Abuse Liability of Suboxone Versus Subutex

October 11, 2016 updated by: New York State Psychiatric Institute

Reinforcing Effects of Intravenous Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intravenous Drug Users (P05207)

The study is designed to compare the abuse liabilities of intravenous buprenorphine and buprenorphine/naloxone in individuals who are physically dependent on sublingual buprenorphine. We hypothesize that the abuse liability of buprenorphine/naloxone is lower than that of buprenorphine alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Drug dependence is a major international public health problem of which opioid dependence, notably involving heroin, is a major component. Opioid dependence affects an estimated 13 million injection drug users (IDUs) worldwide. The high health service costs for the treatment of diseases related to non-medical drug use and the high cost to society of drug-related behavior have prompted researchers to seek new medications and treatment strategies for opioid dependence. Buprenorphine, a mu-opiate receptor partial agonist and kappa-opiate receptor antagonist, is one such new medication that has had a significant role in expanding access to effective opioid dependence treatment. It is available as Subutex (buprenorphine alone) or Suboxone (a combination of buprenorphine and naloxone). Although it is commonly believed that the abuse potential of buprenorphine is low, numerous countries have reported illicit diversion of buprenorphine and a growing population of buprenorphine abusers. Theoretically, Suboxone would have lower abuse potential. When used sublingually, as prescribed, the amount of naloxone absorbed is negligible. However, if a patient crushes the tablet and attempts to inject or sniff the medication, the naloxone will become effective as an opioid antagonist and may precipitate withdrawal signs and symptoms in individuals dependent on full opioid agonists and/or attenuate the euphoric effects of the buprenorphine that is also contained in the medication. To date, few laboratory studies have evaluated the abuse liability of buprenorphine in humans using a drug self-administration protocol. We are proposing to evaluate the abuse potential of intravenous (IV) buprenorphine compared to IV buprenorphine/naloxone in buprenorphine-maintained injection drug users (IDUs), incorporating self-administration procedures with other measures of opioid effects. The proposed study will investigate the conditions that affect the self-administration of IV buprenorphine by buprenorphine abusers. The primary aim of the study is to compare the reinforcing effects of IV buprenorphine and IV buprenorphine/naloxone in IDUs maintained on different doses of sublingual buprenorphine (2, 8, and 24 mg/day). Secondary aims of the study are to compare the subjective, performance and physiological effects of IV buprenorphine and IV buprenorphine/naloxone. IV-administered placebo (saline), naloxone alone, and heroin alone will be tested as neutral, negative, and positive control conditions, respectively. Participants (N=12 completers) will reside on an inpatient unit (the General Clinical Research Unit, GCRU) during a 7 to 8-week study. This research will provide useful information for clinicians treating opioid dependent individuals with buprenorphine, and importantly, will provide information about the abuse potential and effects of buprenorphine on multiple measures of human functioning.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute/Columbia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnostic and Statistical Manual (DSM) IV criteria for heroin dependence
  • No major mood, psychotic, or anxiety disorder
  • Physically healthy
  • Able to perform study procedures
  • 21-45 years of age
  • Normal body weight
  • Current use of i.v. opioids in amounts and/or frequencies that meet or exceed those used in the proposed study (1-2 bags of heroin per occasion at least twice per day)
  • Self-administer at least 4 mg i.v. buprenorphine above placebo levels during the dose run up phase

Exclusion Criteria:

  • DSM IV criteria for dependence on drugs other than opioids, nicotine or caffeine
  • Participants requesting treatment
  • Participants on parole or probation
  • Pregnancy or lactation
  • Birth, miscarriage or abortion within 6 months
  • Current or recent history of significant violent behavior
  • Current major Axis I psychopathology, other than opioid dependence (e.g., mood disorder with functional impairment or suicide risk, schizophrenia), that might interfere with ability to participate in the study
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal
  • Significant suicide risk
  • Current chronic pain
  • Sensitivity, allergy, or contraindication to opioids
  • Current or recent (past 30 days) physical dependence on or treatment with methadone, buprenorphine, or the buprenorphine/naloxone combination

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Heroin
Heroin 25 mg. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: Heroin
Heroin (25 mg)
Other Names:
  • Diacetylmorphine
Active Comparator: Naloxone
Naloxone (NAL) .4 mg. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: Naloxone
.4 mg
Other Names:
  • Naloxone Hydrochloride (HCl)
Experimental: Low Bup Dose
Combined dosing groups of (4 mg and 8mg of Buprenorphine) for participants who administered a maximum of 8 mg of Bup during the qualification phase. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: Low Bup Dose
4 and 8 mg
Other Names:
  • Subutex
Experimental: Low Bup/Nal Dose
Combined dosing groups of (4/1 mg and 8/2mg of Buprenorphine + Naloxone) for participants who administered a maximum of 8 mg of Bup during the qualification phase. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: Low Bup/Nal Dose
Buprenorphine/Naloxone 4/1 mg, 8/2 mg
Other Names:
  • Suboxone
Experimental: High Bup Dose
Combined dosing groups of (8mg and 16mg of Bup) for participants who administered a maximum of 16 mg of Bup during the qualification phase. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: High Bup Dose
8mg and 16 mg
Other Names:
  • Subutex
Experimental: High Bup/Nal Dose
Combined dosing groups of (8/2mg and 16/4mg of Buprenorphine + Naloxone) for participants who administered a maximum of 16 mg of Bup during the qualification phase. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: High Bup/Nal Dose
Buprenorphine/Naloxone 8/2 mg, 16/4 mg
Other Names:
  • Suboxone
Placebo Comparator: Placebo
Intravenous placebo (PCB) administration. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Drug: Placebo (PCB)
Placebo control administration
Other Names:
  • 0 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug's Breakpoint
Time Frame: Single measurement taken following each of the 7 IV experimental doses
Measure of a drug's reinforcing effects. The "Breakpoint" is the point at which the participant stop performing an operant task (clicks on a mouse) in order to received the drug. Therefore, the reported breakpoint is the total amount of work the participant was willing to perform to receive the dose being tested
Single measurement taken following each of the 7 IV experimental doses

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug "Liking"
Time Frame: Peak (highest) rating obtained following drug administration throughout the entire 3 hr session
Participant's subjective ratings of how much they "Like" the dose they just received on a scale of 0 -100.
Peak (highest) rating obtained following drug administration throughout the entire 3 hr session

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

Schering-Plough

Investigators

  • Principal Investigator: Sandra D Comer, PhD, Columbia University/New York State Psychiatric Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

June 11, 2008

First Submitted That Met QC Criteria

July 1, 2008

First Posted (Estimate)

July 4, 2008

Study Record Updates

Last Update Posted (Estimate)

December 5, 2016

Last Update Submitted That Met QC Criteria

October 11, 2016

Last Verified

December 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5518

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data have been published in a peer-reviewed journal.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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