Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone
Overview
- Phase
- Phase 2
- Intervention
- Buprenorphine soluble film
- Conditions
- Opioid-related Disorders
- Sponsor
- Indivior Inc.
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
- •Have physical dependence on alcohol.
- •Have physical dependence on sedative-hypnotics.
Arms & Interventions
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.
Intervention: Buprenorphine soluble film
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.
Intervention: Placebo
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.
Intervention: Buprenorphine/naloxone film strip
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.
Intervention: Placebo
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- 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)
- Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1-6)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)