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

Study Overview
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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.

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

Conditions
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Cocaine Use Disorder

Intervention / Treatment
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* Drug: Extended-Release Naltrexone
* Drug: Extended Release Buprenorphine
* Drug: Placebo (PLB) Injectable
* Drug: Placebo (PLB) Injectable


Participation Criteria
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Eligibility Criteria
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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: 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug intervention (XR-NTX+XR-BUP)<br>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<br>* XR-NTX (Extended-Release Naltrexone) doses of 380mg (Weeks 0, 3 and 6) via intramuscular (IM) injections in the gluteus.<br>* Other names: XR-NTX;Drug: Extended Release Buprenorphine<br>* 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).<br>* Other names: XR-BUP;|
| Placebo Comparator: Placebo<br>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<br>* 3 doses of intramuscular injections (Week 0, 3, 6)<br>* Other names: Injectable matching (to XR-NTX) placebo;Drug: Placebo (PLB) Injectable<br>* 2 doses of subcutaneous injections (Week 0, 4)<br>* Other names: Injectable matching (to XR-BUP) placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Naltrexone, Buprenorphine, Extended release injectable Naltrexone, Extended release injectable Buprenorphine, CUD, Cocaine, Cocaine Abuse