Dexmedetomidine in the Treatment of Agitation Associated With Dementia (TRANQUILITY II)

Study Overview
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Brief Summary
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A study to determine the safety and efficacy of BXCL501 dosing for episodes of agitation associated with dementia when they occur (given as needed [PRN]), for a maximum of 28 doses within a 12-week treatment period.

Detailed Description
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A randomized, double-blind, placebo-controlled, parallel group, 3-arm study assessing efficacy, safety, and tolerability of two doses of BXCL501 in male and female subjects (65 years and older) with acute psychomotor agitation. Subjects will be dosed PRN with a maximum of 28 doses over a 12-week period. Once a subject has received 28 doses of BXCL501, they will continue to be followed for the remainder of the 12-week study period. Approximately 150 subjects will participate in this study. Subjects will receive a single film consisting of BXCL501 40 µg dose or BXCL501 60 µg dose or placebo in a 1:1:1 randomization scheme. Subjects must reside in a care facility where all study-related procedures and study drug dosing will be performed.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy And Safety Study of PRN Dosing of BXCL501 Over A 12 Week Period In Subjects With Agitation Associated With Dementia

Conditions
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Agitation, Dementia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must have a diagnosis of probable AD based on NIA-AA criteria (2018) Episodes of psychomotor agitation (e.g., kick, bite, flailing) Subjects exhibit behaviors that are congruent with the International Psychogeriatric Association criterion for agitation representing a change from the subject's usual behavior A score of 15 to 23 on the Mini-Mental State Exam (MMSE) Subjects who read, understand, and provide written informed consent, or who have a LAR to provide consent on their behalf Subjects who are deemed to be medically appropriate for study participation by the principal investigator Participants who agree to use a medically acceptable and effective birth control method Exclusion Criteria: Subjects with dementia or other memory impairment not due to probable AD. Clinical diagnosis of probable AD should not be applied when there is evidence of a cerebrovascular incident temporally related to the worsening of cognitive function. Subjects with agitation caused by acute intoxication. Subjects with significant risk of suicide or homicide per the investigator's assessment. Subjects who are medically unstable or in recovery. Note: Subjects with a remote (>5 years) history of stroke may be included, regardless of size/location. History of clinically significant syncope or syncopal attacks, orthostatic hypotension within the past 2 years, current evidence of hypovolemia, orthostatic hypotension, bradycardia. Subjects who had a total score of >13 (ie, high fall risk) on the John Hopkins Fall Risk Assessment Tool. Subjects with laboratory or ECG abnormalities. Subjects who have received an investigational drug within 30 days prior to Screening. Subjects who are currently suffering from substance abuse. Patients with a potential cause for delirium (relatively recent onset agitation and dementia)

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: Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1- 40 Micrograms<br>Sublingual film containing 40 Micrograms Dexmedetomidine | Drug: BXCL501<br>* Sublingual Film<br>* Other names: Dexmedetomidine;|
| Experimental: Cohort 2- 60 Micrograms<br>Sublingual film containing 60 Micrograms Dexmedetomidine | Drug: BXCL501<br>* Sublingual Film<br>* Other names: Dexmedetomidine;|
| Placebo Comparator: Placebo<br>Sublingual Placebo film | Drug: Matching Placebo<br>* 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 |
| --- | --- | --- |
| Absolute change from baseline 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 |
| --- | --- | --- |
| Absolute change from baseline in Positive and Negative Syndrome Scale- Excited for the first episode of agitation | 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) | 30 minutes | 
| Absolute change from baseline in Positive and Negative Syndrome Scale- Excited for the first episode of agitation | 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) | 60 minutes | 
| Absolute change from baseline in Positive and Negative Syndrome Scale- Excited for all episodes of agitation | 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 |