Evaluation of the Tolerability of Switching Subjects on Chronic ATC Opioid Therapy to Buprenorphine HCl Buccal Film
Condition: Pain
Intervention: Buprenorphine; Placebo film; Oxycodone; Morphine sulfate; Placebo capsule
Intervention description: Matching placebo buccal film; Oxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets; Morphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets; Oral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets
Intervention MeSH terms: Morphine; Oxycodone; Buprenorphine
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: ATC, Opioid, withdrawal, switch

Summary:

      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.
    

Eligibility criteria:

        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)