Study of Embeda (Kadian NT, ALO-01) in Subjects With Chronic Moderate to Severe Nonmalignant Pain

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00415597
• Collaborator: (none)
• Enrollment: 467
• Locations: 58
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Open-Label, Safety Study to evaluate the long-term safety of Kadian NT (ALO-01) administered for up to 12 months.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: ALO-01 (Morphine Sulfate Plus Naltrexone Hydrochloride ER)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 467 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term, Open-Label Safety Study of ALO-01 (Morphine Sulfate Plus Naltrexone Hydrochloride Extended-Release) Capsules in Subjects With Chronic Moderate to Severe Nonmalignant Pain
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALO-01 Doses given once or twice daily	Drug: ALO-01 (Morphine Sulfate Plus Naltrexone Hydrochloride ER); capsules, available dosage strengths 20, 30, 40, 50, 60, 80, and 100 mg morphine sulfate with 4% by weight naltrexone hydrochloride given once or twice daily; Other Names: Embeda

Outcome Measures

Primary Outcome Measures

1. Subjects With Treatment Emergent Adverse Events [up to 12 months]

   Number of subjects with adverse events (any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product whether or not related to the product).

Secondary Outcome Measures

1. Mean Percent Change From Baseline to 12 Weeks in Brief Pain Inventory Score (BPI) of Average Pain [12 weeks]

   Percent change in pain intensity scale. Average pain intensity over last 24 hours rated at each visit from 0=no pain to 10=worst pain.

2. Mean Percent Change From Baseline to 52 Weeks in Brief Pain Inventory Score (BPI) of Average Pain [52 weeks]

   Percent change in pain intensity scale. Average pain intensity over last 24 hours rated at each visit from 0=no pain to 10=worst pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject 18-70 years of age

• Subject agrees to refrain from taking any opioid medications other than study medication during study period.

• History of chronic moderate to severe pain caused by a nonmalignant condition for at least 3 months prior to baseline

Exclusion Criteria:

• Subject has a documented history of allergic reaction or clinically significant intolerance to morphine or other opioids, such that treatment with morphine is contraindicated.

• Subject is pregnant or breast-feeding.

• Subject is receiving chemotherapy, or has an active malignancy of any type or has been diagnosed with cancer within the past three years (excluding squamous or basal cell carcinoma of the skin).

• Subject has a documented history of drug abuse/dependence/misuse or narcotic analgesic abuse/dependence/misuse within five years prior to the Baseline Visit.

• Subject has a Body Mass Index (BMI)>45kg/m2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Michael Gibson, MD	Birmingham	Alabama	United States	35244
2	Steven Siwek, MD	Phoenix	Arizona	United States	85027
3	Michael Loes, MD	Phoenix	Arizona	United States	85032
4	Allan Soo, MD	Tempe	Arizona	United States	85282
5	Leah Schmidt, DO	Tucson	Arizona	United States	85741
6	Steve Sitar, MD	Anaheim	California	United States	92801
7	Robert Burton, MD	Anaheim	California	United States	92804
8	Arturo Palencia, MD	Bakersfield	California	United States	93311
9	Adam Karnes, MD	Beverly Hills	California	United States	90211
10	Douglas Haselwood, MD	Fair Oaks	California	United States	95628
11	Steven Croft, MD	Delray Beach	Florida	United States	33484
12	Roberto Rodriquez, MD	Hialeah	Florida	United States	33013
13	Orlando Florete, MD	Jacksonville	Florida	United States	32257
14	Michael Link, MD	Kissimmee	Florida	United States	34741
15	Miguel Trevino, MD	Largo	Florida	United States	33770
16	Diego Torres II, MD	Ormond Beach	Florida	United States	32174
17	Martin Hale, MD	Plantation	Florida	United States	33324
18	Margarita Nunez, MD	St. Petersburg	Florida	United States	33702
19	Mary Stedman, MD	Tampa	Florida	United States	33613
20	Raymond Tidman, MD	Blue Ridge	Georgia	United States	30513
21	Arnold Weil	Marietta	Georgia	United States	30060
22	Marvin Tark	Marietta	Georgia	United States	30066
23	Azazuddin Ahmed, MD	Chicago	Illinois	United States	60616
24	Jenecsis Castro-Skoglund, MD	Peoria	Illinois	United States	61614
25	Steven Elliott, MD	Evansville	Indiana	United States	47714
26	John Peppin, DO	West Des Moines	Iowa	United States	50265
27	Randall Brewer, MD	Shreveport	Louisiana	United States	71103
28	David Miller, MD	North Dartmouth	Massachusetts	United States	02747
29	Adnan Dahdul, MD	Springfield	Massachusetts	United States	01103
30	Rebecca Baumbach, MD	Saginaw	Michigan	United States	48602
31	Mel Lucas, MD	Florissant	Missouri	United States	63031
32	Anthony Margherita, MD	St. Louis	Missouri	United States	63141
33	Randale Sechrest, MD	Missoula	Montana	United States	59802
34	John Jacobson, MD	Omaha	Nebraska	United States	68134
35	James Meli, DO	Henderson	Nevada	United States	89014
36	Stephen Miller, MD	Las Vegas	Nevada	United States	89106
37	Vrijendra Kumar, MD	Las Vegas	Nevada	United States	89123
38	Christopher Colopinto, MD	Voorhees	New Jersey	United States	08043
39	Barbara McGuire, MD	Albuquerque	New Mexico	United States	87108
40	Arthur Elkind, MD	Mount Vernon	New York	United States	10550
41	Patrick Box, MD	Charlotte	North Carolina	United States	28210
42	Richard Rauck, MD	Winston-Salem	North Carolina	United States	27103
43	Thomas Littlejohn III, MD	Winston-Salem	North Carolina	United States	27103
44	Gregory Gottschlich, MD	Cincinatti	Ohio	United States	45242
45	Bruce Corser, MD	Cincinnati	Ohio	United States	45227
46	Robert Kalb, MD	Toledo	Ohio	United States	43623
47	Tanna Shaw, MD	Oklahoma City	Oklahoma	United States	73116
48	Joseph Dunn, MD	Eugene	Oregon	United States	97401
49	Lawrence Levinson, MD	Tipton	Pennsylvania	United States	16684
50	William Travis Ellison, MD	Greer	South Carolina	United States	29651
51	William Smith, MD	Knoxville	Tennessee	United States	37920
52	Lee Carter, MD	Milan	Tennessee	United States	38358
53	Walter Chase, MD	Austin	Texas	United States	78705
54	Andrew Klymiuk, MD	Richardson	Texas	United States	75080
55	Francis Burch, MD	San Antonio	Texas	United States	78217
56	Suzanne Gazda, MD	San Antonio	Texas	United States	78229
57	Webster Lynn, MD	Salt Lake City	Utah	United States	84106
58	Richard Eckert, MD	Roanoke	Virginia	United States	24018

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: James B. Jones, MD, PharmD, Alpharma Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00415597
• Other Study ID Numbers: ALO-KNT-302
• First Posted: Dec 25, 2006
• Last Update Posted: Sep 20, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Pfizer: chronic pain; joint pain; back pain; diabetic peripheral neuropathy; post herpetic neuralgia; ALO-01; Embeda; Chronic Non-Malignant Pain
• Additional relevant MeSH terms: Naltrexone; Morphine

Study Results

Participant Flow

Arm/Group Title	ALO-01
Arm/Group Description
Period Title: Enrollment
STARTED	467
COMPLETED	465
NOT COMPLETED	2
Period Title: Enrollment
STARTED	465
COMPLETED	160
NOT COMPLETED	305

Baseline Characteristics

Arm/Group Title	ALO-01
Arm/Group Description
Overall Participants	465
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	417 89.7%
>=65 years	48 10.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (10.56)
Sex: Female, Male (Count of Participants)
Female	245 52.7%
Male	220 47.3%
Brief Pain Inventory (BPI) Average Pain (Units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on scale]	6.0 (1.67)

Outcome Measures

1. Primary Outcome

Title	Subjects With Treatment Emergent Adverse Events
Description	Number of subjects with adverse events (any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product whether or not related to the product).
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Patients treated with study drug

Arm/Group Title	ALO-01
Arm/Group Description
Measure Participants	465
Number [participants]	378 81.3%

2. Secondary Outcome

Title	Mean Percent Change From Baseline to 12 Weeks in Brief Pain Inventory Score (BPI) of Average Pain
Description	Percent change in pain intensity scale. Average pain intensity over last 24 hours rated at each visit from 0=no pain to 10=worst pain.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Patients with data at Week 12

Arm/Group Title	ALO-01
Arm/Group Description
Measure Participants	254
Mean (Standard Deviation) [Percent change]	-31.3 (37.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-01
	Comments	Null hypothesis: Percent change from baseline = 0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Mean Percent Change From Baseline to 52 Weeks in Brief Pain Inventory Score (BPI) of Average Pain
Description	Percent change in pain intensity scale. Average pain intensity over last 24 hours rated at each visit from 0=no pain to 10=worst pain.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Patients with data at Week 52

Arm/Group Title	ALO-01
Arm/Group Description
Measure Participants	162
Mean (Standard Deviation) [Percent change]	-41.5 (39.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-01
	Comments	Null hypothesis: Percent change from baseline = 0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	ALO-01
Arm/Group Description
All Cause Mortality
	ALO-01
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ALO-01
	Affected / at Risk (%)	# Events
Total	33/465 (7.1%)
Cardiac disorders
Acute myocardial infarction	1/465 (0.2%)	1
Angina pectoris	1/465 (0.2%)	1
Cardiac failure congestive	1/465 (0.2%)	1
Coronary artery disease	1/465 (0.2%)	1
Gastrointestinal disorders
Colitis	2/465 (0.4%)	2
Diarrhoea	1/465 (0.2%)	1
Gastrointestinal inflammation	1/465 (0.2%)	1
Pancreatitis	1/465 (0.2%)	1
Vomiting	1/465 (0.2%)	1
General disorders
Chest pain	2/465 (0.4%)	2
Pyrexia	1/465 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	1/465 (0.2%)	1
Infections and infestations
Arthritis bacterial	2/465 (0.4%)	2
Pyelonephritis acute	1/465 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/465 (0.2%)	1
Overdose (insulin)	1/465 (0.2%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/465 (0.2%)	1
Hypoglycaemia	1/465 (0.2%)	1
Ketosis	1/465 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/465 (0.2%)	1
Invertebral disc protrusion	1/465 (0.2%)	1
Osteoarthritis	2/465 (0.4%)	2
Rheumatoid arthritis	1/465 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer stage I	1/465 (0.2%)	1
Nervous system disorders
Carotid artery stenosis	1/465 (0.2%)	1
Lumbar radiculopathy	1/465 (0.2%)	2
Transient ischaemic attack	1/465 (0.2%)	1
Psychiatric disorders
Conversion disorder	1/465 (0.2%)	1
Somatoform disorder	1/465 (0.2%)	1
Suicidal ideation	1/465 (0.2%)	1
Surgical and medical procedures
Appendicectomy	1/465 (0.2%)	1
Hip surgery	1/465 (0.2%)	1
Vascular disorders
Deep vein thrombosis	2/465 (0.4%)	2
Peripheral vascular disorder	1/465 (0.2%)	1
Other (Not Including Serious) Adverse Events
	ALO-01
	Affected / at Risk (%)	# Events
Total	265/465 (57%)
Gastrointestinal disorders
Constipation	148/465 (31.8%)
Nausea	117/465 (25.2%)
Vomiting	54/465 (11.6%)
Diarrhoea	35/465 (7.5%)
General disorders
Fatigue	29/465 (6.2%)
Nervous system disorders
Headache	56/465 (12%)
Somnolence	36/465 (7.7%)
Psychiatric disorders
Insomnia	27/465 (5.8%)
Skin and subcutaneous tissue disorders
Pruritus	29/465 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the Sponsor for review. Sponsor may request a delay in publication to allow the filing of patent applications before publication or release. The sponsor can require deletion of Confidential Information or request correction of inaccuracies.