CompletedPhase 3Results posted

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

A Phase 3, 12-Week, Multicenter, Randomized, Double-blind, Placebo-controlled, 2-Arm, Fixed-dose Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Asset

Brexpiprazole

Listed sites

Recruiting sites

Enrollment

345

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 5-22•Study partner/caregiver required

Primary endpoint

•The CMAI Total Score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID331-14-213

NCT IDNCT03548584

Timeline

Milestones

Study start2018-05-16actual

Study first posted2018-06-07actual

Primary completion2022-05-23actual

Study completion2022-06-01actual

Last update posted2023-09-18actual

Results first posted2023-09-18actual

Assets

Drug assets

Brexpiprazole

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (18)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Other clinical outcomes

Other (unclassified)

Behavior / neuropsychiatric

14 endpoints

Primary/protocol endpoint

Change From Baseline to Week 12 in the CMAI Total Score

Time frame:Baseline and Week 12

change from baseline, improvement

Primary/registry result

Change From Baseline to Week 12 in the CMAI Total Score

Time frame:Baseline and Week 12

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Brexpiprazole 2 and 3 mgn=225 Participants	-22.6	1.08
Placebon=116 Participants	-17.3	1.44

LS Mean Difference-5.3295% CI-8.77 - -1.87p0.0026MMRM

Secondary/protocol endpoint

Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation

Time frame:Baseline and Week 12

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 12 in CMAI Subscale Scores

Time frame:Baseline and Week 12

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation

Time frame:Baseline and Week 12

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Brexpiprazole 2 and 3 mgn=225 Participants	-1.20	0.06
Placebon=116 Participants	-0.93	0.08

LS Mean Difference-0.2795% CI-0.47 - -0.07p0.0078MMRM

Secondary/protocol endpoint

Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 12 in CMAI Subscale Scores

Time frame:Baseline and Week 12

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Brexpiprazole 2 and 3 mgAggressive Behaviorn=225 Participants	-9.09	0.42
Physically Nonaggressive Behaviorn=225 Participants	-6.45	0.40
Verbally Agitated Behaviorn=225 Participants	-4.39	0.31
Hiding and Hoardingn=225 Participants	-1.50	0.17
PlaceboAggressive Behaviorn=116 Participants	-7.13	0.56
Physically Nonaggressive Behaviorn=116 Participants	-5.04	0.53
Verbally Agitated Behaviorn=116 Participants	-3.14	0.40
Hiding and Hoardingn=116 Participants	-1.14	0.23

LS Mean Difference-1.9595% CI-3.28 - -0.63p0.0040MMRM

Aggressive Behavior

LS Mean Difference-1.4195% CI-2.68 - -0.14p0.0296MMRM

Physically Nonaggressive Behavior

LS Mean Difference-1.2495% CI-2.21 - -0.28p0.0113MMRM

Verbally Agitated Behavior

LS Mean Difference-0.3695% CI-0.90 - 0.18p0.1941MMRM

Hiding and Hoarding

Secondary/protocol endpoint

Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

change from baseline, improvement

Secondary/registry result

Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Brexpiprazole 2 and 3 mgChange From Baseline at Week 2n=225 Participants	-5.76	0.71
Change From Baseline at Week 4n=225 Participants	-12.1	0.82
Change From Baseline at Week 6n=225 Participants	-16.2	0.91
Change From Baseline at Week 8n=225 Participants	-19.4	0.96
Change From Baseline at Week 10n=225 Participants	-22.2	0.97
Change From Baseline at Week 12n=225 Participants	-22.6	1.08
PlaceboChange From Baseline at Week 2n=116 Participants	-6.61	0.90
Change From Baseline at Week 4n=116 Participants	-11.0	1.06
Change From Baseline at Week 6n=116 Participants	-13.9	1.19
Change From Baseline at Week 8n=116 Participants	-14.4	1.28
Change From Baseline at Week 10n=116 Participants	-15.7	1.29
Change From Baseline at Week 12n=116 Participants	-17.3	1.44

LS Mean Difference0.8595% CI-1.24 - 2.93p0.4242MMRM

Change From Baseline at Week 2

LS Mean Difference-1.1495% CI-3.63 - 1.34p0.3665MMRM

Change From Baseline at Week 4

LS Mean Difference-2.3295% CI-5.15 - 0.50p0.1065MMRM

Change from Baseline at Week 6

LS Mean Difference-5.0895% CI-8.12 - -2.05p0.0011MMRM

Change from Baseline at Week 8

LS Mean Difference-6.4795% CI-9.54 - -3.40p<.0001MMRM

Change from Baseline at Week 10

LS Mean Difference-5.3295% CI-8.77 - -1.87p0.0026MMRM

Change from Baseline at Week 12

Secondary/registry result

Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Brexpiprazole 2 and 3 mgChange From Baseline at Week 2n=225 Participants	-0.21	0.03
Change From Baseline at Week 4n=225 Participants	-0.53	0.05
Change From Baseline at Week 6n=225 Participants	-0.74	0.05
Change From Baseline at Week 8n=225 Participants	-0.97	0.06
Change From Baseline at Week 10n=225 Participants	-1.14	0.06
Change From Baseline at Week 12n=225 Participants	-1.20	0.06
PlaceboChange From Baseline at Week 2n=116 Participants	-0.27	0.04
Change From Baseline at Week 4n=116 Participants	-0.50	0.06
Change From Baseline at Week 6n=116 Participants	-0.68	0.07
Change From Baseline at Week 8n=116 Participants	-0.70	0.08
Change From Baseline at Week 10n=116 Participants	-0.86	0.08
Change From Baseline at Week 12n=116 Participants	-0.93	0.08

LS Mean Difference0.0595% CI-0.05 - 0.16p0.3048MMRM

Change from Baseline at Week 2

LS Mean Difference-0.0395% CI-0.17 - 0.12p0.7058MMRM

Change from Baseline at Week 4

LS Mean Difference-0.0695% CI-0.23 - 0.10p0.4516MMRM

Change from Baseline at Week 6

LS Mean Difference-0.2795% CI-0.46 - -0.08p0.0052MMRM

Change from Baseline at Week 8

LS Mean Difference-0.2795% CI-0.47 - -0.08p0.0060MMRM

Change from Baseline at Week 10

LS Mean Difference-0.2795% CI-0.47 - -0.07p0.0078MMRM

Change from Baseline at Week 12

Secondary/protocol endpoint

CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period

Time frame:Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Secondary/registry result

CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period

Time frame:Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Brexpiprazole 2 and 3 mg>/= 20%: Week 2n=221 Participants	11.3	-
>/= 20%: Week 4n=225 Participants	29.3	-
>/= 20%: Week 6n=225 Participants	43.1	-
>/= 20%: Week 8n=225 Participants	59.6	-
>/= 20%: Week 10n=225 Participants	65.8	-
>/= 20%: Week 12n=225 Participants	68.4	-
>/= 30%: Week 2n=221 Participants	3.62	-
>/= 30%: Week 4n=225 Participants	10.7	-
>/= 30%: Week 6n=225 Participants	22.7	-
>/= 30%: Week 8n=225 Participants	32.9	-
>/= 30%: Week 10n=225 Participants	38.2	-
>/= 30%: Week 12n=225 Participants	42.7	-
>/= 40%: Week 2n=221 Participants	1.81	-
>/= 40%: Week 4n=225 Participants	4.89	-
>/= 40%: Week 6n=225 Participants	10.7	-
>/= 40%: Week 8n=225 Participants	16.9	-
>/= 40%: Week 10n=225 Participants	20.9	-
>/= 40%: Week 12n=225 Participants	23.1	-
Placebo>/= 20%: Week 2n=114 Participants	13.2	-
>/= 20%: Week 4n=116 Participants	27.6	-
>/= 20%: Week 6n=116 Participants	37.9	-
>/= 20%: Week 8n=116 Participants	38.8	-
>/= 20%: Week 10n=116 Participants	45.7	-
>/= 20%: Week 12n=116 Participants	47.4	-
>/= 30%: Week 2n=114 Participants	3.51	-
>/= 30%: Week 4n=116 Participants	10.3	-
>/= 30%: Week 6n=116 Participants	20.7	-
>/= 30%: Week 8n=116 Participants	19.0	-
>/= 30%: Week 10n=116 Participants	24.1	-
>/= 30%: Week 12n=116 Participants	25.9	-
>/= 40%: Week 2n=114 Participants	1.75	-
>/= 40%: Week 4n=116 Participants	5.17	-
>/= 40%: Week 6n=116 Participants	8.62	-
>/= 40%: Week 8n=116 Participants	8.62	-
>/= 40%: Week 10n=116 Participants	11.2	-
>/= 40%: Week 12n=116 Participants	14.7	-

Ratio of Response Rate1.1095% CI0.64 - 1.91p0.7290Cochran-Mantel-Haenszel

\>/= 20%: Week 2

Ratio of Response Rate1.0995% CI0.78 - 1.52p0.6196Cochran-Mantel-Haenszel

\>/=20%: Week 4

Ratio of Response Rate1.1695% CI0.88 - 1.53p0.2718Cochran-Mantel-Haenszel

\>/=20%: Week 6

Ratio of Response Rate1.5295% CI1.19 - 1.93p0.0004Cochran-Mantel-Haenszel

\>/=20%: Week 8

Ratio of Response Rate1.4295% CI1.15 - 1.76p0.0006Cochran-Mantel-Haenszel

\>/=20%: Week 10

Ratio of Response Rate1.4195% CI1.15 - 1.72p0.0004Cochran-Mantel-Haenszel

\>/=20%: Week 12

Ratio of Response Rate1.2295% CI0.39 - 3.85p0.7211Cochran-Mantel-Haenszel

\>/=30%: Week 2

Ratio of Response Rate1.1195% CI0.57 - 2.14p0.7606Cochran-Mantel-Haenszel

\>/=30%: Week 4

Ratio of Response Rate1.1295% CI0.74 - 1.68p0.5902Cochran-Mantel-Haenszel

\>/=30%: Week 6

Ratio of Response Rate1.7095% CI1.14 - 2.54p0.0054Cochran-Mantel-Haenszel

\>/=30%: Week 8

Ratio of Response Rate1.5995% CI1.11 - 2.26p0.0066Cochran-Mantel-Haenszel

\>/=30%: Week 10

Ratio of Response Rate1.6295% CI1.18 - 2.23p0.0017Cochran-Mantel-Haenszel

\>/=30%: Week 12

Ratio of Response Rate1.1195% CI0.20 - 5.97p0.9074Cochran-Mantel-Haenszel

\>/=40%: Week 2

Ratio of Response Rate0.9895% CI0.36 - 2.64p0.9625Cochran-Mantel-Haenszel

\>/=40%: Week 4

Ratio of Response Rate1.2695% CI0.63 - 2.53p0.5120Cochran-Mantel-Haenszel

\>/=40%: Week 6

Ratio of Response Rate1.9895% CI1.03 - 3.79p0.0244Cochran-Mantel-Haenszel

\>/=40%: Week 8

Ratio of Response Rate1.8695% CI1.08 - 3.18p0.0161Cochran-Mantel-Haenszel

\>/=40%: Week 10

Ratio of Response Rate1.6295% CI1.00 - 2.61p0.0347Cochran-Mantel-Haenszel

\>/=40%: Week 12

Secondary/registry result

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

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Brexpiprazole 2 and 3 mgWeek 2n=221 Participants	8.14	-
Week 4n=225 Participants	20.4	-
Week 6n=225 Participants	33.8	-
Week 8n=225 Participants	44.0	-
Week 10n=225 Participants	50.2	-
Week 12n=225 Participants	52.4	-
PlaceboWeek 2n=114 Participants	14.0	-
Week 4n=116 Participants	19.0	-
Week 6n=116 Participants	26.7	-
Week 8n=116 Participants	31.0	-
Week 10n=116 Participants	34.5	-
Week 12n=116 Participants	37.1	-

Ratio of Response Rate0.6495% CI0.35 - 1.16p0.1503Cochran-Mantel-Haenszel

Week 2

Ratio of Response Rate1.0795% CI0.69 - 1.67p0.7559Cochran-Mantel-Haenszel

Week 4

Ratio of Response Rate1.2395% CI0.88 - 1.72p0.2246Cochran-Mantel-Haenszel

Week 6

Ratio of Response Rate1.3895% CI1.02 - 1.87p0.0276Cochran-Mantel-Haenszel

Week 8

Ratio of Response Rate1.4695% CI1.12 - 1.89p0.0031Cochran-Mantel-Haenszel

Week 10

Ratio of Response Rate1.4795% CI1.14 - 1.89p0.0017Cochran-Mantel-Haenszel

Week 12

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Secondary/registry result

CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Brexpiprazole 2 and 3 mgWeek 2n=221 Participants	4.98	-
Week 4n=225 Participants	21.8	-
Week 6n=225 Participants	35.1	-
Week 8n=225 Participants	44.4	-
Week 10n=225 Participants	52.4	-
Week 12n=225 Participants	52.4	-
PlaceboWeek 2n=114 Participants	5.26	-
Week 4n=116 Participants	12.1	-
Week 6n=116 Participants	23.3	-
Week 8n=116 Participants	24.1	-
Week 10n=116 Participants	33.6	-
Week 12n=116 Participants	40.5	-

Ratio of Response Rate1.1095% CI0.40 - 3.03p0.8549Cochran-Mantel-Haenszel

Week 2

Ratio of Response Rate1.9595% CI1.14 - 3.32p0.0093Cochran-Mantel-Haenszel

Week 4

Ratio of Response Rate1.5695% CI1.10 - 2.22p0.0083Cochran-Mantel-Haenszel

Week 6

Ratio of Response Rate1.8595% CI1.32 - 2.58p<.0001Cochran-Mantel-Haenszel

Week 8

Ratio of Response Rate1.5795% CI1.18 - 2.09p0.0005Cochran-Mantel-Haenszel

Week 10

Ratio of Response Rate1.3295% CI1.03 - 1.69p0.0160Cochran-Mantel-Haenszel

Week 12

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

descriptive

Secondary/registry result/low confidence

Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period

Time frame:Baseline, Weeks 2, 4, 6, 8, 10, and 12

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Brexpiprazole 2 and 3 mgWeek 2n=221 Participants	3.70	0.75
Week 4n=225 Participants	3.19	0.85
Week 6n=225 Participants	2.92	0.94
Week 8n=225 Participants	2.80	1.00
Week 10n=225 Participants	2.62	0.99
Week 12n=225 Participants	2.66	1.09
PlaceboWeek 2n=114 Participants	3.57	0.69
Week 4n=116 Participants	3.39	0.87
Week 6n=116 Participants	3.19	0.95
Week 8n=116 Participants	3.16	1.01
Week 10n=116 Participants	2.97	1.00
Week 12n=116 Participants	2.97	1.12

Mean Difference (Final Values)0.1095% CI-0.05 - 0.26p0.1975Cochran-Mantel-Haenszel

Week 2

Mean Difference (Final Values)-0.2595% CI-0.44 - -0.06p0.0084Cochran-Mantel-Haenszel

Week 4

Mean Difference (Final Values)-0.2695% CI-0.46 - -0.06p0.0101Cochran-Mantel-Haenszel

Week 6

Mean Difference (Final Values)-0.3795% CI-0.59 - -0.15p0.0008Cochran-Mantel-Haenszel

Week 8

Mean Difference (Final Values)-0.3495% CI-0.55 - -0.12p0.0023Cochran-Mantel-Haenszel

Week 10

Mean Difference (Final Values)-0.3395% CI-0.57 - -0.09p0.0070Cochran-Mantel-Haenszel

Week 12

Publications (10)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.