Abuse Liability of Suboxone Versus Subutex

• ClinicalTrials.gov Identifier: NCT00710385
• Recruitment Status: Completed
• First Posted: July 4, 2008
• Results First Posted: December 5, 2016
• Last Update Posted: December 5, 2016
• Sponsor: New York State Psychiatric Institute
• Collaborator: Schering-Plough
• Information provided by (Responsible Party): New York State Psychiatric Institute

Tracking Information

• First Submitted Date: June 11, 2008
• First Posted Date: July 4, 2008
• Results First Submitted Date: August 19, 2011
• Results First Posted Date: December 5, 2016
• Last Update Posted Date: December 5, 2016
• Study Start Date: September 2007
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2016)

Drug's Breakpoint [ Time Frame: 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

• Original Primary Outcome Measures (submitted: July 1, 2008): progressive ratio breakpoint value [ Time Frame: single ]

Current Secondary Outcome Measures (submitted: October 11, 2016)

Drug "Liking" [ Time Frame: 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.

• Original Secondary Outcome Measures (submitted: July 1, 2008): subjective responses, physiological responses, cognitive performance [ Time Frame: multiple ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Abuse Liability of Suboxone Versus Subutex
• Official Title: Reinforcing Effects of Intravenous Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intravenous Drug Users (P05207)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Opioid-related Disorders

Intervention

• Drug: Heroin
  Heroin (25 mg)
  Other Name: Diacetylmorphine
• Drug: Naloxone
  .4 mg
  Other Name: Naloxone Hydrochloride (HCl)
• Drug: Low Bup Dose
  4 and 8 mg
  Other Name: Subutex
• Drug: High Bup Dose
  8mg and 16 mg
  Other Name: Subutex
• Drug: Low Bup/Nal Dose
  Buprenorphine/Naloxone 4/1 mg, 8/2 mg
  Other Name: Suboxone
• Drug: High Bup/Nal Dose
  Buprenorphine/Naloxone 8/2 mg, 16/4 mg
  Other Name: Suboxone
• Drug: Placebo (PCB)
  Placebo control administration
  Other Name: 0 mg

Study Arms

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

• Publications *: 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. Erratum In: Addiction. 2010 Jul;105(7):1332.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 11, 2016): 19
• Original Estimated Enrollment (submitted: July 1, 2008): 12
• Actual Study Completion Date: August 2008
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00710385
• Other Study ID Numbers: 5518
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data have been published in a peer-reviewed journal.

• Current Responsible Party: New York State Psychiatric Institute
• Original Responsible Party: Herbert D. Kleber, M.D., New York State Psychiatric Institute and Columbia University
• Current Study Sponsor: New York State Psychiatric Institute
• Original Study Sponsor: Columbia University
• Collaborators: Schering-Plough

Investigators

• Principal Investigator: Sandra D Comer, PhD; Columbia University/New York State Psychiatric Institute

• PRS Account: New York State Psychiatric Institute
• Verification Date: December 2012