa) (n= 42)	38 5.6%
Misuse Pseudoaddiction: Mod(Ir)/ Mod(Pa) (n= 42)	3 0.4%
Misuse Pseudoaddiction: Mod(Ir)/ High(Pa) (n= 42)	1 0.1%
Misuse Pseudoaddiction: High(Ir)/ Low(Pa) (n= 5)	3 0.4%
Misuse Pseudoaddiction: High(Ir)/ Mod(Pa) (n= 5)	1 0.1%
Misuse Pseudoaddiction: High(Ir)/ High(Pa) (n= 5)	1 0.1%
Misuse Total: Low(Ir)/ Low(Pa) (n= 295)	245 35.8%
Misuse Total: Low(Ir)/ Mod(Pa) (n= 295)	49 7.2%
Misuse Total: Low(Ir)/ High(Pa) (n= 295)	1 0.1%
Misuse Total: Mod(Ir)/ Low(Pa) (n= 56)	40 5.8%
Misuse Total: Mod(Ir)/ Mod(Pa) (n= 56)	14 2%
Misuse Total: Mod(Ir)/ High(Pa) (n= 56)	2 0.3%
Misuse Total: High(Ir)/ Low(Pa) (n= 6)	3 0.4%
Misuse Total: High(Ir)/ Mod(Pa) (n= 6)	2 0.3%
Misuse Total: High(Ir)/ High(Pa) (n= 6)	1 0.1%
Diversion: Low (Ir)/ Low (Pa) (n= 487)	467 68.3%
Diversion: Low (Ir)/ Mod (Pa) (n= 487)	10 1.5%
Diversion: Low (Ir)/ High (Pa) (n= 487)	10 1.5%
Diversion: Mod (Ir)/ Low (Pa) (n= 22)	19 2.8%
Diversion: Mod (Ir)/ Mod (Pa) (n= 22)	2 0.3%
Diversion: Mod (Ir)/ High (Pa) (n= 22)	1 0.1%
Diversion: High (Ir)/ Low (Pa) (n= 5)	3 0.4%
Diversion: High (Ir)/ Mod (Pa) (n= 5)	0 0%
Diversion: High (Ir)/ High (Pa) (n= 5)	2 0.3%
Number of Participants Reporting Concerns With Prescription Opioid (Op) Misuse, Abuse or Diversion (Number) [Number]
Worried getting addicted or hooked to Op:0(n=537)	171 25%
Worried getting addicted or hooked to Op:1(n=537)	47 6.9%
Worried getting addicted or hooked to Op:2(n=537)	53 7.7%
Worried getting addicted or hooked to Op:3(n=537)	47 6.9%
Worried getting addicted or hooked to Op:4(n=537)	30 4.4%
Worried getting addicted or hooked to Op:5(n=537)	53 7.7%
Worried getting addicted or hooked to Op:6(n=537)	28 4.1%
Worried getting addicted or hooked to Op:7(n=537)	33 4.8%
Worried getting addicted or hooked to Op:8(n=537)	31 4.5%
Worried getting addicted or hooked to Op:9(n=537)	11 1.6%
Worried getting addicted or hooked to Op:10(n=537)	33 4.8%
Worried about hard time to stop Op:0(n=537)	138 20.2%
Worried about hard time to stop Op:1(n=537)	50 7.3%
Worried about hard time to stop Op:2(n=537)	67 9.8%
Worried about hard time to stop Op:3(n=537)	45 6.6%
Worried about hard time to stop Op:4(n=537)	20 2.9%
Worried about hard time to stop Op:5(n=537)	54 7.9%
Worried about hard time to stop Op:6(n=537)	26 3.8%
Worried about hard time to stop Op:7(n=537)	39 5.7%
Worried about hard time to stop Op:8(n=537)	35 5.1%
Worried about hard time to stop Op:9(n=537)	27 3.9%
Worried about hard time to stop Op:10(n=537)	36 5.3%
Chewed/crushed Op:tried once/twice(n=534)	31 4.5%
Chewed/crushed Op:few times a year(n=534)	5 0.7%
Chewed/crushed Op:few times a month(n=534)	10 1.5%
Chewed/crushed Op:few times a week(n=534)	7 1%
Chewed/crushed Op:daily(n=534)	5 0.7%
Chewed/crushed Op:never(n=534)	476 69.6%
Reason(Rn)to chew/crush Op:treat pain better(n=71)	35 5.1%
Rn to chew/crush Op:treat new pain(n=71)	4 0.6%
Rn to chew/crush Op:sleep better/relax(n=71)	14 2%
Rn to chew/crush Op:help swallow drug(n=71)	16 2.3%
Rn to chew/crush Op:feel pleasant/high(n=71)	3 0.4%
Rn to chew/crush Op:feel less depressed (n=71)	6 0.9%
Rn to chew/crush Op:feel talkative/outgoing(n=71)	2 0.3%
Rn to chew/crush Op:other(n=71)	29 4.2%
More Op than prescribed:tried once/twice(n=530)	75 11%
More Op than prescribed:few times a year(n=530)	46 6.7%
More Op than prescribed:few times a month(n=530)	116 17%
More Op than prescribed:few times a week(n=530)	58 8.5%
More Op than prescribed:daily(n=530)	23 3.4%
More Op than prescribed:never(n=530)	212 31%
Rn for more Op use:treat pain better(n=315)	274 40.1%
Rn for more Op use:treat new pain(n=315)	42 6.1%
Rn for more Op use:sleep better/relax(n=315)	48 7%
Rn for more Op use:feel pleasant/high(n=315)	3 0.4%
Rn for more Op use:feel less depressed (n=315)	16 2.3%
Rn for more Op use:feel talkative/outgoing(n=315)	3 0.4%
Rn for more Op use: other(n=315)	44 6.4%
Snort,smoke,inject(inj) Op:once/twice(n=533)	7 1%
Snort,smoke,inj Op: few times a year(n=533)	0 0%
Snort,smoke,inj Op:few times a month(n=533)	2 0.3%
Snort,smoke,inj Op:few times a week(n=533)	0 0%
Snort,smoke,inj Op:daily(n=533)	1 0.1%
Snort,smoke,inj Op:never(n=533)	523 76.5%
Rn-snort,smoke,inj:treat pain better(n=37)	10 1.5%
Rn-snort,smoke,inj:treat new pain (n=37)	1 0.1%
Rn-snort,smoke,inj:sleep better/relax(n=37)	2 0.3%
Rn-snort,smoke,inj:feel pleasant/high(n=37)	2 0.3%
Rn-snort,smoke,inj:feel less depressed (n=37)	2 0.3%
Rn-snort,smoke,inj:feel talkative/outgoing(n=37)	2 0.3%
Rn-snort,smoke,inj:other(n=37)	28 4.1%
Alcohol(Alc)use when on Op:tried once/twice(n=534)	32 4.7%
Alc use when on Op:few times a year(n=534)	50 7.3%
Alc use when on Op:few times a month(n=534)	35 5.1%
Alc use when on Op:few times a week(n=534)	19 2.8%
Alc use when on Op:daily(n=534)	7 1%
Alc use when on Op:never(n=534)	391 57.2%
Rn-Alc when on Op:treat pain better(n=170)	10 1.5%
Rn-Alc when on Op:treat new pain(n=170)	1 0.1%
Rn-Alc when on Op:sleep better/relax(n=170)	21 3.1%
Rn-Alc when on Op:enjoy occasional drink(n=170	91 13.3%
Rn-Alc when on Op:feel pleasant/high(n=170)	3 0.4%
Rn-Alc when on Op:feel less depressed(n=170)	4 0.6%
Rn-Alc when on Op:feel talkative/outgoing(n=170)	2 0.3%
Rn-Alc when on Op:other(n=170)	65 9.5%
More than 1 doctor (Dr) for Op:once/twice(n=529)	26 3.8%
More than 1 Dr for Op:sometime(n=529)	12 1.8%
More than 1 Dr for Op:often(n=529)	3 0.4%
More than 1 Dr for Op:never(n=529)	488 71.3%
Rn- more than 1 Dr:treat pain better(n=61)	26 3.8%
Rn- more than 1 Dr: prevent withdrawal(n=61)	6 0.9%
Rn- more than 1 Dr:afraid to ask for more(n=61)	12 1.8%
Rn- more than 1 Dr:feel pleasant/high (n=61)	1 0.1%
Rn- more than 1 Dr:Dr didn't prescribed more(n=61)	11 1.6%
Rn- more than (>) 1 Dr:other(n=61)	24 3.5%
Gave Op to sick/in pain:yes (n=526)	35 5.1%
Gave Op to sick/in pain:yes,once(n=35)	5 0.7%
Gave Op to sick/in pain:yes, 2-5times(n=35)	24 3.5%
Gave Op to sick/in pain:yes,6-10times(n=35)	3 0.4%
Gave Op to sick/in pain:yes, >10 times(n=35)	3 0.4%
Gave Op to sick/in pain:no(n=526)	491 71.8%
Got Op from someone other than a doctor:yes(n=537)	43 6.3%
Got Op from someone other than a doctor:no(n=537)	494 72.2%
Keeps Op hidden or locked:yes(n=535)	373 54.5%
Keeps Op hidden or locked:no(n=535)	162 23.7%
Suspected someone taking Op:yes(n=535)	71 10.4%
Suspected someone taking Op:yes,once(n=70)	30 4.4%
Suspected someone taking Op:yes,few times(n=70)	29 4.2%
Suspected someone taking Op:yes,sometimes (n=70)	8 1.2%
Suspected someone taking Op:yes,all times (n=70)	3 0.4%
Suspected someone taking Op:no(n=535)	464 67.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Number (95% Confidence Interval) [Percentage of participants]	51.3 7.5%

2. Primary Outcome

Title	Percentage of Participants Achieving Stable Dose of EMBEDA Within 6 Weeks Titration Phase Stratified by Prior Opioid Therapy
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. Participants were stratified based on prior opioid therapy. The 'n' is signifying those participants who were evaluated for this measure for each of the prior medication received.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Transdermal Fentanyl (n= 77)	54.5 8%
Immediate-release (IR) Hydrocodone (n= 164)	60.4 8.8%
IR Hydromorphone (n= 22)	63.6 9.3%
IR Oxycodone (n= 160)	48.1 7%
IR Morphine (n= 53)	62.3 9.1%
Methadone (n= 64)	40.6 5.9%
Extended-release (ER) Oxycodone (n= 107)	42.1 6.2%
ER Oxymorphone (n= 25)	56.0 8.2%
Excluded Opioid/ Unclassified (n= 12)	8.3 1.2%

3. Secondary Outcome

Title	Duration to Titrate Participants to Stable Dose
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	351
Mean (Standard Deviation) [Days]	20.0 (8.94)

4. Secondary Outcome

Title	Duration to Titrate Participants to Stable Dose Stratified by Prior Opioid Therapy
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population. Participants were stratified based on prior opioid therapy. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure for each of the prior medication received.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	351
Transdermal Fentanyl (n= 42)	17.8 (5.96)
IR Hydrocodone (n= 99)	20.7 (9.13)
IR Hydromorphone (n= 14)	24.3 (12.55)
IR Oxycodone (n= 77)	19.6 (8.35)
IR Morphine (n= 33)	18.8 (7.82)
Methadone (n= 26)	21.0 (8.70)
ER Oxycodone (n= 45)	20.3 (10.55)
ER Oxymorphone (n= 14)	19.8 (10.71)
Excluded Opioid/ Unclassified (n= 1)	7.0 (NA)

5. Secondary Outcome

Title	Number of Titration Steps to Achieve Stable Dose
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	351
Mean (Standard Deviation) [titration steps]	2.4 (1.37)

6. Secondary Outcome

Title	Number of Titration Steps to Achieve Stable Dose Stratified by Prior Opioid Therapy
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population. Participants were stratified based on prior opioid therapy. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were evaluated for this measure for each of the prior medication received.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	351
Transdermal Fentanyl (n= 42)	2.0 (0.98)
IR Hydrocodone (n= 99)	2.6 (1.41)
IR Hydromorphone (n= 14)	2.6 (1.28)
IR Oxycodone (n= 77)	2.3 (1.40)
IR Morphine (n= 33)	2.3 (1.28)
Methadone (n= 26)	2.7 (1.52)
ER Oxycodone (n= 45)	2.4 (1.50)
ER Oxymorphone (n= 14)	2.5 (1.45)
Excluded Opioid/ Unclassified (n= 1)	1.0 (NA)

7. Secondary Outcome

Title	Percentage of Participants With Rescue Medications Usage During Titration
Description	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.
Time Frame	Baseline through Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	650
Number [Percentage of participants]	79.8 11.7%

8. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory (BPI) at Visit 3 (First Visit After Successful Titration)
Description	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.
Time Frame	Baseline, Visit 3 (up to Week 6)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. The 'n' is signifying those participants who were evaluated for the respective subscale.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	322
Change at Visit 3 (Average Pain) (n=313)	-2.23 (2.13)
Change at Visit 3 (Worst Pain) (n=313)	-2.41 (2.49)
Change at Visit 3 (Least Pain) (n=321)	-1.81 (2.33)
Change at Visit 3 (Relief) (n=0)	NA (NA)
Change at Visit 3 (General Activity) (n=0)	NA (NA)
Change at Visit 3 (Mood) (n=0)	NA (NA)
Change at Visit 3 (Walking Ability) (n=0)	NA (NA)
Change at Visit 3 (Normal Work) (n=0)	NA (NA)
Change at Visit 3(Relationships with Others) (n=0)	NA (NA)
Change at Visit 3 (Sleep) (n=0)	NA (NA)
Change at Visit 3 (Enjoyment of Life) (n=0)	NA (NA)

9. Secondary Outcome

Title	Investigator's Level of Satisfaction With the EMBEDA Conversion Guide
Description	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.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	349
Mean (Standard Deviation) [Units on a Scale]	8.1 (2.11)

10. Other Pre-specified Outcome

Title	Number of Participants With Aberrant Behaviors
Description	Current Opioid Misuse Measure (COMM) is a 17-item self-administered test used to monitor aberrant behavior in participants on opioid therapy. Aberrant behaviors assessed using a 5-point scale [0 = 'never' and 4 = 'very often']. Score range 0-68. Scores greater than or equal to 9 indicated the presence of aberrant behaviors.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Number [Participants]	217 31.7%

11. Other Pre-specified Outcome

Title	Number of Participants With Abnormal Urine Drug Test Results
Description	Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy [3, 4-methylenedioxyamphetamine (MDMA)], cocaine, phencyclidine (PCP) and marijuana [tetrahydrocannabinol (THC)]. Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.
Time Frame	Baseline, Visit 3 (up to Week 6)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. Here, the 'n' is signifying those participants who were evaluable for this measure at the specified time point for this arm group.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Baseline (n= 684)	160 23.4%
Visit 3 (n= 351)	101 14.8%

12. Other Pre-specified Outcome

Title	Number of Participants With Urine Drug Test Results Positive for Unaccounted Opioids
Description	Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy (3, 4-MDMA), cocaine, PCP and marijuana (THC). Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.
Time Frame	Visit 3 (up to Week 6)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	351
Number [Participants]	85 12.4%

13. Other Pre-specified Outcome

Title	Number of Participants With Urine Drug Test Results Positive for Illicit Substances
Description	Urine samples collected were screened using immunoassay techniques for following types of drugs:opioids,barbiturates,benzodiazepines,amphetamines,ecstasy(3,4MDMA),cocaine,PCP,marijuana (THC).Quantitative, confirmatory urine drug testing performed for positive results using gas chromatography or high-pressure liquid chromatography for following analytes: morphine,oxycodone,oxymorphone,hydrocodone,hydromorphone,fentanyl,methadone,benzodiazepines,amphetamines,cocaine,THC,PCP,MDMA. Illicit substances were drugs of categories:marijuana (THC) metabolite,cocaine metabolite,PCP,amphetamine.
Time Frame	Baseline, Visit 3 (up to Week 6)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. Here, the 'n' is signifying those participants who were evaluable for this measure at the specified time point for this arm group.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Baseline (n= 684)	51 7.5%
Visit 3 (n= 351)	24 3.5%

14. Other Pre-specified Outcome

Title	Number of Participants With Greater Than or Equal to One Urine Drug Test Results Negative for Expected Opioid
Description	Urine samples collected were screened using immunoassay techniques for the following types of drugs: opioids, barbiturates, benzodiazepines, amphetamines, ecstasy (3, 4-MDMA), cocaine, PCP and marijuana (THC). Quantitative, confirmatory urine drug testing was performed for positive results using gas chromatography or high-pressure liquid chromatography, for the following analytes: morphine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, methadone, benzodiazepines, amphetamines, cocaine, THC, PCP, and MDMA.
Time Frame	Baseline, Visit 3 (up to Week 6)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed the first study visit and filled a prescription for EMBEDA. Here, the 'n' is signifying those participants who were evaluable for this measure at the specified time point for this arm group.

Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
Measure Participants	684
Baseline (n= 684)	122 17.8%
Visit 3 (n= 351)	11 1.6%

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	EMBEDA
Arm/Group Description	EMBEDA (morphine sulfate/naltrexone hydrochloride) extended-release capsules orally prescribed according to usual clinical practice using a standardized conversion guide. Treatment included titration phase (up to 6 weeks) followed by maintenance phase (8 weeks).
All Cause Mortality
	EMBEDA
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	EMBEDA
	Affected / at Risk (%)	# Events
Total	24/684 (3.5%)
Cardiac disorders
Angina unstable	1/684 (0.1%)
Dyspnoea	1/684 (0.1%)
Myocardial infarction	1/684 (0.1%)
Right ventricular hypertrophy	1/684 (0.1%)
Tachycardia	1/684 (0.1%)
Endocrine disorders
Hyperglycaemia	1/684 (0.1%)
Gastrointestinal disorders
Constipation	2/684 (0.3%)
Diverticulitis	1/684 (0.1%)
Gastroenteritis	1/684 (0.1%)
Nausea	2/684 (0.3%)
Vomiting	1/684 (0.1%)
General disorders
Chest pain	1/684 (0.1%)
Sudden death	1/684 (0.1%)
Hepatobiliary disorders
Hepatitis acute	1/684 (0.1%)
Infections and infestations
Skin infection	1/684 (0.1%)
Injury, poisoning and procedural complications
Radius fracture	1/684 (0.1%)
Investigations
Electrocardiogram t wave inversion	1/684 (0.1%)
Metabolism and nutrition disorders
Dehydration	2/684 (0.3%)
Gout	1/684 (0.1%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/684 (0.1%)
Nervous system disorders
Carotid artery disease	1/684 (0.1%)
Convulsion	1/684 (0.1%)
Dizziness	1/684 (0.1%)
Dyskinesia	1/684 (0.1%)
Transient ishaemic attack	1/684 (0.1%)
Psychiatric disorders
Drug abuse	1/684 (0.1%)
Renal and urinary disorders
Renal failure	1/684 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/684 (0.1%)
Chronic obstructive pulmonary disease	1/684 (0.1%)
Pulmonary hypertension	1/684 (0.1%)
Respiratory distress	1/684 (0.1%)
Vascular disorders
Hypertension	1/684 (0.1%)
Other (Not Including Serious) Adverse Events
	EMBEDA
	Affected / at Risk (%)	# Events
Total	331/684 (48.4%)
Blood and lymphatic system disorders
Anaemia	1/684 (0.1%)
Lymphadenopathy	1/684 (0.1%)
Cardiac disorders
Bradycardia	1/684 (0.1%)
Dyspnoea	5/684 (0.7%)
Oedema peripheral	3/684 (0.4%)
Palpitations	1/684 (0.1%)
Syncope	2/684 (0.3%)
Tachycardia	1/684 (0.1%)
Ear and labyrinth disorders
Tinnitus	1/684 (0.1%)
Vertigo	1/684 (0.1%)
Endocrine disorders
Diabetes mellitus	1/684 (0.1%)
Eye disorders
Blindness transient	1/684 (0.1%)
Cataract	1/684 (0.1%)
Diplopia	1/684 (0.1%)
Eye pain	1/684 (0.1%)
Metamorphopsia	1/684 (0.1%)
Scleral haemorrhage	1/684 (0.1%)
Vision blurred	6/684 (0.9%)
Gastrointestinal disorders
Abdominal discomfort	3/684 (0.4%)
Abdominal distension	1/684 (0.1%)
Abdominal pain	2/684 (0.3%)
Abdominal pain upper	10/684 (1.5%)
Breath odour	1/684 (0.1%)
Constipation	74/684 (10.8%)
Crohn's disease	1/684 (0.1%)
Diarrhoea	8/684 (1.2%)
Dry mouth	11/684 (1.6%)
Dysgeusia	2/684 (0.3%)
Dyspepsia	4/684 (0.6%)
Enteritis infectious	1/684 (0.1%)
Flatulence	1/684 (0.1%)
Food poisoning	1/684 (0.1%)
Gastritis	1/684 (0.1%)
Gastroenteritis viral	2/684 (0.3%)
Gastrooesophageal reflux disease	1/684 (0.1%)
Haematochezia	1/684 (0.1%)
Haemorrhoidal haemorrhage	1/684 (0.1%)
Nausea	55/684 (8%)
Painful defaecation	1/684 (0.1%)
Rectal haemorrhage	1/684 (0.1%)
Tooth disorder	1/684 (0.1%)
Tooth infection	1/684 (0.1%)
Toothache	1/684 (0.1%)
Vomiting	33/684 (4.8%)
General disorders
Adverse drug reaction	4/684 (0.6%)
Adverse event	1/684 (0.1%)
Asthenia	1/684 (0.1%)
Burning sensation	2/684 (0.3%)
Chest discomfort	2/684 (0.3%)
Chest pain	4/684 (0.6%)
Chills	5/684 (0.7%)
Drug intolerance	1/684 (0.1%)
Drug withdrawal syndrome	1/684 (0.1%)
Face oedema	1/684 (0.1%)
Fatigue	20/684 (2.9%)
Feeling abnormal	1/684 (0.1%)
Feeling of body temperature change	1/684 (0.1%)
Flushing	2/684 (0.3%)
Gait disturbance	1/684 (0.1%)
Hot flush	1/684 (0.1%)
Hyperhidrosis	7/684 (1%)
Influenza like illness	2/684 (0.3%)
Irritability	3/684 (0.4%)
Lethargy	5/684 (0.7%)
Oedema	3/684 (0.4%)
Oedema peripheral	6/684 (0.9%)
Pain	9/684 (1.3%)
Thirst	1/684 (0.1%)
Withdrawal syndrome	1/684 (0.1%)
Hepatobiliary disorders
Chronic hepatitis	1/684 (0.1%)
Immune system disorders
Hypersensitivity	1/684 (0.1%)
Urticaria	4/684 (0.6%)
Infections and infestations
Bronchitis	4/684 (0.6%)
Candidiasis	1/684 (0.1%)
Cellulitis	1/684 (0.1%)
Gastroenteritis viral	1/684 (0.1%)
Localised infection	1/684 (0.1%)
Nasopharyngitis	8/684 (1.2%)
Oral candidiasis	1/684 (0.1%)
Pharyngitis	1/684 (0.1%)
Pharyngitis streptococcal	2/684 (0.3%)
Sinusitis	3/684 (0.4%)
Staphylococcal infection	1/684 (0.1%)
Tooth infection	1/684 (0.1%)
Upper respiratory tract infection	6/684 (0.9%)
Urinary tract infection	2/684 (0.3%)
Vulvovaginal mycotic infection	1/684 (0.1%)
Injury, poisoning and procedural complications
Accidental overdose	1/684 (0.1%)
Contusion	3/684 (0.4%)
Fall	1/684 (0.1%)
Foot fracture	1/684 (0.1%)
Foreign body	1/684 (0.1%)
Hand fracture	1/684 (0.1%)
Joint injury	1/684 (0.1%)
Muscle strain	1/684 (0.1%)
Rotator cuff syndrome	1/684 (0.1%)
Skeletal injury	1/684 (0.1%)
Skin laceration	1/684 (0.1%)
Tendonitis	1/684 (0.1%)
Thermal burn	1/684 (0.1%)
Investigations
Blood pressure increased	1/684 (0.1%)
Intraocular pressure increased	1/684 (0.1%)
Metabolism and nutrition disorders
Decreased appetite	5/684 (0.7%)
Dehydration	1/684 (0.1%)
Gout	1/684 (0.1%)
Obesity	1/684 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/684 (0.3%)
Back pain	6/684 (0.9%)
Gout	2/684 (0.3%)
Mobility decreased	1/684 (0.1%)
Muscle spasms	5/684 (0.7%)
Muscle twitching	1/684 (0.1%)
Musculoskeletal chest pain	1/684 (0.1%)
Myalgia	4/684 (0.6%)
Neck pain	1/684 (0.1%)
Pain in extremity	3/684 (0.4%)
Restless legs syndrome	1/684 (0.1%)
Synovial cyst	1/684 (0.1%)
Nervous system disorders
Abnormal dreams	2/684 (0.3%)
Agitation	2/684 (0.3%)
Balance disorder	1/684 (0.1%)
Carpal tunnel syndrome	1/684 (0.1%)
Cognitive disorder	4/684 (0.6%)
Confusional state	5/684 (0.7%)
Disorientation	2/684 (0.3%)
Disturbance in attention	3/684 (0.4%)
Dizziness	17/684 (2.5%)
Dysaesthesia	1/684 (0.1%)
Dysarthria	1/684 (0.1%)
Dysgeusia	1/684 (0.1%)
Dysphemia	1/684 (0.1%)
Dysphonia	2/684 (0.3%)
Headache	37/684 (5.4%)
Hypoaesthesia	1/684 (0.1%)
Insomnia	12/684 (1.8%)
Paraesthesia	1/684 (0.1%)
Presyncope	1/684 (0.1%)
Restless legs syndrome	1/684 (0.1%)
Restlessness	1/684 (0.1%)
Sciatica	1/684 (0.1%)
Sedation	4/684 (0.6%)
Sinus headache	1/684 (0.1%)
Somnolence	25/684 (3.7%)
Tension headache	1/684 (0.1%)
Tremor	4/684 (0.6%)
Urinary incontinence	1/684 (0.1%)
Psychiatric disorders
Affective disorder	1/684 (0.1%)
Aggression	1/684 (0.1%)
Anxiety	2/684 (0.3%)
Crying	1/684 (0.1%)
Delirium	1/684 (0.1%)
Depression	3/684 (0.4%)
Dysphoria	1/684 (0.1%)
Emotional disorder	1/684 (0.1%)
Enuresis	1/684 (0.1%)
Hallucination	2/684 (0.3%)
Hallucinations, mixed	1/684 (0.1%)
Hypersomnia	3/684 (0.4%)
Mood swings	1/684 (0.1%)
Nervousness	3/684 (0.4%)
Nightmare	3/684 (0.4%)
Throat tightness	1/684 (0.1%)
Renal and urinary disorders
Dysuria	4/684 (0.6%)
Pollakiuria	1/684 (0.1%)
Urinary hesitation	2/684 (0.3%)
Urinary retention	2/684 (0.3%)
Reproductive system and breast disorders
Ejaculation disorder	1/684 (0.1%)
Erectile dysfunction	1/684 (0.1%)
Hot flush	1/684 (0.1%)
Polymenorrhoea	1/684 (0.1%)
Sexual dysfunction	1/684 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/684 (0.1%)
Dyspnoea	4/684 (0.6%)
Nasal congestion	3/684 (0.4%)
Oropharyngeal pain	3/684 (0.4%)
Pulmonary congestion	1/684 (0.1%)
Rhinorrhoea	2/684 (0.3%)
Sinus congestion	1/684 (0.1%)
Sleep apnoea syndrome	1/684 (0.1%)
Sneezing	1/684 (0.1%)
Wheezing	2/684 (0.3%)
Skin and subcutaneous tissue disorders
Acne	2/684 (0.3%)
Night sweats	1/684 (0.1%)
Pruritus	18/684 (2.6%)
Pruritus generalised	1/684 (0.1%)
Rash	8/684 (1.2%)
Rash generalised	1/684 (0.1%)
Swelling face	1/684 (0.1%)
Vascular disorders
Deep vein thrombosis	1/684 (0.1%)
Hypertension	1/684 (0.1%)
Hypotension	1/684 (0.1%)

Limitations/Caveats

The study was prematurely terminated due to drug supply issues.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.