Trial Outcomes & Findings for Study to Assess Efficacy and Safety of BNX Sublingual Tablets for the Induction of Treatment of Opioid Dependence (NCT NCT01848054)
NCT ID: NCT01848054
Last Updated: 2017-05-10
Results Overview
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.
COMPLETED
PHASE3
313 participants
Day 3
2017-05-10
Participant Flow
A total of 313 patients were enrolled. Three patients who were randomized did not receive study drug, making the participant flow 310.
Participant milestones
| Measure |
BNX Sublingual Tablets Induction
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Induction Phase
STARTED
|
155
|
155
|
|
Induction Phase
COMPLETED
|
132
|
147
|
|
Induction Phase
NOT COMPLETED
|
23
|
8
|
|
Stabilization/Maintenance
STARTED
|
132
|
147
|
|
Stabilization/Maintenance
COMPLETED
|
92
|
107
|
|
Stabilization/Maintenance
NOT COMPLETED
|
40
|
40
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess Efficacy and Safety of BNX Sublingual Tablets for the Induction of Treatment of Opioid Dependence
Baseline characteristics by cohort
| Measure |
BNX Sublingual Tablets Induction
n=155 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Total
n=310 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.9 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
38.0 years
STANDARD_DEVIATION 10.9 • n=7 Participants
|
38.4 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
100 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
19 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
134 Participants
n=5 Participants
|
135 Participants
n=7 Participants
|
269 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Body mass index (BMI)
|
26.2 kg/m^2
STANDARD_DEVIATION 6.7 • n=5 Participants
|
25.3 kg/m^2
STANDARD_DEVIATION 5.0 • n=7 Participants
|
25.7 kg/m^2
STANDARD_DEVIATION 5.9 • n=5 Participants
|
|
Duration of opioid dependence
|
13.3 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
11.6 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
12.4 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 3Population: 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.
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=128 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=128 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Retention in Treatment in the Per Protocol Population
|
113 participants
|
122 participants
|
SECONDARY outcome
Timeframe: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1Population: Full analysis population
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
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=154 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=154 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive
|
7.21 score x hour
Standard Deviation 4.3
|
6.88 score x hour
Standard Deviation 4.0
|
SECONDARY outcome
Timeframe: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1Population: Full analysis population; patients with missing data were excluded from the analysis and are reflected in the number of participants analyzed
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
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=147 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=153 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive
|
17.7 score x hour
Standard Deviation 13.5
|
17.4 score x hour
Standard Deviation 12.8
|
SECONDARY outcome
Timeframe: Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1Population: Full analysis population; patients with missing data were excluded from the analysis and are reflected in the number of participants analyzed
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")
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=153 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive
|
40.0 score x hour
Standard Deviation 25.3
|
39.5 score x hour
Standard Deviation 24.7
|
SECONDARY outcome
Timeframe: Predose on Days 4, 8, 15, 22, and 29Population: Full analysis population; patients with missing data were excluded from the analysis
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
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=155 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Day 15
|
-11.9 units on a scale
Standard Deviation 4.9
|
-11.1 units on a scale
Standard Deviation 5.2
|
|
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Day 22
|
-12.5 units on a scale
Standard Deviation 4.7
|
-11.6 units on a scale
Standard Deviation 5.0
|
|
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Day 29/premature discontinuation
|
-12.5 units on a scale
Standard Deviation 5.2
|
-11.4 units on a scale
Standard Deviation 5.4
|
|
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Day 4
|
-9.4 units on a scale
Standard Deviation 5.8
|
-8.5 units on a scale
Standard Deviation 5.7
|
|
Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase)
Day 8
|
-11.2 units on a scale
Standard Deviation 4.9
|
-10.1 units on a scale
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: Pre-dose on Days 4, 8, 15, 22, and 29Population: Full analysis population; patients with missing data were excluded from the analysis
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
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=155 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Day 4
|
-24.7 units on a scale
Standard Deviation 16.0
|
-18.9 units on a scale
Standard Deviation 13.8
|
|
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Day 8
|
-27.0 units on a scale
Standard Deviation 15.8
|
-21.3 units on a scale
Standard Deviation 13.6
|
|
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Day 15
|
-29.2 units on a scale
Standard Deviation 15.5
|
-23.3 units on a scale
Standard Deviation 13.7
|
|
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Day 22
|
-30.8 units on a scale
Standard Deviation 15.6
|
-24.1 units on a scale
Standard Deviation 13.8
|
|
Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase)
Day 29/premature discontinuation
|
-30.4 units on a scale
Standard Deviation 16.0
|
-24.3 units on a scale
Standard Deviation 14.2
|
SECONDARY outcome
Timeframe: Pre-dose on Days 4, 8, 15, 22, and 29Population: Full analysis population; patients with missing data were excluded from the analysis
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")
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=155 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Day 4
|
-40.1 units on a scale
Standard Deviation 28.6
|
-34.2 units on a scale
Standard Deviation 29.4
|
|
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Day 8
|
-46.1 units on a scale
Standard Deviation 29.5
|
-39.9 units on a scale
Standard Deviation 27.7
|
|
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Day 15
|
-48.5 units on a scale
Standard Deviation 30.3
|
-44.3 units on a scale
Standard Deviation 26.1
|
|
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Day 22
|
-53.3 units on a scale
Standard Deviation 29.5
|
-47.2 units on a scale
Standard Deviation 25.3
|
|
Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase)
Day 29
|
-52.7 units on a scale
Standard Deviation 29.1
|
-45.1 units on a scale
Standard Deviation 29.8
|
SECONDARY outcome
Timeframe: Day 3Population: Full analysis population; patients with missing data were excluded from the analysis
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.
Outcome measures
| Measure |
BNX Sublingual Tablets Induction
n=155 Participants
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 Participants
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Retention in Treatment in the Full Analysis Population
|
132 participants
|
147 participants
|
Adverse Events
BNX Sublingual Tablets Induction
Buprenorphine Induction
Serious adverse events
| Measure |
BNX Sublingual Tablets Induction
n=155 participants at risk
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 participants at risk
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Blood and lymphatic system disorders
Diabetic ketoacidosis
|
0.65%
1/155 • Number of events 1 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
0.00%
0/155 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
|
Psychiatric disorders
Attempted suicide
|
0.00%
0/155 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
0.65%
1/155 • Number of events 1 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
|
Infections and infestations
Bacteremia secondary to pyelonephritis
|
0.00%
0/155 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
0.65%
1/155 • Number of events 1 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
Other adverse events
| Measure |
BNX Sublingual Tablets Induction
n=155 participants at risk
Days 1-2: Induction on BNX sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
Buprenorphine Induction
n=155 participants at risk
Days 1-2: Induction on buprenorphine sublingual tablets (blinded); Days 3-28: Maintenance treatment with BNX sublingual tablets (open-label)
|
|---|---|---|
|
Gastrointestinal disorders
Nausea (Induction)
|
7.7%
12/155 • Number of events 12 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
8.4%
13/155 • Number of events 13 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
|
Nervous system disorders
Headache (Induction)
|
7.1%
11/155 • Number of events 11 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
7.1%
11/155 • Number of events 11 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
|
Psychiatric disorders
Insomnia (Induction)
|
3.9%
6/155 • Number of events 6 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
7.1%
11/155 • Number of events 11 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
|
Gastrointestinal disorders
Vomiting (Induction)
|
5.2%
8/155 • Number of events 8 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
5.2%
8/155 • Number of events 8 • Blinded Induction Phase (Days 1-2) and Open Label Maintenance Phase (Days 3-28)
The safety population included 310 patients.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place