Long-term Open-Label Safety Study to Evaluate EN3409

• Sponsor: BioDelivery Sciences International (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01755546
• Collaborator: (none)
• Enrollment: 304
• Locations: 57
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the long-terms study is to evaluate the safety, tolerability, and analgesic efficacy of EN3409 in subjects with moderate to severe chronic pain requiring continuous around-the-clock opioid analgesia for an extended period of time.

Condition or Disease	Intervention/Treatment	Phase
Low Back Pain; Osteoarthritis; Neuropathic Pain	Drug: EN3409	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 304 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-label, Long-term Study to Evaluate the Safety, Tolerability, and Analgesic Efficacy of BEMA® Buprenorphine in Subjects With Moderate to Severe Chronic Pain Requiring Continuous Around-the-Clock Opioid Analgesia for an Extended Period of Time
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EN3409 Buprenorphine HCI Buccal File at doses ranging from 300-900 mcg twice daily	Drug: EN3409; Open-Label Buprenorphine HCI Buccal Film at doses 300-900 mcg twice daily; Other Names: Buprenorphine HCI Buccal Film 300-900 mcg twice daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score [48 weeks]

   The NRS Pain intensity score is a segmented version of a visual analog scale used to measure pain. The scale is from 0 (no pain) to 10. Scores between greater than 0 and 3 are considered mild pain, scores from greater than 3 to 6 are moderate and greater than 6 to 10 are severe. The daily average is calculated and the change from baseline at week 48 is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female subjects who are practicing abstinence or using a medically acceptable form of contraception or have been postmenopausal, biologically sterile, or surgically sterile for more than 1 year

• Male subjects who are practicing abstinence, surgically sterile, or are using a medically acceptable form of contraception

• De Novo subject with a clinical diagnosis of moderate to severe noncancer-related CP (eg, CLBP, OA, neuropathic pain) for ≥ 3 months

• De Novo subject that is treating their CP with a stable daily maintenance dose of ATC opioid analgesic medication equivalent to ≥ 60 mg and ≤ 160 mg Morphine Sulfate Equivalent (MSE) per day for ≥ 4 weeks

• Stable health, as determined by the Principal Investigator

• Subject is willing and able to comply with all protocol required visits and assessments

• Rollover subject who has completed the 12-week Double-blind Treatment Phase in the EN3409-307/308 clinical study

Exclusion Criteria:

• A history or current evidence of any clinically significant disorder or any other condition, which in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results

• Females who are pregnant, breastfeeding, or plan to become pregnant during the study

• Current cancer-related pain or received chemotherapy within 6 months of screening

• Subjects receiving opioid analgesic medication < 60 mg MSE per day within 28 days of screening

• De novo subjects receiving opioid analgesic medication at doses of > 160 mg MSE per day within 28 days of screening

• Subjects with a history of other chronic painful conditions, other than the index CP condition, which require frequent analgesic medication

• Reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), acute spinal cord compression, cauda equina compression, acute nerve root compression, meningitis, or discitis

• History of allergy or contraindications to any opioid or acetaminophen

• Surgical procedure for relief of pain within 6 months, or nerve/plexus block within 28 days of screening

• Hypokalemia or clinically unstable cardiac disease

• Moderate to severe hepatic impairment

• Moderate to severe renal impairment

• Current or past history of alcohol or substance

• Positive urine toxicology screen for drugs of abuse

• History of abnormalities on physical exam, vital signs, ECG, or lab values

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkway Medical Center	Birmingham	Alabama	United States	35215
2	Horizon Research Group, Inc	Mobile	Alabama	United States	36608
3	Arizona Research Center	Phoenix	Arizona	United States	85023
4	Global Research, LLC	Anaheim	California	United States	92804
5	Synergy Clinical Research Center of Escondido	Escondido	California	United States	92025
6	RX Clinical Research, Inc.	Garden Grove	California	United States	92843
7	Long Beach Center for Clinical Research	Long Beach	California	United States	90807
8	Adam D. Karns, MD	Los Angeles	California	United States	90036
9	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
10	Clinical Research of West Florida, Inc.	Clearwater	Florida	United States	33765
11	Century Clinical Research, Inc.	Daytona Beach	Florida	United States	32117
12	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
13	Florida Health Center	Fort Lauderdale	Florida	United States	33312
14	Eastern Research, Inc.	Hialeah	Florida	United States	33013
15	Southeast Clinical Research, LLC	Jacksonville	Florida	United States	32216
16	Health Awareness, Inc.	Jupiter	Florida	United States	33458
17	Research Centers of America, LLC	Oakland Park	Florida	United States	33334
18	Compass Research, LLC	Orlando	Florida	United States	32806
19	Ribo Research LLC DBA Peninsula Research	Ormond Beach	Florida	United States	32806
20	Gold Coast Research, LLC	Plantation	Florida	United States	33317
21	Progressive Medical Research	Port Orange	Florida	United States	32127
22	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
23	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
24	National Pain Research Institute, LLC	Winter Park	Florida	United States	32789
25	River Birch Research Alliance, LLC	Blue Ridge	Georgia	United States	30513
26	Drug Studies America	Marietta	Georgia	United States	30060
27	Taylor Research, LLC	Marietta	Georgia	United States	30060
28	In-Quest Medical Research, LLC	Norcross	Georgia	United States	30092
29	Global Scientific Innovations	Evansville	Indiana	United States	47714
30	Integrated Clinical Trials Services, Inc.	West Des Moines	Iowa	United States	50265
31	Willis-Knighton Physician Network	Bossier City	Louisiana	United States	71111
32	Clinical Trials Management, LLC	Metairie	Louisiana	United States	70006
33	Best Clinical Trials, LLC	New Orleans	Louisiana	United States	70115
34	River Cities Clinical Research Center	Shreveport	Louisiana	United States	71105
35	New England Center for Clinical Research, Inc.	Fall River	Massachusetts	United States	02720
36	Great Lakes Research Group, Inc.	Bay City	Michigan	United States	48706
37	Cadillac Clinical Research	Cadillac	Michigan	United States	49601
38	The Center for Clinical Trials	Biloxi	Mississippi	United States	39531
39	Long Island Gastrointestinal Research Group	Great Neck	New York	United States	11023
40	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
41	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
42	Plains Medical Clinic, LLC	Fargo	North Dakota	United States	58104
43	Clinical Inquest Center, Ltd	Beavercreek	Ohio	United States	45432
44	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
45	Prestige Clinical Research	Franklin	Ohio	United States	45005
46	Optimed Research, Ltd.	Tiffin	Ohio	United States	44883
47	Brandywine Clinical Research	Downingtown	Pennsylvania	United States	19335
48	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
49	Pain Specialists of Charleston, P.A.	Charleston	South Carolina	United States	29406
50	Health Concepts	Rapid City	South Dakota	United States	57702
51	FutureSearch Clinical Trials	Austin	Texas	United States	78731
52	KRK Medical Research	Dallas	Texas	United States	75230
53	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
54	Advanced Clinical Research of Houston	Houston	Texas	United States	77062
55	Innovative Clinical Trials	San Antonio	Texas	United States	78229
56	Highland Clinical Research	Salt Lake City	Utah	United States	84124
57	Clinical Investigations Specialist, Inc.	Kenosha	Wisconsin	United States	53142

Sponsors and Collaborators

• BioDelivery Sciences International

Investigators

• Study Director: Andrew Finn, PharmD, BioDelivary Sciences Internantional, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioDelivery Sciences International
• ClinicalTrials.gov Identifier: NCT01755546
• Other Study ID Numbers: EN3409-309
• First Posted: Dec 24, 2012
• Last Update Posted: Oct 18, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by BioDelivery Sciences International: Chronic Pain; CLBP; Chronic Low Back Pain; Back Pain; Osteoarthritis; OA; Neuropathic Pain; Nerve pain; Painful neuropathy
• Additional relevant MeSH terms: Osteoarthritis; Neuralgia; Back Pain; Low Back Pain; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	Overall
Arm/Group Description	All subjects combined, Roll Over and De Novo.
Period Title: Screened and Taper (Rollover and DeNovo)
STARTED	304
COMPLETED	294
NOT COMPLETED	10
Period Title: Screened and Taper (Rollover and DeNovo)
STARTED	294
COMPLETED	224
NOT COMPLETED	70
Period Title: Screened and Taper (Rollover and DeNovo)
STARTED	224
COMPLETED	103
NOT COMPLETED	121

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All subjects combined, Roll Over and De-Novo.
Overall Participants	224
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	193 86.2%
>=65 years	31 13.8%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52 (11.80)
Sex: Female, Male (Count of Participants)
Female	125 55.8%
Male	99 44.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	39 17.4%
Not Hispanic or Latino	185 82.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 1.3%
Asian	6 2.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	57 25.4%
White	158 70.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Weight (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	92.2 (21.57)
Height (cm) (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	169.5 (10.39)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.1 (7.20)
NRS Pain Intensity (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3 (1.30)
Chronic Pain (Count of Participants)
Lower Back Pain	222 99.1%
Neuropathic Pain	1 0.4%
Osteoarthritis	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score
Description	The NRS Pain intensity score is a segmented version of a visual analog scale used to measure pain. The scale is from 0 (no pain) to 10. Scores between greater than 0 and 3 are considered mild pain, scores from greater than 3 to 6 are moderate and greater than 6 to 10 are severe. The daily average is calculated and the change from baseline at week 48 is presented.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Population

Arm/Group Title	Overall
Arm/Group Description	All subjects combined, Roll Over and De-Novo.
Measure Participants	97
Mean (Standard Deviation) [units on a scale]	0.2 (1.78)

Adverse Events

Time Frame	48 Weeks
Arm/Group Title	Overall
Arm/Group Description	All subjects combined, Roll Over and De-Novo.
All Cause Mortality
	Overall
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Overall
	Affected / at Risk (%)	# Events
Total	12/224 (5.4%)
Gastrointestinal disorders
Vomiting	1/224 (0.4%)	1
General disorders
Influenza like illness	1/224 (0.4%)	1
Infections and infestations
Bronchitis	1/224 (0.4%)	1
Cellulitis	1/224 (0.4%)	1
Sepsis	1/224 (0.4%)	1
Urosepsis	1/224 (0.4%)	1
Injury, poisoning and procedural complications
Ankle Fracture	1/224 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/224 (0.4%)	1
Pancreatic carcinoma	1/224 (0.4%)	1
Nervous system disorders
Syncope	1/224 (0.4%)	1
Status migrainosus	1/224 (0.4%)	1
Renal and urinary disorders
Nephrolithiasis	1/224 (0.4%)	1
Renal impairment	1/224 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Overall
	Affected / at Risk (%)	# Events
Total	115/224 (51.3%)
Gastrointestinal disorders
Nausea	18/224 (8%)	18
Vomiting	11/224 (4.9%)	11
Diarrhea	10/224 (4.5%)	10
Constipation	9/224 (4%)	9
Infections and infestations
Upper respiratory tract infection	14/224 (6.3%)	14
Bronchitis	9/224 (4%)	9
Nasopharyngitis	7/224 (3.1%)	7
Injury, poisoning and procedural complications
Fall	7/224 (3.1%)	7
Musculoskeletal and connective tissue disorders
Back pain	13/224 (5.8%)	13
Nervous system disorders
Headache	12/224 (5.4%)	12
Psychiatric disorders
Depression	8/224 (3.6%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.