An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects

• Sponsor: BioDelivery Sciences International (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01666119
• Collaborator: (none)
• Enrollment: 249
• Locations: 10
• Arm: 1
• Duration (Months): 5
• Patients Per Site: 24.9
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief Summary

This is an open label study in opioid dependent subjects maintained on a stabilized dose of Suboxone tablets or films. The purpose is to assess the safety and tolerability of BEMA Buprenorphine NX administered once daily for 12 weeks to opioid dependent subjects stabilized on Suboxone (buprenorphine/naloxone) tablets or films.

Eligible subjects will be converted to an approximately equal dose of BEMA Buprenorphine NX. This dose will be taken throughout the 12-week treatment period with dose adjustments as clinically indicated for either the control of opioid dependence or adverse events (AEs).

Condition or Disease	Intervention/Treatment	Phase
Opioid Dependence	Drug: BEMA Buprenorphine NX films	Phase 2

Detailed Description

This is an open label study in opioid dependent subjects maintained on a stabilized dose of Suboxone tablets or films.

Eligible subjects will be converted to an approximately equal dose of BEMA Buprenorphine NX. This dose will be taken throughout the 12-week treatment period with dose adjustments as clinically indicated for either the control of opioid dependence or adverse events (AEs). Subjects will be monitored for evidence of buccal irritation attributed to the application of the BEMA Buprenorphine NX film and opioid dependence control according to the Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction - A Treatment Improvement Protocol (TIP 40) guidelines for the use of buprenorphine in the management of opioid dependence.

The total duration of participation for each subject will be up to approximately 18 weeks and includes a Screening period (subjects continue to take Suboxone tablets or films), Baseline visit, a 12-week open label treatment period (subjects take BEMA Buprenorphine NX films and at the Day 84 visit, subjects will return to their prior Suboxone treatment), and a Follow-up Visit.

Vital signs, pulse oximetry, opioid withdrawal symptoms, adverse events (AEs), oral examinations, and concomitant medications will be assessed at intervals throughout the study. Clinical laboratory assessments, urine toxicology and buprenorphine testing, and 12-lead electrocardiograms (ECGs) will also be performed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects (BNX-201)
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BEMA Buprenorphine NX films BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone)will be provided in 3.361 and 5.447 cm2 film sizes, respectively.	Drug: BEMA Buprenorphine NX films; BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone) will be provided in 3.361 and 5.447 cm2 film sizes, respectively.; Other Names: BNX

Outcome Measures

Primary Outcome Measures

1. Adverse Events [12 weeks]

   Adverse events that occur in more than 2 subjects. Among the adverse events that occurred in > 2 subjects, the total number of unique events that were experienced are reported.

Secondary Outcome Measures

1. Urine Drug Screen [12 weeks]

   Urine samples collected at screening and baseline to test for the presence of non-prescribed opioids.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent obtained at Screening, prior to any study procedure being performed

2. Male or non-pregnant and non-nursing female. A female of childbearing potential is eligible to participate in this study if she is not pregnant, and is using an acceptable method of birth control

3. Subject is aged 18 to 65 years of age, inclusive

4. Diagnosis of opioid dependence per the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (text revision) (DSM-IV-TR) criteria in the past 12 months including physical dependence on opioids and addiction with compulsive use despite harm

5. Currently taking a stable, single daily dose of 16/4 to 32/8 mg Suboxone tablets or films (buprenorphine/naloxone) for at least 30 days

6. Subject is in good general health; with no clinically significant findings on medical history, physical examination, safety laboratory test and ECG in the judgment of the investigator at screening. Serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values must be within 3-times the upper limit of normal (ULN). Pulse oximetry must be ≥96%, systolic blood pressure ≥110 mmHg, and diastolic blood pressure ≥65 mmHg.

Exclusion Criteria:

1. Hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or clinically significant arrhythmias

2. History of Long QT Syndrome, or an immediate family member with this condition

3. Currently taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone, dofetilide)

4. Uncontrolled hypertension defined as systolic blood pressure >170 mmHg and diastolic blood pressure >90 mmHg at Baseline

5. Pulse oximetry ≤93% at Baseline, regardless of cause

6. Clinically significant abnormality on 12-lead ECG, including a QTc interval >490 milliseconds

7. Use of any medication, nutraceutical or herbal product with CYP3A4 inhibition or induction properties within the past 30 days (see Appendix 4 for a list of applicable drugs). This exclusion also extends to grapefruit juice and grapefruit juice-containing products as well as St. John's wort and St. John's wort-containing products (prescription or nonprescription drugs, vitamins, minerals, or dietary/herbal supplements).

8. Diagnosis of moderate to severe hepatic impairment

9. Use of an investigational drug or device within the last 30 days

10. Participation in a previous clinical study of BEMA Buprenorphine NX or BEMA Buprenorphine

11. History of hypersensitivity, allergy, or intolerance to buprenorphine, naloxone, or related drugs

12. Pierced tongue or mouth

13. Any clinically significant abnormality of the buccal mucosa which could impact drug absorption

14. Suicidal risk, as determined by meeting any of the following:

15. History of suicidal ideation ≤ 3 months prior to Baseline with a score of 4 (intent to act) or 5 (specific plan and intent) on the eC-SSRS

16. History of suicidal behavior ≤ 1 year prior to Baseline (actual attempt, interrupted attempt, aborted attempt and/or preparatory acts/behavior) on the eC-SSRS

17. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35215
2		Haleyville	Alabama	United States	35565
3		Jacksonville	Florida	United States	32256
4		Maitland	Florida	United States	32751
5		North Miami	Florida	United States	33161
6		Prairie Village	Kansas	United States	66206
7		Baltimore	Maryland	United States	21201
8		Fall River	Massachusetts	United States	02720
9		Belvidere	New Jersey	United States	07823
10		Salt Lake City	Utah	United States	84106

Sponsors and Collaborators

• BioDelivery Sciences International

Investigators

• Principal Investigator: Greg Sullivan, MD, Parkway Medical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioDelivery Sciences International
• ClinicalTrials.gov Identifier: NCT01666119
• Other Study ID Numbers: BNX-201
• First Posted: Aug 16, 2012
• Last Update Posted: Apr 4, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by BioDelivery Sciences International: Opioid dependence; Suboxone; addiction; BEMA Buprenorphine NX; oral transmucosal
• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	BEMA Buprenorphine NX Films
Arm/Group Description	BEMA Buprenorphine/NX films (3.5/0.6, 5.25/0.9, 7/1.2, 10.5/1.8, and 14/2.4 mg). BEMA Buprenorphine/NX films (3.5/0.6, 5.25/0.9, 7/1.2, 10.5/1.8, and 14/2.4 mg).
Period Title: Overall Study
STARTED	249
COMPLETED	197
NOT COMPLETED	52

Baseline Characteristics

Arm/Group Title	BEMA Buprenorphine NX Films
Arm/Group Description	BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone)will be provided in 3.361 and 5.447 cm2 film sizes, respectively. BEMA Buprenorphine NX films: BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone) will be provided in 3.361 and 5.447 cm2 film sizes, respectively.
Overall Participants	249
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.7 (10.2)
Sex: Female, Male (Count of Participants)
Female	85 34.1%
Male	164 65.9%
Region of Enrollment (participants) [Number]
United States	249 100%

Outcome Measures

1. Secondary Outcome

Title	Urine Drug Screen
Description	Urine samples collected at screening and baseline to test for the presence of non-prescribed opioids.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Subjects with at least one urine drug screen test during the treatment period.

Arm/Group Title	BEMA Buprenorphine/NX Films
Arm/Group Description	BEMA Buprenorphine/NX films (3.5/0.6mg, 5.25/0.9mg, 7.0/1.2mg, 10.5/1.7mg, 14.0/2.3mg)
Measure Participants	249
Subjects with +-result for non-prescribed opiod	19 7.6%
Number with single positive result	11 4.4%
Number with 2 positive results	4 1.6%
Number with > 2 positive results	4 1.6%

2. Primary Outcome

Title	Adverse Events
Description	Adverse events that occur in more than 2 subjects. Among the adverse events that occurred in > 2 subjects, the total number of unique events that were experienced are reported.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of study drug.

Arm/Group Title	BEMA Buprenorphine/NX Films
Arm/Group Description	BEMA Buprenorphine/NX films (3.5/0.6mg, 5.25/0.9mg, 7.0/1.2mg, 10.5/1.7mg, 14.0/2.3mg)
Measure Participants	249
Number [adverse events]	36

Adverse Events

Arm/Group Title	BEMA Buprenorphine NX Films
Arm/Group Description	BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone)will be provided in 3.361 and 5.447 cm2 film sizes, respectively. BEMA Buprenorphine NX films: BEMA Buprenorphine NX films (3.5/0.6 mg and 5.25/0.9 mg buprenorphine/naloxone) will be provided in 3.361 and 5.447 cm2 film sizes, respectively.
All Cause Mortality
	BEMA Buprenorphine NX Films
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BEMA Buprenorphine NX Films
	Affected / at Risk (%)	# Events
Total	1/249 (0.4%)
Infections and infestations
osteomyelitis	1/249 (0.4%)	1
Psychiatric disorders
suicidal ideation	1/249 (0.4%)	1
Other (Not Including Serious) Adverse Events
	BEMA Buprenorphine NX Films
	Affected / at Risk (%)	# Events
Total	89/249 (35.7%)
General disorders
drug withdrawal syndrome	89/249 (35.7%)	89

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.