An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioDelivery Sciences International
ClinicalTrials.gov Identifier:
NCT01666119
First received: August 13, 2012
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

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).


Condition Intervention Phase
Opioid Dependence
Drug: BEMA Buprenorphine NX films
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study To Assess The Safety And Tolerability Of BEMA® Buprenorphine NX In Opioid Dependent Subjects (BNX-201)

Resource links provided by NLM:


Further study details as provided by BioDelivery Sciences International:

Primary Outcome Measures:
  • 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 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

    The following will be assessed:

    • AEs
    • Oral examination
    • Periodic physical examinations
    • Vital signs and pulse oximetry
    • ECG
    • Periodic clinical laboratory evaluations including hematology, blood chemistry and urinalysis
    • Suicidality assessments


Secondary Outcome Measures:
  • Determine the most appropriate conversion ratio for opioid dependent subjects treated with Suboxone tablets or films to BEMA Buprenorphine NX [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    Eligible subjects stabilized on Suboxone maintenance therapy (8-32 mg/day) will be enrolled and switched to an equivalent dose using 3.5/0.6 mg and 5.25/0.9 mg BEMA Buprenorphine NX.

    At each visit, adverse events (AEs), including behavioral events, will be assessed; oral examinations will be performed to assess local irritation (monthly); and urine samples will be collected and analyzed for opioids of abuse, buprenorphine, and intermittent pregnancy testing.



Enrollment: 249
Study Start Date: August 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BEMA Buprenorphine NX films
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.
Drug: BEMA Buprenorphine NX films
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.

Detailed Description:

This is an open label study in opioid dependent subjects maintained on a stabilized dose of Suboxone 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). Subjects will be monitored for evidence of buccal irritation attributed to the application of the BEMA Buprenorphine NX film and opioid dependence control according to the Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction - A Treatment Improvement Protocol (TIP 40) guidelines for the use of buprenorphine in the management of opioid dependence.

The total duration of participation for each subject will be up to approximately 18 weeks and includes a Screening period (subjects continue to take Suboxone tablets or films), Baseline visit, a 12-week open label treatment period (subjects take BEMA Buprenorphine NX films and at the Day 84 visit, subjects will return to their prior Suboxone treatment), and a Follow-up Visit.

Vital signs, pulse oximetry, opioid withdrawal symptoms, adverse events (AEs), oral examinations, and concomitant medications will be assessed at intervals throughout the study. Clinical laboratory assessments, urine toxicology and buprenorphine testing, and 12-lead electrocardiograms (ECGs) will also be performed.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01666119

Locations
United States, Alabama
Birmingham, Alabama, United States, 35215
Haleyville, Alabama, United States, 35565
United States, Florida
Jacksonville, Florida, United States, 32256
Maitland, Florida, United States, 32751
North Miami, Florida, United States, 33161
United States, Kansas
Prairie Village, Kansas, United States, 66206
United States, Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Fall River, Massachusetts, United States, 02720
United States, New Jersey
Belvidere, New Jersey, United States, 07823
United States, Utah
Salt Lake City, Utah, United States, 84106
Sponsors and Collaborators
BioDelivery Sciences International
Investigators
Principal Investigator: Greg Sullivan, MD Parkway Medical
  More Information

No publications provided

Responsible Party: BioDelivery Sciences International
ClinicalTrials.gov Identifier: NCT01666119     History of Changes
Other Study ID Numbers: BNX-201
Study First Received: August 13, 2012
Last Updated: July 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by BioDelivery Sciences International:
Opioid dependence
Suboxone
addiction
BEMA Buprenorphine NX
oral transmucosal

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Buprenorphine
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotic Antagonists
Narcotics

ClinicalTrials.gov processed this record on April 15, 2014