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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of PRN Dosing of BXCL501 Over a 12 Week Treatment Period in Subjects With Agitation Associated With Dementia

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 168 doses within a 12-week treatment period.

Study Overview

• Status: Terminated
• Conditions: Dementia; Agitation
• Intervention / Treatment: Drug: BXCL501; Drug: Matching Placebo

Detailed Description

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 associated with dementia.

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. Subjects must reside in a care facility where all study-related procedures and study drug dosing will be performed.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720
      • BioXcel Clinical Research Site
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • BioXcel Clinical Research Site
    • Maitland, Florida, United States, 32751
      • BioXcel Clinical Research Site
    • The Villages, Florida, United States, 32162
      • BioXcel Clinical Research Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • BioXcel Clinical Research Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • BioXcel Clinical Research Site
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • BioXcel Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All subjects must have a diagnosis of probable Alzheimer's disease based on NIA-AA criteria (2018). If subject biomarker data are unavailable, per the 2018 NIA-AA diagnostic criteria, the clinical diagnosis of probable AD will be based on the 2011 NIA-AA criteria
2. Episodes of psychomotor agitation (e.g., kick, bite, flailing)
3. Subjects exhibit behaviors that are congruent with the International Psychogeriatric Association criterion for agitation representing a change from the subject's usual behavior
4. A score of 0 to 20 on the Mini-Mental State Exam (MMSE) and require moderate to full assistance with activities of daily living
5. Subjects who read, understand, and provide written informed consent, or who have a LAR to provide consent on their behalf
6. Subjects who are deemed to be medically appropriate for study participation by the principal investigator
7. Participants who agree to use a medically acceptable and effective birth control method

Exclusion Criteria:

1. Subjects with dementia or other memory impairment not due to probable AD.
2. 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.
3. Subjects with agitation caused by acute intoxication.
4. Subjects with significant risk of suicide or homicide per the investigator's assessment.
5. 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.
6. History of clinically significant syncope or syncopal attacks, orthostatic hypotension within the past 2 years, current evidence of hypovolemia, orthostatic hypotension, bradycardia.
7. Subjects with laboratory or ECG abnormalities.
8. Subjects who have received an investigational drug within 30 days prior to Screening.
9. Subjects who are currently suffering from substance abuse.
10. Subjects with a potential cause for delirium (relatively recent onset agitation and dementia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1- 40 Micrograms; Sublingual film containing 40 Micrograms Dexmedetomidine	Drug: BXCL501; Sublingual Film; Other Names: Dexmedetomidine
Experimental: Cohort 2- 60 Micrograms; Sublingual film containing 60 Micrograms Dexmedetomidine	Drug: BXCL501; Sublingual Film; Other Names: Dexmedetomidine
Placebo Comparator: Placebo; Sublingual Placebo film	Drug: Matching Placebo; Sublingual Placebo Film; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 post-dose for first episode of agitation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	60 minutes post-dose for first episode of agitation
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)	30 minutes post-dose for first episode of agitation

Collaborators and Investigators

• Sponsor: BioXcel Therapeutics Inc
• Collaborators: Cognitive Research Corporation
• Investigators: Study Chair: Robert Risinger, MD, BioXcel Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Actual): September 11, 2023
• Study Completion (Actual): September 11, 2023

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Dementia; 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: BXCL501-304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No