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

NCT ID: NCT01871285

Last Updated: 2017-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-07-31

Brief 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.

Conditions

Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

MSE Dose Group 1

Morning and evening dose of buprenorphine HCl buccal film (300 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period

Group Type: EXPERIMENTAL

Buprenorphine

Intervention Type: DRUG

Placebo film

Intervention Type: DRUG

Matching placebo buccal film

Oxycodone

Intervention Type: DRUG

Oxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets

Morphine sulfate

Intervention Type: DRUG

Morphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets

Placebo capsule

Intervention Type: DRUG

Oral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets

MSE Dose Group 2

Morning and evening dose of buprenorphine HCl buccal film (450 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period

Group Type: EXPERIMENTAL

Buprenorphine

Intervention Type: DRUG

Placebo film

Intervention Type: DRUG

Matching placebo buccal film

Oxycodone

Intervention Type: DRUG

Oxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets

Morphine sulfate

Intervention Type: DRUG

Morphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets

Placebo capsule

Intervention Type: DRUG

Oral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets

Interventions

Buprenorphine

Intervention Type: DRUG

Placebo film

Matching placebo buccal film

Intervention Type: DRUG

Oxycodone

Oxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets

Intervention Type: DRUG

Morphine sulfate

Morphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets

Intervention Type: DRUG

Placebo capsule

Oral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets

Intervention Type: DRUG

Other Intervention Names

Buprenorphine buccal film; Buprenorphine HCl buccal film; EN3409; BEMA Buprenorphine; BELBUCA; Placebo buccal film; BEMA placebo; Oxycodone tablets; OxyContin; Oxycodone IR; Morphine sulfate tablets; MS Contin; Morphine sulfate IR; Matching placebo capsules

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioDelivery Sciences International

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Todd Kirby, PhD

Role: STUDY_DIRECTOR

Endo Pharmaceuticals

Locations

Vince and Associates Clinical Research, Inc.

Overland Park, Kansas, United States

CRI Lifetree

Philadelphia, Pennsylvania, United States

CRI Lifetree (Lifetree Clinical Research)

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

EN3409-204

Identifier Type: -

Identifier Source: org_study_id