Dexmedetomidine in the Treatment of Agitation Associated With Bipolar Disorder

Study Overview
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Brief Summary
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This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the acute treatment of agitation in bipolar disorder. The BXCL501-302 study is designed to characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of DEX, HCl) in agitation associated with bipolar disorder.

Detailed Description
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The study will enroll approximately 375 subjects randomized 1:1:1 to dose regimens of 180µg, 120µg BXCL501, or placebo stratified by age < 65 and age ≥ 65. Male and female adults with acute agitation associated with bipolar disorder will be enrolled. Eligible subjects (acutely agitated subjects with bipolar disorder, generally hypomanic, manic or mixed episodes) may be identified in outpatient clinics, mental health, psychiatric or medical emergency services including medical/psychiatric observation units, or as newly admitted to a hospital setting for acute agitation or already in hospital for chronic underlying conditions. Subjects will be domiciled in a clinical research setting or hospitalized to remain under medical supervision while undergoing screening procedures to assess eligibility. Efficacy and safety assessments will be conducted periodically before and after dosing.

Official Title
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A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine Efficacy and Safety of BXCL501 In Agitation Associated With Bipolar Disorder

Conditions
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Agitation Associated With Bipolar Disorder, Agitation,Psychomotor, Bipolar Disorder

Intervention / Treatment
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* Drug: Sublingual film containing Dexmedetomidine (BXCL501)
* Drug: Placebo Film


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18 to 75 years, inclusive. Patients who have met DSM-5 criteria for bipolar I or II disorder. Patients who are judged to be clinically agitated at Screening and Baseline with a total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility, uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC). Patients who have a score of ≥ 4 on at least 1 of the 5 items on the PEC at Baseline. Patients who read, understand and provide written informed consent. Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG with rhythm strip, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator. Participants who agree to use a medically acceptable and effective birth control method Exclusion Criteria: Patients with agitation caused by acute intoxication, including positive identification of alcohol by breathalyzer or drugs of abuse (with the exception of THC) during urine screening. Use of benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotic drugs in the 4 hours before study treatment. Treatment with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin) or other prohibited medications. Patients who are judged to be at significant risk of suicide. Female patients who have a positive pregnancy test at screening or are breastfeeding. Patients who have hydrocephalus, seizure disorder, or history of significant head trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor, encephalopathy, meningitis, Parkinson's disease or focal neurological findings. History of syncope or other syncopal attacks, current evidence of hypovolemia, orthostatic hypotension. Patients with laboratory or ECG abnormalities considered clinically significant by the investigator. Patients with serious or unstable medical illnesses. Patients who have received an investigational drug within 30 days prior to the current agitation episode. Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving DEX.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: phase III, randomized, double-blind, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 120 Micrograms<br>Sublingual film containing 120 Micrograms Dexmedetomidine | Drug: Sublingual film containing Dexmedetomidine (BXCL501)<br>* Sublingual film containing Dexmedetomidine (BXCL501)<br>* Other names: Dexmedetomidine;|
| Experimental: 180 Micrograms<br>Sublingual film containing 180 Micrograms Dexmedetomidine | Drug: Sublingual film containing Dexmedetomidine (BXCL501)<br>* Sublingual film containing Dexmedetomidine (BXCL501)<br>* Other names: Dexmedetomidine;|
| Placebo Comparator: Placebo<br>Sublingual placebo film | Drug: Placebo Film<br>* Placebo Film for BXCL501<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe). | Baseline and 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score Over Time | Effect on agitation onset was measured by change from baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) total score. The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items -poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe). | Baseline and 20, 30, 45, 60, 90, 120 minutes post-dose |