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

An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects (BNX-201)

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).

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.

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:

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

15. 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