An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects
Condition: Opioid Dependence
MeSH terms: Opioid-Related Disorders
Intervention: BEMA Buprenorphine NX films
Intervention 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.
Intervention MeSH terms: Buprenorphine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 249.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Opioid dependence; Suboxone; addiction; BEMA Buprenorphine NX; oral transmucosal

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).
    

Eligibility criteria:

        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