Randomized, placebo-controlled trial of injectable extended-release naltrexone and injectable extended-release buprenorphine for cocaine use disorder (CURB-2): Study rationale and design.

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.