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

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).

Timeline

Start

2023-04-18

Primary completion

2025-06-27

Completion

2025-07-21

Publications

• Background Center for Behavioral Health Statistics and Quality. 2019 National Survey on Drug Use and Health (NSDUH): CAI Specifications for Programming (English Version). Substance Abuse and Mental Health Services Administration, editor. Rockville, MD; 2018.
• Background Czoty PW, Stoops WW, Rush CR. Evaluation of the "Pipeline" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research. Pharmacol Rev. 2016 Jul;68(3):533-62. doi: 10.1124/pr.115.011668.
• Background Whitfield TW Jr, Schlosburg JE, Wee S, Gould A, George O, Grant Y, Zamora-Martinez ER, Edwards S, Crawford E, Vendruscolo LF, Koob GF. kappa Opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake. J Neurosci. 2015 Mar 11;35(10):4296-305. doi: 10.1523/JNEUROSCI.1978-13.2015.
• Background Ling W, Hillhouse MP, Saxon AJ, Mooney LJ, Thomas CM, Ang A, Matthews AG, Hasson A, Annon J, Sparenborg S, Liu DS, McCormack J, Church S, Swafford W, Drexler K, Schuman C, Ross S, Wiest K, Korthuis PT, Lawson W, Brigham GS, Knox PC, Dawes M, Rotrosen J. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016 Aug;111(8):1416-27. doi: 10.1111/add.13375. Epub 2016 Apr 21.
• Background Trivedi MH, Wisniewski SR, Morris DW, Fava M, Kurian BT, Gollan JK, Nierenberg AA, Warden D, Gaynes BN, Luther JF, Rush AJ. Concise Associated Symptoms Tracking scale: a brief self-report and clinician rating of symptoms associated with suicidality. J Clin Psychiatry. 2011 Jun;72(6):765-74. doi: 10.4088/JCP.11m06840.
• Background dela Cruz AM, Bernstein IH, Greer TL, Walker R, Rethorst CD, Grannemann B, Carmody T, Trivedi MH. Self-rated measure of pain frequency, intensity, and burden: psychometric properties of a new instrument for the assessment of pain. J Psychiatr Res. 2014 Dec;59:155-60. doi: 10.1016/j.jpsychires.2014.08.003. Epub 2014 Aug 27.
• Background Ling W, Farabee D, Liepa D, Wu LT. The Treatment Effectiveness Assessment (TEA): an efficient, patient-centered instrument for evaluating progress in recovery from addiction. Subst Abuse Rehabil. 2012 Jan 1;3(1):129-136. doi: 10.2147/SAR.S38902.
• Background Pettinati HM, Kampman KM, Lynch KG, Suh JJ, Dackis CA, Oslin DW, O'Brien CP. Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence. J Subst Abuse Treat. 2008 Jun;34(4):378-90. doi: 10.1016/j.jsat.2007.05.011. Epub 2007 Jul 30.
• Background Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers. Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6.
• Background Winhusen TM, Kropp F, Lindblad R, Douaihy A, Haynes L, Hodgkins C, Chartier K, Kampman KM, Sharma G, Lewis DF, VanVeldhuisen P, Theobald J, May J, Brigham GS. Multisite, randomized, double-blind, placebo-controlled pilot clinical trial to evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine dependence. J Clin Psychiatry. 2014 Jul;75(7):757-64. doi: 10.4088/JCP.13m08862.
• Background Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential - United States, 2003-2017. MMWR Morb Mortal Wkly Rep. 2019 May 3;68(17):388-395. doi: 10.15585/mmwr.mm6817a3.
• Trivedi MH, Kalmin MM, Carmody T, Chongsi EM, Ghitza UE, Jha MK, Mayes TL, Casey-Willingham A, Sethuram S, Marino EN, Monastirsky M, Shoptaw SJ. Randomized, placebo-controlled trial of injectable extended-release naltrexone and injectable extended-release buprenorphine for cocaine use disorder (CURB-2): Study rationale and design. Contemp Clin Trials. 2025 Jul;154:107954. doi: 10.1016/j.cct.2025.107954. Epub 2025 May 11.

Drugs

Indications