Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2) (CURB-2)

October 19, 2025 updated by: Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center

Randomized, Placebo-Controlled Trial of Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2)

This is an 8-week, double-blind, randomized placebo-controlled trial of the efficacy of a combination of extended-release naltrexone (XR-NTX) and extended-release buprenorphine (XR-BUP) compared to matched placebo injections (PBO-Inj) for the treatment of cocaine use disorder (CUD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The primary objective of this study is to assess the efficacy of XR-NTX plus XR-BUP as a combination pharmacotherapy for CUD. Approximately four hundred and twenty-six adults will be randomized into the study at 8-12 sites in the U.S. Eligibility will be determined during a maximum 21-day screening period. After screening/baseline is completed and eligibility is confirmed, participants will be randomized and begin the 1-week medication induction phase followed by the 8-week medication phase of the trial.

Participants will be randomized in a 1:1 ratio to either 1) XR-NTX + XR-BUP arm and receive injections of extended-release naltrexone (XR-NTX; as Vivitrol®) and extended-release buprenorphine (XR-BUP; as SublocadeTM), or to 2) PBO-Inj matching the timeline and delivery methods of injections for the XR-NTX + XR-BUP arm. XR-NTX or PBO-Inj injections will be provided on the day of randomization and in Weeks 3 and 6. XR-BUP or PBO-Inj injections will be provided on days 3-5 following randomization and in week 4. During the 1-week induction phase and the 8-week medication phase, participants will be asked to attend clinic twice weekly for collection of urine samples and to complete assessments as indicated on the schedule of assessments. Following the 8-week medication phase, participants will be asked to attend clinic weekly for the follow-up phase during Weeks 9-12.

Participants will be involved in the study for approximately 16 weeks, including a screening/baseline period of up to 3 weeks (i.e., 21 days), 1 week for randomization and medication induction, 8 weeks of medication, and 4 weeks of follow-up. The screening phase may differ by participant in the length of time needed to complete preliminary eligibility assessments. Randomization and medication induction visit may take approximately 2 hours. Twice-weekly visits during the medication phase will range from about 20 to 90 minutes in length depending on scheduled assessments. Medication administration visits may require an additional 2 hours. Visits in the follow-up phase will take place approximately 30-60 minutes to complete. An 8-week medication period was selected based on expected time for group differences to emerge and for pragmatic issues related to medication dosing.

Enrollment is expected to take place over a period of approximately 13 months, with an approximate total of 16 months of study visits.

Study Type

Interventional

Enrollment (Actual)

427

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • University of Alabama at Birmingham
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Los Angeles, California, United States, 90038
        • UCLA Vine Street Clinic
      • San Francisco, California, United States, 94102
        • Center on Substance Use and Health (CSUH)
    • Florida
      • Tampa, Florida, United States, 33605
        • Cove Behavioral Health
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60608
        • University of Illinois at Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21229
        • Mountain Manor Treatment Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Berman Center for Outcomes and Clinical Research at Hennepin Healthcare
    • New York
      • New York, New York, United States, 10029
        • Addictions Institute of Mount Sinai
    • Texas
      • Dallas, Texas, United States, 75247
        • UTSW Medical Center, Center for Depression Research and Clinical Care
      • San Antonio, Texas, United States, 78229
        • University of Texas Health San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Individuals must meet all of the inclusion criteria and no exclusion criteria in order to be eligible to participate in the study, including but not limited to:

Inclusion Criteria:

  1. Be 18 to 65 years of age;
  2. Be interested in reducing or stopping cocaine use.
  3. Be willing to comply with all study procedures and medication instructions.

Exclusion Criteria:

1. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug intervention (XR-NTX+XR-BUP)

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
Drug: Extended-Release Naltrexone
XR-NTX (Extended-Release Naltrexone) doses of 380mg (Weeks 0, 3 and 6) via intramuscular (IM) injections in the gluteus.
Other Names:
  • XR-NTX
Drug: Extended Release Buprenorphine
Extended-Release buprenorphine (XR-BUP) two doses of 300mg XR-BUP (Weeks 0, 4) via subcutaneous injections in the abdomen. Option for 100mg at Weeks 3 and 6 (if needed to alleviate side effects).
Other Names:
  • XR-BUP
Placebo Comparator: Placebo

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)
Drug: Placebo (PLB) Injectable matched to XR-NTX
3 doses of intramuscular injections (Week 0, 3, 6)
Other Names:
  • Injectable matching (to XR-NTX) placebo
Drug: Placebo (PLB) Injectable matched to XR-BUP
2 doses of subcutaneous injections (Week 0, 4)
Other Names:
  • Injectable matching (to XR-BUP) placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Cocaine-negative UDS
Time Frame: Week 5 up to Week 8
The primary outcome measure is the proportion of cocaine-negative UDS obtained during Weeks 5 through 8 of the medication phase as measured for the XR-NTX + XR-BUP and PBO-Inj conditions. The primary outcome (UDS) has been chosen because it is an objective measure of cocaine use and was the outcome showing significant improvement over placebo in the original CURB trial.
Week 5 up to Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who Self-report cocaine use
Time Frame: 8 Weeks
Self-report elicited through Timeline Followback (TLFB) on days of cocaine use during Weeks 0-8;
8 Weeks
Mean self reported cocaine craving score
Time Frame: 8 Weeks

Cocaine craving as measured by the Visual Analog Craving Scales (VAS) during Weeks 0-8.

Possible scores range from 0 to 100, with higher scores indicating worse craving.
8 Weeks
Measures of safety (adverse events)
Time Frame: 8 weeks
Number and severity of adverse events reported during Weeks 0-8; Number and outcomes (non-fatal and fatal) of overdose events during Weeks 0-8
8 weeks
Mean self reported overall functioning
Time Frame: Week 8
Self-report overall functioning as measured by the Treatment Effectiveness Assessment (TEA) at Week 8. Possible scores range from 1 to 10 for each of the 4 domains, with higher scores indicating better outcome.
Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Madhukar Trivedi, MD, UT Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 18, 2023

Primary Completion (Actual)

June 27, 2025

Study Completion (Actual)

July 21, 2025

Study Registration Dates

First Submitted

February 17, 2022

First Submitted That Met QC Criteria

March 1, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Estimated)

October 21, 2025

Last Update Submitted That Met QC Criteria

October 19, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU-2021-0223
  • UG1DA020024 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data from this study will be available to researchers on the website https://datashare.nida.nih.gov/ after the study is complete and the data is analyzed. This website will not include information that can identify individual study participants. The following information will be posted: Study protocol, reference to study publication of primary outcome, data sets (SAS and ASCII ), annotated case report forms, define file (also known as Data Dictionary), study-specific de-identification notes. Prior to downloading any study data, the user will be prompted to complete a registration agreement for data use. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the National Institute on Drug Abuse (NIDA) Data Share Agreement.

IPD Sharing Time Frame

This will be available five months after all sites are closed. No yet determined duration of availability.

IPD Sharing Access Criteria

Researchers who are active users on the https://datashare.nida.nih.gov/ site. Primary data will be available to the public in the NIDA data repository on this site as well.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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