Randomized, placebo-controlled trial of injectable extended-release naltrexone and injectable extended-release buprenorphine for cocaine use disorder (CURB-2): Study rationale and design
07/2025
Journal Article
Authors:
Trivedi, M. H.;
Kalmin, M. M.;
Carmody, T.;
Chongsi, E. M.;
Ghitza, U. E.;
Jha, M. K.;
Mayes, T. L.;
Casey-Willingham, A.;
Sethuram, S.;
Marino, E. N.;
Monastirsky, M.;
Shoptaw, S. J.
Volume:
154
Journal:
Contemp Clin Trials
PMID:
40360074
URL:
https://www.ncbi.nlm.nih.gov/pubmed/40360074
Keywords:
Humans *Cocaine-Related Disorders/drug therapy *Narcotic Antagonists/administration & dosage/therapeutic use Delayed-Action Preparations *Naltrexone/administration & dosage/therapeutic use Randomized Controlled Trials as Topic
*Buprenorphine/administration & dosage/therapeutic use Male Adult Clinical Trials, Phase II as Topic Double-Blind Method Drug Therapy, Combination Female Multicenter Studies as Topic
Middle Aged Young Adult Injections Buprenorphine Clinical trial Cocaine use disorder Naltrexone Treatment
Abstract:
BACKGROUND: Cocaine remains the most abused stimulant, causing considerable morbidity and mortality. Despite decades of research, there is no FDA-approved medication to treat cocaine use disorder (CUD). In individuals with cocaine and opioid dependence/abuse, extended-release injectable naltrexone (XR-NTX) and sublingual buprenorphine (BUP; 16 mg with naloxone; Suboxone) reduced cocaine use compared to placebo and XR-NTX in the 'Cocaine Use Reduction with Buprenorphine' (CURB; CTN-0048) study. OBJECTIVES: The CURB-2 (CTN-0109) study aims to examine whether administering XR-NTX in combination with extended-release injectable buprenorphine (XR-BUP), thus creating a "kappa antagonist," is an effective pharmacotherapy compared to placebo for the treatment of CUD. STUDY DESIGN: CURB-2 is a fully powered, phase IIb, randomized, placebo-controlled trial. Approximately 426 participants will be randomized across 12 study sites in the United States. There will be a 1-week medication induction phase, an 8-week active medication phase, and a 4-week follow-up phase. XR-NTX (Day 1, Week 3, Week 6) will be administered before XR-BUP (Day 4, Week 4). With naltrexone blocking the mu-opioid receptors, the reinforcing effects of buprenorphine will be blocked while leaving the kappa antagonist effects. DISCUSSION: If this kappa antagonist approach demonstrates efficacy in reducing urine-verified cocaine use compared to placebo, XR-NTX and XR-BUP combination therapy would be an important tool in addressing cocaine use disorder. CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05262270.