Heroin DependencePhase 3NCT01760473
Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone
A Phase 3 study testing Intranasal challenge drug in people with Heroin Dependence, run by New York State Psychiatric Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Heroin Dependence
- What is being tested?
- Intranasal challenge drug
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute and Columbia University
New York, New York, 10032
About this study
Official title: Reinforcing Effects of Intranasal Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intranasal Drug Users
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.
Read the 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.
- Conditions
- Heroin Dependence
- Being tested
- Intranasal challenge drug
- Keywords
- opioid dependence
- Medical subject headings
- Heroin Dependence, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal challenge drugDrug
Each of the experimental challenge drugs were administered intranasally to all participants in random order.
| Study group | Role | What they receive |
|---|---|---|
| Bup 8 | Experimental | Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally. Receives: Drug: Intranasal challenge drug |
| Bup 16 | Experimental | Intranasal challenge drug: 16 mg of Buprenorphine administered intranasally. Receives: Drug: Intranasal challenge drug |
| Bup/Nal 8/2 | Experimental | Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 2 mg of Naloxone. Receives: Drug: Intranasal challenge drug |
| Bup/Nal 8/8 | Experimental | Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 8 mg of Naloxone. Receives: Drug: Intranasal challenge drug |
| Bup/Nal 8/16 | Experimental | Intranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 16 mg of Naloxone. Receives: Drug: Intranasal challenge drug |
| Bup/Nal 16/4 | Experimental | Intranasal challenge drug: 16 mg of Buprenorphine administered intranasally with 4 mg of Naloxone. Receives: Drug: Intranasal challenge drug |
| Heroin | Active comparator | Intranasal challenge drug: 24 mg of heroin administered intranasally. Receives: Drug: Intranasal challenge drug |
| Placebo | Sham comparator | Intranasal challenge drug: Intranasal lactose powder. Receives: Drug: Intranasal challenge drug |
| Naloxone 4 mg | Active comparator | Intranasal challenge drug: Intranasal Naloxone 4mg. Receives: Drug: Intranasal challenge drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Self-administration
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.
Measured: Throughout the testing sessions (approximately 9 weeks).
Secondary outcomes (1)
SOWS
Subjective opioid withdrawal scale (SOWS) measure (0-64). Greater score indicates more severe withdrawal.
Measured: Throughout the testing sessions (approximately 9 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study startMay 2009
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heroin DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Indivior Inc.
- Responsible party
- Sponsor
- Investigators
- Sandra Comer, PHD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760473
- Sponsor's protocol ID
- #5879
- Status last verified
- Aug 2017
- First submitted
- 1 May 2009
- Last updated
- 8 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reinforcing Effects of Intranasal Buprenorphine Versus Buprenorphine/Naloxone in Buprenorphine-maintained Intranasal Drug Users
- ClinicalTrials.gov ID
- NCT01760473
- Acronym / sponsor ID
- #5879
- Conditions
- Heroin Dependence
- Keywords
- opioid dependence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Indivior Inc.
- Study start
- May 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 4 Jan 2013 (estimated)
- Results
- Posted 8 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 9
- 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.
| Arm | Type | Receives |
|---|---|---|
| Bup 8 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 8 mg of Buprenorphine administered intranasally. |
| Bup 16 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 16 mg of Buprenorphine administered intranasally. |
| Bup/Nal 8/2 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 2 mg of Naloxone. |
| Bup/Nal 8/8 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 8 mg of Naloxone. |
| Bup/Nal 8/16 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 8 mg of Buprenorphine administered intranasally with 16 mg of Naloxone. |
| Bup/Nal 16/4 | Experimental | Drug: Intranasal challenge drugIntranasal challenge drug: 16 mg of Buprenorphine administered intranasally with 4 mg of Naloxone. |
| Heroin | Active comparator | Drug: Intranasal challenge drugIntranasal challenge drug: 24 mg of heroin administered intranasally. |
| Placebo | Sham comparator | Drug: Intranasal challenge drugIntranasal challenge drug: Intranasal lactose powder. |
| Naloxone 4 mg | Active comparator | Drug: Intranasal challenge drugIntranasal challenge drug: Intranasal Naloxone 4mg. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intranasal challenge drugEach of the experimental challenge drugs were administered intranasally to all participants in random order. | Drug | Bup 16, Bup 8, Bup/Nal 16/4, Bup/Nal 8/16, Bup/Nal 8/2, Bup/Nal 8/8, Heroin, Naloxone 4 mg, Placebo |
Primary outcome
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.
1 secondary outcome
SOWS
Time frame: Throughout the testing sessions (approximately 9 weeks).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandra Comer, PHD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intranasal challenge drug in people with Heroin Dependence, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug Self-administration (time frame: Throughout the testing sessions (approximately 9 weeks).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2017.