Opioid-related Disorders
Conditions
Keywords
Opioid dependence, Opioid withdrawal symptoms
Brief summary
The purpose of this study is to compare the presence, degree, time course and profile of opioid withdrawal symptoms associated with induction onto new formulations of buprenorphine or buprenorphine/naloxone in persons with active opioid dependence. The primary outcome measure is the severity of withdrawal symptoms measured using the Clinical Opiate Withdrawal Scale (COWS). The primary study hypothesis is that neither drug formulation will precipitate an opioid withdrawal syndrome.
Detailed description
Buprenorphine sublingual and buccal soluble films are being developed to be used for the same indication and over the same buprenorphine dose range as Subutex and Suboxone sublingual tablets in the treatment of opioid dependence. However, only films administered by the sublingual route were evaluated in this study. The soluble film dosage is expected to provide the following enhancements and potential advantages over the current Subutex and Suboxone product: * Mitigation against unintentional pediatric exposure by providing child-resistant packaging in unit dose format. * Improvement in subject convenience and compliance by ensuring rapid disintegration. * Protection against diversion by providing a dosage form that is very difficult for the subject to remove from the sublingual or buccal mucosa after administration. This provides assurance to the caregiver that the dose has actually been taken appropriately in a supervised setting. * Provision of a unit dose product format for hospital and institutional use. * Decreased product damage during shipping as compared to Subutex and Suboxone tablets.
Interventions
DRUGBuprenorphine soluble film
Buprenorphine soluble film strips administered sublingually with doses escalated from 12 mg per day up to 24 mg daily for 5 days of total treatment.
Buprenorphine/naloxone soluble film strips administered sublingually with doses escalated from 12 mg buprenorphine/3 mg naloxone to 24 mg buprenorphine /6 mg naloxone daily for 5 days of total treatment.
DRUGPlacebo
Placebo soluble film administered on the same schedule as active treatment to maintain the study blind.
Sponsors
Indivior Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subject must: * Provide written informed consent. * Have a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of opioid dependence. * Be male or female, 18 to 65 years of age, inclusive. * If female, have a negative pregnancy test during screening and agree to use an acceptable method of birth control.
Exclusion criteria
Subjects must not: * Have participated in an experimental drug or device study within the last 30 days. * Be currently (past 30 days from start of screening) engaged in opioid agonist, opioid partial agonist, or opioid antagonist treatment. * If female, be breast feeding or lactating. * Have any medical condition that in the opinion of the physician investigator would preclude the subject from completing the study. * Have any clinically significant non-substance use psychiatric disorder (e.g., schizophrenia). * Have current suicidal ideation. * Have a Mini Mental Status Exam score less than 24. * Have physical dependence on alcohol. * Have physical dependence on sedative-hypnotics. * Have active aphthous stomatitis. * Have active oral herpes. * Need on-going prescription medications that interact with the P450 3A4 (a member of the cytochrome P450 superfamily of enzymes) system.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 | 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. |
| Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 | 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. |
| Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5) | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
| Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| 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? | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 | 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. |
| Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | Day 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. Severity was graded by the investigator as mild (grade 1), moderate (grade 2) and severe (grade 3). |
| 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? | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Sublingual Buprenorphine Soluble Film 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. | 20 |
| Sublingual Buprenorphine/Naloxone Soluble Film 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. | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Sublingual Buprenorphine Soluble Film | Sublingual Buprenorphine/Naloxone Soluble Film | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 18 Participants | 38 Participants |
| Age, Continuous | 40.2 years STANDARD_DEVIATION 10 | 40.2 years STANDARD_DEVIATION 7.9 | 40.2 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 18 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 13 Participants | 25 Participants |
| Region of Enrollment United States | 20 participants | 18 participants | 38 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 20 | 18 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 18 |
Outcome results
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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 | Baseline | 9.1 units on a scale | Standard Deviation 5.5 |
| Sublingual Buprenorphine Soluble Film | 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 | Peak | 4.2 units on a scale | Standard Deviation 2.4 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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 | Baseline | 10.1 units on a scale | Standard Deviation 6.4 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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 | Peak | 5.7 units on a scale | Standard Deviation 3.2 |
Comparison: 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.p-value: <0.0001Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 61.2 units on a scale | Standard Deviation 40 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 59.4 units on a scale | Standard Deviation 34.1 |
p-value: <0.0001Repeated measures model
Secondary
Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline | 6.24 mm | Standard Deviation 0.97 |
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration | Peak | 4.39 mm | Standard Deviation 6.27 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline | 6.11 mm | Standard Deviation 0.88 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration | Peak | 5.99 mm | Standard Deviation 0.98 |
p-value: 0.035Repeated measures model
Secondary
Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration | Peak | 4.39 mm | Standard Deviation 1.27 |
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline | 6.24 mm | Standard Deviation 0.97 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration | Baseline | 6.11 mm | Standard Deviation 0.88 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration | Peak | 4.32 mm | Standard Deviation 1.08 |
p-value: <0.0001Repeated measures model
Secondary
Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5) | End of Induction | 5.3 mm | Standard Deviation 1.2 |
| Sublingual Buprenorphine Soluble Film | Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5) | Peak Post Induction | 4.1 mm | Standard Deviation 1.1 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5) | End of Induction | 5.1 mm | Standard Deviation 1.2 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5) | Peak Post Induction | 3.6 mm | Standard Deviation 0.9 |
p-value: <0.0001Repeated measures model
Secondary
Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction | End of Induction | 0.6 units on a scale | Standard Deviation 0.5 |
| Sublingual Buprenorphine Soluble Film | Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction | Peak Post Induction | 1.0 units on a scale | Standard Deviation 1 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction | End of Induction | 1.0 units on a scale | Standard Deviation 1 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction | Peak Post Induction | 2.6 units on a scale | Standard Deviation 2.4 |
p-value: 0Repeated measures model
Secondary
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
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
Population: The randomized population included all subjects who were randomized to soluble films and received at least one dose of soluble films.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With any TEAE | 20 participants |
| Sublingual Buprenorphine Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 1 TEAE | 15 participants |
| Sublingual Buprenorphine Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 2 TEAE | 19 participants |
| Sublingual Buprenorphine Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 3 TEAE | 0 participants |
| Sublingual Buprenorphine/Naloxone Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 3 TEAE | 0 participants |
| Sublingual Buprenorphine/Naloxone Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With any TEAE | 18 participants |
| Sublingual Buprenorphine/Naloxone Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 2 TEAE | 16 participants |
| Sublingual Buprenorphine/Naloxone Soluble Film | Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) | With grade 1 TEAE | 16 participants |
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 4.4 units on a scale | Standard Deviation 11.8 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 12.5 units on a scale | Standard Deviation 34.2 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 6.1 units on a scale | Standard Deviation 12.5 |
p-value: 0.762Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 62.3 units on a scale | Standard Deviation 35.1 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 57.6 units on a scale | Standard Deviation 31.4 |
p-value: <0.0001Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 2.1 units on a scale | Standard Deviation 6.1 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 12.5 units on a scale | Standard Deviation 34.2 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 4.5 units on a scale | Standard Deviation 12.3 |
p-value: 0.349Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 44.3 units on a scale | Standard Deviation 31.5 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 50.4 units on a scale | Standard Deviation 26 |
p-value: <0.0001Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak | 5.8 units on a scale | Standard Deviation 12.9 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Baseline | 0.0 units on a scale | Standard Deviation 0.3 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak | 13.7 units on a scale | Standard Deviation 24 |
p-value: 0.006Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | End of Induction | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak Post Induction | 0.4 units on a scale | Standard Deviation 1.2 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | End of Induction | 0.3 units on a scale | Standard Deviation 0.8 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak Post Induction | 0.4 units on a scale | Standard Deviation 1.2 |
p-value: 0.117Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | End of Induction | 0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak Post Induction | 0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | End of Induction | 0.3 units on a scale | Standard Deviation 0.7 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak Post Induction | 0.7 units on a scale | Standard Deviation 1.6 |
p-value: 0.238Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | End of Induction | 7.9 units on a scale | Standard Deviation 16.8 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak Post Induction | 53.2 units on a scale | Standard Deviation 41 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | End of Induction | 15.9 units on a scale | Standard Deviation 28.6 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak Post Induction | 47.4 units on a scale | Standard Deviation 27.8 |
p-value: <0.0001Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | End of Induction | 11.0 units on a scale | Standard Deviation 26 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak Post Induction | 61.7 units on a scale | Standard Deviation 39.8 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | End of Induction | 20.2 units on a scale | Standard Deviation 30 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak Post Induction | 52.9 units on a scale | Standard Deviation 33.1 |
p-value: <0.0001Repeated measures model
Secondary
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?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | 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? | End of Induction | 14.9 units on a scale | Standard Deviation 29.6 |
| Sublingual Buprenorphine Soluble Film | 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? | Peak Post Induction | 61.7 units on a scale | Standard Deviation 41 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | End of Induction | 24.3 units on a scale | Standard Deviation 37 |
| Sublingual Buprenorphine/Naloxone Soluble Film | 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? | Peak Post Induction | 55.4 units on a scale | Standard Deviation 35.8 |
p-value: <0.0001Repeated measures model
Secondary
Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You?
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sublingual Buprenorphine Soluble Film | Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You? | End of Induction | 0.0 units on a scale | Standard Deviation 0 |
| Sublingual Buprenorphine Soluble Film | Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You? | Peak Post Induction | 8.2 units on a scale | Standard Deviation 18.2 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You? | End of Induction | 6.3 units on a scale | Standard Deviation 25 |
| Sublingual Buprenorphine/Naloxone Soluble Film | Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: How High Are You? | Peak Post Induction | 12.9 units on a scale | Standard Deviation 30.1 |
p-value: 0.028Repeated measures model