Efficacy of Buprenorphine and XR-Naltrexone Combination for Relapse Prevention in Opioid Use Disorder

NCT05011266 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB #8171U01DA046430
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief 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. 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. The NYSPI site, which provides study oversight (no direct participant involvement) is currently paused and has been paused since an institutional pause on human subjects research began in June, 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.

Conditions

Opioid-use Disorder

Keywords

opioid use disorder; treatment; buprenorphine; extended release naltrexone

Outcome Measures

Primary Outcomes (1)

• Proportion of participants receiving XR-naltrexone injections

  Proportion of patients successfully retained to receive six consecutive XR-naltrexone injection.

  20 weeks

Study Arms (2)

Buprenorphine-naloxone

EXPERIMENTAL

Buprenorphine/naloxone 5.7 mg /1.4 mg/day sub-lingual tablets

Drug: Buprenorphine/naloxone

Placebo

PLACEBO COMPARATOR

placebo sub-lingual tablet

Drug: Placebo

Interventions

Buprenorphine/naloxone DRUG

5.7 mg buprenorphine/1.4 mg naloxone sub-lingual daily

Also known as: Zubsolv

Buprenorphine-naloxone

Placebo DRUG

placebo sub-lingual tablet daily

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Methadone maintenance within 2 weeks of XR-NTX induction or any use of methadone in the week prior to XR-NTX induction
• 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).
• 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.
• 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).

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Avery Road Treatment Center (ARTC)

Rockville, Maryland, 20853, United States

RECRUITING

Stars/Nyspi

New York, New York, 10019, United States

ACTIVE NOT RECRUITING

Related Publications (1)

• 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.

  PMID: 40342086 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Adam Bisaga, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adam Bisaga, md

CONTACT

646-774-6155; amb107@columbia.edu

Matisyahu Shulman, MD

CONTACT

matisyahu.shulman@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Model Details: parallel arm, double-blind, placebo-controlled buprenorphine compared to placebo

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 18, 2021
• Study Start: April 18, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: beginning twelve months and ending 5 years after article publication
• Access Criteria: to researcher who provides a methodologically sound proposal to achieve aims in approved proposal

Locations

US (2)