Study to Assess Efficacy and Safety of BNX Sublingual Tablets for the Induction of Treatment of Opioid Dependence

This study has been completed.
Sponsor:
Collaborator:
Worldwide Clinical Trials
Information provided by (Responsible Party):
Orexo AB
ClinicalTrials.gov Identifier:
NCT01848054
First received: May 2, 2013
Last updated: June 22, 2015
Last verified: June 2015
  Purpose

The purpose of the study was to assess the efficacy of induction treatment with buprenorphine/naloxone (BNX) sublingual tablet s compared with induction treatment with buprenorphine only. The hypothesis is that starting directly on OX219 works equally well (e.g. not significantly worse) as starting on buprenorphine only and switching to OX219 on Day 3.


Condition Intervention Phase
Opioid-Related Disorders,
Opiate Dependence
Drug: Buprenorphine/naloxone sublingual tablets
Drug: Buprenorphine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Blinded, Active-controlled Non-inferiority Study of the Efficacy and Safety of OX219 for the Induction of Treatment of Opioid Dependence

Resource links provided by NLM:


Further study details as provided by Orexo AB:

Primary Outcome Measures:
  • Retention in Treatment in the Per Protocol Population [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Retention in treatment at Day 3 in the per protocol population (n=256) was defined as the number of patients in each induction arm completing the induction phase and who received study medication on Day 3. Treatment with BNX sublingual tablets was considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between BNX and generic buprenorphine was ≥-10% in the number of patients retained in treatment on Day 3.


Secondary Outcome Measures:
  • Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive [ Time Frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1 ] [ Designated as safety issue: No ]
    Least squares mean AUC in COWS total score on Days 1 to 3; COWS scores range from 0-48, with a lower score being more favorable

  • AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive [ Time Frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1 ] [ Designated as safety issue: No ]
    Least squares mean AUC day 1 pre-dose through Day 3 in SOWS; SOWS scores range from 0-64, with a lower score being more favorable

  • AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive [ Time Frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1 ] [ Designated as safety issue: No ]
    Least squares mean AUC measurement in VAS score for cravings on Days 1 to 3; the VAS craving scores range from 0 ("no cravings") to 100 ("most intense craving I have ever had")

  • Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase) [ Time Frame: Predose on Days 4, 8, 15, 22, and 29 ] [ Designated as safety issue: No ]
    Mean change from baseline in COWS total scores during the maintenance phase (Days 4, 8, 15, 22, and 29); COWS scores range from 0-48, with a lower score being more favorable

  • Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase) [ Time Frame: Pre-dose on Days 4, 8, 15, 22, and 29 ] [ Designated as safety issue: No ]
    Mean change from baseline in SOWS total scores during the maintenance phase (Days 4, 8, 15, 22, and 29); SOWS scores range from 0-64, with a lower score being more favorable

  • Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase) [ Time Frame: Pre-dose on Days 4, 8, 15, 22, and 29 ] [ Designated as safety issue: No ]
    Mean change from baseline in VAS scores for cravings during the maintenance phase (Days 4, 8, 15, 22, and 29); the VAS craving scores range from 0 ("no cravings") to 100 ("most intense craving I have ever had")

  • Retention in Treatment in the Full Analysis Population [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Retention in treatment at Day 3 in the full analysis population (N=310) was defined as the number of patients in each induction arm completing the induction phase and who received study medication on Day 3. Treatment with BNX sublingual tablets was considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between BNX and generic buprenorphine was ≥-10% in the number of patients retained in treatment on Day 3.


Enrollment: 313
Study Start Date: June 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BNX Sublingual Tablets Induction

Day 1-2 (Blinded Induction): BNX sublingual tablets

Day 3-28 (Open-label Maintenance): BNX sublingual tablets

Drug: Buprenorphine/naloxone sublingual tablets
Advanced-formulation buprenorphine/naloxone sublingual tablets
Other Names:
  • Zubsolv
  • OX219
Active Comparator: Buprenorphine Induction

Day 1-2 (Blinded Induction): Generic buprenorphine sublingual tablets

Day 3-28 (Open-label Maintenance): BNX sublingual tablets

Drug: Buprenorphine/naloxone sublingual tablets
Advanced-formulation buprenorphine/naloxone sublingual tablets
Other Names:
  • Zubsolv
  • OX219
Drug: Buprenorphine
Buprenorphine sublingual tablets
Other Name: Generic buprenorphine

Detailed Description:

This was a prospective, randomized, multicenter, blinded, parallel-group, active-controlled, non-inferiority study conducted at 13 sites within the US. Eligible patients participated in 8 treatment visits on Days 1, 2, 3, 4, 8, 15, 22, and 29. Effectiveness of treatment was assessed as follows:

  • Retention in treatment at Day 3
  • Clinician and patient assessments of opioid withdrawal symptoms
  • Assessment opioid cravings
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to read, comprehend, and sign the informed consent form and willingly provide written informed consent
  • Prepared to engage in opioid replacement therapy and to abstain from opioid utilization other than the study drug, and from other illicit drugs
  • Male or female, 18 to 65 years of age (inclusive)
  • Met clinical criteria for opioid dependence in past 12 months based on DSM-IV-TR
  • Provided buprenorphine-negative urine drug screen prior to randomization
  • Provided negative urine pregnancy test
  • Females of childbearing potential were required to be using a reliable method of contraception (e.g., hormonal, condom with spermicide, intrauterine device [IUD]) after the screening visit and for the duration of the study
  • Participants receiving opioids for pain must receive clearance from their prescribing physician to be withdrawn from their prescribed opioids
  • Generally good health as determined by the investigator
  • Participants should demonstrate at least mild withdrawal symptoms (defined as a COWS score >9 at Day 1 predose)

Exclusion Criteria:

  • Females who are pregnant or lactating, or planning to be pregnant during study
  • Any previous prescribed treatment with buprenorphine monotherapy (e.g., generic buprenorphine sublingual tablets)
  • Prescribed treatment with buprenorphine or naloxone within 90 days prior to start of treatment
  • Methadone patients with any daily dose over 30 mg during the past week and who received the last dose of methadone less than 30 hours prior to start of treatment
  • Participants who are unwilling or unable to comply with the requirements of the protocol
  • Participants who are participating in any other clinical study in which medication(s) are being delivered or who have used an investigational drug or device within the last 30 days
  • Participants with any known allergy or sensitivity or intolerance to buprenorphine, naloxone, or any related drug
  • Participants who are on the staff, affiliated with, or a family member of the staff personnel directly involved with this study
  • Participants with serious untreated Axis I DSM-IV-TR psychiatric comorbidity
  • Tongue piercing or other piercings in the mouth, including lips and cheek
  • Participants with current or history of clinically significant medical disorder or condition
  • Participants who are human immunodeficiency virus (HIV)-seropositive with a CD4+ count <200 or active acquired immune deficiency syndrome (AIDS)
  • Participants who have any Class III or IV congestive heart failure, symptomatic myocardial ischemia, a history of long QT syndrome.
  • Participants who are currently taking Class 1A antiarrhythmic medications or Class III antiarrhythmic medications
  • Participants who have uncontrolled hypertension or clinically significant ECG abnormalities
  • Participants who have a pulse oximetry ≤93% at screening, due to any medical reason.
  • Individuals with AST or ALT levels ≥3 X the upper limit of normal or total bilirubin or creatinine ≥1.5 X ULN, on the screening laboratory assessments
  • Participants with known significant liver disease.
  • Participants who take any medication, nutraceutical, herbal product with known CYP3A4 inhibition or induction properties within 14 days of screening.
  • Participants who are at suicidal risk
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848054

Locations
United States, Alabama
Birmingham, Alabama, United States
Haleyville, Alabama, United States
United States, California
National City, California, United States
Oceanside, California, United States
United States, Florida
Jacksonville, Florida, United States
Maitland, Florida, United States
North Miami, Florida, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Fall River, Massachusetts, United States
United States, Mississippi
Flowood, Mississippi, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Texas
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
Sponsors and Collaborators
Orexo AB
Worldwide Clinical Trials
Investigators
Principal Investigator: Lynn Webster Life Tree Pain Clinic, 3838 S 700 E Suite 200, Salt Lake City, UT 84106
  More Information

No publications provided

Responsible Party: Orexo AB
ClinicalTrials.gov Identifier: NCT01848054     History of Changes
Other Study ID Numbers: OX219-007
Study First Received: May 2, 2013
Results First Received: April 10, 2015
Last Updated: June 22, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Orexo AB:
opioid dependence, buprenorphine/naloxone, sublingual

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

ClinicalTrials.gov processed this record on June 29, 2015