Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo-controlled crossover laboratory study.

BACKGROUND AND

OBJECTIVES

Noradrenergic dysregulation is important in the pathophysiology of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD); pharmacotherapies targeting adrenergic function have potential as treatment for comorbidity. Dexmedetomidine (sublingual film formulation-BXCL501; IGALMI) is a highly potent, selective ⍺2-adrenergic receptor agonist and may be superior to other pharmacotherapeutic approaches. A within subjects, phase 1b safety laboratory study was conducted to evaluate adverse effects of BXCL501 when combined with alcohol; BXCL501's potential efficacy was also explored.

METHODS

Heavy drinker participants with a diagnosis of or who were at risk for PTSD participated in three separate test days which included pretreatment with BXCL501 (40 µg, 80 µg or placebo) administered in a randomized, double-blind fashion, followed by three testing conditions: alcohol cue reactivity, trauma-induced reactivity, and IV ethanol administration. Safety outcomes included blood pressure (BP) and sedation. Exploratory outcomes included alcohol craving, trauma-induced anxiety and craving and subjective effects of alcohol.

RESULTS

Ten of twelve randomized participants competed the entire study. BXCL501 (80 µg) was associated with expected mild changes in BP and sedation; administration with alcohol did not affect those parameters. There were no clinically significant adverse effects. BXCL501 attenuated trauma-induced anxiety and attenuated subjective effects of alcohol.

DISCUSSIONS AND

CONCLUSIONS

BXCL501 is safe for use in humans who may drink alcohol while undergoing treatment. BXCL501 may be explored as a potential treatment for PTSD and AUD.

SCIENTIFIC SIGNIFICANCE: This is the first study to provide scientific support for BXCL501's potential to treat PTSD and comorbid AUD.