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

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT05011266

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

180

Enrollment

Location

Arms

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Opioid-use Disorder	Drug: Buprenorphine/naloxone Drug: Placebo	Phase 2/Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

parallel arm, double-blind, placebo-controlled buprenorphine compared to placeboparallel arm, double-blind, placebo-controlled buprenorphine compared to placebo

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double blind masking

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buprenorphine-naloxone Buprenorphine/naloxone 5.7 mg /1.4 mg/day sub-lingual tablets	Drug: Buprenorphine/naloxone 5.7 mg buprenorphine/1.4 mg naloxone sub-lingual daily Other Names: Zubsolv
Placebo Comparator: Placebo placebo sub-lingual tablet	Drug: Placebo placebo sub-lingual tablet daily Other Names: PBO

Arm

Intervention/Treatment

Experimental: Buprenorphine-naloxone

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

Drug: Buprenorphine/naloxone

5.7 mg buprenorphine/1.4 mg naloxone sub-lingual daily

Other Names:

Zubsolv

Placebo Comparator: Placebo

placebo sub-lingual tablet

Drug: Placebo

placebo sub-lingual tablet daily

Other Names:

PBO

Outcome Measures

Primary Outcome Measures

Proportion of participants receiving XR-naltrexone injections [24 weeks]
Proportion of patients successfully retained to receive six consecutive XR-naltrexone injection.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 naloxone challenge 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) within normal ranges.
Participants with active opioid use and those who recently completed detoxification and received XR-NTX are eligible for the study.
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.

Exclusion Criteria:

Methadone maintenance or any use of illicit 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 and no more than 3 days per week). If consenting after initial XR-NTX injection, any use of buprenorphine since XR-NTX induction is exclusionary.
Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with AST/ALT> 3 times normal, AIDS (CD4 count under 200 or medically ill), unstable diabetes or unstable heart disease.
Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-5 Schizophrenia or any psychotic disorder, severe Major Depressive Disorder, chronic Neurocognitive Disorder, or suicide risk or a suicide attempt within the past year
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.
History of accidental drug overdose in the prior 6 months defined as an episode of opioid-induced unconsciousness, whether or not medical treatment was sought or received.
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 Sattuts Exam screen.
Participants who had 30 or more opioid-free days prior to consent 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).