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

Phase 2
Recruiting
Conditions
Cocaine Use Disorder
Interventions
Drug: Extended-Release Naltrexone
Drug: Placebo (PLB) Injectable matched to XR-NTX
Drug: Placebo (PLB) Injectable matched to XR-BUP
Registration Number
NCT05262270
Lead Sponsor
University of Texas Southwestern Medical Center
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).

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
426
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Drug intervention (XR-NTX+XR-BUP)Extended-Release NaltrexoneThe 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
PlaceboPlacebo (PLB) Injectable matched to XR-NTXMatched 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)
PlaceboPlacebo (PLB) Injectable matched to XR-BUPMatched 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 intervention (XR-NTX+XR-BUP)Extended Release BuprenorphineThe 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
Primary Outcome Measures
NameTimeMethod
Proportion of Cocaine-negative UDSWeek 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.

Secondary Outcome Measures
NameTimeMethod
Number of participants who Self-report cocaine use8 Weeks

Self-report elicited through Timeline Followback (TLFB) on days of cocaine use during Weeks 0-8;

Mean self reported cocaine craving score8 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.

Measures of safety (adverse events)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

Mean self reported overall functioningWeek 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.

Trial Locations

Locations (12)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

UCLA Vine Street Clinic

🇺🇸

Los Angeles, California, United States

Center on Substance Use and Health (CSUH)

🇺🇸

San Francisco, California, United States

Cove Behavioral Health

🇺🇸

Tampa, Florida, United States

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Mountain Manor Treatment Center

🇺🇸

Baltimore, Maryland, United States

Berman Center for Outcomes and Clinical Research at Hennepin Healthcare

🇺🇸

Minneapolis, Minnesota, United States

Addictions Institute of Mount Sinai

🇺🇸

New York, New York, United States

UTSW Medical Center, Center for Depression Research and Clinical Care

🇺🇸

Dallas, Texas, United States

University of Texas Health San Antonio

🇺🇸

San Antonio, Texas, United States

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