Buprenorphine + XR-Naltrexone for Opioid Use Disorder
(COMBO Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byAdam Bisaga, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: New York State Psychiatric Institute
Must be taking: XR-naltrexone
Must not be taking: Methadone, Buprenorphine
Disqualifiers: Severe mental disorder, Severe alcohol use, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Do I have to stop taking my current medications for the trial?
The trial requires that you stop taking methadone and limit buprenorphine use before starting the treatment. If you are on methadone, you must stop at least two weeks before starting, and if you use buprenorphine, you must limit it to no more than 8 mg per day for three days a week before starting.
What data supports the effectiveness of the drug Buprenorphine/naloxone for opioid use disorder?
Research shows that both buprenorphine-naloxone and extended-release naltrexone are effective in reducing opioid relapse in people with opioid use disorder. Additionally, buprenorphine-naloxone has been shown to improve outcomes for individuals seeking treatment for opioid use disorder, although adherence to the medication can be a challenge.
12345Is the combination of Buprenorphine and XR-Naltrexone safe for humans?
Buprenorphine, often combined with naloxone, has a high safety profile and is well-tolerated in treating opioid dependence, though it has been subject to misuse. Extended-release naltrexone (XR-NTX) is considered similarly safe to sublingual buprenorphine-naloxone for opioid use disorder, but it can be difficult to start due to detoxification requirements.
46789How is the drug Buprenorphine/naloxone unique for treating opioid use disorder?
Buprenorphine/naloxone is unique because it combines a long-acting partial agonist (which activates opioid receptors) and an antagonist (which blocks opioid effects), offering higher bioavailability and faster dissolve time compared to other formulations, potentially improving patient adherence and reducing the risk of misuse.
38101112Eligibility Criteria
Adults aged 18-65 with opioid use disorder for at least six months, confirmed by tests or recent detox treatment, and in good health based on medical exams. They must understand the difference between agonist and antagonist treatments and be interested in antagonist-based relapse prevention without severe alcohol or sedative use, significant liver issues, suicidal tendencies, pregnancy, or certain medication allergies.Inclusion Criteria
I have completed detox and received an XR-NTX shot within the last 2 weeks.
I have been diagnosed with opioid addiction for at least 6 months.
Voluntarily seeking treatment for opioid use disorder
+9 more
Exclusion Criteria
I am over 60 and may have early cognitive decline, as shown by my MMSE score.
I do not have a severe addiction to alcohol or sedatives that would complicate medical detox.
- Suicidal or homicidal
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Detoxification
Participants undergo detoxification and receive the first XR-Naltrexone injection if they consent
1-2 weeks
Treatment
Participants receive XR-naltrexone injections every four weeks for 24 weeks, with adjunctive buprenorphine-naloxone or placebo
24 weeks
6 visits (in-person) for injections, weekly medication management visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing if combining buprenorphine-naloxone with extended-release naltrexone (XR-naltrexone) improves treatment retention and mood over 24 weeks compared to a placebo. Participants will receive XR-naltrexone injections every four weeks for a total of six doses in this double-blind study.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Buprenorphine-naloxoneExperimental Treatment1 Intervention
Buprenorphine/naloxone 5.7 mg /1.4 mg/day sub-lingual tablets
Group II: PlaceboPlacebo Group1 Intervention
placebo sub-lingual tablet
Buprenorphine/naloxone is already approved in European Union, United States, Canada, Australia for the following indications:
🇪🇺 Approved in European Union as Suboxone for:
- Opioid dependence
- Opioid use disorder
🇺🇸 Approved in United States as Suboxone for:
- Opioid dependence
- Opioid use disorder
🇨🇦 Approved in Canada as Suboxone for:
- Opioid dependence
- Opioid use disorder
🇦🇺 Approved in Australia as Suboxone for:
- Opioid dependence
- Opioid use disorder
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stars/NyspiNew York, NY
Avery Road Treatment Center (ARTC)Rockville, MD
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Who Is Running the Clinical Trial?
New York State Psychiatric InstituteLead Sponsor
National Institute on Drug Abuse (NIDA) (DA038095)Collaborator
National Institute on Drug Abuse (NIDA)Collaborator
References
Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. [2023]Buprenorphine-naloxone is a medication shown to improve outcomes for individuals seeking treatment for opioid use disorder (OUD); however, outcomes are limited by low medication adherence rates. This is especially true during the early stages of treatment.
Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. [2023]This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).
Is extended release naltrexone superior to buprenorphine-naloxone to reduce drinking among outpatients receiving treatment for opioid use disorder? A secondary analysis of the CTN X:BOT trial. [2023]The comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR-NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD.
Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018]To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.
Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. [2020]Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder.
Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care. [2015]Buprenorphine is well known in the treatment of opioid dependence. Despite a high safety profile and good tolerance buprenorphine has been subject to misuse and diversion. To reduce misuse the antagonist naloxone was added and the 4:1 combination of buprenorphine-naloxone was launched in Germany in March 2007. On the basis of the results from international clinical trials a non-interventional study was conducted to gather data on safety, effectiveness, retention and acceptability of buprenorphine-naloxone in the treatment of opioid dependent patients in routine care.
Extended-release buprenorphine outcomes among treatment resistant veterans. [2022]Background: Buprenorphine Extended-Release (BUP-XR) is an FDA approved, monthly subcutaneous injection for opioid use disorder. This formulation provides an alternative for patients who have difficulty adhering to daily sublingual buprenorphine; however, its cost may be prohibitive compared to other medication alternatives.Objectives: The objective of this project was to evaluate the effectiveness of BUP-XR and provide a rationale for its utilization in health care facilitates.Methods: Across two VA outpatient clinics, twenty-six (22 male, 4 female) clinically complex patients received at least one BUP-XR injection between December 1, 2018 and April 1, 2020. The sample was high risk for hospital admission and mortality. Data was collected retrospectively from the medical records. Outcomes examined included: medication adherence, urine drug and alcohol screenings, emergency department visits, hospital admissions, and housing status. Within-subject comparisons were made between the six month period prior to and following the first injection.Results: Treatment retention was robust, as 81% of the sample received six or more monthly BUP-XR injections. Most patients (77%) maintained 300 mg dosage and a majority (70%) missed or were late for at least one injection. BUP-XR was associated with reduction in: emergency department visits, days of hospitalization, non-prescribed opioid use, and homelessness. Mortality rate was 23%.Conclusions: BUP-XR with a flexible dosing schedule and a nonstandard default dose of 300 mgs resulted in robust retention, provided effective treatment of OUD, and reduced health care utilization for these complex patients with high mortality risk. However, due to the lack of statistical significance generalization of these findings is limited.
Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids.
Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX). [2022]The National Drug Abuse Treatment Clinical Trials Network (CTN) multisite comparative-effectiveness study ("X:BOT") by Lee et al. (2018) found that, once initiated, extended-release naltrexone (XR-NTX) is as similarly safe and effective as sublingual buprenorphine-naloxone (BUP-NX) for the treatment of opioid use disorder (OUD). However, the detoxification hurdle makes XR-NTX much more difficult to initiate than BUP-NX. This hurdle highlights the need to better understand how patients transition from active opioid use to XR-NTX treatment.
Buprenorphine/Naloxone (Zubsolv®): A Review in Opioid Dependence. [2021]A new sublingual buprenorphine/naloxone tablet (hereafter referred to as buprenorphine/naloxone; Zubsolv®), combining a long-acting partial µ receptor agonist and an opioid antagonist, is approved for the treatment of opioid dependence in adults and adolescents aged > 15 years. This formulation has a higher bioavailability, better taste and faster sublingual dissolve time than a reference sublingual buprenorphine/naloxone tablet (Suboxone®), advantages that provide greater patient preference (potentially improving adherence) and importantly may reduce the risk of buprenorphine parenteral abuse by providing similar buprenorphine exposure at an ≈ 30% lower dosage than reference buprenorphine/naloxone. In large phase III trials of up to 28 days, buprenorphine/naloxone was associated with high treatment retention rates during the induction and stabilization phases, and also reduced opioid craving and opioid withdrawal symptoms. Although noninferiority of buprenorphine/naloxone to sublingual buprenorphine tablet during the 2-day induction phase was only shown in one of the two similarly designed trials, pooled analyses confirmed that treatment retention rates were similar in the buprenorphine/naloxone and buprenorphine groups. Where evaluated, noninferiority of buprenorphine/naloxone to sublingual buprenorphine/naloxone film (only approved in the USA) was also demonstrated at 15 days in the stabilization phase. During the 24-week extension study, buprenorphine/naloxone maintenance therapy sustained improvements in opioid craving and addiction severity scores. Buprenorphine/naloxone was generally well tolerated, displaying a tolerability profile that was generally consistent with that seen with reference buprenorphine/naloxone. In conclusion, with potentially greater patient preference and a lower potential for parenteral buprenorphine abuse than reference buprenorphine/naloxone, buprenorphine/naloxone expands the treatment options available for adults and adolescent (aged > 15 years) patients with opioid dependence.
Extended-release Buprenorphine Administered at Discharge in Hospitalized Persons With Opioid Use Disorder: A Case Series. [2023]Monthly subcutaneous injectable buprenorphine (XR-Bup) is an option for treatment of opioid use disorder (OUD) that addresses some sublingual buprenorphine adherence barriers and is infrequently offered to hospitalized patients with OUD.
Does XR injectable naltrexone prevent relapse as effectively as daily sublingual buprenorphine-naloxone? [2021]YES. MONTHLY EXTENDED-RELEASE INJECTABLE NALTREXONE (XR-NTX) TREATS OPIOID USE DISORDER AS EFFECTIVELY AS DAILY SUBLINGUAL BUPRENORPHINE-NALOXONE (BUP-NX) WITHOUT CAUSING ANY INCREASE IN SERIOUS ADVERSE EVENTS OR FATAL OVERDOSES. (STRENGTH OF RECOMMENDATION: A, 2 GOOD-QUALITY RCTS).