Sublingual dexmedetomidine (BXCL501) for people with alcohol use disorder and PTSD

Effect of Sublingual Formulation of Dexmedetomidine HCl (BXCL501) on Ethanol in Heavy Drinkers With PTSD - Outpatient Study

This outpatient study will try a daily sublingual dexmedetomidine film (BXCL501) for up to 28 days in adults with alcohol use disorder who also have PTSD or a qualifying trauma to see if it is safe and shows early signs of benefit.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 21 Years to 65 Years
• Sex: All
• Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance (Academic / other)
• Locations: 1 site (West Haven, Connecticut)
• Trial ID: NCT06335407 on ClinicalTrials.gov

What this trial studies

This is a phase 1b, open-label, single-arm outpatient safety study enrolling heavy drinkers with comorbid PTSD or a qualifying lifetime traumatic event. Participants will receive escalating sublingual BXCL501 over 28 days (starting 40 µg once daily and potentially increasing to 80 µg twice daily if tolerated) with clinic visits on day 1, day 5 (±2 days), and weekly through week 3. The primary focus is safety and tolerability, with secondary observation of signals of efficacy on drinking and PTSD-related measures. The protocol aims for at least 10 completers to inform whether later-phase trials are warranted.

Who should consider this trial

Good fit: Ideal candidates are adults 21–65 with a current diagnosis of alcohol use disorder, a lifetime Criterion A traumatic event (or PTSD), a PCL-5 score >15, and at least one heavy drinking episode in the last 30 days who can attend outpatient clinic visits and follow study procedures.

Not a fit: People who do not meet the AUD or trauma/PTSD criteria, who are outside the 21–65 age range, or who have clinically significant cardiac conduction problems or other medical contraindications are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could offer a non-respiratory-depressing, non-injectable medication option that may reduce heavy drinking and help PTSD-related symptoms in an outpatient setting.

How similar studies have performed: There is prior early-phase work with sublingual BXCL501 including an alcohol interaction study and other neuropsychiatric safety data, but outpatient treatment of AUD with comorbid PTSD using this formulation remains relatively novel.

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

Where this trial is running

West Haven, Connecticut

• VA Connecticut Healthcare System — West Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Ismene Petrakis, MD — VA Connecticut Healthcare System
• Study coordinator: Ismene Petrakis, MD

Conditions Alcohol Use Disorder; Post Traumatic Stress Disorder; Alcohol Used Disorder; Alcohol Use; Heavy Drinkers; Dexmedetomidine HCl