BXCL501 · program

Dexmedetomidine sublingual film (BXCL501) for Acute Stress Disorder

Phase 2RecruitingBioXcel Therapeutics, Inc. (BTAI)

Indications for BXCL501: Acute Stress Disorder · Phase 2 Schizophrenia · Filed (NDA) Opioid use disorder · Phase 1/2 Agitation in Alzheimer's disease · Phase 3

Phase 2a investigator-/government-sponsored program evaluating sublingual dexmedetomidine (BXCL501) for the early treatment of acute stress reactions / acute stress disorder (ASD) and prevention of progression to chronic posttraumatic neuropsychiatric symptoms. The single trial, RISE (NCT06943404, 'BXCL501 After Stress to Increase Recovery Success'), is sponsored by the University of North Carolina, Chapel Hill (Institute for Trauma Recovery; PI Samuel McLean, MD, MPH), with BioXcel Therapeutics supplying the drug, and is funded by a $2.8M U.S. Department of Defense / Department of War grant (HT9425-24-1-1108) to UNC running Sept 15 2024 - Sept 14 2026. The randomized, double-blind, placebo-controlled study (n=100, estimated) enrolls adults presenting to the emergency department with acute stress reactions after a motor vehicle collision; BXCL501 is dosed sublingually (120 mcg in the ED, a second dose at/before bedtime, then daily bedtime doses for 14 days). Primary endpoint: change in Acute Stress Disorder Scale (ASDS) at Week 1 and Week 3. The trial started 23 Feb 2026 and first-patient enrollment was announced 8 Apr 2026; estimated primary completion 29 Sep 2026. No regulatory designations are held for the ASD indication (Breakthrough/Fast Track designations apply to the agitation indications, not ASD).

Data current as of

Development timeline

Phase 2Oct 2024 – Sept 2026
  1. UpcomingPhase 2a RISE study of sublingual dexmedetomidine (BXCL501) in acute stress reactions after motor vehicle collision: topline expected after the estimated Sep 2026 primary completion.
  2. BioXcel announced enrollment of the first patients in the Department of War-funded Phase 2a study of BXCL501 for acute stress reactions, led by the UNC Institute for Trauma Recovery; the study evaluates reduction of ASR symptom severity, neurocognitive function, and prevention of progression to chronic posttraumatic neuropsychiatric symptoms.↗
  3. Phase 2a RISE trial (NCT06943404), sponsored by University of North Carolina, Chapel Hill, started (actual study start date 2026-02-23). Randomized, double-blind, placebo-controlled study of sublingual dexmedetomidine vs placebo in adults with acute stress reactions after a motor vehicle collision; primary endpoint = change in ASDS at Week 1 and Week 3.
  4. BioXcel announced a $2.8M U.S. Department of Defense grant to the UNC Institute for Trauma Recovery (Sept 15 2024 - Sept 14 2026, PI Samuel McLean MD MPH) to fund a double-blind, placebo-controlled study of BXCL501 (sublingual dexmedetomidine) for acute stress disorder, targeting ~100 patients with ASD from motor vehicle collisions, with enrollment expected to begin in 1H 2025.↗

Readouts

  • 2H 2026AnticipatedTopline dataNCT06943404

    Phase 2a RISE study of sublingual dexmedetomidine (BXCL501) in acute stress reactions after motor vehicle collision: topline expected after the estimated Sep 2026 primary completion.

Clinical trials in Acute Stress Disorder

NCT06943404RISEPhase 2Recruitingn=100

Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With a Sublingual Formulation of Dexmedetomidine (BXCL501)

Started Feb 2026· Primary completion Sept 2026· 📍 3 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
Dexmedetomidine sublingual film (IGALMI)oral dissolving film
120 mcg and 180 mcg films (cuttable to 60 mcg / 90 mcg); initial dose with up to two additional doses at least 2 hours apart
SublingualSingle doset½ 2.8 h · Tmax 2 h · F 72%

Mechanism of action (compound-wide)

Dexmedetomidine is a potent, highly selective alpha-2 adrenergic receptor agonist (the pharmacologically active S-enantiomer of medetomidine), with reported alpha-2:alpha-1 selectivity on the order of ~1600:1. Agonism at the presynaptic alpha-2A adrenoceptor (ADRA2A) in the locus coeruleus reduces noradrenergic outflow, producing sedation/anxiolysis without significant respiratory depression. In agitation, sublingual dexmedetomidine is hypothesized to calm hyperadrenergic arousal that drives acute agitation episodes. Alpha-2B and alpha-2C subtypes are additional adrenoceptor targets.

TargetActionAffinity
alpha-2A adrenoceptorprimaryADRA2AAgonist—ⓘ
alpha-2B adrenoceptorADRA2BAgonist—ⓘ
alpha-2C adrenoceptorADRA2CAgonist—ⓘ

← Full BXCL501 compound page (identity, identifiers, all indications)

Sources

  1. alpha-2A adrenoceptor (ADRA2A, object 25) — dexmedetomidine listed as partial agonist — IUPHAR/BPS Guide to Pharmacology
  2. BioXcel announces enrollment of first patients in U.S. Department of War-funded Phase 2a study of BXCL501 for acute stress reactions — BioXcel Therapeutics (GlobeNewswire wire release)
  3. BioXcel announces U.S. Department of Defense grant to UNC to fund study of BXCL501 (sublingual dexmedetomidine) for treating acute stress disorder ($2.8M, Sept 2024 - Sept 2026) — BioXcel Therapeutics (GlobeNewswire wire release)
  4. Dexmedetomidine (ligand 521) — selective alpha-2 adrenoceptor agonist — IUPHAR/BPS Guide to Pharmacology
  5. IGALMI (dexmedetomidine film) - FDA prescribing information — DailyMed / NIH
  6. RISE — Phase 2 study of sublingual dexmedetomidine (BXCL501) for acute stress reactions/ASD after motor vehicle collision (NCT06943404) — ClinicalTrials.gov