Protocol Title: Effect of Sublingual formulation of Dexmedetomidine HCl (BXCL501) on Ethanol in Heavy Drinkers with PTSD
Objective: 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 providing support to conduct later phase clinical trials.
Hypothesis 1 (Specific Aim 1):
1a. To evaluate whether pretreatment with BXCL501 40 ug and 80 ug attenuates stress reactivity in individuals with alcohol use disorder with comorbid PTSD (clinical or subclinical).
1b. To evaluate whether pretreatment with BXCL501 40 ug and 80 ug attenuates cue reactivity in individuals with AUD with comorbid PTSD (clinical or subclinical).
Hypothesis 2 (Specific Aim 2): To evaluate whether pretreatment with BXCL501 40 ug and 80 mg alters subjective effects of ethanol in a laboratory setting.
Hypothesis 3 (Specific Aim 3):
To evaluate the effects of up to BXCL501 80 ug per day for 28 days on craving for alcohol, drinking behavior, symptoms of PTSD and mood, and cognitive function, including memory and reaction time in individuals with AUD and comorbid PTSD (clinical or subclinical) recruited from the community.
Primary Inclusion Criteria: Individuals, aged 21-50, with both AUD and PTSD.
Subject Completion Target: n = 16
** Study Synopsis: This is a phase 1/phase 2 double-blind, placebo-controlled, within-subjects modified dose-escalating designed study that includes 3 laboratory test sessions following pretreatment with BXCL/placebo for each of 16 participants. Participants will consist of individuals with AUD and PTSD (clinical or subclinical) and will be assigned to participate in a laboratory study (n=16) where they receive sublingual BXCL501 40 ug and 80 ug and placebo in a randomized fashion for a laboratory study consisting of 3 separate test days. After the first 6 subjects participate, the latter 10 subjects will participate in an additional outpatient phase -in this phase they will receive BXCL501 for a total of 28 days -subjects will have upward titration and will receive doses of 40 ug of for 3 days, 40 ug BID for 3 days, followed by a single daily dose of 80 ug for remaining 22 days. Subjects will be followed closely and assessed for craving for alcohol, drinking behavior, symptoms of PTSD and mood, and cognitive function, including memory and reaction time.