Pharmacotherapy Strategies for Opioid Use Disorder

Recruiting at 25 trial locations

Overseen By Ashley Naeger, MSW

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Buprenorphine, Naltrexone

Must not be taking: Methadone, Opioids

Disqualifiers: Severe psychiatric, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

2190 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a two phase study investigating combinations of pharmacological and behavioral interventions to optimize the treatment of Opioid Use Disorder (OUD). The Retention Phase will assess strategies for improving retention on buprenorphine (BUP) and extended-release injectable naltrexone (XR-NTX). The Discontinuation Phase will assess which approaches are most likely to lead to long-term success (absence of relapse), and what characteristics of participants distinguish those who can safely discontinue Medications for Opioid Use Disorder (MOUD) from those who remain at risk of relapse and should not discontinue.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on methadone or have a serious medical or psychiatric condition that requires different care, you may not be eligible to participate.

What data supports the effectiveness of this drug for opioid use disorder?

Research shows that buprenorphine, especially in extended-release forms like Sublocade, helps reduce opioid use and improve treatment retention. Additionally, combining buprenorphine with naloxone (as in Suboxone) is effective in managing opioid use disorder by reducing misuse and increasing safety. ^{1 2 3 4 5}

Is the treatment for opioid use disorder safe for humans?

Buprenorphine, used in various forms like Suboxone and Sublocade, is generally considered safe for treating opioid use disorder, with a lower risk of overdose compared to methadone. However, it can still pose risks such as withdrawal and misuse, and some forms require surgical procedures for implantation. ^{1 2 6 7 8}

How is the drug SL-BUP, XR-NTX unique for treating opioid use disorder?

SL-BUP, XR-NTX combines buprenorphine, which partially activates opioid receptors to reduce cravings, with naltrexone, which blocks these receptors to prevent misuse. This combination offers a unique approach by using both a partial agonist and an antagonist, potentially improving adherence and reducing the risk of misuse compared to other treatments. ^{1 4 5 9 10}

Research Team

Roger Weiss, MD

Principal Investigator

Harvard Medical School/McLean Hospital

Edward V Nunes, MD

Principal Investigator

New York State Psychiatric Institute/Columbia University Irving Medical Center

John Rotrosen, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults with opioid use disorder seeking treatment can join this study. They must be in stable health, speak English, and women should use birth control if applicable. Excluded are those with severe medical or mental conditions, certain substance dependencies, legal constraints that prevent participation, or who have used specific mHealth apps recently.

Inclusion Criteria

In good-enough general health (meaning good enough health to be in outpatient treatment) as determined by the study medical clinician on the basis of medical history, review of systems, and physical/mental status exam, to permit treatment with XR-NTX or BUP

Willing and able to provide written informed consent

I am looking for treatment for opioid addiction and considering buprenorphine or naltrexone.

Exclusion Criteria

Serious medical, psychiatric, or co-occurring substance use disorder or concomitant medication that, in the opinion of the study medical clinician, makes the patient not appropriate for outpatient treatment with buprenorphine or XR-NTX, but instead requires a higher or different level of care. Examples include: Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments; Severe, untreated or inadequately treated psychiatric condition (e.g., active psychosis, uncontrolled bipolar disorder) as assessed by history and/or clinical interview, requiring a different level of care (e.g., hospitalization); Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use, requiring a different level of care (e.g., hospitalization); Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization); Known allergy or sensitivity to preferred medication or its components; Maintenance on methadone at the time of signing consent; For those preferring XR-NTX, presence of pain of sufficient severity as to require ongoing pain management with opioids; For those preferring XR-NTX, body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX (e.g., BMI>40, excess fat tissue over the buttocks, emaciation); If female, currently pregnant or breastfeeding or planning on conception; Are currently in jail, prison or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities; Have used the reSET or reSET-O mHealth apps in the 3 months prior to consent; Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area)

Serious medical or psychiatric disorder or concomitant medication that, in the opinion of the study medical clinician, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study. Examples include: Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments; Severe, untreated, or inadequately treated psychiatric condition (e.g., active psychosis, uncontrolled bipolar disorder) as assessed by history and/or clinical interview, requiring a different level of care (e.g., hospitalization); Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization); For participants entering the study taking buprenorphine, presence of pain requiring or likely requiring ongoing pain management with buprenorphine or other opioids; If female, currently pregnant or breastfeeding or planning on conception; Use of opioids (other than buprenorphine), cocaine, methamphetamine, or non-prescribed benzodiazepines in the past 12 weeks; Meets current DSM-5 criteria for any current alcohol use disorder; Are currently in jail, prison or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities; Have used the Connections mHealth app in the 3 months prior to consent; Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area)

I want to stop my medication for opioid use disorder after talking with my doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Retention Phase

Strategies to improve retention in treatment on medications for opioid use disorder (MOUD) are tested.

26 weeks

Weekly visits (in-person or virtual)

Discontinuation Phase

Approaches to safely discontinue MOUD and achieve long-term success without relapse are assessed.

24-48 weeks

Bi-weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation.

24 weeks

Monthly visits (in-person or virtual)

Treatment Details

Interventions

• MM
• MMD
• MMR
• SL-BUP
• XR-BUP
• XR-NTX

Trial Overview The trial is testing combinations of medications like buprenorphine (BUP) and extended-release naltrexone (XR-NTX), along with behavioral strategies to improve retention in treatment for opioid addiction and to determine safe discontinuation methods for long-term success without relapse.

Participant Groups

Group I: Retention: XR-NTX + MMR Experimental Treatment 2 Interventions

Extended-release injectable naltrexone (XR-NTX) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group II: Retention: XR-NTX + MM Experimental Treatment 2 Interventions

Extended-release injectable naltrexone (XR-NTX) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group III: Retention: XR-BUP + MMR Experimental Treatment 2 Interventions

Extended-release injectable buprenorphine (XR-BUP) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group IV: Retention: XR-BUP + MM Experimental Treatment 2 Interventions

Extended-release injectable buprenorphine (XR-BUP) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group V: Retention: SL-BUP standard dose + MMR Experimental Treatment 2 Interventions

Standard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MMR, consisting of Medical Management and usual counseling, plus a technology-based behavioral component.

Group VI: Retention: SL-BUP standard dose + MM Experimental Treatment 2 Interventions

Standard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group VII: Retention: SL-BUP high dose + MMR Experimental Treatment 2 Interventions

High dose sublingual buprenorphine-naloxone (SL-BUP) 32mg/day target plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group VIII: Retention: SL-BUP high dose + MM Experimental Treatment 2 Interventions

High dose sublingual buprenorphine-naloxone (SL-BUP) 32mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group IX: Discontinuation: Discontinue XR-NTX with XR-NTX + MMD Experimental Treatment 2 Interventions

Start on XR-NTX, taper with XR-NTX, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group X: Discontinuation: Discontinue XR-NTX with XR-NTX + MM Experimental Treatment 2 Interventions

Start on XR-NTX, taper with XR-NTX, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XI: Discontinuation: Discontinue XR-BUP with XR-BUP + MMD Experimental Treatment 2 Interventions

Start on XR-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XII: Discontinuation: Discontinue XR-BUP with XR-BUP + MM Experimental Treatment 2 Interventions

Start on XR-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XIII: Discontinuation: Discontinue SL-BUP with XR-BUP + MMD Experimental Treatment 2 Interventions

Start on SL-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XIV: Discontinuation: Discontinue SL-BUP with XR-BUP + MM Experimental Treatment 2 Interventions

Start on SL-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XV: Discontinuation: Discontinue SL-BUP with SL-BUP + MMD Experimental Treatment 2 Interventions

Start on SL-BUP, taper with SL-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XVI: Discontinuation: Discontinue SL-BUP with SL-BUP + MM Experimental Treatment 2 Interventions

Start on SL-BUP, taper with SL-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

SL-BUP is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Suboxone for:

• Opioid use disorder

Approved in United States as Suboxone for:

• Opioid use disorder

Approved in Canada as Suboxone for:

• Opioid use disorder

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

New York State Psychiatric Institute

Collaborator

Trials

481

Recruited

154,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Harvard Medical School (HMS and HSDM)

Collaborator

Trials

208

Recruited

1,421,000+

Mclean Hospital

Collaborator

Trials

221

Recruited

22,500+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Findings from Research

In a study involving 302 participants with cocaine dependence and a history of opioid dependence, buprenorphine + naloxone (BUP) combined with extended-release injectable naltrexone (XR-NTX) showed a significant reduction in cocaine use for those receiving 16 mg/day of BUP compared to placebo, indicating its potential effectiveness in this population.

However, no significant differences were observed in the primary outcome for the 4 mg/day BUP group compared to placebo, suggesting that higher doses may be necessary for efficacy, while adherence, retention, and adverse events were similar across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Ling, W., Hillhouse, MP., Saxon, AJ., et al.[2018]

In a study of 533 participants over 18 months after stopping extended-release buprenorphine injection (BUP-XR), 47% reported sustained opioid abstinence, with higher rates of abstinence linked to longer treatment durations.

More than 60% of participants showed stable or improved outcomes in health-related quality of life and mental health scores, indicating that BUP-XR has a long-term positive impact on recovery from opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. Boyett, B., Nadipelli, VR., Solem, CT., et al.[2023]

A study comparing two groups of patients with opioid use disorder found that those receiving longer prescriptions of buprenorphine (up to 4 weeks) had a longer median time to treatment discontinuation (33.1 weeks) compared to those with shorter prescriptions (1-2 weeks, 22.4 weeks), suggesting that longer prescriptions may improve treatment retention.

Despite the differences in treatment retention, other outcomes such as non-prescription opioid use and urine screen results did not significantly differ between the groups, indicating that while prescription length may help keep patients in treatment longer, it does not necessarily lead to better overall outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India. Ghosh, A., Mahintamani, T., Kathiravan, S., et al.[2023]

Lofexidine is being developed to help manage withdrawal symptoms in opioid addiction, while Probuphine® offers a six-month delivery of buprenorphine, reducing concerns about misuse and child exposure.

New formulations like Suboxone® (sublingual film) and Vivitrol® (injectable depot) enhance safety and compliance in treatment, with Suboxone® being less prone to diversion and Vivitrol® providing consistent opioid receptor blockade for a month.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective review and commentary on emerging pharmacotherapies for opioid addiction. Ling, W., Mooney, L., Zhao, M., et al.[2021]

Buprenorphine-naloxone (bup/nx) is a safe and effective treatment for opioid-use disorders, functioning as a partial μ-opioid agonist with a lower abuse potential compared to methadone, making it suitable for both inpatient and outpatient settings.

A stepwise approach to long-term treatment with bup/nx, involving regular monitoring, leads to better outcomes in reducing illicit opioid use and improving overall patient functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence. Mauger, S., Fraser, R., Gill, K.[2022]

Buprenorphine (BUP) is effective for treating opioid use disorder, requiring specific levels of mu-opioid receptor (μOR) availability to prevent withdrawal symptoms and block the effects of abused opioids, with optimal dosing often exceeding 16 mg for some patients.

The study suggests that imposing fixed limits on BUP dosing or reimbursement policies is inappropriate, as individual patient needs can vary significantly based on their μOR availability and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Greenwald, MK., Comer, SD., Fiellin, DA.[2021]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2021]

New prolonged-release formulations of buprenorphine, including a six-month implant and two subcutaneous injection depots, aim to improve patient comfort and safety by reducing the need for daily intake and minimizing risks associated with sublingual forms.

These formulations have shown promise in addressing concerns about treatment adherence, particularly for stabilized patients, while also raising some apprehensions about potential coercive use among opioid users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. Chappuy, M., Trojak, B., Nubukpo, P., et al.[2022]

Buprenorphine is an effective treatment for opioid use disorder, supported by numerous studies, yet many patients do not receive it or any other medical treatment.

New long-acting injectable formulations of buprenorphine may enhance treatment adherence and reduce the risk of misuse, addressing some of the barriers to effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Treatment for Opioid Use Disorder: An Overview. Shulman, M., Wai, JM., Nunes, EV.[2022]

In a 24-week study involving 570 patients with opioid use disorder, those who were homeless had a significantly lower relapse rate when treated with extended-release naltrexone (51.6%) compared to buprenorphine-naloxone (70.4%).

Conversely, non-homeless patients had a higher relapse rate with extended-release naltrexone (70.9%) compared to buprenorphine-naloxone (53.1%), indicating that demographic factors like homelessness can influence the effectiveness of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. Nunes, EV., Scodes, JM., Pavlicova, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Selective review and commentary on emerging pharmacotherapies for opioid addiction. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. [2021]

8. France pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Buprenorphine Treatment for Opioid Use Disorder: An Overview. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. [2021]