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

• Sponsor: Orexo AB (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01848054
• Collaborator: Worldwide Clinical Trials (Other)
• Enrollment: 313
• Locations: 14
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 22.4
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Opioid-Related Disorders; Opiate Dependence	Drug: Buprenorphine/naloxone sublingual tablets; Drug: Buprenorphine	Phase 3

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 313 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Generic buprenorphine

Outcome Measures

Primary Outcome Measures

1. Retention in Treatment in the Per Protocol Population [Day 3]

   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

1. Area Under the Curve (AUC) in Clinical Opiate Withdrawal Scale (COWS) Total Score on Days 1 to 3 Inclusive [Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1]

   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

2. AUC in Subjective Opiate Withdrawal Scale (SOWS) Total Score on Days 1 to 3 Inclusive [Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1]

   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

3. AUC in Visual Analog Scale (VAS) Score for Craving on Days 1 to 3 Inclusive [Pre-dose on Days 1-3 and 0.5, 1, 1.5, 3, and 6 hours post-dose on Day 1]

   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")

4. Mean Change From Baseline in COWS Total Score After Day 3 (Maintenance Phase) [Predose on Days 4, 8, 15, 22, and 29]

   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

5. Mean Change From Baseline in SOWS Total Score After Day 3 (Maintenance Phase) [Pre-dose on Days 4, 8, 15, 22, and 29]

   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

6. Mean Change From Baseline in the VAS Score for Cravings After Day 3 (Maintenance Phase) [Pre-dose on Days 4, 8, 15, 22, and 29]

   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")

7. Retention in Treatment in the Full Analysis Population [Day 3]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: 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:

• 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

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Haleyville	Alabama	United States
3		National City	California	United States
4		Oceanside	California	United States
5		Jacksonville	Florida	United States
6		Maitland	Florida	United States
7		North Miami	Florida	United States
8		Baltimore	Maryland	United States
9		Fall River	Massachusetts	United States
10		Flowood	Mississippi	United States
11		Philadelphia	Pennsylvania	United States
12		Charleston	South Carolina	United States
13		Houston	Texas	United States
14		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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Orexo AB
• ClinicalTrials.gov Identifier: NCT01848054
• Other Study ID Numbers: OX219-007
• First Posted: May 7, 2013
• Last Update Posted: May 10, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Orexo AB: opioid dependence, buprenorphine/naloxone, sublingual
• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone

Study Results

Participant Flow

Pre-assignment Detail	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
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: Induction Phase
STARTED	132	147
COMPLETED	92	107
NOT COMPLETED	40	40

Baseline Characteristics

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction	Total
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 Participants	155	155	310
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.9 (10.6)	38.0 (10.9)	38.4 (10.7)
Sex: Female, Male (Count of Participants)
Female	55 35.5%	52 33.5%	107 34.5%
Male	100 64.5%	103 66.5%	203 65.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%	0 0%	1 0.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	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%
Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.2 (6.7)	25.3 (5.0)	25.7 (5.9)
Duration of opioid dependence (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (9.3)	11.6 (9.2)	12.4 (9.3)

Outcome Measures

1. Primary Outcome

Title	Retention in Treatment in the Per Protocol Population
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

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction
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)
Measure Participants	128	128
Number [participants]	113 72.9%	122 78.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BNX Sublingual Tablets Induction, Buprenorphine Induction
	Comments
	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
	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
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

Outcome Measure Data

Analysis Population Description

Full analysis population

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction
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)
Measure Participants	154	154
Least Squares Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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)
Measure Participants	147	153
Least Squares Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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
Measure Participants	153	155
Least Squares Mean (Standard Deviation) [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)
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

Outcome Measure Data

Analysis Population Description

Full analysis population; patients with missing data were excluded from the analysis

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction
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)
Measure Participants	155	155
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)
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

Outcome Measure Data

Analysis Population Description

Full analysis population; patients with missing data were excluded from the analysis

Arm/Group Title	BNX Induction	Buprenorphine Induction
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)
Measure Participants	155	155
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)
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

Outcome Measure Data

Analysis Population Description

Full analysis population; patients with missing data were excluded from the analysis

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction
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)
Measure Participants	155	155
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
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

Outcome Measure Data

Analysis Population Description

Full analysis population; patients with missing data were excluded from the analysis

Arm/Group Title	BNX Sublingual Tablets Induction	Buprenorphine Induction
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)
Measure Participants	155	155
Number [participants]	132 85.2%	147 94.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BNX Sublingual Tablets Induction, Buprenorphine Induction
	Comments
	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
	Method	t-test, 2 sided
	Comments	Comparisons between treatment groups were reported with 2-sided p values using 95% CIs for the difference.

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BNX Sublingual Tablets Induction		Buprenorphine Induction
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/155 (0.6%)		2/155 (1.3%)
Blood and lymphatic system disorders
Diabetic ketoacidosis	1/155 (0.6%)	1	0/155 (0%)	0
Infections and infestations
Bacteremia secondary to pyelonephritis	0/155 (0%)	0	1/155 (0.6%)	1
Psychiatric disorders
Attempted suicide	0/155 (0%)	0	1/155 (0.6%)	1
Other (Not Including Serious) Adverse Events
	BNX Sublingual Tablets Induction		Buprenorphine Induction
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/155 (23.9%)		43/155 (27.7%)
Gastrointestinal disorders
Nausea (Induction)	12/155 (7.7%)	12	13/155 (8.4%)	13
Vomiting (Induction)	8/155 (5.2%)	8	8/155 (5.2%)	8
Nervous system disorders
Headache (Induction)	11/155 (7.1%)	11	11/155 (7.1%)	11
Psychiatric disorders
Insomnia (Induction)	6/155 (3.9%)	6	11/155 (7.1%)	11

Limitations/Caveats

[Not Specified]

More Information

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.