Sublingual dexmedetomidine (BXCL501) reduces opioid withdrawal symptoms: findings from a multi-site, phase 1b/2, randomized, double-blind, placebo-controlled trial

ABSTRACT

Background: Like other alpha-2-adrenergic receptor agonists, dexmedetomidine may reduce the severity of opioid withdrawal but with fewer adverse cardiovascular effects.

Objective: This study assessed the safety of sublingual dexmedetomidine (BXCL501) and its preliminary efficacy in treating opioid withdrawal (ClinicalTrials.gov: NCT04470050).

Methods: Withdrawal was induced among individuals with physiological dependence on opioids via discontinuation of oral morphine (Days 1–5). Participants were randomized to receive placebo or active BXCL501: 30, 60, 90, 120, 180, and 240 μg twice daily (Days 6–12). Treatment-emergent adverse events (TEAEs) were the primary outcome measure. Secondary outcomes included the Clinical and Subjective Opiate Withdrawal Scales (COWS and SOWS-Gossop, respectively), and the Agitation and Calmness Evaluation Scale (ACES).

Results: Of 225 participants enrolled, 90 discontinued during morphine stabilization. Post-BXCL501 randomization (Day 6) data were available from 135 participants (73% male), with 33% completing thru Day 12. In total, 36 subjects reported 1 or more TEAE. Higher doses of BXCL501 (i.e. 180 and 240 µg, twice daily) increased the frequency of: hypotension, orthostatic hypotension, and somnolence. TEAEs related to BXCL501 were mild or moderate in severity, except for one participant in the 120 µg condition whose orthostatic hypotension and bradycardia were classified as severe. Higher BXCL501 dose conditions (120, 180, and 240 µg) resulted in statistically significant reductions in COWS & SOWS scores. Mean ratings on the ACES were between 3 (mild), 4 (normal), and 5 (mild calmness), with few significant differences as a function of dose.

Conclusions: These findings support the continued development of BXCL501 for the management of opioid withdrawal.

KEYWORDS:

• Opioid withdrawal
• dexmedetomidine
• medications development
• opioid use disorder
• opioid dependence

Acknowledgments

The research team would like to thank the study participants, along with the support staff who helped ensure the safe and successful completion of this study.

Disclosure statement

In the past three years, Dr. Jones has received compensation in the form of partial salary support from studies supported by BioXcel Therapeutics. Dr. Comer has received research funding from Alkermes, BioXcel Therapeutics, Braeburn Pharmaceuticals, Cerecor Inc., Corbus, Go Medical, Intra-cellular Therapies, Janssen, and Lyndra. Dr. Comer has also consulted for: Alkermes, Charleston Labs, Clinilabs, Collegium, Depomed, Epiodyne, Mallinckrodt, Nektar, Newron, Opiant, Otsuka, and Sun Pharma. Dr. Levin has no pertinent disclosures. The remaining authors are employees of BioXcel Therapeutics.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/00952990.2022.2144743

Additional information

Funding

This study was funded by BioXcel Therapeutics who contributed to the design of this study as well as the preparation, review, and approval of the manuscript. The first (JDJ) and senior authors (FRL and SDC) of Columbia University Irving Medical Center, were provided with full access to the study data.