Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2) (CURB-2)
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|ClinicalTrials.gov Identifier: NCT05262270|
Recruitment Status : Not yet recruiting
First Posted : March 2, 2022
Last Update Posted : November 9, 2022
|Condition or disease||Intervention/treatment||Phase|
|Cocaine Use Disorder||Drug: Extended-Release Naltrexone Drug: Extended Release Buprenorphine Drug: Placebo (PLB) Injectable||Phase 2|
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. To document current ongoing cocaine use, participants must submit at least 2 urine samples positive for cocaine of a possible 3 tests to occur within a 10-day period during which clinic visits occur with at least 2 days between visits. In addition, participants must meet diagnostic criteria for moderate or severe CUD per DSM-5 (4 or more criteria) at screening. 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. Confirmation of opioid-free status (urine drug screen) will take place after confirmation of eligibility and before randomization. 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 (Clinical Trial)|
|Estimated Enrollment :||426 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||This is a double-blind, placebo-controlled study.|
|Official Title:||Randomized, Placebo-Controlled Trial of Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2)|
|Estimated Study Start Date :||January 2023|
|Estimated Primary Completion Date :||January 2025|
|Estimated Study Completion Date :||July 2026|
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 Name: 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 Name: 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
3 doses of intramuscular injections (Week 0, 3, 6)
Other Name: Injectable matching (to XR-NTX) placebo
Drug: Placebo (PLB) Injectable
2 doses of subcutaneous injections (Week 0, 4)
Other Name: Injectable matching (to XR-BUP) placebo
- 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.
- 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;
- 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.
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05262270
|Contact: Sangita Sethuram, MBA, CCRP||214-645-4357||CURB2@UTSouthwestern.edu|
|Contact: Angela Casey-Willingham||214-645-4357||Angela.Casey-Willingham@UTSouthwestern.edu|
|Principal Investigator:||Madhukar Trivedi, MD||UT Southwestern Medical Center|
|Study Director:||Geoffrey Obel, DrPh||UT Southwestern Medical Center|