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

NCT ID: NCT06335407

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-28
• Study Completion Date: 2026-05-31

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.

Detailed Description

BXCL501 is a sublingual film containing dexmedetomidine. Dexmedetomidine is an alpha-2 adrenergic receptor agonist and has higher intrinsic activity and is more potent in vitro than either clonidine or lofexidine. The drug has a high free brain to free plasma ratio after dosing in rats that persists after plasma concentrations are cleared. Dexmedetomidine does not depress respiratory function. It is not predicted to have abuse potential. BXCL501 will bypass 1st pass metabolism and produce fewer problems in participants with compromised liver function.

This laboratory study is a phase 1b, open label, single arm safety study which is a follow-up to the Effect of Sublingual formulation of Dexmedetomidine HCl (BXCL501) on Ethanol in Heavy Drinkers with PTSD - Alcohol Interaction Study Previously conducted. Participants will be heavy drinkers with comorbid PTSD (or no diagnosis of PTSD but have experienced at least one qualifying Criterion A traumatic event). For the study at least 10 completers will participate in an outpatient study. Participants will receive BXCL501 for 28 days. 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. Participants will be seen in the clinic on days 1, 5 (+/- 2 days), and during weeks 1, 2, 3, and 4 with the study nurse and/or research staff to assess side effects as well as drinking, PTSD symptoms, cognitive function, memory, sleep and mood.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

BXCL501 Dose Range 40µg to 160µg

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.

Group Type: OTHER

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

Other Intervention Names

BXCL501 40µg; BXCL501 80µg

Eligibility Criteria

Inclusion Criteria

1. Veterans and non-Veterans, ages 21 to 65;

2. Able to read and write in English and sign the informed consent;

3. Willing to comply with all study procedures and be available for the duration of the study;

4. ECG that demonstrates no clinically significant conduction issues or arrhythmias;

5. 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);

6. Have a current diagnosis of Alcohol use disorder (AUD) (mild, moderate, or severe) as determined by MINI-5;

7. Have a lifetime traumatic event in their lifetime that meets Criterion A for PTSD as determined by screening interview and the MINI-5;

8. Have a PCL-5 score > 15 prior to starting the study medication;

9. 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));

10. 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.

Exclusion Criteria

1. Current bipolar disorder or psychotic disorders as determined by MINI-5;

2. Current diagnosis of a substance use disorder (other than alcohol, nicotine, or marijuana) as determined by MINI-5;

3. Females who are pregnant, nursing, or planning to become pregnant during study participation;

4. 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.

5. Recent history of complicated alcohol withdrawal, alcohol withdrawal seizures, or delirium tremens (DTs);

6. Score > 4 on Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) at screening;

7. 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;

8. 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).

9. Clinically significant medical conditions including hepatic (ascites, bilirubin >10% above the upper limit of normal [ULN] or liver function tests [LFT] >3 × ULN);

10. Renal impairment as measured by BUN/Creatinine;

11. 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);

12. History of allergic reactions to dexmedetomidine or known allergy to dexmedetomidine;

13. Participation in a clinical trial of a pharmacological agent within 30 days prior to screening;

14. Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the study visit schedule or requirements

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

VA Connecticut Healthcare System

FED

Sponsor Role: collaborator

BioXcel Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

RTI International

OTHER

Sponsor Role: collaborator

Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ismene Petrakis, MD

Role: PRINCIPAL_INVESTIGATOR

VA Connecticut Healthcare System

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ismene Petrakis, MD

Role: CONTACT

ismene.petrakis@yale.edu

(203) 932-5711 ext. 1-3121

Jenelle Newcomb, BA

Role: CONTACT

jenelle.leblanc@yale.edu

(203) 932-5711 ext. 12874

Facility Contacts

Jenelle Newcomb, BA

Role: primary

jenelle.leblanc@yale.edu

(203) 932-5711 ext. 12874

Ismene Petrakis, MD

Role: backup

ismene.petrakis@yale.edu

(203) 932-5711 ext. 12244

Related Links

http://pasa-research.org/

PASA Website

Other Identifiers

W81XWH-21-2-0026

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AS210006-A08

Identifier Type: -

Identifier Source: org_study_id