Opioid-use DisorderPhase 2/3COMBONCT05011266
Efficacy of Buprenorphine and XR-Naltrexone Combination for Relapse Prevention in Opioid Use Disorder
A Phase 2/3 study testing Buprenorphine/naloxone in people with Opioid-use Disorder, run by New York State Psychiatric Institute at 2 sites in United States.
Trial summary
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid-use Disorder
- What is being tested?
- Buprenorphine/naloxone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Apr 2023to 1 Jan 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals between the ages of 18-65 (inclusive) interested in antagonist-based relapse prevention treatment
- Meets current DSM-5 criteria for current opioid use disorder of at least six months duration supported by urine toxicology positive for opioids OR positive naloxone challenge (defined by 3-point increase in COWS) if seeking detoxification and XR-NTX induction OR confirmed recent detoxification treatment for opioids.
- In otherwise good health based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) with no clinically significant abnormalities
- Participants who completed detoxification and received XR-NTX are eligible for the study. Participants may be enrolled up to 2 weeks following an initial XR-NTX injection given in any outside research or community-based treatment setting (inpatient, outpatient residential).
- Seeking treatment for opioid use disorder, willing to accept treatment with XR-NTX and, in the judgment of the treating physician, is a good candidate for naltrexone-based treatment.
- Voluntarily seeking treatment for opioid use disorder.
- Able to give written informed consent to participate in the study and showing a thorough understanding of the difference between agonist and antagonist-based treatment.
Who cannot join
- Methadone maintenance within 2 weeks of XR-NTX induction or any use of methadone in the week prior to XR-NTX induction
- Maintenance on buprenorphine or frequent buprenorphine use in the week prior to XR-NTX induction (must be using no more than 8 mg of buprenorphine per day for no more than 3 days per week). If consenting after initial XR-NTX injection, any use of buprenorphine since XR-NTX induction is exclusionary.
- Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make a detoxification and naltrexone initiation, or maintenance treatment with XR-NTX in combination with buprenorphine, hazardous (relative contraindications) or requires a different level of care. Examples include:
- Disabling or terminal medical illness (e.g., uncompensated heart failure, severe acute hepatitis, cirrhosis or end-stage liver disease) as assessed by medical history and/or review of systems.
- Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview.
- Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use likely to require a complicated medical detoxification (routine alcohol and sedative detoxifications may be included).
Show all 15Show fewer
- Suicidal or homicidal
- AST/ALT \> 3x normal limit
- Pregnancy, lactation, or a plan of becoming pregnant. Women need to have negative blood pregnancy test at screening and agree to practice dual contraceptives.
- Physiological dependence on alcohol or sedative-hypnotics with impending withdrawal. Other substance use diagnoses are not exclusionary.
- History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam.
- Painful medical condition that requires ongoing opioid analgesia or anticipated surgery necessitating opioid medications.
- Individuals above 60 with possible early cognitive decline or other neurodegenerative conditions as evidenced by a score of less than 25 on a Mini Mental Status Exam screen.
- Participants who had 30 or more opioid-free days prior to randomization will not be eligible.
- Participants more than 2 weeks following an initial XR-NTX injection (given in any outside research or community-based treatment setting, for example inpatient, outpatient residential).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Onumara Opara, MPH contact
United States2 sites, 1 recruiting
- Terminated
Stars/Nyspi
New York, New York, 10019
- Recruiting
Avery Road Treatment Center (ARTC)
Rockville, Maryland, 20853
Praveena Machineni, 240-739-0626, PMachineni@marylandtreatment.org
Lauren Rudin, 240-739-0601, LRudin@marylandtreatment.org
About this study
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. This is a two arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine-naloxone will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with extended release naltrexone (XR-naltrexone) administered every four weeks for a total of 6 injections.
Read the detailed description
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. Adding buprenorphine-naloxone after the patient initiated XR-naltrexone will not produce mu opioid agonist effect but kappa antagonist effects of buprenorphine may provide additional relief of protracted withdrawal, craving, and mood disturbances persisting in patients treated with XR-naltrexone and possibly contributing to premature treatment discontinuation and relapse. This is a parallel arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with XR-naltrexone administered every four weeks. Individuals with Opioid Use Disorder (OUD) and beginning treatment with XR-naltrexone for maintenance treatment will be randomized to treatment with adjunctive buprenorphine-naloxone or placebo with 5 additional doses of XR-naltrexone, given every four weeks, and weekly medication management. The study will provide detoxification and a first XR-Naltrexone injection if a participant consents before the first XR-naltrexone injection. In all participants randomization will occur after first XR-NTX injection. Buprenorphine-naloxone (sub-lingual (SL), 4/1 mg/day) or placebo will be started after a first XR-naltrexone dose and tapered off at study completion.
- Conditions
- Opioid-use Disorder
- Being tested
- Buprenorphine/naloxone, Placebo
- Keywords
- opioid use disorder, treatment, buprenorphine, extended release naltrexone
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Buprenorphine/naloxoneDrug
Also called Zubsolv
5.7 mg buprenorphine/1.4 mg naloxone sub-lingual daily
PlaceboDrug
Also called PBO
placebo sub-lingual tablet daily
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine-naloxone | Experimental | Buprenorphine/naloxone 5.7 mg /1.4 mg/day sub-lingual tablets Receives: Drug: Buprenorphine/naloxone |
| Placebo | Placebo comparator | placebo sub-lingual tablet Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants receiving XR-naltrexone injections
Proportion of patients successfully retained to receive six consecutive XR-naltrexone injection.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start18 Apr 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid-use DisorderStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- parallel arm, double-blind, placebo-controlled buprenorphine compared to placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Adam Bisaga, New York State Psychiatric Institute
- Investigators
- Adam Bisaga, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05011266
- Sponsor's protocol ID
- IRB #8171
- Other IDs
- U01DA046430
- Acronym
- COMBO
- Status last verified
- May 2026
- First submitted
- 16 Aug 2021
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results published in this report (after de-identification) (text, tables, figures)
Publications
Kornor H, Lobmaier PPK, Kunoe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140. doi: 10.1002/14651858.CD006140.pub3.
PubMed 40342086
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Buprenorphine and XR-Naltrexone Combination for Relapse Prevention in Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT05011266
- Acronym / sponsor ID
- COMBO / IRB #8171
- Conditions
- Opioid-use Disorder
- Keywords
- opioid use disorder, treatment, buprenorphine, extended release naltrexone
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 18 Apr 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. This is a two arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine-naloxone will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with extended release naltrexone (XR-naltrexone) administered every four weeks for a total of 6 injections.
Detailed description
This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. Adding buprenorphine-naloxone after the patient initiated XR-naltrexone will not produce mu opioid agonist effect but kappa antagonist effects of buprenorphine may provide additional relief of protracted withdrawal, craving, and mood disturbances persisting in patients treated with XR-naltrexone and possibly contributing to premature treatment discontinuation and relapse. This is a parallel arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with XR-naltrexone administered every four weeks. Individuals with Opioid Use Disorder (OUD) and beginning treatment with XR-naltrexone for maintenance treatment will be randomized to treatment with adjunctive buprenorphine-naloxone or placebo with 5 additional doses of XR-naltrexone, given every four weeks, and weekly medication management. The study will provide detoxification and a first XR-Naltrexone injection if a participant consents before the first XR-naltrexone injection. In all participants randomization will occur after first XR-NTX injection. Buprenorphine-naloxone (sub-lingual (SL), 4/1 mg/day) or placebo will be started after a first XR-naltrexone dose and tapered off at study completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- parallel arm, double-blind, placebo-controlled buprenorphine compared to placebo
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine-naloxone | Experimental | Drug: Buprenorphine/naloxoneBuprenorphine/naloxone 5.7 mg /1.4 mg/day sub-lingual tablets |
| Placebo | Placebo comparator | Drug: Placeboplacebo sub-lingual tablet |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Individuals between the ages of 18-65 (inclusive) interested in antagonist-based relapse prevention treatment
- Meets current DSM-5 criteria for current opioid use disorder of at least six months duration supported by urine toxicology positive for opioids OR positive naloxone challenge (defined by 3-point increase in COWS) if seeking detoxification and XR-NTX induction OR confirmed recent detoxification treatment for opioids.
- In otherwise good health based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) with no clinically significant abnormalities
- Participants who completed detoxification and received XR-NTX are eligible for the study. Participants may be enrolled up to 2 weeks following an initial XR-NTX injection given in any outside research or community-based treatment setting (inpatient, outpatient residential).
- Seeking treatment for opioid use disorder, willing to accept treatment with XR-NTX and, in the judgment of the treating physician, is a good candidate for naltrexone-based treatment.
Key exclusion criteria (15 listed)
- Methadone maintenance within 2 weeks of XR-NTX induction or any use of methadone in the week prior to XR-NTX induction
- Maintenance on buprenorphine or frequent buprenorphine use in the week prior to XR-NTX induction (must be using no more than 8 mg of buprenorphine per day for no more than 3 days per week). If consenting after initial XR-NTX injection, any use of buprenorphine since XR-NTX induction is exclusionary.
- Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make a detoxification and naltrexone initiation, or maintenance treatment with XR-NTX in combination with buprenorphine, hazardous (relative contraindications) or requires a different level of care. Examples include:
- AST/ALT \> 3x normal limit
- Pregnancy, lactation, or a plan of becoming pregnant. Women need to have negative blood pregnancy test at screening and agree to practice dual contraceptives.
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 |
|---|---|---|
| Buprenorphine/naloxoneAlso: Zubsolv5.7 mg buprenorphine/1.4 mg naloxone sub-lingual daily | Drug | Buprenorphine-naloxone |
| PlaceboAlso: PBOplacebo sub-lingual tablet daily | Drug | Placebo |
Primary outcome
Proportion of participants receiving XR-naltrexone injections
Time frame: 20 weeks
Proportion of patients successfully retained to receive six consecutive XR-naltrexone injection.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Derived from this study: PubMed 40342086Kornor H, Lobmaier PPK, Kunoe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140. doi: 10.1002/14651858.CD006140.pub3.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results published in this report (after de-identification) (text, tables, figures)
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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.
Onumara Opara, MPH contact
Adam Bisaga, MD principal investigator
New York State Psychiatric Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Buprenorphine/naloxone in people with Opioid-use Disorder, run by New York State Psychiatric Institute at 2 sites 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 7 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Adam Bisaga, MD (646-774-6155, amb107@columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants receiving XR-naltrexone injections (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05011266, which also lists 1 linked publication.
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 19 May 2026.