Longterm Safety Study of BEMA Buprenorphine in Subjects With Chronic Pain

• Sponsor: BioDelivery Sciences International (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01298765
• Collaborator: (none)
• Enrollment: 302
• Locations: 26
• Arm: 1
• Duration (Months): 17.1
• Patients Per Site: 11.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether BEMA Buprenorphine is safe in the treatment of chronic pain.

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

Detailed Description

This is an open label study of up to approximately 52 weeks duration to assess the safety and effectiveness of BEMA Buprenorphine in the management of moderate to severe chronic pain.

BEMA Buprenorphine is an oral transmucosal form of the opioid analgesic, buprenorphine hydrochloride, intended for application to the buccal mucosa. Buprenorphine is a synthetic opioid that is classified as a partial μ-receptor agonist and a Schedule III controlled substance in the United States.

Study Design

• Study Type: Interventional
• Actual Enrollment: 302 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-Week, Open Label, Longterm Treatment Evaluation of the Safety and Efficacy of BEMA® Buprenorphine in Subjects With Moderate to Severe Chronic Pain
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BEMA Buprenorphine buprenorphine buccal soluble film	Drug: BEMA Buprenorphine; buccal soluble film; applied to the buccal mucosa twice daily; Other Names: buprenorphine buccal soluble film

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in NRS Pain Intensity [Baseline up to approximately Week 52]

   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 used to calculate the change from baseline at week 52.

Secondary Outcome Measures

1. Patient Global Impression of Change in Pain Intensity [Baseline to Week 28]

   Patient Global Impression of Change in Pain Intensity at Week 28 as measured by a 7 point scale. Patients measure their improvement from 7='very much improved', 6='much improved', 5='minimally improved', 4='no change', 3='minimally worse', 2='much worse', 1='very much worse'.

2. Treatment Satisfaction Questionnaire for Medication/Global Satisfaction [Baseline to Week 28]

   Treatment Satisfaction Questionnaire for Medication/Global Satisfaction at Week 28. Patients complete a 14 item questionaire that measures 4 scales based on side effects, effectiveness, convenience and global satisfaction. All items have either five or seven responses (except item 4), scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales have a non-neutral midpoint, such that there are more positive response options than negative response options. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring. If an item score is missing and half of the items in the domain are complete, domain scores may be imputed from the person-specific mean score of completed items

3. Subjects Overall Satisfaction With Study Drug [Baseline to Week 52]

   Subjects Overall Satisfaction with Study Drug as measured on a 5 point scale, with 1 being not satisfied and 5 being very satisified.

4. Investigator's Overall Satisfaction With Study Drug [Baseline to Week 52]

   Investigator's Overall Satisfaction with Study Drug measured on a 5-point scale, with 1 being not satisfied and 5 being very satisfied.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or non-pregnant and non-nursing female aged 18 or older

• History of moderate to severe chronic pain:

1. Subjects completing study BUP-301 (low back pain) or

2. Osteoarthritis or neuropathic pain, or subjects not completing study BUP-301 (low back pain), pain for ≥3 months with a pain intensity ≥5 [11 point NRS] reported at the titration period Day 0/1 visit following a washout period (opioids, NSAIDs, and muscle relaxants) of approximately 12 to 24 hours AND currently taking ≤60 mg oral morphine equivalent/day (including opioid-naïve) for 1 week or longer

• Stable health, as determined by the Investigator, on the basis of medical history, physical examination, and laboratory results so as to comply with all study procedures

• Female subjects of childbearing potential must be using a recognized effective method of birth control

• Written informed consent obtained prior to any procedure being performed

Exclusion Criteria:

• Cancer related pain

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

• Surgical procedure for pain within 2 months, or nerve/plexus block within 4 weeks, prior to titration period Day 0/1 visit

• History of severe emesis with opioids

• Clinically significant sleep apnea in the judgment of the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Mobile	Alabama	United States
3		Phoenix	Arizona	United States
4		Arcadia	California	United States
5		Fresno	California	United States
6		La Jolla	California	United States
7		Long Beach	California	United States
8		Westminster	Colorado	United States
9		DeLand	Florida	United States
10		Jupiter	Florida	United States
11		Plantation	Florida	United States
12		Port Orange	Florida	United States
13		Marietta	Georgia	United States
14		Bloomington	Illinois	United States
15		Evansville	Indiana	United States
16		Leawood	Kansas	United States
17		Watertown	Massachusetts	United States
18		Las Vegas	Nevada	United States
19		New York	New York	United States
20		Raleigh	North Carolina	United States
21		Winston-Salem	North Carolina	United States
22		Altoona	Pennsylvania	United States
23		Austin	Texas	United States
24		El Paso	Texas	United States
25		Salt Lake City	Utah	United States
26		West Jordan	Utah	United States

Sponsors and Collaborators

• BioDelivery Sciences International

Investigators

• Study Director: Andrew Finn, PharmD, BioDelivery Sciences International

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioDelivery Sciences International
• ClinicalTrials.gov Identifier: NCT01298765
• Other Study ID Numbers: BUP-305
• First Posted: Feb 18, 2011
• Last Update Posted: Aug 7, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by BioDelivery Sciences International: buccal soluble film
• Additional relevant MeSH terms: Neuralgia; Low Back Pain; Chronic Pain; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine; buccal soluble film; applied to the buccal mucosa twice daily
Period Title: Titration Period
STARTED	302
COMPLETED	226
NOT COMPLETED	76
Period Title: Titration Period
STARTED	226
COMPLETED	127
NOT COMPLETED	99

Baseline Characteristics

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Overall Participants	302
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	235 77.8%
>=65 years	67 22.2%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.5 (12.45)
Sex: Female, Male (Count of Participants)
Female	183 60.6%
Male	119 39.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%
Asian	4 1.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	58 19.2%
White	237 78.5%
More than one race	0 0%
Unknown or Not Reported	2 0.7%
Weight (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	92.86 (22.250)
Height (cm) (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	169.14 (10.540)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.226 (6.8542)
NRS Pain Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.3 (1.94)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in NRS Pain Intensity
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 used to calculate the change from baseline at week 52.
Time Frame	Baseline up to approximately Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Measure Participants	127
Mean (Standard Deviation) [units on a scale]	-0.24 (1.803)

2. Secondary Outcome

Title	Patient Global Impression of Change in Pain Intensity
Description	Patient Global Impression of Change in Pain Intensity at Week 28 as measured by a 7 point scale. Patients measure their improvement from 7='very much improved', 6='much improved', 5='minimally improved', 4='no change', 3='minimally worse', 2='much worse', 1='very much worse'.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Measure Participants	98
Mean (Standard Deviation) [units on a scale]	5.5 (1.31)

3. Secondary Outcome

Title	Treatment Satisfaction Questionnaire for Medication/Global Satisfaction
Description	Treatment Satisfaction Questionnaire for Medication/Global Satisfaction at Week 28. Patients complete a 14 item questionaire that measures 4 scales based on side effects, effectiveness, convenience and global satisfaction. All items have either five or seven responses (except item 4), scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales have a non-neutral midpoint, such that there are more positive response options than negative response options. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring. If an item score is missing and half of the items in the domain are complete, domain scores may be imputed from the person-specific mean score of completed items
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Measure Participants	97
Mean (Standard Deviation) [units on a scale]	76.6 (15.93)

4. Secondary Outcome

Title	Subjects Overall Satisfaction With Study Drug
Description	Subjects Overall Satisfaction with Study Drug as measured on a 5 point scale, with 1 being not satisfied and 5 being very satisified.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Measure Participants	122
Mean (Standard Deviation) [units on a scale]	4.1 (0.80)

5. Secondary Outcome

Title	Investigator's Overall Satisfaction With Study Drug
Description	Investigator's Overall Satisfaction with Study Drug measured on a 5-point scale, with 1 being not satisfied and 5 being very satisfied.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
Measure Participants	122
Mean (Standard Deviation) [units on a scale]	4.2 (0.78)

Adverse Events

Time Frame	52 Weeks
Adverse Event Reporting Description	Adverse Events that are considered treatment-emergent that occurred during the titration period.
Arm/Group Title	BEMA Buproneorphine Overall
Arm/Group Description	buprenorphine buccal soluble film BEMA Buprenorphine (All Doses): buccal soluble film; applied to the buccal mucosa twice daily
All Cause Mortality
	BEMA Buproneorphine Overall
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BEMA Buproneorphine Overall
	Affected / at Risk (%)	# Events
Total	4/302 (1.3%)
Cardiac disorders
Arrhythmia	1/302 (0.3%)	1
Atrial Fibrillation	1/302 (0.3%)	1
General disorders
Oedema	1/302 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/302 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/302 (0.3%)	1
Other (Not Including Serious) Adverse Events
	BEMA Buproneorphine Overall
	Affected / at Risk (%)	# Events
Total	31/302 (10.3%)
Cardiac disorders
Arrhythmia	1/302 (0.3%)	1
Gastrointestinal disorders
Nausea	9/302 (3%)	9
Abdominal Pain Upper	1/302 (0.3%)	1
Constipation	2/302 (0.7%)	2
Dyspepsia	1/302 (0.3%)	1
Flatulence	1/302 (0.3%)	1
Vomiting	1/302 (0.3%)	1
General disorders
Fatigue	5/302 (1.7%)	5
Irritability	2/302 (0.7%)	2
Infections and infestations
Wound Infection Staphylococcal	1/302 (0.3%)	1
Injury, poisoning and procedural complications
Contusion	1/302 (0.3%)	1
Metabolism and nutrition disorders
Anorexia	1/302 (0.3%)	1
Gout	1/302 (0.3%)	1
Musculoskeletal and connective tissue disorders
Epicondylitis	1/302 (0.3%)	1
Muscle Spasms	1/302 (0.3%)	1
Nervous system disorders
Balance Disorder	1/302 (0.3%)	1
Cognitive Disorder	1/302 (0.3%)	1
Dizziness	3/302 (1%)	3
Headache	2/302 (0.7%)	2
Hypoaesthesia	1/302 (0.3%)	1
Somnolence	1/302 (0.3%)	1
Psychiatric disorders
Anxiety	2/302 (0.7%)	2
Depression	1/302 (0.3%)	1
Insomnia	1/302 (0.3%)	1
Somnolence	1/302 (0.3%)	1
Suicidal Ideation	1/302 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/302 (0.3%)	1
Skin and subcutaneous tissue disorders
Hypoaesthesia Facial	1/302 (0.3%)	1
Pruritus	1/302 (0.3%)	1
Urticaria	1/302 (0.3%)	1

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.