An Efficacy, and Safety Study Of BXCL501 For The Treatment Of Agitation Associated With Dementia

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled parallel group 3-arm study assessing efficacy, safety, and tolerability of two doses BXCL501 in male and female geriatric residents (65 years and older) with acute agitation associated with all forms of dementia (i.e., probably Alzheimer's Disease, vascular dementia; mixed; frontotemporal dementia) excluding Parkinson's-Related Dementia and Lewy Body Dementia.

Detailed Description
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The study will enroll at least 75 subjects to receive a single film consisting of BXCL501 40 μg dose, BXCL501 60 μg dose, or matching placebo film. Subjects must reside in a residential care facility and must require at least moderate assistance with activities of daily living (e.g., bathing, dressing, and toileting). The subject must be able to self-administer the film to participate in the study. The effects of BXCL 501 on acute agitation will be assessed by the following scales: PEC, PAS, ACES, and CGI-I.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of BXCL501 For The Treatment of Agitation Associated With Dementia

Conditions
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Agitation, Dementia

Intervention / Treatment
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* Drug: BXCL501
* Drug: BXCL501
* Drug: Placebo film


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals diagnosed with any form of dementia (i.e., probable Alzheimer's Disease; vascular dementia; mixed; frontotemporal dementia) Subjects who have met DSM-5 criteria for dementia (major neurocognitive disorder) who have instances of acute psychomotor agitation. History of psychomotor agitation (e.g., kick, bite, flailing) to the point that it impairs social activities, requires staffing, or medical intervention, or impairs ability for functional activities of daily living. Subjects are expected to exhibit behaviors that are congruent with the International Psychogeriatric Association criterion for agitation representing a change from the subject's usual behavior. Subjects who have a score of ≤16 on the Mini-Mental State Exam (MMSE). Subjects with a remote (>5 years) history of stroke may be included, regardless of size/location. Subjects who read, understand, and provide written informed consent, or who have a legally authorized representative (LAR). Subjects who are deemed to be medically appropriate for study participation by the principal investigator. Subjects who are at their current location for at least 14 days before screening and plan to remain at the same location for the duration of the study. Subjects who have the capability to participate in the study and self-administer the investigational product. Subjects who are on a stable concomitant medications regimen for the treatment of any concurrent conditions for at least one month prior to the screening visit. Exclusion Criteria: Subjects who have dementia associated with Parkinson's disease and/or Lewy Body Disease are excluded. Subjects suffering from alcohol and/or substance abuse. Subjects with agitation caused by acute intoxication must be excluded. Subjects with significant risk of suicide or homicide per the investigator's assessment. Subjects who have hydrocephalus, seizure disorder, or history of significant head trauma, subarachnoid bleeding, brain tumor, encephalopathy, meningitis, or focal neurological findings, with a recent (1 year) large (non-microvascular) stroke who may be considered medically unstable or in recovery must be excluded. History of clinically significant syncope or syncopal attacks, orthostatic hypotension within the past 2 years. Subjects with laboratory or ECG abnormalities. Subjects with serious, unstable, or uncontrolled medical illnesses must be excluded. Subjects who have received an investigational drug within 30 days prior to Screening must be excluded. Subjects who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving dexmedetomidine must be excluded. Subjects whose agitation is attributed to pain or infection, delirium, concomitant medications, environmental conditions, or another psychiatric condition or medical condition as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 65 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: Study will randomize subjects 1:1:1 to receive BXCL501 40 μg, BXCL501 60 μg, or matching placebo film
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 micrograms<br>Sublingual film containing 40 micrograms Dexmedetomidine | Drug: BXCL501<br>* Sublingual film containing 40 Micrograms BXCL501<br>* Other names: Dexmedetomidine;|
| Experimental: 60 micrograms<br>Sublingual film containing 60 micrograms Dexmedetomidine | Drug: BXCL501<br>* Sublingual film containing 60 Micrograms BXCL501<br>* Other names: Dexmedetomidine;|
| Experimental: Placebo<br>Sublingual Placebo film | Drug: Placebo film<br>* Matching Sublingual Placebo film<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe). | 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for Pittsburgh Agitation Scale | The Pittsburgh Agitation Scale (PAS) assesses agitation for individuals with dementia across four behavior groups: aberrant vocalizations, motor agitation, aggressiveness, and resisting care. Each behavior group is scored ranging from 0 (not present) to 4 (maximally present). | 120 minutes | 
| Change From Baseline for Agitation-Calmness Evaluation Scale | The Agitation-Calmness Evaluation Scale (ACES) is a single item measure rating overall agitation and sedation, where 1 indicates marked agitation; 2 - moderate agitation; 3 - mild agitation; 4 - normal behavior; 5 - mild calmness; 6 - moderate calmness; 7 - marked calmness; 8 - deep sleep; and 9 - unarousable | 120 minutes | 
| Clinical Global Impression - Improvement | The Clinical Global Impression - Improvement (CGI-I) for agitation in response to treatment measures the current level of agitation relative to the level of agitation prior to administration of study intervention. The CGI-I scores range from 1 to 7 with a score of 1 indicating very much improved, and a score of 7 indicating very much worse. | 120 minutes |