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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Buprenorphine soluble film | Experimental | 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. |
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| Buprenorphine/naloxone soluble film | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Buprenorphine soluble film | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Subject must:
Exclusion Criteria:
Subjects must not:
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| Name | Affiliation | Role |
|---|---|---|
| Eric C. Strain, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21224 | United States |
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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 data were collected by the investigator during daily subject interviews.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA (11.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rolley E. Johnson, PharmD, Vice President, Clinical, Scientific and Regulatory Affairs | Reckitt Benckiser Pharmaceuticals, Inc. | 804-379-1090 | 7089 | ed.johnson@reckittbenckiser.com |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D000069479 | Buprenorphine, Naloxone Drug Combination |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Buprenorphine/naloxone film strip | Drug | 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. |
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| Placebo | Drug | Placebo soluble film administered on the same schedule as active treatment to maintain the study blind. |
|
| End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 |
| 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. | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: 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?" | 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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 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?" | 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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 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: "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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 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: "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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
| 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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 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: "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. | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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. | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
| 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). | Day 1-6 |
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ID | Title | Description |
|---|---|---|
| OG000 | 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. |
| OG001 | 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. |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | mm | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | mm | Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | mm | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5 |
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| 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). | The randomized population included all subjects who were randomized to soluble films and received at least one dose of soluble films. | Posted | Number | participants | Day 1-6 |
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| 0 |
| 20 |
| 20 |
| 20 |
| EG001 | 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. | 0 | 18 | 18 | 18 |
| Lacrimation increased | Ear and labyrinth disorders | MedDRA (11.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Stomach discomfort | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Chills | General disorders | MedDRA (11.0) | Systematic Assessment |
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| Cold sweat | General disorders | MedDRA (11.0) | Systematic Assessment |
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| Hot flush | General disorders | MedDRA (11.0) | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA (11.0) | Systematic Assessment | Injection site AEs were due to morphine injections. |
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| Injection site pruritus | General disorders | MedDRA (11.0) | Systematic Assessment | Injection site AEs were due to morphine injections. |
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| Irritability | General disorders | MedDRA (11.0) | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
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| Joint abscess | Infections and infestations | MedDRA (11.0) | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA (11.0) | Systematic Assessment |
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| Tuberculosis skin test positive | Investigations | MedDRA (11.0) | Systematic Assessment |
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| Abscess limb | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
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| Restlessness | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA (11.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
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| Drug withdrawal syndrome | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
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| Hyperventilation | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (11.0) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Yawning | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Piloerection | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Tinea pedis | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (11.0) | Systematic Assessment |
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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.
| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D009270 | Naloxone |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| With grade 2 TEAE |
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| With grade 3 TEAE |
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