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

NCT ID: NCT05262270

Last Updated: 2025-10-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

427 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-18

Study Completion Date

2025-07-21

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Cocaine Use Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
This is a double-blind, placebo-controlled study.

Study Groups

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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

Group Type EXPERIMENTAL

Extended-Release Naltrexone

Intervention Type DRUG

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

Extended Release Buprenorphine

Intervention Type DRUG

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).

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)

Group Type PLACEBO_COMPARATOR

Placebo (PLB) Injectable matched to XR-NTX

Intervention Type DRUG

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

Placebo (PLB) Injectable matched to XR-BUP

Intervention Type DRUG

2 doses of subcutaneous injections (Week 0, 4)

Interventions

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Extended-Release Naltrexone

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

Intervention Type 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).

Intervention Type DRUG

Placebo (PLB) Injectable matched to XR-NTX

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

Intervention Type DRUG

Placebo (PLB) Injectable matched to XR-BUP

2 doses of subcutaneous injections (Week 0, 4)

Intervention Type DRUG

Other Intervention Names

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XR-NTX XR-BUP Injectable matching (to XR-NTX) placebo Injectable matching (to XR-BUP) placebo

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Madhukar H. Trivedi, MD

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Madhukar Trivedi, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

UCLA Vine Street Clinic

Los Angeles, California, United States

Site Status

Center on Substance Use and Health (CSUH)

San Francisco, California, United States

Site Status

Cove Behavioral Health

Tampa, Florida, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Mountain Manor Treatment Center

Baltimore, Maryland, United States

Site Status

Berman Center for Outcomes and Clinical Research at Hennepin Healthcare

Minneapolis, Minnesota, United States

Site Status

Addictions Institute of Mount Sinai

New York, New York, United States

Site Status

UTSW Medical Center, Center for Depression Research and Clinical Care

Dallas, Texas, United States

Site Status

University of Texas Health San Antonio

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 27255266 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25762676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26948856 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21733477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25194231 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23580868 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17664051 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25603822 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24911028 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31048676 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40360074 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form: Part 1 - For All sites and California site

View Document

Document Type: Informed Consent Form: Part-2- For UCSF site

View Document

Document Type: Informed Consent Form: Part 2- For UIC site

View Document

Document Type: Informed Consent Form: Part 2- For Mt. Sinai site

View Document

Document Type: Informed Consent Form: Part 2- For Rest of the sites including UTSW (lead site)

View Document

Other Identifiers

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UG1DA020024

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2021-0223

Identifier Type: -

Identifier Source: org_study_id

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