NCT04827056

Effect of Sublingual Formulation of Dexmedetomidine HCl (BXCL501) - Alcohol Interaction Study

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

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) and also shows potential signals of efficacy thereby supporting the conduct of later phase clinical trials. Safety endpoints will be compared following an alcohol challenge without and concurrent with BXCL501 treatment.

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 1, double-blind, placebo-controlled, within subjects study. This study will consist of 3 laboratory test sessions following pretreatment with BXCL501/placebo for 10 heavy drinker participants with comorbid PTSD. Participants (n=10) will participate in a laboratory study with 3 test days (minimum of 2 days, but no longer than 2 weeks between each test session); for each test day they will be assigned to receive sublingual BXCL501 40µg, 80µg and placebo in a randomized fashion. Test sessions will be conducted to evaluate stress (PTSD) reactivity and alcohol cue reactivity. Participants will also receive IV ethanol administered via "clamp methodology" to assess for the effects of BXCL501 in combination with ethanol. Since this is the first time BXCL501 is being tested in combination with alcohol administration, the study team will be using a modified randomization where participants will not receive the 80µg dose until they have received the 40µg dose.

Conditions

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

Interventions

Type	Name	Description
DRUG	Placebo	Placebo will be administered orally, as individual films in the SL space.
DRUG	Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 40µg	BXCL 501 40µg will be administered orally, as individual films in the SL space.
DRUG	Dexmedetomidine (DEX) for sublingual (SL) administration (BXCL501) - 80µg	BXCL 501 80µg will be administered orally, as individual films in the SL space.
PROCEDURE	Ethanol Infusion	Study team will be using a modified alcohol-IV clamp procedure developed and standardized by Subramanian and colleagues (Subramanian, Heil et al. 2002). The infusion will be performed using a 6% ethanol solution in 0.9% saline. The computer assisted administration program automatically calculates and corrects the infusion rate based on real-time BrAC data entry by staff, based on the pharmacokinetic profile of each subject (targeting a breath alcohol concentration (BrAC) of 100 mg%).
BEHAVIORAL	PTSD Reactivity Condition	Participants will be exposed to two conditions in random order: PTSD cues and neutral cues. The cues will consist of a 5 minute presentation of the stimulus (trauma or neutral) followed by immediate evaluation of craving and anxiety. There will be a relaxation procedure between each condition. The imagery scripts are developed based on the scene construction questionnaire developed by Lang et al (Lang, Kozak et al. 1980, Lang, Levin et al. 1983) using a standardized format designed by Sinha (Sinha 2001).
BEHAVIORAL	Alcohol Cue Reactivity	Participants will be exposed to two conditions: a neutral cue (water) followed by an alcohol cue. Individuals will be instructed that they may smell and handle the beverage, but they cannot consume the beverage. Following the presentation, the research assistant takes the beverage and leaves the room, while the subject completes the anxiety and alcohol craving assessments.

Timeline

• Start date: 2021-11-09
• Primary completion: 2023-05-02
• Completion: 2023-06-02
• First posted: 2021-04-01
• Last updated: 2023-10-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study