NCT05262270

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
427

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2023

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2022

Completed
13 days until next milestone

First Posted

Study publicly available on registry

March 2, 2022

Completed
1.1 years until next milestone

Study Start

First participant enrolled

April 18, 2023

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 27, 2025

Completed
24 days until next milestone

Study Completion

Last participant's last visit for all outcomes

July 21, 2025

Completed
Last Updated

October 21, 2025

Status Verified

October 1, 2025

Enrollment Period

2.2 years

First QC Date

February 17, 2022

Last Update Submit

October 19, 2025

Conditions

Cocaine Use Disorder

Keywords

NaltrexoneBuprenorphineExtended release injectable NaltrexoneExtended release injectable BuprenorphineCUDCocaineCocaine Abuse

Outcome Measures

Primary Outcomes (1)

  • Proportion of Cocaine-negative UDS

    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 Outcomes (4)

  • Number of participants who Self-report cocaine use

    8 Weeks

  • Mean self reported cocaine craving score

    8 Weeks

  • Measures of safety (adverse events)

    8 weeks

  • Mean self reported overall functioning

    Week 8

Study Arms (2)

Drug intervention (XR-NTX+XR-BUP)

EXPERIMENTAL

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 NaltrexoneDrug: Extended Release Buprenorphine

Placebo

PLACEBO COMPARATOR

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-NTXDrug: Placebo (PLB) Injectable matched to XR-BUP

Interventions

Extended-Release NaltrexoneDRUG

XR-NTX (Extended-Release Naltrexone) doses of 380mg (Weeks 0, 3 and 6) via intramuscular (IM) injections in the gluteus.

Also known as: XR-NTX
Drug intervention (XR-NTX+XR-BUP)
Extended Release BuprenorphineDRUG

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).

Also known as: XR-BUP
Drug intervention (XR-NTX+XR-BUP)
Placebo (PLB) Injectable matched to XR-NTXDRUG

3 doses of intramuscular injections (Week 0, 3, 6)

Also known as: Injectable matching (to XR-NTX) placebo
Placebo
Placebo (PLB) Injectable matched to XR-BUPDRUG

2 doses of subcutaneous injections (Week 0, 4)

Also known as: Injectable matching (to XR-BUP) placebo
Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35209, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

UCLA Vine Street Clinic

Los Angeles, California, 90038, United States

Location

Center on Substance Use and Health (CSUH)

San Francisco, California, 94102, United States

Location

Cove Behavioral Health

Tampa, Florida, 33605, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Mountain Manor Treatment Center

Baltimore, Maryland, 21229, United States

Location

Berman Center for Outcomes and Clinical Research at Hennepin Healthcare

Minneapolis, Minnesota, 55404, United States

Location

Addictions Institute of Mount Sinai

New York, New York, 10029, United States

Location

UTSW Medical Center, Center for Depression Research and Clinical Care

Dallas, Texas, 75247, United States

Location

University of Texas Health San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (12)

  • Center for Behavioral Health Statistics and Quality. 2019 National Survey on Drug Use and Health (NSDUH): CAI Specifications for Programming (English Version). Substance Abuse and Mental Health Services Administration, editor. Rockville, MD; 2018.

    BACKGROUND

  • Czoty PW, Stoops WW, Rush CR. Evaluation of the "Pipeline" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research. Pharmacol Rev. 2016 Jul;68(3):533-62. doi: 10.1124/pr.115.011668.

    PMID: 27255266BACKGROUND

  • Whitfield TW Jr, Schlosburg JE, Wee S, Gould A, George O, Grant Y, Zamora-Martinez ER, Edwards S, Crawford E, Vendruscolo LF, Koob GF. kappa Opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake. J Neurosci. 2015 Mar 11;35(10):4296-305. doi: 10.1523/JNEUROSCI.1978-13.2015.

    PMID: 25762676BACKGROUND

  • Ling W, Hillhouse MP, Saxon AJ, Mooney LJ, Thomas CM, Ang A, Matthews AG, Hasson A, Annon J, Sparenborg S, Liu DS, McCormack J, Church S, Swafford W, Drexler K, Schuman C, Ross S, Wiest K, Korthuis PT, Lawson W, Brigham GS, Knox PC, Dawes M, Rotrosen J. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016 Aug;111(8):1416-27. doi: 10.1111/add.13375. Epub 2016 Apr 21.

    PMID: 26948856BACKGROUND

  • Trivedi MH, Wisniewski SR, Morris DW, Fava M, Kurian BT, Gollan JK, Nierenberg AA, Warden D, Gaynes BN, Luther JF, Rush AJ. Concise Associated Symptoms Tracking scale: a brief self-report and clinician rating of symptoms associated with suicidality. J Clin Psychiatry. 2011 Jun;72(6):765-74. doi: 10.4088/JCP.11m06840.

    PMID: 21733477BACKGROUND

  • dela Cruz AM, Bernstein IH, Greer TL, Walker R, Rethorst CD, Grannemann B, Carmody T, Trivedi MH. Self-rated measure of pain frequency, intensity, and burden: psychometric properties of a new instrument for the assessment of pain. J Psychiatr Res. 2014 Dec;59:155-60. doi: 10.1016/j.jpsychires.2014.08.003. Epub 2014 Aug 27.

    PMID: 25194231BACKGROUND

  • Ling W, Farabee D, Liepa D, Wu LT. The Treatment Effectiveness Assessment (TEA): an efficient, patient-centered instrument for evaluating progress in recovery from addiction. Subst Abuse Rehabil. 2012 Jan 1;3(1):129-136. doi: 10.2147/SAR.S38902.

    PMID: 23580868BACKGROUND

  • Pettinati HM, Kampman KM, Lynch KG, Suh JJ, Dackis CA, Oslin DW, O'Brien CP. Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence. J Subst Abuse Treat. 2008 Jun;34(4):378-90. doi: 10.1016/j.jsat.2007.05.011. Epub 2007 Jul 30.

    PMID: 17664051BACKGROUND

  • Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers. Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6.

    PMID: 25603822BACKGROUND

  • Winhusen TM, Kropp F, Lindblad R, Douaihy A, Haynes L, Hodgkins C, Chartier K, Kampman KM, Sharma G, Lewis DF, VanVeldhuisen P, Theobald J, May J, Brigham GS. Multisite, randomized, double-blind, placebo-controlled pilot clinical trial to evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine dependence. J Clin Psychiatry. 2014 Jul;75(7):757-64. doi: 10.4088/JCP.13m08862.

    PMID: 24911028BACKGROUND

  • Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential - United States, 2003-2017. MMWR Morb Mortal Wkly Rep. 2019 May 3;68(17):388-395. doi: 10.15585/mmwr.mm6817a3.

    PMID: 31048676BACKGROUND

  • Trivedi MH, Kalmin MM, Carmody T, Chongsi EM, Ghitza UE, Jha MK, Mayes TL, Casey-Willingham A, Sethuram S, Marino EN, Monastirsky M, Shoptaw SJ. Randomized, placebo-controlled trial of injectable extended-release naltrexone and injectable extended-release buprenorphine for cocaine use disorder (CURB-2): Study rationale and design. Contemp Clin Trials. 2025 Jul;154:107954. doi: 10.1016/j.cct.2025.107954. Epub 2025 May 11.

    PMID: 40360074DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

phospholamban

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental Disorders

Study Officials

  • Madhukar Trivedi, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
This is a double-blind, placebo-controlled study.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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). XR-NTX is delivered via intramuscular (IM) injection in the gluteus; XR-BUP is delivered via subcutaneous (SQ) injection in the abdomen.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

February 17, 2022

First Posted

March 2, 2022

Study Start

April 18, 2023

Primary Completion

June 27, 2025

Study Completion

July 21, 2025

Last Updated

October 21, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, CSR
Time Frame
This will be available five months after all sites are closed. No yet determined duration of availability.
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.
More information

Locations

US(12)