Effect of Sublingual Formulation of Dexmedetomidine Hydrochloride (HCl) (BXCL501) - Outpatient Study

NCT06335407 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AS210006-A08W81XWH-21-2-0026
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of the proposed study is to determine if Dexmedetomidine HCl (BXCL501) is safe for treatment of alcohol use disorder (AUD) with comorbid posttraumatic stress disorder (PTSD) in an outpatient setting and also shows potential signals of efficacy thereby supporting the conduct of later phase clinical trials.

Conditions

Alcohol Use Disorder (AUD); Post Traumatic Stress Disorder (PTSD)

Keywords

Alcohol Used Disorder (AUD); Post Traumatic Stress Disorder (PTSD); Alcohol Use; Heavy Drinkers; Dexmedetomidine HCl (BXCL501)

Outcome Measures

Primary Outcomes (3)

• Change in Blood Pressure (Systolic and Diastolic) from baseline (pre-treatment) through day 28.

  Participants will undergo vital signs on baseline, day 5, day 7, and weeks 2-4. The change in blood pressure is computed as the difference in measurements taken across all study timepoints from the baseline visit (pre-treatment).

  From day 1 through day 28

• Change in anxiety (measured via the State Trait Anxiety Inventory - STAI-6) from baseline (pre-treatment) through day 28.

  Participants will take the STAI-6 assessment on baseline, day 5, day 7, and weeks 2-4. The change in STAI-6 score is computed as the difference in measurements taken across all study timepoints from the baseline visit (pre-treatment).

  From day 1 through 28 days

• Number and Proportion of Adverse Events

  Adverse Events will be monitored and documented through each dose escalation phase after the first dose administration.

  From day 1 through 28 days

Secondary Outcomes (10)

• Change in PTSD symptoms (measured via the PTSD Checklist for Diagnostic and Statistical Manual (DSM-5) - Posttraumatic Stress Disorder Checklist (PCL-5) from baseline (pre-treatment) through day 28.

  From day 1 through 28 days

• Change in alcoholic consumption (measured via the Timeline Follow-Back Method - TLFB) from baseline (pre-treatment) through day 28.

  From day 1 through 28 days

• Change in compulsive drinking (measured via the Obsessive Compulsive Drinking Scale - OCDS) from baseline (pre-treatment) through day 28.

  From day 1 through 28 days

• Change in mood (measured by the Differential Emotions Scale - DES-R) from baseline (pre-treatment) through day 28.

  From day 1 through 28 days

• Change in depression (measured by the Patient Health Questionnaire-9 - PHQ-9) from baseline (pre-treatment) through day 28.

  From day 1 through 28 days

Study Arms (1)

BXCL501 Dose Range 40µg to 160µg

OTHER

Participants will receive 40µg on days 1-2. On days 3 and 4, participants will receive 40µg twice per day. On days 5 and 6 participants will receive 40µg in the morning and 80µg in the evening. On days 7-28 participants will receive 80µg in the morning and evening. Dose escalation will follow the above schedule based on tolerability assessed by clinician.

Drug: Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 40µg; Drug: Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 80µg

Interventions

Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 40µg DRUG

BXCL 501 40µg will be administered orally, as individual films in the Sub Lingual (SL) space.

Also known as: BXCL501 40µg

BXCL501 Dose Range 40µg to 160µg

Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 80µg DRUG

BXCL 501 80µg will be administered orally, as individual films in the SL space

Also known as: BXCL501 80µg

BXCL501 Dose Range 40µg to 160µg

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veterans and non-Veterans, ages 21 to 65;
• Able to read and write in English and sign the informed consent;
• Willing to comply with all study procedures and be available for the duration of the study;
• ECG that demonstrates no clinically significant conduction issues or arrhythmias;
• Have no clinically significant contraindications, in the judgement of the PI/study physician, for study participation (based on self-reported medical history and brief physical examination);
• Have a current diagnosis of Alcohol use disorder (AUD) (mild, moderate, or severe) as determined by MINI-5;
• Have a lifetime traumatic event in their lifetime that meets Criterion A for PTSD as determined by screening interview and the MINI-5;
• Have a PCL-5 score \> 15 prior to starting the study medication;
• Must have \> 1 heavy drinking episodes (\>4 standard drink units (SDU) for men; \>3 SDU for women) in the last 30 days (assessed by the Timeline Follow Back (TLFB));
• Females of childbearing potential (not surgically sterilized (tubal ligation/hysterectomy) or not post-menopausal (no menstrual period for \> 6 months)) must be willing to use a medically acceptable and effective birth control method for 1 month before the study and while participating in the study. Medically acceptable methods of contraception that may be used by the participant include abstinence, birth control pills or patches, birth control implants, diaphragm, intrauterine device (IUD), or condoms.

You may not qualify if:

• Current bipolar disorder or psychotic disorders as determined by MINI-5;
• Current diagnosis of a substance use disorder (other than alcohol, nicotine, or marijuana) as determined by MINI-5;
• Females who are pregnant, nursing, or planning to become pregnant during study participation;
• Current physiological alcohol dependence requiring a higher level of care (e.g., detox) as determined by study physician conducting physical examination and CIWA score. Tolerance to alcohol will be allowed.
• Recent history of complicated alcohol withdrawal, alcohol withdrawal seizures, or delirium tremens (DTs);
• Score \> 4 on Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) at screening;
• History of major medical illnesses including liver disease, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the participant to be in the study;
• Clinically significant history of cardiac disease including (a) chronic hypertension (even if adequately controlled by antihypertensive medications); (b) history of syncope or other syncopal attacks; (c) current evidence of orthostatic hypotension (defined as a decrease in systolic BP of 20 mm Hg or decrease in diastolic BP of 10mm Hg within 3 minutes); (d) resting heart rate of \<55 beats per minute; (e) systolic blood pressure \<110mmHg or diastolic BP \<70mmHg; or (f) participants with a QTC interval \>440msec (males) or \>460msec (females).
• Clinically significant medical conditions including hepatic (ascites, bilirubin \>10% above the upper limit of normal \[ULN\] or liver function tests \[LFT\] \>3 × ULN);
• Renal impairment as measured by BUN/Creatinine;
• Currently taking the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation including sedative/hypnotics, barbiturates, antihistamines, sedative antidepressants (e.g. doxepin, mirtazapine, trazodone), and triptans (e.g., sumatriptan); c) antihypertensive medications; d) alpha-2-adrenergic agonists (clonidine, guanfacine, lofexidine); or adrenergic agents prescribed for other reasons are excluded (prazosin). (Permitted Concomitant Medications: The concomitant medications allowed in the study include non-sedative antidepressants used to treat PTSD);
• History of allergic reactions to dexmedetomidine or known allergy to dexmedetomidine;
• Participation in a clinical trial of a pharmacological agent within 30 days prior to screening;
• Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the study visit schedule or requirements

Sponsors & Collaborators

• Pharmacotherapies for Alcohol and Substance Use Disorders Alliance: lead
• United States Department of Defense: collaborator
• Congressionally Directed Medical Research Programs: collaborator
• VA Connecticut Healthcare System: collaborator
• BioXcel Therapeutics Inc: collaborator
• Yale University: collaborator
• RTI International: collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

RECRUITING

Related Links

• PASA Website

MeSH Terms

Conditions

Alcoholism; Stress Disorders, Post-Traumatic; Alcohol Drinking

Interventions

Dexmedetomidine; Organization and Administration

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Health Services Administration

Study Officials

• Ismene Petrakis, MD

  VA Connecticut Healthcare System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ismene Petrakis, MD

CONTACT

(203) 932-5711; ismene.petrakis@yale.edu

Jenelle Newcomb, BA

CONTACT

(203) 932-5711; jenelle.leblanc@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: no one will be masked
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive 40µg on days 1-2. On days 3 and 4, participants will receive 40µg twice per day. On days 5 and 6 participants will receive 40µg in the morning and 80µg in the evening. If dosing is tolerated, per clinical judgement, participants will begin to receive 80µg twice per day on days 7-28.

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 28, 2024
• Study Start: July 28, 2025
• Primary Completion: March 30, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)