The primary aim of this study is to determine if chronic pain subjects on around-the-clock opioids who are receiving 100 to 220 mg oral morphine sulfate equivalent (MSE) can be safely transitioned on to buprenorphine hydrochloride (HCl) buccal film at 50% of their MSE dose without inducing opioid withdrawal or reversing analgesic effects.

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)