Abuse Liability of Suboxone Versus Subutex

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00710385
First received: June 11, 2008
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Opioid-related Disorders
Drug: heroin, naloxone, buprenorphine, buprenorphine/naloxone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Reinforcing Effects of Intravenous Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intravenous Drug Users (P05207)

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • progressive ratio breakpoint value [ Time Frame: single ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • subjective responses, physiological responses, cognitive performance [ Time Frame: multiple ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: September 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Challenge Doses Drug: heroin, naloxone, buprenorphine, buprenorphine/naloxone
Dosage form: intravenous Dosage: heroin (25 mg), naloxone (0.5-4 mg), buprenorphine (2-16 mg), buprenorphine/naloxone (2/0.5-16/4 mg)
Other Names:
  • Diacetylmorphine
  • Narcan
  • Subutex
  • Suboxone

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.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • AST or 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00710385

Locations
United States, New York
New York State Psychiatric Institute/Columbia University
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Schering-Plough
Investigators
Principal Investigator: Sandra D Comer, PhD Columbia University/New York State Psychiatric Institute
  More Information

No publications provided by Columbia University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Herbert D. Kleber, M.D., New York State Psychiatric Institute and Columbia University
ClinicalTrials.gov Identifier: NCT00710385     History of Changes
Other Study ID Numbers: 5518
Study First Received: June 11, 2008
Last Updated: June 27, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Buprenorphine
Heroin
Naloxone
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotic Antagonists
Narcotics

ClinicalTrials.gov processed this record on July 20, 2014