Agitation Associated With Alzheimer's Dementia, Alzheimer Dementia
Conditions
Keywords
Agitation
Brief summary
This study compares the efficacy of 2 doses of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type.
Detailed description
This is a phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose trial designed to assess the efficacy, safety, and tolerability of brexpiprazole compared with placebo. The trial consists of a 12-week double-blind treatment period with a 30 day follow-up. The trial population will include male and female participants between 55 and 90 years of age (inclusive) with a diagnosis of probable Alzheimer's disease, who are residing either in an institutionalized setting or in a non-institutionalized setting where the participant is not living alone. This trial will analyze data gathered from approximately 330 participants at multiple countries. Participants may also be eligible to enter an active treatment extension trial.
Interventions
DRUGBrexpiprazole
Oral tablets
OTHERPlacebo
Oral tablets
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Participants with a diagnosis of probable Alzheimer's disease. * Participants with a diagnosis of agitation * Participants with a MMSE score of 5 to 22, inclusive, at screening and baseline visits. * Participants with a previous MRI or CT scan of the brain, that was performed after the onset of symptoms of dementia, with findings consistent with a diagnosis of Alzheimer's disease. * Participants who are residing at their current location for at least 28 days before screening and are expected to remain at the same location for the duration of the trial. * Institutionalized participants with an identified caregiver who has sufficient contact (minimum of 2 hours per day for 4 days per week) to describe the participant's symptoms and has direct observation of the participant's behavior. Non-institutionalized participants may not be living alone and must have an identified caregiver who has sufficient contact (minimum of 2 hours per day for 4 days per week) to describe the participant's symptoms and has direct observation of the participant's behavior. * Participants with onset of symptoms of agitation at least 2 weeks prior to screening visit. * Participants will and able to discontinue all prohibited concomitant medications to meet protocol required washouts prior to and during the trial period.
Exclusion criteria
* Participants with dementia or other memory impairment not due to Alzheimer's disease. * Participants with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism. * Participants who had an insufficient response, based on the investigator's judgment, to 2 or more previous antipsychotic medications. * Participants who have been diagnosed with an Axis I disorder. * Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders. * Participants with uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension. * Participants with diabetes mellitus (insulin-dependent and non-insulin-dependent) may be eligible for the trial if their condition is stable and well-controlled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in the CMAI Total Score | Baseline and Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. Mixed model repeated measures (MMRM) was used for the analysis. As prespecified in the statistical analysis plan (SAP), data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in CMAI Subscale Scores | Baseline and Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. It consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding, as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The four subscales include 12, 6, 4, and 2 items, respectively. The score of the subscale is the sum of the individual items included in the subscale, so the score range for each of the 4 subscales is 0 to 84, 0 to 42, 0 to 28, and 0 to 14, respectively. Higher scores indicate worsening of the condition. A negative change from baseline=improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Baseline, Weeks 2, 4, 6, 8, 10, and 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Baseline, Weeks 2, 4, 6, 8, 10, and 12 | CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation | Baseline and Week 12 | CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Weeks 2, 4, 6, 8, 10, and 12 | The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Baseline, Weeks 2, 4, 6, 8, 10, and 12 | The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Baseline, Weeks 2, 4, 6, 8, 10, and 12 | CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
| Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Baseline, Weeks 2, 4, 6, 8, 10, and 12 | CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg. |
Countries
United States
Participant flow
Recruitment details
A total of 345 participants were randomized, and participated in the study from 16 May 2018 to 1 June 2022.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 2 mg Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 mg, once daily until Week 12. | 75 |
| Brexpiprazole 3 mg Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 3 mg/day from Day 29. Participants continued to receive brexpiprazole 3 mg, once daily until Week 12. | 153 |
| Placebo Participants received matching placebo, once daily for 12 weeks. | 117 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 11 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Non-compliance with Study Drug | 0 | 1 | 0 |
| Overall Study | Reason not Specified (Not Related to Coronavirus Disease 2019 [COVID-19]) | 0 | 2 | 2 |
| Overall Study | Site Terminated by Sponsor | 1 | 3 | 2 |
| Overall Study | Subject Withdrew Consent to Participate | 5 | 5 | 3 |
Baseline characteristics
| Characteristic | Total | Brexpiprazole 2 mg | Brexpiprazole 3 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 74.0 years STANDARD_DEVIATION 7.5 | 74.3 years STANDARD_DEVIATION 7.3 | 74.6 years STANDARD_DEVIATION 8 | 73.0 years STANDARD_DEVIATION 7 |
| Cohen-Mansfield Agitation Inventory (CMAI) Total Score | 80 score on a scale STANDARD_DEVIATION 17 | 78.6 score on a scale STANDARD_DEVIATION 15.5 | 81.2 score on a scale STANDARD_DEVIATION 17.2 | 79.4 score on a scale STANDARD_DEVIATION 17.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 108 Participants | 25 Participants | 46 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 50 Participants | 107 Participants | 80 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 | 4 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 5 Participants | 6 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 329 Participants | 70 Participants | 144 Participants | 115 Participants |
| Sex: Female, Male Female | 195 Participants | 43 Participants | 92 Participants | 60 Participants |
| Sex: Female, Male Male | 150 Participants | 32 Participants | 61 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 1 / 153 | 0 / 117 |
| other Total, other adverse events | 5 / 73 | 10 / 153 | 8 / 116 |
| serious Total, serious adverse events | 0 / 73 | 6 / 153 | 3 / 116 |
Outcome results
Primary
Change From Baseline to Week 12 in the CMAI Total Score
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. Mixed model repeated measures (MMRM) was used for the analysis. As prespecified in the statistical analysis plan (SAP), data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline and Week 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in the CMAI Total Score | -22.6 score on a scale | Standard Error 1.08 |
| Placebo | Change From Baseline to Week 12 in the CMAI Total Score | -17.3 score on a scale | Standard Error 1.44 |
p-value: 0.002695% CI: [-8.77, -1.87]MMRM
Secondary
CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 2 | 4.98 percentage of participants |
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 4 | 21.8 percentage of participants |
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 6 | 35.1 percentage of participants |
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 8 | 44.4 percentage of participants |
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 10 | 52.4 percentage of participants |
| Brexpiprazole 2 and 3 mg | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 12 | 52.4 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 10 | 33.6 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 2 | 5.26 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 8 | 24.1 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 4 | 12.1 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 12 | 40.5 percentage of participants |
| Placebo | CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 6 | 23.3 percentage of participants |
Comparison: Week 2p-value: 0.854995% CI: [0.4, 3.03]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.009395% CI: [1.14, 3.32]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.008395% CI: [1.1, 2.22]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: <0.000195% CI: [1.32, 2.58]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.000595% CI: [1.18, 2.09]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.01695% CI: [1.03, 1.69]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period
CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 2 | -0.21 score on a scale | Standard Error 0.03 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 4 | -0.53 score on a scale | Standard Error 0.05 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 6 | -0.74 score on a scale | Standard Error 0.05 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 8 | -0.97 score on a scale | Standard Error 0.06 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 10 | -1.14 score on a scale | Standard Error 0.06 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 12 | -1.20 score on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 10 | -0.86 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 2 | -0.27 score on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 8 | -0.70 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 4 | -0.50 score on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 12 | -0.93 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period | Change From Baseline at Week 6 | -0.68 score on a scale | Standard Error 0.07 |
Comparison: Change from Baseline at Week 2p-value: 0.304895% CI: [-0.05, 0.16]MMRM
Comparison: Change from Baseline at Week 4p-value: 0.705895% CI: [-0.17, 0.12]MMRM
Comparison: Change from Baseline at Week 6p-value: 0.451695% CI: [-0.23, 0.1]MMRM
Comparison: Change from Baseline at Week 8p-value: 0.005295% CI: [-0.46, -0.08]MMRM
Comparison: Change from Baseline at Week 10p-value: 0.00695% CI: [-0.47, -0.08]MMRM
Comparison: Change from Baseline at Week 12p-value: 0.007895% CI: [-0.47, -0.07]MMRM
Secondary
Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 2 | -5.76 score on a scale | Standard Error 0.71 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 4 | -12.1 score on a scale | Standard Error 0.82 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 6 | -16.2 score on a scale | Standard Error 0.91 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 8 | -19.4 score on a scale | Standard Error 0.96 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 10 | -22.2 score on a scale | Standard Error 0.97 |
| Brexpiprazole 2 and 3 mg | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 12 | -22.6 score on a scale | Standard Error 1.08 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 10 | -15.7 score on a scale | Standard Error 1.29 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 2 | -6.61 score on a scale | Standard Error 0.9 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 8 | -14.4 score on a scale | Standard Error 1.28 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 4 | -11.0 score on a scale | Standard Error 1.06 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 12 | -17.3 score on a scale | Standard Error 1.44 |
| Placebo | Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period | Change From Baseline at Week 6 | -13.9 score on a scale | Standard Error 1.19 |
Comparison: Change From Baseline at Week 2p-value: 0.424295% CI: [-1.24, 2.93]MMRM
Comparison: Change From Baseline at Week 4p-value: 0.366595% CI: [-3.63, 1.34]MMRM
Comparison: Change from Baseline at Week 6p-value: 0.106595% CI: [-5.15, 0.5]MMRM
Comparison: Change from Baseline at Week 8p-value: 0.001195% CI: [-8.12, -2.05]MMRM
Comparison: Change from Baseline at Week 10p-value: <0.000195% CI: [-9.54, -3.4]MMRM
Comparison: Change from Baseline at Week 12p-value: 0.002695% CI: [-8.77, -1.87]MMRM
Secondary
Change From Baseline to Week 12 in CMAI Subscale Scores
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. It consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding, as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The four subscales include 12, 6, 4, and 2 items, respectively. The score of the subscale is the sum of the individual items included in the subscale, so the score range for each of the 4 subscales is 0 to 84, 0 to 42, 0 to 28, and 0 to 14, respectively. Higher scores indicate worsening of the condition. A negative change from baseline=improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline and Week 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in CMAI Subscale Scores | Aggressive Behavior | -9.09 score on a scale | Standard Error 0.42 |
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in CMAI Subscale Scores | Physically Nonaggressive Behavior | -6.45 score on a scale | Standard Error 0.4 |
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in CMAI Subscale Scores | Verbally Agitated Behavior | -4.39 score on a scale | Standard Error 0.31 |
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in CMAI Subscale Scores | Hiding and Hoarding | -1.50 score on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline to Week 12 in CMAI Subscale Scores | Hiding and Hoarding | -1.14 score on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to Week 12 in CMAI Subscale Scores | Aggressive Behavior | -7.13 score on a scale | Standard Error 0.56 |
| Placebo | Change From Baseline to Week 12 in CMAI Subscale Scores | Verbally Agitated Behavior | -3.14 score on a scale | Standard Error 0.4 |
| Placebo | Change From Baseline to Week 12 in CMAI Subscale Scores | Physically Nonaggressive Behavior | -5.04 score on a scale | Standard Error 0.53 |
Comparison: Aggressive Behaviorp-value: 0.00495% CI: [-3.28, -0.63]MMRM
Comparison: Physically Nonaggressive Behaviorp-value: 0.029695% CI: [-2.68, -0.14]MMRM
Comparison: Verbally Agitated Behaviorp-value: 0.011395% CI: [-2.21, -0.28]MMRM
Comparison: Hiding and Hoardingp-value: 0.194195% CI: [-0.9, 0.18]MMRM
Secondary
Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation
CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 0=not assessed; 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline and Week 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation | -1.20 score on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation | -0.93 score on a scale | Standard Error 0.08 |
p-value: 0.007895% CI: [-0.47, -0.07]MMRM
Secondary
Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period
CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 2 | 3.70 score on a scale | Standard Deviation 0.75 |
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 4 | 3.19 score on a scale | Standard Deviation 0.85 |
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 6 | 2.92 score on a scale | Standard Deviation 0.94 |
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 8 | 2.80 score on a scale | Standard Deviation 1 |
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 10 | 2.62 score on a scale | Standard Deviation 0.99 |
| Brexpiprazole 2 and 3 mg | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 12 | 2.66 score on a scale | Standard Deviation 1.09 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 10 | 2.97 score on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 2 | 3.57 score on a scale | Standard Deviation 0.69 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 8 | 3.16 score on a scale | Standard Deviation 1.01 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 4 | 3.39 score on a scale | Standard Deviation 0.87 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 12 | 2.97 score on a scale | Standard Deviation 1.12 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period | Week 6 | 3.19 score on a scale | Standard Deviation 0.95 |
Comparison: Week 2p-value: 0.197595% CI: [-0.05, 0.26]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.008495% CI: [-0.44, -0.06]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.010195% CI: [-0.46, -0.06]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: 0.000895% CI: [-0.59, -0.15]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.002395% CI: [-0.55, -0.12]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.00795% CI: [-0.57, -0.09]Cochran-Mantel-Haenszel
Secondary
CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 2 | 11.3 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 4 | 29.3 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 6 | 43.1 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 8 | 59.6 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 10 | 65.8 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 12 | 68.4 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 2 | 3.62 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 4 | 10.7 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 6 | 22.7 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 8 | 32.9 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 10 | 38.2 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 12 | 42.7 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 2 | 1.81 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 4 | 4.89 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 6 | 10.7 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 8 | 16.9 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 10 | 20.9 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 12 | 23.1 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 4 | 5.17 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 2 | 13.2 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 8 | 19.0 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 4 | 27.6 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 12 | 14.7 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 6 | 37.9 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 10 | 24.1 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 8 | 38.8 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 6 | 8.62 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 10 | 45.7 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 12 | 25.9 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 20%: Week 12 | 47.4 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 10 | 11.2 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 2 | 3.51 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 2 | 1.75 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 4 | 10.3 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 40%: Week 8 | 8.62 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period | >/= 30%: Week 6 | 20.7 percentage of participants |
Comparison: \>/= 20%: Week 2p-value: 0.72995% CI: [0.64, 1.91]Cochran-Mantel-Haenszel
Comparison: \>/=20%: Week 4p-value: 0.619695% CI: [0.78, 1.52]Cochran-Mantel-Haenszel
Comparison: \>/=20%: Week 6p-value: 0.271895% CI: [0.88, 1.53]Cochran-Mantel-Haenszel
Comparison: \>/=20%: Week 8p-value: 0.000495% CI: [1.19, 1.93]Cochran-Mantel-Haenszel
Comparison: \>/=20%: Week 10p-value: 0.000695% CI: [1.15, 1.76]Cochran-Mantel-Haenszel
Comparison: \>/=20%: Week 12p-value: 0.000495% CI: [1.15, 1.72]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 2p-value: 0.721195% CI: [0.39, 3.85]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 4p-value: 0.760695% CI: [0.57, 2.14]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 6p-value: 0.590295% CI: [0.74, 1.68]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 8p-value: 0.005495% CI: [1.14, 2.54]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 10p-value: 0.006695% CI: [1.11, 2.26]Cochran-Mantel-Haenszel
Comparison: \>/=30%: Week 12p-value: 0.001795% CI: [1.18, 2.23]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 2p-value: 0.907495% CI: [0.2, 5.97]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 4p-value: 0.962595% CI: [0.36, 2.64]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 6p-value: 0.51295% CI: [0.63, 2.53]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 8p-value: 0.024495% CI: [1.03, 3.79]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 10p-value: 0.016195% CI: [1.08, 3.18]Cochran-Mantel-Haenszel
Comparison: \>/=40%: Week 12p-value: 0.034795% CI: [1, 2.61]Cochran-Mantel-Haenszel
Secondary
CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period
The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Population: The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 2 | 8.14 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 4 | 20.4 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 6 | 33.8 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 8 | 44.0 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 10 | 50.2 percentage of participants |
| Brexpiprazole 2 and 3 mg | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 12 | 52.4 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 10 | 34.5 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 2 | 14.0 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 8 | 31.0 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 4 | 19.0 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 12 | 37.1 percentage of participants |
| Placebo | CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period | Week 6 | 26.7 percentage of participants |
Comparison: Week 2p-value: 0.150395% CI: [0.35, 1.16]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.755995% CI: [0.69, 1.67]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.224695% CI: [0.88, 1.72]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: 0.027695% CI: [1.02, 1.87]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.003195% CI: [1.12, 1.89]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.001795% CI: [1.14, 1.89]Cochran-Mantel-Haenszel