Extended-Release Naltrexone + Buprenorphine for Cocaine Use Disorder

(CURB-2 Trial)

Recruiting at11 trial locations

Overseen by Madhukar Trivedi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two medications, naltrexone and buprenorphine, for adults addicted to cocaine. Naltrexone blocks the high from cocaine, while buprenorphine helps reduce cravings and withdrawal symptoms. The goal is to see if this combination is more effective. Buprenorphine has been proposed as a treatment for cocaine abuse, and its combination with naltrexone has shown potential in reducing cocaine intake.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team to understand any specific requirements.

What data supports the effectiveness of the drug combination of extended-release naltrexone and buprenorphine for cocaine use disorder?

Research suggests that buprenorphine, especially when combined with naltrexone, may help reduce cocaine use, as seen in studies like the Cocaine Use Reduction with Buprenorphine (CURB) study. While no definitive medications for cocaine dependence have been identified, these drugs show potential in reducing cocaine use. ^{1 2 3 4 5}

Is the combination of extended-release naltrexone and buprenorphine safe for humans?

The combination of buprenorphine and extended-release naltrexone has been studied for safety in treating cocaine and opioid dependence. These treatments are generally well tolerated, with safety profiles consistent with their use in opioid dependence, suggesting they are safe for human use. ^{1 2 3 4 6}

How is the drug combination of extended-release naltrexone and buprenorphine unique for treating cocaine use disorder?

This drug combination is unique because it uses extended-release forms of naltrexone and buprenorphine, which are typically used for opioid use disorder, to potentially reduce cocaine use. There are no standard medications for cocaine use disorder, making this approach novel by repurposing drugs effective for other substance use disorders. ^{1 2 3 4 7}

Research Team

Madhukar Trivedi, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

Adults aged 18-65 with moderate to severe Cocaine Use Disorder, who want to reduce or stop cocaine use. They must have used cocaine frequently in the past month and not be using opioids. Women should agree to birth control measures. People with certain psychiatric conditions, heart issues, liver problems, blood disorders, or those at risk for serotonin syndrome are excluded.

Inclusion Criteria

Be interested in reducing or stopping cocaine use

Be willing to comply with all study procedures and medication instructions

I am between 18 and 65 years old.

Exclusion Criteria

Have any condition for which, in the opinion of the site investigator or designee, study participation would not be in their best interest or that could prevent, limit, or confound the protocol-specified assessments.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Varies by participant

Medication Induction

Participants are randomized and begin the 1-week medication induction phase

1 week

1 visit (in-person)

Medication

Participants receive XR-NTX and XR-BUP or placebo injections and attend clinic twice weekly for assessments

8 weeks

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

4 visits (in-person)

Treatment Details

Interventions

• Extended Release Buprenorphine (Partial Opioid Agonist)
• Extended-Release Naltrexone (Opioid Antagonist)
• Placebo Injectable (Medication)

Trial Overview The trial is testing if a combination of extended-release naltrexone (XR-NTX) and extended-release buprenorphine (XR-BUP) is more effective than placebo injections in treating Cocaine Use Disorder over an 8-week period. Participants will be randomly assigned to receive either the medication combo or placebo.

Participant Groups

Group I: Drug intervention (XR-NTX+XR-BUP) Experimental Treatment 2 Interventions

The study intervention is three doses of 380mg XR-NTX (Weeks 0, 3 and 6) and two doses of 300mg XR-BUP (Weeks 0, 4). Drug: XR-NTX XR-NTX: 3 intramuscular injections administered Week 0, 3, 6. Other Names: Extended Release Injectable Naltrexone Arm: Experimental Drug: XR-BUP XR-BUP: 2 subcutaneous injections administered Week 0, 4. Other Names: Extended Release Injectable Buprenorphine Arm: Experimental

Group II: Placebo Placebo Group 2 Interventions

Matched placebo injections (PBO-Inj) for the treatment of cocaine use disorder (CUD). Drug: Placebo (PLB) Injectable Placebo: 3 intramuscular injections administered Week 0, 3, 6. Other Names: Injectable matching (to XR-NTX) placebo Arm: Placebo Comparator - matched Placebo (PLB) Drug: Placebo (PLB) Injectable Placebo: 2 subcutaneous injections administered Week 0, 4. Other Names: Injectable matching (to XR-BUP) placebo Arm: Placebo Comparator - matched Placebo (PLB)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

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]

In a study involving 570 adults with opioid use disorder, buprenorphine-naloxone was found to be more cost-effective than extended-release naltrexone, being preferred in 97% of cases at 24 weeks and 85% at 36 weeks based on quality-adjusted life-years (QALYs).

The analysis suggests that buprenorphine-naloxone is the better first-line treatment option, especially for patients needing detoxification before starting extended-release naltrexone, although the study had limitations such as a relatively short follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. Murphy, SM., McCollister, KE., Leff, JA., et al.[2020]

The CURB study is a multi-site, double-blind, placebo-controlled trial involving 300 participants to evaluate the safety and efficacy of sublingual buprenorphine (BUP) combined with extended-release injectable naltrexone (XR-NTX) for treating cocaine dependence in individuals with a history of opioid use disorders.

The study aims to determine if BUP can effectively reduce cocaine use while XR-NTX prevents the development of physical dependence on BUP, with participants receiving cognitive behavioral therapy alongside their medication regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology. Mooney, LJ., Nielsen, S., Saxon, A., et al.[2021]

The new sublingual buprenorphine/naloxone tablet (Zubsolv®) has higher bioavailability and better taste, which may improve patient adherence and reduce the risk of misuse compared to the reference product (Suboxone®).

In large phase III trials lasting up to 28 days, Zubsolv® demonstrated high treatment retention rates and effectively reduced opioid cravings and withdrawal symptoms, making it a viable option for treating opioid dependence in adults and adolescents over 15 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine/Naloxone (Zubsolv®): A Review in Opioid Dependence. Heo, YA., Scott, LJ.[2021]

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

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. [2020]

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

Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness implications of increasing the efficiency of the extended-release naltrexone induction process for the treatment of opioid use disorder: a secondary analysis. [2022]

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

Buprenorphine/Naloxone (Zubsolv®): A Review in Opioid Dependence. [2021]

7. 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]