Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Reckitt Benckiser Pharmaceuticals Inc.
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01760473
First received: May 1, 2009
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Heroin Dependence
Drug: Buprenorphine/naloxone
Drug: Buprenorphine
Drug: Naloxone
Drug: Placebo
Drug: Heroin
Phase 3

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

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

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: 90 minutes ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: May 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Challenge doses
Placebo, Heroin, Naloxone, Buprenorphine, Buprenorphine/Naloxone
Drug: Buprenorphine/naloxone
administered intranasally
Other Name: Suboxone
Drug: Buprenorphine
administered intranasally
Other Name: Subutex
Drug: Naloxone
negative control
Other Name: Narcan
Drug: Placebo
neutral control
Other Name: Lactose
Drug: Heroin
positive control
Other Name: Diacetylmorphine

Detailed Description:

Although sublingual buprenorphine is an effective treatment for opioid addiction, the medication itself has abuse liability and, in some countries, has largely replaced heroin as the opioid drug of choice. In response to the reports of diversion and abuse of sublingual (SL) buprenorphine, a potentially less abusable formulation of buprenorphine that contains naloxone is being marketed in several countries. However, the relative abuse liability of buprenorphine alone and the buprenorphine/naloxone combination in buprenorphine-dependent individuals is unclear. Preliminary data from a study funded by Schering-Plough Corporation suggest that the buprenorphine/naloxone combination, when given intravenously (IV), does indeed have less abuse liability than IV buprenorphine in buprenorphine-dependent individuals. In addition to IV abuse of buprenorphine, epidemiological data suggest that buprenorphine is widely abused by the intranasal (IN) route. However, no data exist on the abuse liability of either IN buprenorphine alone or the buprenorphine/naloxone combination. Several studies have shown that naloxone is an effective antagonist of opioid agonist effects when given intravenously, but it is not clear whether naloxone given intranasally is as effective as when it is given by other routes of administration. Some studies have suggested that they are equally effective (Loimer et al., 1994), but others have shown that naloxone given intranasally is less effective (i.e., has a slower onset of effects) than when given by other routes of administration (Kelly et al., 2005). How this may impact on the ability of naloxone to reduce the reinforcing effects of IN buprenorphine is unclear. The primary aim of the current study proposal is to compare the reinforcing effects of IN buprenorphine and buprenorphine/naloxone in IN opioid abusers who are maintained on SL buprenorphine using a study design parallel to that used in our recent studies of the abuse liability of IV buprenorphine and buprenorphine/naloxone. Placebo, heroin, and naloxone will be used as neutral, positive, and negative controls, respectively. Secondary aims are to compare the subjective, performance, and physiological effects of IN buprenorphine and buprenorphine/naloxone. Overall, this study will complement our investigations of IV buprenorphine products by allowing for a complete overview within the same laboratory self-administration model of both the intravenous and intranasal abuse liability of buprenorphine versus buprenorphine/naloxone in individuals maintained on buprenorphine. The primary aim of the study is to compare the reinforcing effects of IN buprenorphine and IN buprenorphine/naloxone in opioid abusers maintained on different doses of sublingual buprenorphine. Secondary aims of the study are to compare the subjective, performance and physiological effects of IN buprenorphine and IN buprenorphine/naloxone. IN-administered placebo (lactose powder), 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 (5-South) during a 7 to 8-week study. This research will provide useful information to 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 opioids in amounts and/or frequencies that meet or exceed those used in the proposed study (e.g., 1-2 bags of heroin per occasion at least twice per day)
  • Self-administer IN buprenorphine above placebo levels during the qualification phase (see below)

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: NCT01760473

Locations
United States, New York
New York State Psychiatric Institute and Columbia University
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Reckitt Benckiser Pharmaceuticals Inc.
Investigators
Principal Investigator: Sandra Comer, PHD New York State Psychiatric Institute
  More Information

No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01760473     History of Changes
Other Study ID Numbers: #5879
Study First Received: May 1, 2009
Last Updated: January 2, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
opioid dependence

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

ClinicalTrials.gov processed this record on September 18, 2014