First Participants Enrolled in Phase 2a Study of BXCL501 for Treatment of Acute Stress Reactions

BioXcel Therapeutics today announced the enrollment of the first participants in a US Department of War (DoW)-funded phase 2a clinical trial evaluating sublingual dexmedetomidine (BXCL501) for the treatment of acute stress reactions (ASR), also known as acute stress disorder. The double-blind, placebo-controlled trial (NCT06943404) is designed to enroll 100 participants experiencing ASRs following motor vehicle collisions and will investigate the potential of BXCL501 to reduce ASR symptom severity, improve neurocognitive function, and prevent the progression to chronic posttraumatic neuropsychiatric symptoms.¹

The trial is being led by the University of North Carolina at Chapel Hill (UNC) Institute of Trauma Recovery and marks a significant milestone in the collaboration between BioXcel Therapeutics and UNC. BioXcel Therapeutics will supply BXCL501 for the trial.

“Supporting service men and women resilience and effectively treating ASRs is an urgent military priority,” said Samuel McLean, MD, MPH, a professor of psychiatry and emergency medicine, the director of the Institute for Trauma Recovery at the UNC School of Medicine, and principal investigator of the study. “We are excited to evaluate BXCL501 as a potential treatment to address this critical unmet need of service men and women and civilians experiencing ASRs.”

ASRs, which affect more than 40 million Americans who seek emergency department care annually after traumatic stress exposure (such as a motor vehicle collision), occur in the days and weeks after trauma. Symptoms include anxiety, sleep disturbance, concentration difficulty, pain, and somatic symptoms such as dizziness and lightheadedness. Chronic adverse posttraumatic neuropsychiatric symptoms occur when ASRs do not resolve, and include persistent pain, posttraumatic stress, and depressive symptoms. ASRs are common among service men and women, police, other first responders, and survivors of shootings and natural disasters.^2,3

“We look forward to supporting Dr McLean and his team at UNC on this important study evaluating BXCL501 for the treatment of ASRs,” said Vimal Mehta, PhD, the chief executive officer of BioXcel Therapeutics. “The results from this study could have clinical benefit for this patient population and support BXCL501’s potential as a pipeline-in-a-product.”

The 2023 VA/DoW Clinical Practice Guidelines for management of posttraumatic stress disorder (PTSD) and ASR recommend trauma-focused psychotherapy, specifically cognitive-behavioral therapy, as the primary treatment to reduce ASR symptoms and prevent PTSD. Generally, pharmacotherapy is not recommended for treating ASR and benzodiazepines are contraindicated. Investigators believe a positive outcome from this trial could contribute to a reassessment of those guidelines and establish a pharmacological treatment pathway for patients with ASR who have an immediate and critical need for treatment.⁴

The ASR research is supported by the DoW under award number HT9425-24-1-1108.

BXCL501 is also currently being evaluated for the treatment of opioid withdrawal symptoms in adults with opioid use disorder undergoing a methadone taper. Study data suggest that BXCL501 may be as effective as or superior to lofexidine (Lucemyra) for reducing the symptoms of opioid withdrawal during a methadone taper, while also possessing a more convenient dosing regimen and a favorable tolerability profile. BXCL501 differs from other available treatments, as it is a nonopioid, orally dissolving thin film formulation of dexmedetomidine administered twice daily.⁵

Notably, BXCL501 is being evaluated in phase 3 pivotal studies for the treatment of acute agitation associated with bipolar disorder, schizophrenia, and Alzheimer disease.^6,7

References

1. BioXcel Therapeutics announces enrollment of first patients in U.S. Department of War-funded study of BXCL501 (sublingual dexmedetomidine) for treatment of acute stress reactions. News release. April 8, 2026. Accessed April 8, 2026. https://www.globenewswire.com/news-release/2026/04/08/3269975/0/en/BioXcel-Therapeutics-Announces-Enrollment-of-First-Patients-in-U-S-Department-of-War-Funded-Study-of-BXCL501-Sublingual-Dexmedetomidine-for-Treatment-of-Acute-Stress-Reactions.html

2. Adler AB, Svetlitzky V, Gutierrez IA. Post-traumatic stress disorder risk and witnessing team members in acute psychological stress during combat. BJPsych Open. 2020;6(5):e98.

3. Lewis GC, Platts-Mills TF, Liberzon I, et al. Incidence and predictors of acute psychological distress and dissociation after motor vehicle collision: a cross-sectional study. J Trauma Dissociation. 2014;15(5):527-547.

4. Management of Posttraumatic Stress Disorder and Acute Stress Disorder 2023. US Department of Veterans Affairs. June 3, 2009. Accessed April 8, 2026. www.healthquality.va.gov/guidelines/mh/ptsd/

5. Kuntz L. BXCL501 for treatment of opioid withdrawal: positive phase 2 topline results. Psychiatric Times. March 5, 2026. https://www.psychiatrictimes.com/view/bxcl501-for-treatment-of-opioid-withdrawal-positive-phase-2-topline-results

6. Kuntz L. Primary end point of phase 3 trial met: BXCL501 for agitation associated with bipolar disorders or schizophrenia. Psychiatric Times. August 27, 2025. https://www.psychiatrictimes.com/view/primary-endpoint-of-phase-3-trial-met-bxcl501-for-agitation-associated-with-bipolar-disorders-or-schizophrenia

7. O’Brien E. Phase 3 study on treatment of agitation in Alzheimer disease doses first patient. Psychiatric Times. May 3, 2022. https://www.psychiatrictimes.com/view/phase-iii-study-on-treatment-of-agitation-in-alzheimer-disease-doses-first-patient