Abuse Liability of Suboxone Versus Subutex

Opioid-related Disorders Clinical Trial

Official title:

Reinforcing Effects of Intravenous Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intravenous Drug Users (P05207)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00710385
• Other study ID #: 5518
• Status: Completed
• Phase: Phase 3
• First received: June 11, 2008
• Last updated: June 27, 2011
• Start date: September 2007
• Est. completion date: August 2008

Study information

• Verified date: June 2011
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Opioid-related Disorders

Intervention

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)

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute/Columbia University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Schering-Plough

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progressive ratio breakpoint value		single	No
Secondary	subjective responses, physiological responses, cognitive performance		multiple	Yes