BXCL501 · program

Dexmedetomidine sublingual film (BXCL501) for Opioid use disorder

Phase 1/2ActiveBioXcel 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

Investigator-sponsored Phase 1/2 program evaluating PRN/twice-daily sublingual dexmedetomidine (BXCL501) for the treatment of acute opioid withdrawal during a 7-day inpatient methadone taper. The defining study, NCT05712707 (registered lead sponsor New York State Psychiatric Institute; Columbia University-led, NIDA-funded; BioXcel a drug-supplying collaborator), is a 4-arm trial (BXCL501 180 ug BID, BXCL501 240 ug BID, placebo, lofexidine 0.54 mg QID positive control). On 5 Mar 2026 BioXcel announced positive topline results: the 240 ug BID dose reduced opioid-withdrawal symptoms vs placebo (>30% reduction in SOWS-Gossop, peak days 3-4) and numerically exceeded the lofexidine control with a better tolerability profile (orthostatic hypotension 18% for 180 ug vs 50% for lofexidine, p<0.05; no sedation/somnolence in BXCL501 arms vs 5% for lofexidine). No p-value was disclosed for the placebo efficacy comparison. The data were framed as non-pivotal and supportive of potential future development requiring larger confirmatory trials; no regulatory path or timing has been committed. BXCL501 is NOT approved for opioid withdrawal or opioid use disorder (the molecule is separately approved as Igalmi for acute agitation in bipolar I/II disorder and schizophrenia).

Data current as of

Development timeline

Phase 1/2Feb 2023 – Mar 2026
  1. metInvestigator-sponsored Phase 1/2 (NCT05712707) topline: BXCL501 240 ug BID reduced opioid-withdrawal symptoms vs placebo (>30% SOWS-Gossop reduction) and numerically beat lofexidine with fewer adverse events.↗
  2. NCT05712707 reached its actual primary completion date (2025-06-30); study status ACTIVE_NOT_RECRUITING.
  3. Investigator-sponsored Phase 1/2 study NCT05712707 (lead sponsor New York State Psychiatric Institute; Columbia University-led, NIDA-funded; BioXcel collaborator) started: 4-arm randomized, double-blind, placebo-controlled trial of sublingual dexmedetomidine (BXCL501) vs lofexidine and placebo for opioid withdrawal during a 7-day inpatient methadone taper.

Readouts

  • 2026-03-05ReportedTopline datametNCT05712707

    Investigator-sponsored Phase 1/2 (NCT05712707) topline: BXCL501 240 ug BID reduced opioid-withdrawal symptoms vs placebo (>30% SOWS-Gossop reduction) and numerically beat lofexidine with fewer adverse events. ↗

  • Date TBDAnticipatedTopline data

    Larger confirmatory trial of BXCL501 in opioid withdrawal anticipated but not designed/scheduled as of Mar 2026. ↗

Clinical trials in Opioid use disorder

NCT05712707Phase 1/2Activen=160

Phase 1B Study of Sublingual Dexmedetomidine, an Alpha 2 Adrenergic Agonist, for Treating Opioid Withdrawal

Started Feb 2023· Primary completion Jun 2025· 📍 4 sites across 1 country (United States)

metprimarySafety: frequency of adverse events with BXCL501 relative to placebo and lofexidine in opioid-dependent subjects with OUD over the 7-day inpatient period (registered primary outcome)

Registered primary outcome was safety (adverse-event frequency). BXCL501 was reported well tolerated vs the lofexidine control: orthostatic hypotension 18% at 180 ug vs 50% for lofexidine (p<0.05); no sedation/somnolence in BXCL501 arms vs 5% for lofexidine. No safety signal precluding development was reported.

metsecondaryOpioid withdrawal severity by Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop), BXCL501 240 ug BID vs placebo during a 7-day methadone taper (key efficacy measure) — >30% reduction in SOWS-Gossop with 240 ug BID vs placebo; peak improvement days 3-4 (no formal effect size or p-value disclosed)

Key efficacy readout: BXCL501 240 ug BID reduced opioid-withdrawal symptoms vs placebo (>30% reduction in SOWS-Gossop, peak days 3-4) and numerically exceeded the lofexidine positive control. The 5 Mar 2026 topline PR did not disclose a p-value or formal effect size for the placebo comparison; outcome='met' reflects the company's stated positive topline. Data framed as non-pivotal, supporting potential future development requiring larger confirmatory trials.

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 Phase 2 topline results from Columbia University-led study of BXCL501 for treatment of opioid withdrawal — BioXcel Therapeutics (GlobeNewswire wire release)
  3. Dexmedetomidine (ligand 521) — selective alpha-2 adrenoceptor agonist — IUPHAR/BPS Guide to Pharmacology
  4. IGALMI (dexmedetomidine film) - FDA prescribing information — DailyMed / NIH
  5. Phase 1B Study of Sublingual Dexmedetomidine (BXCL501) for Treating Opioid Withdrawal (NCT05712707) — ClinicalTrials.gov