Agitation, Dementia
Conditions
Brief summary
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
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.
Interventions
DRUGBXCL501
Sublingual Film
DRUGMatching Placebo
Sublingual Placebo Film
Sponsors
BioXcel Therapeutics Inc
Cognitive Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Double-Blinded
Intervention model description
Randomized
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All subjects must have a diagnosis of probable AD based on NIA-AA criteria (2018) 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 15 to 23 on the Mini-Mental State Exam (MMSE) 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 who had a total score of \>13 (ie, high fall risk) on the John Hopkins Fall Risk Assessment Tool. 8. Subjects with laboratory or ECG abnormalities. 9. Subjects who have received an investigational drug within 30 days prior to Screening. 10. Subjects who are currently suffering from substance abuse. Patients with a potential cause for delirium (relatively recent onset agitation and dementia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score for the First Episode of Agitation | 120 minutes | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | 30 minutes | 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) |
| Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for All Episodes of Agitation | 120 minutes | 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) |
Countries
United States
Contacts
STUDY_CHAIRBioXcel MM, MD
BioXcel Therapeutics
Participant flow
Recruitment details
The study was conducted in United States from 18 April 2022 to 21 April 2023.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1- 40 Micrograms Sublingual film containing 40 Micrograms Dexmedetomidine
BXCL501: Sublingual Film | 48 |
| Cohort 2- 60 Micrograms Sublingual film containing 60 Micrograms Dexmedetomidine
BXCL501: Sublingual Film | 50 |
| Placebo Sublingual Placebo film
Matching Placebo: Sublingual Placebo Film | 51 |
| Total | 149 |
Baseline characteristics
| Characteristic | Cohort 1- 40 Micrograms | Cohort 2- 60 Micrograms | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 79.4 Years STANDARD_DEVIATION 6.44 | 79.5 Years STANDARD_DEVIATION 8.14 | 80.0 Years STANDARD_DEVIATION 7.48 | 79.6 Years STANDARD_DEVIATION 7.35 |
| Baseline Positive and Negative Syndrome Scale - Excited Component (PEC) | 17.3 units on a scale STANDARD_DEVIATION 2.18 | 18.0 units on a scale STANDARD_DEVIATION 2.26 | 17.5 units on a scale STANDARD_DEVIATION 2.62 | 17.6 units on a scale STANDARD_DEVIATION 2.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 22 Participants | 19 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 28 Participants | 32 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 5 Participants | 11 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 35 Participants | 43 Participants | 39 Participants | 117 Participants |
| Sex: Female, Male Female | 27 Participants | 30 Participants | 33 Participants | 90 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 18 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 48 | 1 / 50 | 1 / 51 |
| other Total, other adverse events | 6 / 48 | 16 / 50 | 2 / 51 |
| serious Total, serious adverse events | 0 / 48 | 0 / 50 | 0 / 51 |
Outcome results
Primary
Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score 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)
Time frame: 120 minutes
Population: Full analysis set included all subjects who took any study medication and who had both baseline and at least one efficacy assessment after dosing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 40 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score for the First Episode of Agitation | -5.7 score on a scale | Standard Error 0.6 |
| Cohort 2- 60 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score for the First Episode of Agitation | -7.5 score on a scale | Standard Error 0.6 |
| Placebo | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score for the First Episode of Agitation | -5.4 score on a scale | Standard Error 0.6 |
Secondary
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)
Time frame: 120 minutes
Population: Full Analysis Set (FAS) included all subjects who took any study medication and who had both baseline and at least one efficacy assessment after dosing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 40 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for All Episodes of Agitation | -5.8 score on a scale | Standard Error 0.5 |
| Cohort 2- 60 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for All Episodes of Agitation | -7.4 score on a scale | Standard Error 0.5 |
| Placebo | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for All Episodes of Agitation | -5.2 score on a scale | Standard Error 0.5 |
Secondary
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)
Time frame: 30 minutes
Population: Full Analysis Set (FAS) included all subjects who took any study medication and who had both baseline and at least one efficacy assessment after dosing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 40 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -2.5 score on a scale | Standard Error 0.5 |
| Cohort 2- 60 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -3.6 score on a scale | Standard Error 0.5 |
| Placebo | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -3.4 score on a scale | Standard Error 0.5 |
Secondary
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)
Time frame: 60 minutes
Population: Full Analysis Set (FAS) included all subjects who took any study medication and who had both baseline and at least one efficacy assessment after dosing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 40 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -4.2 score on a scale | Standard Error 0.6 |
| Cohort 2- 60 Micrograms | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -6.2 score on a scale | Standard Error 0.6 |
| Placebo | Absolute Change From Baseline in Positive and Negative Syndrome Scale- Excited for the First Episode of Agitation | -4.2 score on a scale | Standard Error 0.6 |