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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Agitation; Schizophreniform Disorders
• Intervention / Treatment: Drug: Sublingual film containing dexmedetomidine (BXCL501)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dana Im, MD; Phone Number: 617-732-5640; Email: dim@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention - BXCL501

Drug: Sublingual film containing dexmedetomidine (BXCL501); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease Attributes; Schizophrenia Spectrum and Other Psychotic Disorders; Dyskinesias; Psychomotor Disorders; Bipolar and Related Disorders; Emergencies; Schizophrenia; Psychotic Disorders; Psychomotor Agitation; Bipolar Disorder; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2023p001864

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes