BXCL501 · program

Dexmedetomidine sublingual film (BXCL501) for Agitation in Alzheimer's disease

Phase 3ActiveBioXcel Therapeutics, Inc. (BTAI)
  • Breakthrough Therapy
  • Fast Track

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 3 TRANQUILITY program evaluating PRN sublingual dexmedetomidine (BXCL501) for the acute treatment of agitation associated with Alzheimer's dementia. TRANQUILITY I (NCT04251910, Phase 1b/2) supported the FDA Breakthrough Therapy designation for dementia-related agitation. The pivotal TRANQUILITY II study (NCT05271552, Phase 3, n=151) MET its primary endpoint, with the 60 mcg dose producing a statistically significant 7.5-point reduction from baseline in PEC total score at 2 hours vs 5.4 with placebo (p=0.0112). Two confirmatory PRN studies, TRANQUILITY III (NCT05665088) and BXCL501-203 (NCT05276830), were terminated for business reasons (not safety/efficacy). On 10 Apr 2024 BioXcel announced a single confirmatory TRANQUILITY In-Care pivotal Phase 3 (~150 patients in care settings, 60 mcg, 12-week PRN, PEC at 2h primary). As of the 15 May 2026 Q1-2026 business update the In-Care trial had not yet started; the molecule remains separately FDA-approved (Igalmi) for bipolar/schizophrenia agitation but is NOT approved for the Alzheimer's-agitation indication. Note: BioXcel disclosed substantial-doubt going-concern as of Q1 2026.

Data current as of

Development timeline

Phase 3Jun 2023 – May 2026
  1. Q1-2026 business update: BXCL501 remains in Phase 3 development for agitation in Alzheimer's dementia; the TRANQUILITY In-Care pivotal trial had not yet started (CRO selection / protocol finalization). Company disclosed substantial doubt about going concern ($17.2M cash at 31 Mar 2026).↗
  2. BioXcel announced the design of a single confirmatory TRANQUILITY In-Care pivotal Phase 3 (~150 patients in care settings, 60 mcg PRN over 12 weeks; PEC at 2h primary) for agitation associated with Alzheimer's dementia; the earlier TRANQUILITY III (NCT05665088) and BXCL501-203 (NCT05276830) PRN studies had been terminated for business reasons.↗
  3. metTRANQUILITY II Phase 3 met its primary endpoint: 60 mcg sublingual dexmedetomidine cut PEC by 7.5 points at 2h vs 5.4 placebo (p=0.0112).↗
Phase 1/2Jan 2022
  1. TRANQUILITY I (NCT04251910), a Phase 1b/2 ascending-dose efficacy/PK/safety study in agitation associated with dementia (n=100), completed; data supported the FDA Breakthrough Therapy designation for dementia-related agitation.

Readouts

  • 2023-06-29ReportedTopline datametNCT05271552

    TRANQUILITY II Phase 3 met its primary endpoint: 60 mcg sublingual dexmedetomidine cut PEC by 7.5 points at 2h vs 5.4 placebo (p=0.0112). ↗

  • Date TBDAnticipatedTopline data

    Confirmatory TRANQUILITY In-Care Phase 3 (~150 patients, 60 mcg PRN, care setting) planned but not yet started as of Q1 2026. ↗

Clinical trials in Agitation in Alzheimer's disease

NCT05665088TRANQUILITY IIIPhase 3Discontinuedn=13

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of PRN Dosing of BXCL501 Over a 12 Week Treatment Period in Subjects With Agitation Associated With Dementia (TRANQUILITY III)

Started Dec 2022· Primary completion Sept 2023

terminatedprimaryChange from baseline in PEC total score at 120 minutes (first agitation episode)

Terminated for business reasons (not due to safety or efficacy concerns) after only 13 of a planned cohort enrolled; no efficacy conclusion.

NCT05271552TRANQUILITY IIPhase 3Completedn=151

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy And Safety Study of PRN Dosing of BXCL501 Over A 12 Week Period In Subjects With Agitation Associated With Dementia (TRANQUILITY II)

Started Apr 2022· Primary completion Apr 2023

metsecondaryChange in PEC total score at 1 hour post-dose, 60 mcg vs placebo (0.0185)

Key secondary endpoint met at 1 hour for the 60 mcg dose (p=0.0185). The 30-minute secondary timepoint was not met.

metprimaryAbsolute change from baseline in PEC total score at 120 minutes (first agitation episode), 60 mcg vs placebo — 7.5-point reduction (60 mcg) vs 5.4 (placebo) (0.0112)

Primary endpoint met: 60 mcg BXCL501 produced a statistically significant 7.5-point reduction from baseline in PEC total score at 2 hours vs 5.4 with placebo (p=0.0112). 149 patients dosed (60 mcg n=50, 40 mcg n=48, placebo n=51).

NCT05276830BXCL501-203Phase 2Discontinuedn=5

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of BXCL501 For The Treatment of Agitation Associated With Dementia

Started Feb 2022· Primary completion Apr 2022

terminatedprimaryChange in PEC total score at 120 minutes post-treatment

Terminated for business reasons (not due to safety or efficacy concerns) after only 5 participants enrolled; no efficacy conclusion.

NCT04251910TRANQUILITY IPhase 1/2Completedn=100

A Phase Ib/II, Multicenter, Randomized, Double Blind, Placebo Controlled, Ascending Dose Finding, Efficacy, Pharmacokinetic and Safety Study of BXCL501 In Agitation Associated With Dementia

Started Dec 2019· Primary completion Jan 2022

metprimaryMean change from baseline in PEC total score at 2 hours post-dose

Ascending dose-finding Phase 1b/2 in agitation associated with dementia (n=100); results supported the FDA Breakthrough Therapy designation for dementia-related agitation and advancement to the pivotal TRANQUILITY II Phase 3.

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 positive topline results from TRANQUILITY II Phase 3 in Alzheimer's-disease-related agitation — BioXcel Therapeutics / IR
  3. BioXcel announces TRANQUILITY In-Care pivotal Phase 3 trial plan with BXCL501 for agitation associated with Alzheimer's dementia — BioXcel Therapeutics (GlobeNewswire wire release)
  4. BioXcel Therapeutics Provides Business Update and Reports First Quarter 2026 Financial Results — BioXcel Therapeutics (GlobeNewswire wire release)
  5. BXCL501-203 — Phase 2 BXCL501 in agitation associated with dementia, terminated (NCT05276830) — ClinicalTrials.gov
  6. Dexmedetomidine (ligand 521) — selective alpha-2 adrenoceptor agonist — IUPHAR/BPS Guide to Pharmacology
  7. IGALMI (dexmedetomidine film) - FDA prescribing information — DailyMed / NIH
  8. TRANQUILITY I — Phase 1b/2 of BXCL501 in agitation associated with dementia (NCT04251910) — ClinicalTrials.gov
  9. TRANQUILITY II — Phase 3 PRN BXCL501 in agitation associated with dementia (NCT05271552) — ClinicalTrials.gov
  10. TRANQUILITY III — Phase 3 PRN BXCL501 in agitation associated with dementia, terminated (NCT05665088) — ClinicalTrials.gov