Abuse Liability of Suboxone Versus Subutex

Phase 3

Completed

Conditions: Opioid-related Disorders

Interventions: Drug: Low Bup Dose
Drug: High Bup/Nal Dose
Drug: Low Bup/Nal Dose
Drug: High Bup Dose
Drug: Placebo (PCB)
Drug: Naloxone
Drug: Heroin

Registration Number: NCT00710385

Lead Sponsor: New York State Psychiatric Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Low Bup Dose	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.
High Bup/Nal Dose	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.
Low Bup/Nal Dose	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.
High Bup Dose	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.
Placebo	Placebo (PCB)	Intravenous placebo (PCB) administration. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Naloxone	Naloxone	Naloxone (NAL) .4 mg. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.
Heroin	Heroin	Heroin 25 mg. Administered intravenously, while participants were under 2, 8 and 24 sublingual (SL) Bup maintenance conditions.

Primary Outcome Measures

Name	Time	Method
Drug's Breakpoint	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

Secondary Outcome Measures

Name	Time	Method
Drug "Liking"	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.