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CompletedNCT01848054Updated May 10, 2017Results posted

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

A Phase 3 interventional study of Buprenorphine/naloxone sublingual tablets and Buprenorphine in Opioid-Related Disorders and Opiate Dependence, sponsored by Orexo AB. Completed at 14 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-05-10.

Sponsored by Orexo AB · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
313
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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.

Read the 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
02

Conditions studied

  • Opioid-Related Disorders
  • Opiate Dependence

Keywords

  • opioid dependence, buprenorphine/naloxone, sublingual
03

In context

Opioid-Related Disorders

1,411 studies on the registry are indexed under Opioid-Related Disorders; 290 are open to participants now.

This study's enrollment of 313 is above the median of 63 across 1,123 interventional studies indexed under Opioid-Related Disorders.

Browse Opioid-Related Disorders studies →

Lead sponsor

Orexo AB is the lead sponsor of 5 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
313 participants (actual)

Study arms

  • 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

  • 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 · Drug: Buprenorphine

Interventions

  • DrugBuprenorphine/naloxone sublingual tablets

    Advanced-formulation buprenorphine/naloxone sublingual tablets

    Also known as: Zubsolv, OX219

  • DrugBuprenorphine

    Buprenorphine sublingual tablets

    Also known as: Generic buprenorphine

06

What researchers measure

Primary outcomes

  1. Retention in Treatment in the Per Protocol Population

    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.

    Time frame: Day 3

Secondary outcomes

  1. Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive

    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

    Time frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1

  2. AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive

    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

    Time frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1

  3. AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive

    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")

    Time frame: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1

  4. Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)

    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

    Time frame: Predose on Days 4, 8, 15, 22, and 29

  5. Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)

    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

    Time frame: Pre-dose on Days 4, 8, 15, 22, and 29

  6. Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)

    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")

    Time frame: Pre-dose on Days 4, 8, 15, 22, and 29

  7. Retention in Treatment in the Full Analysis Population

    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.

    Time frame: Day 3

07

Results

Posted Jun 24, 2015

Participant flow

Induction Phase
Participant flow — Induction Phase
MilestoneBNX Sublingual Tablets InductionBuprenorphine Induction
Started155155
Completed132147
Not completed238
Stabilization/Maintenance
Participant flow — Stabilization/Maintenance
MilestoneBNX Sublingual Tablets InductionBuprenorphine Induction
Started132147
Completed92107
Not completed4040

Outcome measures

PrimaryRetention in Treatment in the Per Protocol Population

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.

Time frame:
Day 3
Reported as:
Number · participants
Retention in Treatment in the Per Protocol Population
participantsBNX Sublingual Tablets InductionBuprenorphine Induction
Retention in Treatment in the Per Protocol Population113122
Statistical analysis
  • BNX Sublingual Tablets Induction vs Buprenorphine Induction · t-test, 2 sided · p = <0.05Comparisons between treatment groups were reported with 2-sided p values using 95% CIs for the difference.
SecondaryArea Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive

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

Time frame:
Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1
Reported as:
Least squares mean · score x hour
Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive
score x hourBNX Sublingual Tablets InductionBuprenorphine Induction
Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive7.21 ± 4.36.88 ± 4.0
SecondaryAUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive

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

Time frame:
Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1
Reported as:
Least squares mean · score x hour
AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive
score x hourBNX Sublingual Tablets InductionBuprenorphine Induction
AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive17.7 ± 13.517.4 ± 12.8
SecondaryAUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive

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")

Time frame:
Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1
Reported as:
Least squares mean · score x hour
AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive
score x hourBNX Sublingual Tablets InductionBuprenorphine Induction
AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive40.0 ± 25.339.5 ± 24.7
SecondaryMean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)

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

Time frame:
Predose on Days 4, 8, 15, 22, and 29
Reported as:
Mean · units on a scale
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
units on a scaleBNX Sublingual Tablets InductionBuprenorphine Induction
Day 4-9.4 ± 5.8-8.5 ± 5.7
Day 8-11.2 ± 4.9-10.1 ± 5.3
Day 15-11.9 ± 4.9-11.1 ± 5.2
Day 22-12.5 ± 4.7-11.6 ± 5.0
Day 29/premature discontinuation-12.5 ± 5.2-11.4 ± 5.4
SecondaryMean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)

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

Time frame:
Pre-dose on Days 4, 8, 15, 22, and 29
Reported as:
Mean · units on a scale
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
units on a scaleBNX InductionBuprenorphine Induction
Day 4-24.7 ± 16.0-18.9 ± 13.8
Day 8-27.0 ± 15.8-21.3 ± 13.6
Day 15-29.2 ± 15.5-23.3 ± 13.7
Day 22-30.8 ± 15.6-24.1 ± 13.8
Day 29/premature discontinuation-30.4 ± 16.0-24.3 ± 14.2
SecondaryMean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)

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")

Time frame:
Pre-dose on Days 4, 8, 15, 22, and 29
Reported as:
Mean · units on a scale
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
units on a scaleBNX Sublingual Tablets InductionBuprenorphine Induction
Day 4-40.1 ± 28.6-34.2 ± 29.4
Day 8-46.1 ± 29.5-39.9 ± 27.7
Day 15-48.5 ± 30.3-44.3 ± 26.1
Day 22-53.3 ± 29.5-47.2 ± 25.3
Day 29-52.7 ± 29.1-45.1 ± 29.8
SecondaryRetention in Treatment in the Full Analysis Population

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.

Time frame:
Day 3
Reported as:
Number · participants
Retention in Treatment in the Full Analysis Population
participantsBNX Sublingual Tablets InductionBuprenorphine Induction
Retention in Treatment in the Full Analysis Population132147
Statistical analysis
  • BNX Sublingual Tablets Induction vs Buprenorphine Induction · t-test, 2 sided · p = <0.05Comparisons between treatment groups were reported with 2-sided p values using 95% CIs for the difference.

Adverse events

Collected over Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BNX Sublingual Tablets Induction—1/155 (0.6%)37/155 (23.9%)
Buprenorphine Induction—2/155 (1.3%)43/155 (27.7%)
Most frequent serious events
Most frequent serious events
EventBNX Sublingual Tablets InductionBuprenorphine Induction
Diabetic ketoacidosisBlood and lymphatic system disorders1/1550/155
Attempted suicidePsychiatric disorders0/1551/155
Bacteremia secondary to pyelonephritisInfections and infestations0/1551/155
Most frequent other events
Most frequent other events
EventBNX Sublingual Tablets InductionBuprenorphine Induction
Nausea (Induction)Gastrointestinal disorders12/15513/155
Headache (Induction)Nervous system disorders11/15511/155
Insomnia (Induction)Psychiatric disorders6/15511/155
Vomiting (Induction)Gastrointestinal disorders8/1558/155

Baseline characteristics

Age, Continuous
Age, Continuous(years)BNX Sublingual Tablets InductionBuprenorphine InductionTotal
Mean38.9 ± 10.638.0 ± 10.938.4 ± 10.7
Sex: Female, Male
Sex: Female, Male(Participants)BNX Sublingual Tablets InductionBuprenorphine InductionTotal
Female5552107
Male100103203
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BNX Sublingual Tablets InductionBuprenorphine InductionTotal
American Indian or Alaska Native101
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American191938
White134135269
More than one race112
Unknown or Not Reported000
Body mass index (BMI)
Body mass index (BMI)(kg/m^2)BNX Sublingual Tablets InductionBuprenorphine InductionTotal
Mean26.2 ± 6.725.3 ± 5.025.7 ± 5.9
Duration of opioid dependence
Duration of opioid dependence(years)BNX Sublingual Tablets InductionBuprenorphine InductionTotal
Mean13.3 ± 9.311.6 ± 9.212.4 ± 9.3
08

Study locations

14 sites
  • Birmingham, Alabama, United States
  • Haleyville, Alabama, United States
  • National City, California, United States
  • Oceanside, California, United States
  • Jacksonville, Florida, United States
  • Maitland, Florida, United States
  • North Miami, Florida, United States
  • Baltimore, Maryland, United States
  • Fall River, Massachusetts, United States
  • Flowood, Mississippi, United States
  • Philadelphia, Pennsylvania, United States
  • Charleston, South Carolina, United States
  • Houston, Texas, United States
  • Salt Lake City, Utah, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 10, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01848054
Lead sponsor
Orexo AB
Collaborators
Worldwide Clinical Trials
Responsible party
Sponsor
First posted
May 7, 2013
Start date
Jun 2013
Primary completion
Jan 2014
Completion
Jan 2014
Results posted
Jun 24, 2015
Last update
May 10, 2017

Study contacts

Lynn Webster
principal investigator · Life Tree Pain Clinic, 3838 S 700 E Suite 200, Salt Lake City, UT 84106

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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