Clinical trial NCT00637000: Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone
Official title: Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-related Disorders
Keywords: Opioid dependence
Opioid withdrawal symptoms
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-17
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: 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
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
Secondary outcomes:
measure: Severity of Withdrawal Symptoms Measured Using the Clinical Opiate Withdrawal Scale (COWS) at the End of Induction and the Peak COWS Post Induction
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: Pupil Diameter Measurements at Baseline and the Maximum Pupil Diameter up to 23.5 Hours After the First Administration
timeFrame: Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1
measure: Pupil Diameter Measurements at Baseline and the Minimum Pupil Diameter up to 23.5 Hours After the First Administration
timeFrame: Baseline: 15 minutes prior to first administration on Day 1. Peak: 15 minutes - 23.5 hours post administration on Day 1
measure: Pupil Diameter Measurements At End of Induction (End of Day 2) and the Minimum Pupil Diameter During the Post Induction Period (Days 3-5)
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: 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?"
timeFrame: Baseline: 30 minutes prior to first administration on Day 1. Peak: up to 23.5 hours post administration on Day 1
measure: Visual Analog Scale (VAS) Scores at End of Induction Period and the Post-induction Period (Maximum Increase) for the Question: "How High Are You?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: 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?"
timeFrame: End of Induction: 47.5 hours after first administration Peak Post Induction: Days 3-5
measure: Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1-6
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Eric C. Strain, M.D.
role: PRINCIPAL_INVESTIGATOR
References: