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Trial record 9 of 186 for:    BUPRENORPHINE AND NALOXONE

Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone

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ClinicalTrials.gov Identifier: NCT00637000
Recruitment Status : Completed
First Posted : March 17, 2008
Results First Posted : May 9, 2014
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
Indivior Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Opioid-related Disorders
Interventions Drug: Buprenorphine soluble film
Drug: Buprenorphine/naloxone film strip
Drug: Placebo
Enrollment 38
Recruitment Details Patient enrollment commenced 03/19/08 and was completed 09/19/08. The study site was an in-patient research-based clinic affiliated with Johns Hopkins University School of Medicine.
Pre-assignment Details During screening run-in, subjects received 30 mg morphine subcutaneously up to 4 times/day for up to 13 days. Subjects underwent two test sessions, consisting of a challenge of naloxone (0.4 mg) or placebo intramuscularly and evaluation for the severity of withdrawal. Subjects able to detect withdrawal were randomized to treatment.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Period Title: Overall Study
Started 20 [1] 18 [1]
Evaluable 18 16
Completed 16 15
Not Completed 4 3
Reason Not Completed
Withdrawal by Subject             4             3
[1]
Randomized and treated
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film Total
Hide Arm/Group Description

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Total of all reporting groups
Overall Number of Baseline Participants 20 18 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 18 participants 38 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
20
 100.0%
18
 100.0%
38
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 18 participants 38 participants
40.2  (10) 40.2  (7.9) 40.2  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 18 participants 38 participants
Female
5
  25.0%
7
  38.9%
12
  31.6%
Male
15
  75.0%
11
  61.1%
26
  68.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 18 participants 38 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
20
 100.0%
18
 100.0%
38
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 18 participants 38 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   5.6%
1
   2.6%
Black or African American
8
  40.0%
4
  22.2%
12
  31.6%
White
12
  60.0%
13
  72.2%
25
  65.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 18 participants 38 participants
20 18 38
1.Primary Outcome
Title Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at Baseline and the Peak COWS up to 23.5 Hours After the First Administration
Hide Description

The COWS is an 11-item instrument used to assess symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the response to each of the 11 items and cover a range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderate/severe withdrawal, and 37-48 severe withdrawal.

The baseline COWS was the score obtained 30 minutes prior to administration of soluble films on Day 1. Peak COWS was the highest COWS score obtained between 1-23.5 hours post administration on Day 1.

Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 9.1  (5.5) 10.1  (6.4)
Peak 4.2  (2.4) 5.7  (3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments To test the primary study hypothesis that neither soluble film formulation would precipitate an opioid withdrawal syndrome, peak COWS score in the 23.5 hour period after the initial soluble film administration were compared to pre-administration baseline COWS scores (30 minutes prior to soluble film administration) using a group by time repeated measures model with a first-order autoregressive covariance structure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments The statistical method used was a group by time repeated measures model with a first-order autoregressive covariance structure
2.Secondary Outcome
Title Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction
Hide Description

The COWS is an 11-item instrument used to assess symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the response to each of the 11 items and cover a range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderate/severe withdrawal, and 37-48 severe withdrawal.

The end of induction COWS was the score obtained 47.5 hours after first administration of soluble films on Day 1. Peak post induction COWS was the highest COWS score obtained on Days 2-5.

Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 0.6  (0.5) 1.0  (1.0)
Peak Post Induction 1.0  (1.0) 2.6  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
3.Secondary Outcome
Title Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration
Hide Description Pupil diameter was measured at baseline and at intervals post drug administration on Day 1. Peak measurement is the maximum pupil diameter recorded from 15 minutes to 23.5 hours post administration of study intervention.
Time Frame Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: mm
Baseline 6.24  (0.97) 6.11  (0.88)
Peak 4.39  (6.27) 5.99  (0.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
4.Secondary Outcome
Title Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration
Hide Description Pupil diameter was measured at baseline and at intervals post drug administration on Day 1. Peak measurement is the minimum pupil diameter recorded from 15 minutes to 23.5 hours post administration of study intervention.
Time Frame Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: mm
Baseline 6.24  (0.97) 6.11  (0.88)
Peak 4.39  (1.27) 4.32  (1.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
5.Secondary Outcome
Title Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5)
Hide Description Pupil diameter was measured at the end of induction (47.5 hours after the first administration of study intervention) and at intervals during the post-induction period (Days 3-5). Peak post induction measurement is the minimum pupil diameter recorded during days 3-5.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: mm
End of Induction 5.3  (1.2) 5.1  (1.2)
Peak Post Induction 4.1  (1.1) 3.6  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
6.Secondary Outcome
Title Visual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: "How High Are You?"
Hide Description

A visual analog scale (VAS) was used by participants to answer the subjective question, "How high are you?". The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=not high and 100=extremely high.

The baseline VAS was the score obtained 30 minutes prior to administration of soluble films on Day 1. Peak VAS was the highest VAS score obtained between 1-23.5 hours post administration on Day 1.

Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 0.0  (0.3)
Peak 5.8  (12.9) 13.7  (24.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
7.Secondary Outcome
Title Visual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: “Do You Feel Any Drug Effect?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you feel any drug effect?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no effect and 100=maximum effect.
Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 0.0  (0.0)
Peak 44.3  (31.5) 50.4  (26.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
8.Secondary Outcome
Title Visual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: “Does the Drug Have Any Good Effects?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you feel any good effects?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no good effects and 100=maximum good effects.
Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 0.0  (0.0)
Peak 62.3  (35.1) 57.6  (31.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
9.Secondary Outcome
Title Visual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: “Does the Drug Have Any Bad Effects?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Does the drug have any bad effects?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no bad effects and 100=maximum bad effects.
Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 12.5  (34.2)
Peak 4.4  (11.8) 6.1  (12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.762
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
10.Secondary Outcome
Title CVisual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: “Do You Like the Drug?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you like the drug?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no liking and 100=maximum liking.
Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 0.0  (0.0)
Peak 61.2  (40.0) 59.4  (34.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
11.Secondary Outcome
Title Visual Analog Scale (VAS) Score at Baseline and the Peak (Maximum Increase) VAS up to 23.5 Hours After First Administration for the Question: “Does the Drug Make You Sick?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Does the drug make you sick?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no effect and 100=maximum effect.
Time Frame Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.0  (0.0) 12.5  (34.2)
Peak 2.1  (6.1) 4.5  (12.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments The p-value is not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
12.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: "How High Are You?"
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, "How high are you?". The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=not high and 100=extremely high.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 0.0  (0.0) 6.3  (25.0)
Peak Post Induction 8.2  (18.2) 12.9  (30.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
13.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: “Do You Feel Any Drug Effect?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you feel any drug effect?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no effect and 100=maximum effect.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 7.9  (16.8) 15.9  (28.6)
Peak Post Induction 53.2  (41.0) 47.4  (27.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
14.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: “Do You Feel Any Good Effects?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you feel any good effects?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no good effects and 100=maximum good effects.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 11.0  (26.0) 20.2  (30.0)
Peak Post Induction 61.7  (39.8) 52.9  (33.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
15.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: “Does the Drug Have Any Bad Effects?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Does the drug have any bad effects?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no bad effects and 100=maximum bad effects.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 0.0  (0.0) 0.3  (0.8)
Peak Post Induction 0.4  (1.2) 0.4  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.117
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
16.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: “Do You Like the Drug?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Do you like the drug?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no liking and 100=maximum liking.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 14.9  (29.6) 24.3  (37.0)
Peak Post Induction 61.7  (41.0) 55.4  (35.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
17.Secondary Outcome
Title Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: “Does the Drug Make You Sick?”
Hide Description A visual analog scale (VAS) was used by participants to answer the subjective question, “Does the drug make you sick?”. The question was one of six used to measure the extent of opioid blockade following study intervention. VAS questions were selected based on previous demonstration of their sensitivity to opioid agonist and antagonist effects (Preston et al., 1988). Participants indicated how high they feel by marking a score on a horizontal line with 0=no effect and 100=maximum effect.
Time Frame End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the evaluable population includes all subjects randomized to the study who completed the study through the first two days of soluble films administration and assessments for 23.5 hours after the first day of soluble films administration.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 18 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
End of Induction 0  (0) 0.3  (0.7)
Peak Post Induction 0  (0) 0.7  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sublingual Buprenorphine Soluble Film, Sublingual Buprenorphine/Naloxone Soluble Film
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.238
Comments The p-value was not adjusted for multiple comparisons.
Method Repeated measures model
Comments Group by time repeated measures model with a first-order autoregressive covariance structure.
18.Secondary Outcome
Title Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description

Treatment-emergent AEs were defined as those starting on the day of the first treatment with buprenorphine soluble films or buprenorphine/ naloxone soluble films until residential research facility release, which typically happened on Day 6.

Severity was graded by the investigator as mild (grade 1), moderate (grade 2) and severe (grade 3).

Time Frame Day 1-6
Hide Outcome Measure Data
Hide Analysis Population Description
The randomized population included all subjects who were randomized to soluble films and received at least one dose of soluble films.
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description:

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Overall Number of Participants Analyzed 20 18
Measure Type: Number
Unit of Measure: participants
With any TEAE 20 18
With grade 1 TEAE 15 16
With grade 2 TEAE 19 16
With grade 3 TEAE 0 0
Time Frame Days 1-6. Treatment-emergent AEs were defined as those starting on the day of the first treatment with buprenorphine soluble films or buprenorphine/ naloxone soluble films until residential research facility release, which typically happened on Day 6.
Adverse Event Reporting Description Adverse event data were collected by the investigator during daily subject interviews.
 
Arm/Group Title Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Hide Arm/Group Description

Day 1: Buprenorphine soluble film administered at a dose of 4 mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2-5: Buprenorphine soluble film administered at a dose of 16 mg to 24 mg once per day, plus placebo. Dosing occurred at 0900 hours.

Day 1: Buprenorphine/naloxone soluble film administered at a dose of 4mg/1mg 3 times per day, plus placebo. Dosing occurred at 0900, 1100, and 2000 hours.

Days 2 to 5: Buprenorphine/naloxone soluble film administered at a dose of 16mg/4 mg to 24 mg/6 mg once per day, plus placebo. Dosing occurred at 0900 hours.

All-Cause Mortality
Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/18 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sublingual Buprenorphine Soluble Film Sublingual Buprenorphine/Naloxone Soluble Film
Affected / at Risk (%) Affected / at Risk (%)
Total   20/20 (100.00%)   18/18 (100.00%) 
Cardiac disorders     
Tachycardia  1  6/20 (30.00%)  3/18 (16.67%) 
Ear and labyrinth disorders     
Lacrimation increased  1  4/20 (20.00%)  5/18 (27.78%) 
Gastrointestinal disorders     
Abdominal pain  1  1/20 (5.00%)  3/18 (16.67%) 
Constipation  1  5/20 (25.00%)  6/18 (33.33%) 
Dental caries  1  0/20 (0.00%)  1/18 (5.56%) 
Diarrhoea  1  3/20 (15.00%)  0/18 (0.00%) 
Dyspepsia  1  2/20 (10.00%)  4/18 (22.22%) 
Nausea  1  6/20 (30.00%)  5/18 (27.78%) 
Stomach discomfort  1  9/20 (45.00%)  9/18 (50.00%) 
Toothache  1  2/20 (10.00%)  1/18 (5.56%) 
Vomiting  1  2/20 (10.00%)  3/18 (16.67%) 
General disorders     
Chills  1  2/20 (10.00%)  2/18 (11.11%) 
Cold sweat  1  6/20 (30.00%)  5/18 (27.78%) 
Hot flush  1  0/20 (0.00%)  2/18 (11.11%) 
Injection site erythema  1 [1]  0/20 (0.00%)  1/18 (5.56%) 
Injection site pruritus  1 [1]  0/20 (0.00%)  1/18 (5.56%) 
Irritability  1  5/20 (25.00%)  7/18 (38.89%) 
Infections and infestations     
Fungal infection  1  0/20 (0.00%)  1/18 (5.56%) 
Joint abscess  1  0/20 (0.00%)  1/18 (5.56%) 
Investigations     
Liver function test abnormal  1  0/20 (0.00%)  1/18 (5.56%) 
Tuberculosis skin test positive  1  3/20 (15.00%)  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders     
Abscess limb  1  0/20 (0.00%)  1/18 (5.56%) 
Arthralgia  1  5/20 (25.00%)  5/18 (27.78%) 
Back pain  1  3/20 (15.00%)  4/18 (22.22%) 
Myalgia  1  3/20 (15.00%)  1/18 (5.56%) 
Pain in extremity  1  5/20 (25.00%)  1/18 (5.56%) 
Nervous system disorders     
Dizziness  1  0/20 (0.00%)  1/18 (5.56%) 
Headache  1  11/20 (55.00%)  10/18 (55.56%) 
Restlessness  1  9/20 (45.00%)  8/18 (44.44%) 
Tremor  1  5/20 (25.00%)  2/18 (11.11%) 
Psychiatric disorders     
Anxiety  1  9/20 (45.00%)  11/18 (61.11%) 
Drug withdrawal syndrome  1  14/20 (70.00%)  13/18 (72.22%) 
Hyperventilation  1  0/20 (0.00%)  1/18 (5.56%) 
Insomnia  1  13/20 (65.00%)  12/18 (66.67%) 
Renal and urinary disorders     
Dysuria  1  0/20 (0.00%)  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  0/20 (0.00%)  1/18 (5.56%) 
Rhinorrhoea  1  10/20 (50.00%)  6/18 (33.33%) 
Yawning  1  4/20 (20.00%)  4/18 (22.22%) 
Skin and subcutaneous tissue disorders     
Erythema  1  0/20 (0.00%)  1/18 (5.56%) 
Piloerection  1  2/20 (10.00%)  7/18 (38.89%) 
Pruritus  1  0/20 (0.00%)  1/18 (5.56%) 
Tinea pedis  1  0/20 (0.00%)  1/18 (5.56%) 
Rash  1  2/20 (10.00%)  0/18 (0.00%) 
Vascular disorders     
Hypertension  1  2/20 (10.00%)  0/18 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
[1]
Injection site AEs were due to morphine injections.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Rolley E. Johnson, PharmD, Vice President, Clinical, Scientific and Regulatory Affairs
Organization: Reckitt Benckiser Pharmaceuticals, Inc.
Phone: 804-379-1090 ext 7089
EMail: ed.johnson@reckittbenckiser.com
Layout table for additonal information
Responsible Party: Indivior Inc.
ClinicalTrials.gov Identifier: NCT00637000     History of Changes
Other Study ID Numbers: RB-US-07-0002
First Submitted: March 10, 2008
First Posted: March 17, 2008
Results First Submitted: September 30, 2010
Results First Posted: May 9, 2014
Last Update Posted: June 5, 2017