Efficacy and Safety Study of Buprenorphine HCl Buccal Film in Subjects With Low Back Pain

• Sponsor: BioDelivery Sciences International (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01256450
• Collaborator: (none)
• Enrollment: 334
• Locations: 24
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 13.9
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether buprenorphine hydrochloride (HCl) buccal film is effective and safe in the treatment of chronic low back pain (CLBP).

Condition or Disease	Intervention/Treatment	Phase
Pain; Low Back Pain	Drug: Buprenorphine; Drug: Placebo	Phase 3

Detailed Description

This is an enriched enrollment, randomized withdrawal study with an open label, dose-titration period followed by a randomized, double-blind, placebo-controlled treatment period of 12 weeks. During the double-blind treatment period, this study will evaluate the effectiveness of buprenorphine HCl buccal film versus placebo buccal film in treating CLBP in subjects.

Buprenorphine HCl buccal film 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: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-Week, Placebo Controlled, Double Blind, Randomized Withdrawal Study to Evaluate the Efficacy and Safety of Buprenorphine HCl Buccal Film in Subjects With Moderate to Severe Chronic Low Back Pain
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Pain Intensity From Baseline to Week 12 [Baseline, Week 12]

   Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).

Secondary Outcome Measures

1. Change From Baseline in Pain Intensity Over Time Using NRS Scale [Baseline; Day 14, Day 28, Day 42, Day 56, Day 70, and Day 84]

   Change in pain intensity = average of daily pain scores from the last 7 days prior to each visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).

2. Number of Participants With Response to Treatment as Assessed by an NRS Scale [Week 12]

   Responses are defined as the relative improvement in pain score at week 12 from baseline, calculated from ratings of average pain intensity over the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).

3. Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks) [Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)]

   Treatment failure is defined as study discontinuation due to lack of efficacy or due to adverse event in the double-blind treatment phase.

4. Subject Impression of Change in Pain Intensity From Baseline to Week 12 Using PGIC Scale [Baseline, Week 12]

   Subjects assessed changes in activity, limitations, symptoms, and overall quality of life related to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC), a balanced 7-point scale from 1 (no change or condition got worse) to 7 (a great deal better and considerable improvement that has made all the difference).

5. Change From Baseline to Week 12 in Treatment Satisfaction Using TSQM [Baseline, Week 12]

   The Treatment Satisfaction Questionnaire for Medication (TSQM) is a 14-item instrument used to assess the subject's satisfaction with the ability of the study medication to prevent or treat the condition of chronic low back pain (CLBP) for effectiveness, side effects, convenience, and global satisfaction. Scores range from 0 to 100, where a higher score indicates less dissatisfaction (ie, greater satisfaction).

6. Change From Baseline to Week 12 in Roland Morris Disability Questionnaire [Baseline, Week 12]

   Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.

7. Change From Baseline to Week 12 in Subject's Overall Satisfaction With Study Drug [Baseline, Week 12]

   Subjects were asked to rate their overall satisfaction with their study drug on a 5-point scale ranging from 1 (poor) to 5 (excellent).

8. Change From Baseline to Week 12 in Investigator's Overall Satisfaction With Study Drug [Baseline, Week 12]

   Investigators rated their overall satisfaction with the study drug administered to a given subject on a 5-point scale ranging from 1 (poor) to 5 (excellent).

9. Use of Rescue Medication [Day 7, 14, 28, 42, 56, 70, 84, and 91 within double-blind treatment phase]

   Calculated from the use of rescue medication recorded in subject diary as the sum of all rescue medication tablets used in the last 7 days previous to the derived visit, divided by the number of days in this duration where the amount was reported.

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 low back pain for ≥3 months with a pain intensity ≥5 [11 point numerical rating scale] reported at the open-label titration period Day 0/1 visit following a washout period (opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and muscle relaxants) of approximately 12 to 24 hours

• Currently taking ≤60 mg oral morphine/day or equianalgesic dose of another opioid (including opioid naïve) for 1 week or longer

• Stable health, as determined by the Investigator, on the basis of medical history, physical examination, and screening 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 at Screening, prior to any procedure being performed

Exclusion Criteria:

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

• Surgical procedure for back pain within 2 months prior to screening or nerve/plexus block within 4 weeks of screening

• Hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia

• Corrected QT (QTc) interval of >450 milliseconds on the 12-lead electrocardiogram (ECG)

• History of long QT syndrome, or an immediate family member with this condition

• Diagnosis of moderate to severe hepatic impairment.

• History of severe emesis with opioids

• Clinically significant sleep apnea

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Orthopaedic Center - Research	Birmingham	Alabama	United States	35209
2	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
3	Arizona Research Center	Phoenix	Arizona	United States	85023
4	Neuro-Pain Medical Center	Fresno	California	United States	93710
5	University of California, San Diego Medical Center, UCSD Center for Pain Medicine	La Jolla	California	United States	92037
6	Collaborative Neuroscience Network, Inc.	Long Beach	California	United States	90806
7	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
8	Health Awareness, Inc.	Jupiter	Florida	United States	33458
9	Gold Coast Research, LLC	Plantation	Florida	United States	33317
10	Accord Clinical Research, LLC	Port Orange	Florida	United States	32129
11	Taylor Research, LLC	Marietta	Georgia	United States	30060
12	Millennium Pain Center	Bloomington	Illinois	United States	61701
13	MediSphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
14	International Clinical Research Institute	Leawood	Kansas	United States	66211
15	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472
16	Office of Stephen H. Miller, MD	Las Vegas	Nevada	United States	89144
17	Research Across American	New York	New York	United States	10022
18	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
19	The Center for Clinical Research, LLC	Winston-Salem	North Carolina	United States	27103
20	Allegheny Pain Management	Altoona	Pennsylvania	United States	16602
21	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
22	Southwest Urgent Care Center	El Paso	Texas	United States	79902
23	Lifetree Clinical Research	Salt Lake City	Utah	United States	84106
24	Advanced Clinical Research	West Jordan	Utah	United States	84088

Sponsors and Collaborators

• BioDelivery Sciences International

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioDelivery Sciences International
• ClinicalTrials.gov Identifier: NCT01256450
• Other Study ID Numbers: BUP-301
• First Posted: Dec 8, 2010
• Last Update Posted: Feb 27, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by BioDelivery Sciences International: buccal soluble film; enriched enrollment; randomized withdrawal
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Buprenorphine

Study Results

Participant Flow

Pre-assignment Detail	Of 334 subjects who were enrolled in the open-label (OL) titration phase; a total of 235 completed the open-label titration phase and were randomized in the double-blind (DB) treatment phase.

Arm/Group Title	OL Buprenorphine HCl Buccal Film	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine hydrochloride (HCl) buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for up to 4 weeks in the open-label titration period	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Period Title: Open-label Titration
STARTED	334	0	0
COMPLETED	235	0	0
NOT COMPLETED	99	0	0
Period Title: Open-label Titration
STARTED	0	117	118
COMPLETED	0	89	81
NOT COMPLETED	0	28	37

Baseline Characteristics

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film	Total
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Total of all reporting groups
Overall Participants	117	118	235
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	100 85.5%	100 84.7%	200 85.1%
>=65 years	17 14.5%	18 15.3%	35 14.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52.0	51.5	52.0
Gender (Count of Participants)
Female	62 53%	66 55.9%	128 54.5%
Male	55 47%	52 44.1%	107 45.5%
Region of Enrollment (participants) [Number]
United States	117 100%	118 100%	235 100%

Outcome Measures

1. Primary Outcome

Title	Change in Pain Intensity From Baseline to Week 12
Description	Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on Intent-to-Treat (ITT) population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Mean (Standard Deviation) [units on a scale]	0.33 (1.944)	0.46 (2.093)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Buprenorphine HCl Buccal Film, DB Placebo Film
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.5870
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.646 to 0.366
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Pain Intensity Over Time Using NRS Scale
Description	Change in pain intensity = average of daily pain scores from the last 7 days prior to each visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	Baseline; Day 14, Day 28, Day 42, Day 56, Day 70, and Day 84

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Day 14	0.21 (1.469)	0.25 (1.624)
Day 28	0.20 (1.539)	0.29 (1.877)
Day 42	0.13 (1.535)	0.25 (1.840)
Day 56	0.21 (1.709)	0.23 (1.926)
Day 70	0.15 (1.783)	0.35 (2.056)
Day 84	0.29 (1.984)	0.38 (2.058)

3. Secondary Outcome

Title	Number of Participants With Response to Treatment as Assessed by an NRS Scale
Description	Responses are defined as the relative improvement in pain score at week 12 from baseline, calculated from ratings of average pain intensity over the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
≥0% Response	117 100%	118 100%
≥10% Response	48 41%	32 27.1%
≥20% Response	37 31.6%	30 25.4%
≥30% Response	28 23.9%	27 22.9%
≥40% Response	19 16.2%	23 19.5%
≥50% Response	13 11.1%	20 16.9%
≥60% Response	11 9.4%	16 13.6%
≥70% Response	8 6.8%	13 11%
≥80% Response	5 4.3%	9 7.6%
≥90% Response	5 4.3%	7 5.9%
≥100% Response	3 2.6%	6 5.1%

4. Secondary Outcome

Title	Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)
Description	Treatment failure is defined as study discontinuation due to lack of efficacy or due to adverse event in the double-blind treatment phase.
Time Frame	Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Number [percentage of participants]	9.4 8%	11.9 10.1%

5. Secondary Outcome

Title	Subject Impression of Change in Pain Intensity From Baseline to Week 12 Using PGIC Scale
Description	Subjects assessed changes in activity, limitations, symptoms, and overall quality of life related to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC), a balanced 7-point scale from 1 (no change or condition got worse) to 7 (a great deal better and considerable improvement that has made all the difference).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Mean (Standard Deviation) [units on a scale]	-0.32 (2.091)	-0.92 (2.110)

6. Secondary Outcome

Title	Change From Baseline to Week 12 in Treatment Satisfaction Using TSQM
Description	The Treatment Satisfaction Questionnaire for Medication (TSQM) is a 14-item instrument used to assess the subject's satisfaction with the ability of the study medication to prevent or treat the condition of chronic low back pain (CLBP) for effectiveness, side effects, convenience, and global satisfaction. Scores range from 0 to 100, where a higher score indicates less dissatisfaction (ie, greater satisfaction).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Effectiveness	-2.06 (25.172)	-9.03 (27.804)
Side effects	3.09 (14.137)	10.88 (18.243)
Convenience	-3.12 (13.294)	-0.00 (14.081)
Global satisfaction	-8.19 (26.146)	-11.73 (26.829)

7. Secondary Outcome

Title	Change From Baseline to Week 12 in Roland Morris Disability Questionnaire
Description	Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Mean (Standard Deviation) [units on a scale]	0.09 (5.606)	1.00 (4.319)

8. Secondary Outcome

Title	Change From Baseline to Week 12 in Subject's Overall Satisfaction With Study Drug
Description	Subjects were asked to rate their overall satisfaction with their study drug on a 5-point scale ranging from 1 (poor) to 5 (excellent).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Mean (Standard Deviation) [units on a scale]	-0.30 (1.409)	-0.48 (1.329)

9. Secondary Outcome

Title	Change From Baseline to Week 12 in Investigator's Overall Satisfaction With Study Drug
Description	Investigators rated their overall satisfaction with the study drug administered to a given subject on a 5-point scale ranging from 1 (poor) to 5 (excellent).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication.

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Mean (Standard Deviation) [units on a scale]	-0.27 (1.312)	-0.37 (1.369)

10. Secondary Outcome

Title	Use of Rescue Medication
Description	Calculated from the use of rescue medication recorded in subject diary as the sum of all rescue medication tablets used in the last 7 days previous to the derived visit, divided by the number of days in this duration where the amount was reported.
Time Frame	Day 7, 14, 28, 42, 56, 70, 84, and 91 within double-blind treatment phase

Outcome Measure Data

Analysis Population Description

Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication

Arm/Group Title	DB Buprenorphine HCl Buccal Film	DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period	Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period
Measure Participants	117	118
Day 7	0.87 (1.143)	0.82 (1.103)
Day 14	0.93 (1.135)	1.03 (1.289)
Day 28	0.93 (1.239)	1.02 (1.325)
Day 42	0.97 (1.250)	1.04 (1.358)
Day 56	0.89 (1.245)	0.99 (1.364)
Day 70	0.83 (1.197)	0.98 (1.611)
Day 84	0.97 (1.277)	0.91 (1.276)
Follow-up Day 91	0.79 (1.143)	1.07 (1.370)

Adverse Events

Time Frame	From study drug dispensing in open-label titration phase to about 1 week after last dose (Day 91/follow-up visit) in the double-blind phase, up to 17 weeks
Adverse Event Reporting Description	Analysis for open-label titration phase based on Safety population; all enrolled subjects who receive at least 1 dose of study drug. Analysis for double-blind treatment phase is based on Randomized population; all subjects who were randomized into double-blind treatment, even if study drug was not taken.
Arm/Group Title	OL Buprenorphine HCl Buccal Film		DB Buprenorphine HCl Buccal Film		DB Placebo Film
Arm/Group Description	Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for up to 4 weeks in the open-label titration period		Buprenorphine HCl buccal film, 60, 120, 180, or 240 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind period		Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind period
All Cause Mortality
	OL Buprenorphine HCl Buccal Film		DB Buprenorphine HCl Buccal Film		DB Placebo Film
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	OL Buprenorphine HCl Buccal Film		DB Buprenorphine HCl Buccal Film		DB Placebo Film
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/330 (0.3%)		1/117 (0.9%)		0/118 (0%)
Infections and infestations
PNEUMONIA	1/330 (0.3%)	1	0/117 (0%)	0	0/118 (0%)	0
Investigations
BLOOD CREATININE INCREASED	1/330 (0.3%)	1	0/117 (0%)	0	0/118 (0%)	0
Nervous system disorders
CEREBROVASCULAR ACCIDENT	0/330 (0%)	0	1/117 (0.9%)	1	0/118 (0%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	1/330 (0.3%)	1	0/117 (0%)	0	0/118 (0%)	0
Other (Not Including Serious) Adverse Events
	OL Buprenorphine HCl Buccal Film		DB Buprenorphine HCl Buccal Film		DB Placebo Film
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	163/330 (49.4%)		36/117 (30.8%)		28/118 (23.7%)
Gastrointestinal disorders
CONSTIPATION	36/330 (10.9%)	37	7/117 (6%)	7	3/118 (2.5%)	4
NAUSEA	108/330 (32.7%)	118	11/117 (9.4%)	11	10/118 (8.5%)	11
VOMITING	19/330 (5.8%)	19	6/117 (5.1%)	7	4/118 (3.4%)	4
Infections and infestations
NASOPHARYNGITIS	7/330 (2.1%)	7	3/117 (2.6%)	3	7/118 (5.9%)	7
Nervous system disorders
DIZZINESS	30/330 (9.1%)	35	4/117 (3.4%)	4	1/118 (0.8%)	1
HEADACHE	39/330 (11.8%)	45	12/117 (10.3%)	14	5/118 (4.2%)	6
Psychiatric disorders
INSOMNIA	8/330 (2.4%)	9	7/117 (6%)	7	3/118 (2.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The oral or written use of study results by the Investigator is not permitted without the express written consent from the Sponsor.