Sublingual Dexmedetomidine for Treating Opioid Withdrawal

Summary

A major challenge to seeking treatment for opioid use disorder (OUD) is the withdrawal symptoms associated with cessation of opioid use. The signs and symptoms of opioid withdrawal include irritability, anxiety, muscular and abdominal pains, chills, nausea, diarrhea, yawning, runny eyes and nose, sweating, sneezing, weakness, and insomnia. The current gold standard of treatment involves a gradual reduction of the opioid drug dosage (tapering). However, as all opioids have potential for abuse and require careful dosing due to side effects (e.g., respiratory depression), a non-opioid medication to facilitate withdrawal severity would be of great value. Commonly used non-opioid medications like lofexidine have concerning side effects including sedation and low blood pressure. BioXcel Therapeutics has developed BXCL501 (dexmedetomidine: sublingual film) to reduce symptoms associated with opioid withdrawal. Dexmedetomidine is currently used as an intravenous anesthetic for its anxiety-reducing, sedative, and analgesic properties. The current study will seek to compare the safety and efficacy of BXCL501 relative to lofexidine and placebo in subjects with OUD who are physically dependent on opioids. Throughout a 7-day inpatient withdrawal period (using a methadone taper) opioid-dependent participants will receive sublingual BXCL501, placebo, or lofexidine. In comparison to lofexidine, dexmedetomidine is expected to have a superior safety profile with limited adverse effects on blood pressure and heart rhythm. Three sites will participate in this study: NYSPI, Clinilabs, Inc., and Yale University. The NYSPI site is currently paused and has been paused since an institutional pause on human subjects research began in June 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.

Timeline

Start

2023-02-28

Primary completion

2025-06-30

Completion

2026-08-31

Publications

• Background Antoine D, Huhn AS, Strain EC, Turner G, Jardot J, Hammond AS, Dunn KE. Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone. Am J Addict. 2021 Jan;30(1):83-87. doi: 10.1111/ajad.13069. Epub 2020 Jun 23.
• Background Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-1948. doi: 10.1016/S0140-6736(20)30852-7.
• Background Maze M, Segal IS, Bloor BC. Clonidine and other alpha2 adrenergic agonists: strategies for the rational use of these novel anesthetic agents. J Clin Anesth. 1988;1(2):146-57. doi: 10.1016/0952-8180(88)90034-7.
• Background Cedarbaum JM, Aghajanian GK. Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol. 1977 Aug 15;44(4):375-85. doi: 10.1016/0014-2999(77)90312-0. No abstract available.
• Background Fishman M, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW; CLEEN-SLATE Team. Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. J Addict Med. 2019 May/Jun;13(3):169-176. doi: 10.1097/ADM.0000000000000474.
• Background Shokri H, Ali I. A randomized control trial comparing prophylactic dexmedetomidine versus clonidine on rates and duration of delirium in older adult patients undergoing coronary artery bypass grafting. J Clin Anesth. 2020 May;61:109622. doi: 10.1016/j.jclinane.2019.09.016. Epub 2019 Oct 23.

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