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Trial record 41 of 186 for:    BUPRENORPHINE AND NALOXONE

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

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ClinicalTrials.gov Identifier: NCT01848054
Recruitment Status : Completed
First Posted : May 7, 2013
Results First Posted : June 24, 2015
Last Update Posted : May 10, 2017
Sponsor:
Collaborator:
Worldwide Clinical Trials
Information provided by (Responsible Party):
Orexo AB

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Opioid-Related Disorders
Opiate Dependence
Interventions Drug: Buprenorphine/naloxone sublingual tablets
Drug: Buprenorphine
Enrollment 313
Recruitment Details  
Pre-assignment Details A total of 313 patients were enrolled. Three patients who were randomized did not receive study drug, making the participant flow 310.
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label) Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Period Title: Induction Phase
Started 155 155
Completed 132 147
Not Completed 23 8
Period Title: Stabilization/Maintenance
Started 132 147
Completed 92 107
Not Completed 40 40
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction Total
Hide Arm/Group Description Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label) Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label) Total of all reporting groups
Overall Number of Baseline Participants 155 155 310
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 155 participants 310 participants
38.9  (10.6) 38.0  (10.9) 38.4  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 155 participants 310 participants
Female
55
  35.5%
52
  33.5%
107
  34.5%
Male
100
  64.5%
103
  66.5%
203
  65.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 155 participants 310 participants
American Indian or Alaska Native
1
   0.6%
0
   0.0%
1
   0.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
19
  12.3%
19
  12.3%
38
  12.3%
White
134
  86.5%
135
  87.1%
269
  86.8%
More than one race
1
   0.6%
1
   0.6%
2
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Body mass index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 155 participants 155 participants 310 participants
26.2  (6.7) 25.3  (5.0) 25.7  (5.9)
Duration of opioid dependence  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 155 participants 310 participants
13.3  (9.3) 11.6  (9.2) 12.4  (9.3)
1.Primary Outcome
Title Retention in Treatment in the Per Protocol Population
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 128 128
Measure Type: Number
Unit of Measure: participants
113 122
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BNX Sublingual Tablets Induction, Buprenorphine Induction
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The primary efficacy analysis of retention in treatment at Day 3 was assessed in the per protocol population. In addition, a sensitivity analysis assessed retention in treatment in the full analysis population. For these assessments, the margin to determine non-inferiority (i.e., lower limit of the 95% CI for the difference between BNX and generic buprenorphine of ≥–10%) was selected based on clinical experience to justify comparison between the 2 treatments.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Comparisons between treatment groups were reported with 2-sided p values using 95% CIs for the difference.
2.Secondary Outcome
Title Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 154 154
Least Squares Mean (Standard Deviation)
Unit of Measure: score x hour
7.21  (4.3) 6.88  (4.0)
3.Secondary Outcome
Title AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis and are reflected in the number of participants analyzed
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 147 153
Least Squares Mean (Standard Deviation)
Unit of Measure: score x hour
17.7  (13.5) 17.4  (12.8)
4.Secondary Outcome
Title AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis and are reflected in the number of participants analyzed
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)

Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with OX219 buprenorphine/naloxone sublingual tablets (open-label)

OX219 buprenorphine/naloxone: OX219 buprenorphine/naloxone sublingual tablets

Buprenorphine: Buprenorphine sublingual tablets

Overall Number of Participants Analyzed 153 155
Least Squares Mean (Standard Deviation)
Unit of Measure: score x hour
40.0  (25.3) 39.5  (24.7)
5.Secondary Outcome
Title Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Day 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 155 155
Mean (Standard Deviation)
Unit of Measure: units on a scale
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)
6.Secondary Outcome
Title Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis
Arm/Group Title BNX Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 155 155
Mean (Standard Deviation)
Unit of Measure: units on a scale
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)
7.Secondary Outcome
Title Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Overall Number of Participants Analyzed 155 155
Mean (Standard Deviation)
Unit of Measure: units on a scale
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)
8.Secondary Outcome
Title Retention in Treatment in the Full Analysis Population
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis population; patients with missing data were excluded from the analysis
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description:
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with OX219 buprenorphine/naloxone sublingual tablets (open-label)
Overall Number of Participants Analyzed 155 155
Measure Type: Number
Unit of Measure: participants
132 147
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BNX Sublingual Tablets Induction, Buprenorphine Induction
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The primary efficacy analysis of retention in treatment at Day 3 was assessed in the per protocol population. In addition, a sensitivity analysis assessed retention in treatment in the full analysis population. For these assessments, the margin to determine non-inferiority (i.e., lower limit of the 95% CI for the difference between BNX and generic buprenorphine of ≥–10%) was selected based on clinical experience to justify comparison between the 2 treatments.
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Comparisons between treatment groups were reported with 2-sided p values using 95% CIs for the difference.
Time Frame Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
Adverse Event Reporting Description The safety population included 310 patients.
 
Arm/Group Title BNX Sublingual Tablets Induction Buprenorphine Induction
Hide Arm/Group Description Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label) Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
All-Cause Mortality
BNX Sublingual Tablets Induction Buprenorphine Induction
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BNX Sublingual Tablets Induction Buprenorphine Induction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/155 (0.65%)      2/155 (1.29%)    
Blood and lymphatic system disorders     
Diabetic ketoacidosis  1 [1]  1/155 (0.65%)  1 0/155 (0.00%)  0
Infections and infestations     
Bacteremia secondary to pyelonephritis  1 [2]  0/155 (0.00%)  0 1/155 (0.65%)  1
Psychiatric disorders     
Attempted suicide  1 [2]  0/155 (0.00%)  0 1/155 (0.65%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
[1]
Considered unrelated to study treatment; reported during the blinded induction phase
[2]
Considered unrelated to study treatment; reported during the open-label maintenance phase
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BNX Sublingual Tablets Induction Buprenorphine Induction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   37/155 (23.87%)      43/155 (27.74%)    
Gastrointestinal disorders     
Nausea (Induction)  1 [1]  12/155 (7.74%)  12 13/155 (8.39%)  13
Vomiting (Induction)  1 [1]  8/155 (5.16%)  8 8/155 (5.16%)  8
Nervous system disorders     
Headache (Induction)  1 [1]  11/155 (7.10%)  11 11/155 (7.10%)  11
Psychiatric disorders     
Insomnia (Induction)  1 [1]  6/155 (3.87%)  6 11/155 (7.10%)  11
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
[1]
Adverse events reported during the blinded induction phase
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lynn R. Webster, MD
Organization: PRA International
Phone: 801-892-5140
EMail: LRWebsterMD@gmail.com
Layout table for additonal information
Responsible Party: Orexo AB
ClinicalTrials.gov Identifier: NCT01848054     History of Changes
Other Study ID Numbers: OX219-007
First Submitted: May 2, 2013
First Posted: May 7, 2013
Results First Submitted: April 10, 2015
Results First Posted: June 24, 2015
Last Update Posted: May 10, 2017