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

NCT00637000 | Completed Phase 2 Results

• 1 other identifier: RB-US-07-0002
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid-related Disorders

Keywords

Opioid dependence; Opioid withdrawal symptoms

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (17)

• 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

• 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 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) 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

Study Arms (2)

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.

Drug: Buprenorphine soluble film; Drug: Placebo

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.

Drug: Buprenorphine/naloxone film strip; Drug: Placebo

Interventions

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.

Also known as: Subutex

Buprenorphine soluble film

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.

Also known as: Suboxone

Buprenorphine/naloxone soluble film

Placebo DRUG

Placebo soluble film administered on the same schedule as active treatment to maintain the study blind.

Buprenorphine soluble film; Buprenorphine/naloxone soluble film

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Rolley E. Johnson, PharmD, Vice President, Clinical, Scientific and Regulatory Affairs
• Organization: Reckitt Benckiser Pharmaceuticals, Inc.

ed.johnson@reckittbenckiser.com

804-379-1090

Study Officials

• Eric C. Strain, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2008
• First Posted: March 17, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: June 5, 2017
• Results First Posted: May 9, 2014

Record last verified: 2017-04

Locations

US (1)