Clinical trial NCT01760473: Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone
Official title: Reinforcing Effects of Intranasal Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intranasal Drug Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heroin Dependence
Keywords: opioid dependence
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Indivior Inc.
First posted: 2013-01-04
Enrollment: 27
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In this study's design, all participants received each of the 9 intranasal test drugs under investigation. This study employed a Latin-square randomization procedure, therefore, the sequence of testing for the 9 intranasal drugs was unique for each participant.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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 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

Primary outcomes:
measure: Drug Self-administration
timeFrame: Throughout the testing sessions (approximately 9 weeks).
Secondary outcomes:
measure: SOWS
timeFrame: Throughout the testing sessions (approximately 9 weeks).
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute and Columbia University
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Sandra Comer, PHD
role: PRINCIPAL_INVESTIGATOR
References: