Evaluation of the Tolerability of Switching Subjects on Chronic ATC Opioid Therapy to Buprenorphine HCl Buccal Film

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure being
performed

2. Male or non-lactating female subjects 18 to 60 years of age at time of consent

3. Female subjects who are non-pregnant on the basis of screening serum pregnancy test
and who are practicing abstinence or using a medically acceptable form of
contraception (eg, intrauterine device, hormonal birth control, or double barrier
method) or have been post-menopausal, biologically sterile, or surgically sterile
(ie, hysterectomy, bilateral oophorectomy, or tubal ligation) for more than 1 year

4. Male subjects who are practicing abstinence, surgically sterile or are using a
medically acceptable form of contraception

5. Subjects with a ≥6 months history of chronic pain (including peripheral neuropathic
pain) requiring ATC opioid therapy with ≥80 mg but ≤220 mg MSE per day for at least
28 days

6. Receiving one of the following opioids ATC for ≥28 days: (i) Morphine Sulfate; (ii)
Oxycodone hydrochloride

7. Displays signs and symptoms of withdrawal (ie, COWS score ≥5) within 5 minutes
following naloxone challenge

8. Able to understand the study procedures, complete the assessment scales, and
communicate meaningfully with study personnel

9. Stable health, as determined by the Principal Investigator, on the basis of medical
history, physical examination, and screening laboratory results

Exclusion Criteria:

1. Inability to meet study participation requirements, including two 2-night stays with
pharmacokinetic sampling

2. A history or current evidence of clinically significant pulmonary (eg, asthma,
chronic obstructive pulmonary disease, cor pulmonale or severe bronchial asthma ),
gastrointestinal, hepatic, renal, hematologic, immunologic, endocrine, neurologic,
oncologic or psychiatric disorder or any other condition, including evidence of
abnormalities on physical examination, abnormal vital signs, electrocardiogram (ECG),
or clinical laboratory values which in the opinion of the Investigator, would
jeopardize the safety of the subject or impact the validity of the study results

3. Supine systolic blood pressure >180 mm Hg or <90 mm Hg or diastolic blood pressure >
105 mm Hg or <50 mm Hg at screening (may be repeated once)

4. COWS score greater than 4 prior to the screening naloxone challenge

5. Aspartate aminotransferase or alanine aminotransferase >3 times the upper limits of
normal or serum creatinine >1.9 mg/dL at Screening, or any laboratory abnormality
which, in the opinion of the Investigator, would contraindicate study participation

6. Use of monoamine oxidase inhibitors within 14 days of screening or during the study

7. Use of any medication, nutraceutical or herbal product with cytochrome P450 3A4
inhibition or induction properties within the past 30 days

8. Donation of 450 mL or more of blood within 30 days prior to screening or a hemoglobin
value <11.0 g/dL at screening

9. Documented history of alcohol and/or substance abuse (excluding nicotine and/or
caffeine) within 5 years prior to screening, and/or is currently in treatment or is
seeking treatment for alcohol and/or substance abuse, as assessed by the Diagnostic
and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria

10. Positive alcohol breath test at screening

11. Positive urine toxicology screen for drugs of abuse at screening

12. History of hypersensitivity, allergy, or contraindication to any opioid or clinically
significant intolerance to buprenorphine or naloxone

13. History of seizures, convulsions, or increased intra-cranial pressure (history of
pediatric febrile seizures is permitted)

14. History of significant head injury within 6 months of screening

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

16. Participation in the treatment phase of a clinical research study involving any
investigational drug within 28 days (or 5 elimination half-lives, whichever is
longer) of screening

17. Previous participation in this clinical study or any other clinical study involving
BEMA buprenorphine (buprenorphine HCl buccal film)

18. In the Investigator's opinion at significant risk for suicidal behavior based on the
Columbia Suicide Severity Rating Scale (C-SSRS)

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

20. History of myocardial infarction

21. Corrected QT interval (QTcF) of ≥450 milliseconds on the 12-lead ECG

22. History of long QT syndrome or a family member with this condition

23. Use of class IA antiarrhythmic medications or class III antiarrhythmic medications
within 14 days of screening

24. Current use of α2 agonist antihypertensives (eg, clonidine), 5-HT3 antagonists (eg,
ondansetron), benzodiazepines, or other medications that would be anticipated to
confound detection of signs and symptoms of opioid withdrawal

25. Involvement in the planning and/or conduct of the study (applies to both sponsor or
designee staff and staff at the study sites)