Trial · NCT03548584

A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated With Dementia of the Alzheimer's Type

NCT03548584, Phase 3, Completed, Otsuka Pharmaceutical Development & Commercialization, Inc.; results first posted 2023-09-18

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated With Dementia of the Alzheimer's Type. Trials, record NCT03548584. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03548584

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated With Dementia of the Alzheimer's Type
NCT number: NCT03548584
Status: Completed
Phases: Phase 3
Enrollment: 345 participants, actual
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Conditions: Agitation Associated With Alzheimer's Dementia, Alzheimer Dementia
Interventions: Brexpiprazole, Placebo
First posted: 2018-06-07
Last updated: 2023-09-18
Results first posted: 2023-09-18

Source ClinicalTrials.gov

Registered outcomes9

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
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	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.
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	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.

Source ClinicalTrials.gov

Outcomes9

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline to Week 12 in the CMAI Total Score	Baseline and Week 12	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.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	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	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.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline to Week 12 in CMAI Subscale Scores	Baseline and Week 12	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.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	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 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.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	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	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.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	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	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.	score on a scale	MEAN
SECONDARY	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 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.	percentage of participants	NUMBER
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	Baseline, Weeks 2, 4, 6, 8, 10, and 12	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.	percentage of participants	NUMBER
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	Baseline, Weeks 2, 4, 6, 8, 10, and 12	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.	percentage of participants	NUMBER

Source ClinicalTrials.gov

Results by group108

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Change From Baseline to Week 12 in the CMAI Total Score	Brexpiprazole 2 and 3 mg		-22.6	Standard Error 1.08	score on a scale
Change From Baseline to Week 12 in the CMAI Total Score	Placebo		-17.3	Standard Error 1.44	score on a scale
Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation	Brexpiprazole 2 and 3 mg		-1.20	Standard Error 0.06	score on a scale
Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation	Placebo		-0.93	Standard Error 0.08	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Brexpiprazole 2 and 3 mg	Aggressive Behavior	-9.09	Standard Error 0.42	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Placebo	Aggressive Behavior	-7.13	Standard Error 0.56	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Brexpiprazole 2 and 3 mg	Physically Nonaggressive Behavior	-6.45	Standard Error 0.40	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Placebo	Physically Nonaggressive Behavior	-5.04	Standard Error 0.53	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Brexpiprazole 2 and 3 mg	Verbally Agitated Behavior	-4.39	Standard Error 0.31	score on a scale
Change From Baseline to Week 12 in CMAI Subscale Scores	Placebo	Verbally Agitated Behavior	-3.14	Standard Error 0.40	score on a scale

1 to 10 of 108Source ClinicalTrials.gov

See all 108 results by group

Participant flow12

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Brexpiprazole 2 mg	75
Overall Study	STARTED	Brexpiprazole 3 mg	153
Overall Study	STARTED	Placebo	117
Overall Study	Intent-to-treat Population	Brexpiprazole 2 mg	73
Overall Study	Intent-to-treat Population	Brexpiprazole 3 mg	153
Overall Study	Intent-to-treat Population	Placebo	116
Overall Study	COMPLETED	Brexpiprazole 2 mg	68
Overall Study	COMPLETED	Brexpiprazole 3 mg	130
Overall Study	COMPLETED	Placebo	104
Overall Study	NOT COMPLETED	Brexpiprazole 2 mg	7

1 to 10 of 12Source ClinicalTrials.gov

See all 12 participant flow

Adverse events45

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Headache	Nervous system disorders	Brexpiprazole 2 mg	5	73
other	Headache	Nervous system disorders	Brexpiprazole 3 mg	10	153
other	Headache	Nervous system disorders	Placebo	8	116
serious	Cardiac failure	Cardiac disorders	Brexpiprazole 2 mg	0	73
serious	Cardiac failure	Cardiac disorders	Brexpiprazole 3 mg	1	153
serious	Cardiac failure	Cardiac disorders	Placebo	0	116
serious	Covid-19	Infections and infestations	Brexpiprazole 2 mg	0	73
serious	Covid-19	Infections and infestations	Brexpiprazole 3 mg	1	153
serious	Covid-19	Infections and infestations	Placebo	0	116
serious	Pneumonia	Infections and infestations	Brexpiprazole 2 mg	0	73

1 to 10 of 45Source ClinicalTrials.gov

See all 45 adverse events

Adverse event totals9

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Brexpiprazole 2 mg	0	75
Total, all-cause mortality	Brexpiprazole 3 mg	1	153
Total, all-cause mortality	Placebo	0	117
Total, other adverse events	Brexpiprazole 2 mg	5	73
Total, other adverse events	Brexpiprazole 3 mg	10	153
Total, other adverse events	Placebo	8	116
Total, serious adverse events	Brexpiprazole 2 mg	0	73
Total, serious adverse events	Brexpiprazole 3 mg	6	153
Total, serious adverse events	Placebo	3	116

Source ClinicalTrials.gov

Papers12

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
37930669	DERIVED	PubMed
39108660	DERIVED	PubMed
40681915	DERIVED	PubMed
40847656	DERIVED	PubMed
41439450	DERIVED	PubMed
41533472	DERIVED	PubMed
41591746	DERIVED	PubMed
41689409	DERIVED	PubMed
41961243	DERIVED	PubMed
42052145	DERIVED	PubMed

1 to 10 of 12

See all 12 papers

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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