Clinical trial NCT00710385: Abuse Liability of Suboxone Versus Subutex
Official title: Reinforcing Effects of Intravenous Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intravenous Drug Users (P05207)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid-related Disorders
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-07-04
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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 criteria: 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

Primary outcomes:
measure: Drug's Breakpoint
timeFrame: Single measurement taken following each of the 7 IV experimental doses
Secondary outcomes:
measure: Drug "Liking"
timeFrame: Peak (highest) rating obtained following drug administration throughout the entire 3 hr session
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute/Columbia University
state: New York
Study officials:
affiliation: Columbia University/New York State Psychiatric Institute
name: Sandra D Comer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Comer SD, Sullivan MA, Vosburg SK, Manubay J, Amass L, Cooper ZD, Saccone P, Kleber HD. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Addiction. 2010 Apr;105(4):709-18. doi: 10.1111/j.1360-0443.2009.02843.x.