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

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