Agitation in Patients With Dementia of the Alzheimer's Type, Agitation,Psychomotor, Alzheimer Disease
Conditions
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled study, to assess the efficacy and safety of AXS-05 in the treatment of agitation in patients with Alzheimer's disease.
Interventions
Sponsors
Axsome Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of probable Alzheimer's disease (AD) based on the 2011 National Institute on Aging-Alzheimer Association (NIA-AA) criteria. * Diagnosis of clinically signification agitation resulting from probable AD according to the International Psychogeriatric Association (IPA) provisional definition of agitation.
Exclusion criteria
* Patient has dementia predominantly of non-Alzheimer's type. * Unable to comply with study procedures. * Medically inappropriate for study participation in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CMAI Total Score | 5 weeks | The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver-rated questionnaire that assesses the frequency of agitation-related and disruptive behaviors in subjects with dementia. The scale contains 29 behaviors or items organized into four subscales: physically aggressive, physically non-aggressive, verbally aggressive, and verbally non-aggressive. The CMAI is administered by interviewing the caregiver and asking him or her to rate the frequency with which the subject manifests each behavior using a seven-point scale: 1=never (better outcome), 7=several times an hour (worse outcome). The CMAI total score is the sum of the scores for all of the items in the CMAI. CMAI total scores range from a minimum of 29 (better outcome) to a maximum of 203 (worse outcome). |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AXS-05 AXS-05 tablets taken by mouth for 5 weeks.
AXS-05: AXS-05 | 159 |
| Bupropion Bupropion tablets taken by mouth for 5 weeks.
Bupropion: Bupropion | 49 |
| Placebo Placebo tablets taken by mouth for 5 weeks.
Placebo: Placebo | 158 |
| Total | 366 |
Baseline characteristics
| Characteristic | AXS-05 | Bupropion | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 75.3 years STANDARD_DEVIATION 5.71 | 76.4 years STANDARD_DEVIATION 6.13 | 74.6 years STANDARD_DEVIATION 6.11 | 75.1 years STANDARD_DEVIATION 5.95 |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 12 Participants | 5 Participants | 25 Participants | 42 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 141 Participants | 43 Participants | 130 Participants | 314 Participants |
| Sex: Female, Male Female | 91 Participants | 22 Participants | 92 Participants | 205 Participants |
| Sex: Female, Male Male | 68 Participants | 27 Participants | 66 Participants | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 159 | 1 / 49 | 1 / 158 |
| other Total, other adverse events | 33 / 159 | 17 / 49 | 24 / 158 |
| serious Total, serious adverse events | 5 / 159 | 4 / 49 | 9 / 158 |
Outcome results
Primary
Change in CMAI Total Score
The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver-rated questionnaire that assesses the frequency of agitation-related and disruptive behaviors in subjects with dementia. The scale contains 29 behaviors or items organized into four subscales: physically aggressive, physically non-aggressive, verbally aggressive, and verbally non-aggressive. The CMAI is administered by interviewing the caregiver and asking him or her to rate the frequency with which the subject manifests each behavior using a seven-point scale: 1=never (better outcome), 7=several times an hour (worse outcome). The CMAI total score is the sum of the scores for all of the items in the CMAI. CMAI total scores range from a minimum of 29 (better outcome) to a maximum of 203 (worse outcome).
Time frame: 5 weeks
Population: modified Intent-to-Treat (mITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AXS-05 | Change in CMAI Total Score | -15.4 score on a scale | Standard Error 1.25 |
| Bupropion | Change in CMAI Total Score | -10.0 score on a scale | Standard Error 3.02 |
| Placebo | Change in CMAI Total Score | -11.5 score on a scale | Standard Error 1.1 |
p-value: 0.01Mixed Models Analysis
p-value: <0.001Mixed Models Analysis