Efficacy of BNX Sublingual Tablets Versus BNX Sublingual Film for Treatment of Opioid-Dependent Adults

NCT ID: NCT01908842

Last Updated: 2017-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 759 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-04-30

Brief Summary

The purpose of this study was to assess retention in treatment after induction with buprenorphine/naloxone (BNX) sublingual tablets compared with generic buprenorphine and after stabilization with BNX sublingual tablets compared with BNX film. Secondary objectives included assessment of treatment effects on opioid withdrawal symptoms, opioid cravings, and safety.

Detailed Description

This prospective, randomized, multicenter, parallel-group, non-inferiority study was conducted at 43 centers in the United States from August 2013 to April 2014. A non-inferior design was used because both products contain the same active components, and it was considered unethical to include a placebo arm. The study comprised an induction phase of 2 days and a stabilization phase of 20 days, with study visits scheduled on Days 1, 2, 3, 4, 8, 15, and 22. Eligible opioid-dependent patients were randomly assigned within 14 days of screening to induction with either the BNX sublingual tablets or generic buprenorphine tablets for 2 days. On Day 3, patients initially allocated to buprenorphine were switched to BNX film, whereas those allocated to BNX sublingual tablets continued on the same treatment. On Day 15, patients receiving BNX film were switched to BNX sublingual tablets, and those on BNX sublingual tablets were switched to BNX film. At the final study visit on Day 22, patients were offered the option of continuing in an open-label follow-up study of BNX sublingual tablets.

Conditions

Opioid Dependence, on Agonist Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Buprenorphine; then OL BNX film, then BNX tablets

Days 1-2: Generic buprenorphine sublingual tablets (blinded); Days 3 to 14: Buprenorphine/naloxone sublingual film (open-label); Days 15-21: BNX sublingual tablets (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets

Group Type: ACTIVE_COMPARATOR

BNX sublingual tablets

Intervention Type: DRUG

Buprenorphine/naloxone sublingual tablets

BNX sublingual film

Intervention Type: DRUG

Buprenorphine/naloxone sublingual film

Buprenorphine

Intervention Type: DRUG

Buprenorphine sublingual tablets

BNX tablets, then OL BNX tablets, then BNX film

Days 1-2: BNX sublingual tablets (blinded); Days 3 to 14: BNX sublingual tablets (open-label); Days 15-21: Buprenorphine/naloxone sublingual film (open-label); Day 22: Offered option in continuing in open-label follow-up study of BNX sublingual tablets

Group Type: EXPERIMENTAL

BNX sublingual tablets

Intervention Type: DRUG

Buprenorphine/naloxone sublingual tablets

BNX sublingual film

Intervention Type: DRUG

Buprenorphine/naloxone sublingual film

Interventions

BNX sublingual tablets

Buprenorphine/naloxone sublingual tablets

Intervention Type: DRUG

BNX sublingual film

Buprenorphine/naloxone sublingual film

Intervention Type: DRUG

Buprenorphine

Buprenorphine sublingual tablets

Intervention Type: DRUG

Other Intervention Names

OX219; Zubsolv; Suboxone film; Generic buprenorphine

Eligibility Criteria

Inclusion Criteria

1. Male/female 18-65 years old

2. Able to read, comprehend & sign the informed consent form

3. Meet opioid dependence criteria in DSM-IV-TR the past 12 months

4. Have a buprenorphine-negative UDS &/or urine dipstick

5. Prepared to abstain from opioids other than the study drug & from other addictive drugs

6. Negative urine pregnancy test

7. Females of childbearing potential who use a reliable method of contraception. Females of non-childbearing potential; surgically sterile or post-menopausal as defined by being at least 50 years of age & having an absence of menses for at least 2 years

8. Clearance from the prescribing MD to be withdrawn from their prescribed opioids for subjects receiving opioids for pain

9. Lack of clinically significant abnormalities in health assessments performed at screening. Unclear cases should be approved by the medical monitor

10. At least mild withdrawal symptoms (COWS ≥9)

Exclusion Criteria

1. Pregnant, lactating or planning to be pregnant during study

2. Unwilling/unable to comply with the requirements of the protocol (e.g., pending incarceration) are in a situation/condition that may interfere with participation in the study

3. Prescribed treatment with generic buprenorphine monotherapy within 90 days prior start of treatment

4. Daily dose of methadone over 30 mg during the past week or who received the last dose of methadone less than 30 hours prior to treatment

5. Participating in other clinical studies in which medications is delivered or who have used an investigational drug/device within the last 30 days

6. Allergy, sensitivity or intolerance to BUP, NAL or any related drug; history of drug hypersensitivity or intolerance which, in the opinion of the investigator, would compromise the safety of the subject/study

7. Staff, affiliated with, or family member of the staff directly involved with this study

8. Serious untreated Axis I DSM-IV-TR psychiatric comorbidity (actively suicidal or homicidal, have untreated schizophrenia)

9. Tongue/oral deformities that may affect the absorption of the drug products

10. Current/history of clinically significant medical disorder or condition which would jeopardize the safety or impact the validity of the results. Unclear cases should be discussed with & approved by the medical monitor

11. HIV-seropositive with a CD4+ count <200, active AIDS defining infection in the last 120 days

12. Have Class III/IV congestive heart failure, symptomatic myocardial ischemia or history of long QT syndrome (or an immediate family member with this condition)

13. Currently taking Class 1A antiarrhythmic medications (e.g., quinidine, procainamide, & disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, & dofetilide)

14. Have uncontrolled hypertension, pulse oximetry ≤92%or clinically significant abnormality on 12-lead ECG, including a corrected QT (QTc) interval >450 ms

15. Severe liver disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Worldwide Clinical Trials

OTHER

Sponsor Role: collaborator

Orexo AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erik Gunderson

Role: PRINCIPAL_INVESTIGATOR

University of Virginia, PO Box 800623, Charlottesville, VA 22911

Locations

Baldwin County, Alabama, United States

Houston County, Alabama, United States

Maricopa, Arizona, United States

Beverly Hills, California, United States

Los Angeles County, California, United States

Riverside County, California, United States

San Diego County, California, United States

Broward County, Florida, United States

Colombia County, Florida, United States

Duval County, Florida, United States

Greater Metro Orlando, Florida, United States

Lake County, Florida, United States

Miami-Dade County, Florida, United States

Osceola County, Florida, United States

Palm Beach County, Florida, United States

DeKalb County, Georgia, United States

Chicagoland, Illinois, United States

Johnson County, Kansas, United States

Kenton County, Kentucky, United States

Caddo Parish, Louisiana, United States

Baltimore County, Maryland, United States

Bristol County, Massachusetts, United States

Saint Louis Metro Area, Missouri, United States

Camden County, New Jersey, United States

Warren County, New Jersey, United States

Warren County, Ohio, United States

Oklahoma County, Oklahoma, United States

Portland Metropolitan Area, Oregon, United States

Allegheny County, Pennsylvania, United States

Delaware County, Pennsylvania, United States

Philadelphia County, Pennsylvania, United States

Charleston County, South Carolina, United States

Dallas County, Texas, United States

Salt Lake County, Utah, United States

Charlottesville Metropolitan Area, Virginia, United States

Benton County, Washington, United States

Countries

United States

References

Gunderson EW, Hjelmstrom P, Sumner M; 006 Study Investigators. Effects of a higher-bioavailability buprenorphine/naloxone sublingual tablet versus buprenorphine/naloxone film for the treatment of opioid dependence during induction and stabilization: a multicenter, randomized trial. Clin Ther. 2015 Oct 1;37(10):2244-55. doi: 10.1016/j.clinthera.2015.08.025. Epub 2015 Sep 26.

Reference Type: DERIVED

PMID: 26412801 (View on PubMed)

Other Identifiers

OX219-006 Protocol Amendment 4

Identifier Type: -

Identifier Source: org_study_id