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Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone

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ClinicalTrials.gov Identifier: NCT01760473
Recruitment Status : Completed
First Posted : January 4, 2013
Results First Posted : September 8, 2017
Last Update Posted : September 8, 2017
Sponsor:
Collaborator:
Indivior Inc.
Information provided by (Responsible Party):
New York State Psychiatric Institute

Tracking Information
First Submitted Date  ICMJE May 1, 2009
First Posted Date  ICMJE January 4, 2013
Results First Submitted Date  ICMJE October 11, 2016
Results First Posted Date  ICMJE September 8, 2017
Last Update Posted Date September 8, 2017
Study Start Date  ICMJE May 2009
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2017)
Drug Self-administration [ Time Frame: Throughout the testing sessions (approximately 9 weeks). ]
The maximum number of responses (clicks on a computer mouse) the participant was willing to perform in order to receive a dose of the intranasal challenge drug under investigation.
Original Primary Outcome Measures  ICMJE
 (submitted: January 2, 2013)
progressive ratio breakpoint value [ Time Frame: single ]
Change History Complete list of historical versions of study NCT01760473 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2017)
SOWS [ Time Frame: Throughout the testing sessions (approximately 9 weeks). ]
Subjective opioid withdrawal scale (SOWS) measure (0-64). Greater score indicates more severe withdrawal.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2013)
subjective responses, physiological responses, cognitive performance [ Time Frame: 90 minutes ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone
Official Title  ICMJE Reinforcing Effects of Intranasal Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intranasal Drug Users
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Heroin Dependence
Intervention  ICMJE Drug: Intranasal challenge drug
Each of the experimental challenge drugs were administered intranasally to all participants in random order.
Study Arms  ICMJE
  • Experimental: Bup 8
    Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally.
    Intervention: Drug: Intranasal challenge drug
  • Experimental: Bup 16
    Intranasal challenge drug: 16 mg of Buprenorphine administered intranasally.
    Intervention: Drug: Intranasal challenge drug
  • Experimental: Bup/Nal 8/2
    Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 2 mg of Naloxone.
    Intervention: Drug: Intranasal challenge drug
  • Experimental: Bup/Nal 8/8
    Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 8 mg of Naloxone.
    Intervention: Drug: Intranasal challenge drug
  • Experimental: Bup/Nal 8/16
    Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 16 mg of Naloxone.
    Intervention: Drug: Intranasal challenge drug
  • Experimental: Bup/Nal 16/4
    Intranasal challenge drug: 16 mg of Buprenorphine administered intranasally with 4 mg of Naloxone.
    Intervention: Drug: Intranasal challenge drug
  • Active Comparator: Heroin
    Intranasal challenge drug: 24 mg of heroin administered intranasally.
    Intervention: Drug: Intranasal challenge drug
  • Sham Comparator: Placebo
    Intranasal challenge drug: Intranasal lactose powder.
    Intervention: Drug: Intranasal challenge drug
  • Active Comparator: Naloxone 4 mg
    Intranasal challenge drug: Intranasal Naloxone 4mg.
    Intervention: Drug: Intranasal challenge drug
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2015)
27
Original Estimated Enrollment  ICMJE
 (submitted: January 2, 2013)
12
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01760473
Other Study ID Numbers  ICMJE #5879
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE Indivior Inc.
Investigators  ICMJE
Principal Investigator: Sandra Comer, PHD New York State Psychiatric Institute
PRS Account New York State Psychiatric Institute
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP