Pilot Study 1: Efficacy and Safety of Sublingual Dexmedetomidine (BXCL501) for the Treatment of Agitation in the Emergency Department

Study Overview
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Brief Summary
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This is a single-arm pilot study to examine the impact of BXCL501 (sublingual film formulation of dexmedetomidine) administration on reducing the severity of undifferentiated acute agitation in patients presenting to the emergency department with underlying bipolar disorder or schizophrenia. This study is designed to evaluate BXCL501 for its FDA-approved indication -- treatment of agitation associated with bipolar disorder or schizophrenia -- applied in the emergency department setting.

Detailed Description
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This pilot study will enroll 30 male and female adults with primary psychiatric complaint and a documented diagnosis of bipolar I disorder, bipolar II disorder, schizophrenia, schizoaffective disorder, or schizophreniform disorder, presenting to the emergency department with clinical signs of acute agitation. Eligible subjects will receive an initial dose of BXCL501 (180mcg) and a repeat dose (90mcg) 2 hours after the first BXCL501 dose in the event of persistent or recurrent agitation (up to two repeat doses) while under medical supervision in the emergency department. Efficacy and safety assessments will be conducted periodically before and after dosing.

Official Title
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Pilot Study 1: Efficacy and Safety of Sublingual Dexmedetomidine (BXCL501) for the Treatment of Agitation in the Emergency Department

Conditions
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Agitation, Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorders, Bipolar Disorder

Intervention / Treatment
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* Drug: Sublingual film containing dexmedetomidine (BXCL501)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking adults age ≥18 years Patients with an established diagnosis of (1) bipolar I disorder, (2) bipolar II disorder, (3) schizophrenia, (4) schizoaffective disorder, or (5) schizophreniform disorder Judged to be clinically agitated at the time of Screening and Baseline with a AMSS ≥2 Able to read, understand, and provide written informed consent Subject judged to be likely capable of self-administration of BXCL501 sublingually or buccally Exclusion Criteria: Likely to be discharged, admitted, or transferred from the ED within 6 hours after study medication administration Administration of benzodiazepines or antipsychotic drugs in the 2 hours before study treatment Treatment with alpha-1 noradrenergic antagonists Female patients who are pregnant or are breastfeeding Hypotension (systolic blood pressure <100 mmHg or diastolic blood pressure <60 mmHg) and/or bradycardia (heart rate <55 beats per minute) at the time of Screening or Baseline evaluation History of dysautonomia Patient with a known diagnosis of familial long QT syndrome, second degree or third degree atrioventricular block without pacemaker, or sick sinus syndrome Patients with serious or unstable medical illnesses determined by the study investigators or qualified designees Patients with history of allergic reactions to dexmedetomidine Patients previously enrolled and completed the current study Patients actively enrolled in other ED-based studies involving pharmacological or behavioral interventions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention - BXCL501<br> | Drug: Sublingual film containing dexmedetomidine (BXCL501)<br>* Enrolled participants will receive an initial dose of BXCL501 180mcg. Following the FDA dosing suggestions, participants with mild or moderate hepatic impairment (Child-Pugh Class A or B) will receive a reduced initial dose of 120mcg and participants with severe hepatic impairment (Child-Pugh Class C) will receive a reduced initial dose of 90mcg. Geriatric patients (≥ 65 years old) will receive a reduced initial dose of 120mcg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in the Altered Mental Status Scale (AMSS) score | AMSS is a 9-point scale ranging from -4 (most sedated) to 4 (most agitated). | 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in the Richmond Agitation Sedation Scale (RASS) score | RASS is a 10-point scale with four levels of anxiety or agitation (+1 to +4), one denoting a calm, alert state (0), and five levels of sedation (-1 to -5). | 120 minutes | 
| Absolute change from baseline in the Behavioral Activity Rating Scale (BARS) score | BARS is a 7-point scale ranging from 1 (difficult or unable to arouse) to 7 (violent, requires restraints). | 120 minutes | 
| Absolute change from baseline in the Broset Violence Checklist (BVC) score | BVC is a six-item instrument with a total score ranging from 0 (no agitation) to 6 (severely agitated). | 120 minutes | 
| Times, in minutes, from BXCL501 administration to adequate sedation, defined as Altered Mental Status Scale (AMSS) score <1 | AMSS is a 9-point scale ranging from -4 (most sedated) to 4 (most agitated). | To be determined - will be measured for 120 minutes | 
| Times, in minutes, from BXCL501 administration to adequate sedation, defined as Richmond Agitation Sedation Scale (RASS) score <1 | RASS is a 10-point scale with four levels of anxiety or agitation (+1 to +4), one denoting a calm, alert state (0), and five levels of sedation (-1 to -5). | To be determined - will be measured for 120 minutes | 
| Times, in minutes, from BXCL501 administration to adequate sedation, defined as Behavioral Activity Rating Scale (BARS) score <5 | BARS is a 7-point scale ranging from 1 (difficult or unable to arouse) to 7 (violent, requires restraints). | To be determined - will be measured for 120 minutes | 
| Times, in minutes, from BXCL501 administration to adequate sedation, defined as Broset Violence Checklist (BVC) score <1 | BVC is a six-item instrument with a total score ranging from 0 (no agitation) to 6 (severely agitated). | To be determined - will be measured for 120 minutes |