Agitation Associated With Alzheimer's DementiaPhase 3NCT03548584
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 study testing Brexpiprazole in people with Agitation Associated With Alzheimer's Dementia and Alzheimer Dementia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 90 years
- Conditions the study is for
- Agitation Associated With Alzheimer's Dementia, Alzheimer Dementia
- What is being tested?
- Brexpiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 345 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2018to 1 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
For additional information regarding sites, contact 844-687-8522
Los Angeles, California, 90036
About this study
Official title: 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
This study compares the efficacy of 2 doses of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type.
Read the 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.
- Being tested
- Brexpiprazole, Placebo
- Keywords
- Agitation
- Medical subject headings
- Alzheimer Disease, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called OPC-34712
Oral tablets
PlaceboOther
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Brexpiprazole 2 mg | Experimental | Participants followed a titration schedule, to gradually increase their dose from 0.5 milligrams per day (mg/day) in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 milligrams (mg), once daily until Week 12. Receives: Drug: Brexpiprazole |
| Brexpiprazole 3 mg | Experimental | 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. Receives: Drug: Brexpiprazole |
| Placebo | Placebo comparator | Participants received matching placebo, once daily for 12 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (8)
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline, Weeks 2, 4, 6, 8, 10, and 12
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.
Measured: Baseline, Weeks 2, 4, 6, 8, 10, and 12
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.
Measured: Baseline, Weeks 2, 4, 6, 8, 10, and 12
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.
Measured: Weeks 2, 4, 6, 8, 10, and 12
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.
Measured: Baseline, Weeks 2, 4, 6, 8, 10, and 12
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.
Measured: Baseline, Weeks 2, 4, 6, 8, 10, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2018
- Study start16 May 2018
- Primary completion23 May 2022
- Study completion1 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Agitation Associated With Alzheimer's DementiaStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 345 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03548584
- Sponsor's protocol ID
- 331-14-213
- Status last verified
- Sep 2023
- First submitted
- 7 May 2018
- Last updated
- 18 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Publications
Porsteinsson AP, Chumki SR, Palma AM, Zhang Z, Wang D, Such P, Montano CB. Brexpiprazole for Individual Agitation Symptoms in Alzheimer's Dementia: A Caregiver-Centered Post Hoc Analysis. Neurol Ther. 2026 Oct 16. doi: 10.1007/s40120-026-01037-4. Online ahead of print.
PubMed 42888370Montano CB, Chumki SR, Wang D, Palma AM, Zhang Z, Porsteinsson AP. Brexpiprazole With Antidepressants for Agitation in Alzheimer's Dementia: Post Hoc Analysis. Am J Geriatr Psychiatry. 2026 Jun 30:S1064-7481(26)00450-1. doi: 10.1016/j.jagp.2026.06.015. Online ahead of print.
PubMed 42502037Tariot PN, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Montano CB. Brexpiprazole for Agitation in Patients with Alzheimer's Dementia with and without Co-Occurring Psychosis: Post Hoc Analysis of Short- and Long-Term Trials. Neuropsychiatr Dis Treat. 2026 Apr 21;22:586701. doi: 10.2147/NDT.S586701. eCollection 2026.
PubMed 42052145Porsteinsson AP, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Shah A, Kalu U, Montano CB. Short-Term and Long-Term Safety Analyses of Brexpiprazole for Agitation Associated with Dementia due to Alzheimer's Disease: Timing and Duration of Adverse Events. Drug Saf. 2026 Aug;49(8):969-983. doi: 10.1007/s40264-026-01670-w. Epub 2026 Apr 10.
PubMed 41961243Stroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Grossberg GT. Brexpiprazole for treating agitation in different groups of people with Alzheimer's dementia: a plain language summary. Neurodegener Dis Manag. 2026 Apr;16(2):113-121. doi: 10.1080/17582024.2026.2623968. Epub 2026 Feb 14.
PubMed 41689409Cummings JL, Chumki SR, Chang D, Zhang Z, Brubaker M, Hefting N, Such P, Wang D, Grossberg GT. Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials. Clin Drug Investig. 2026 Mar;46(3):281-292. doi: 10.1007/s40261-025-01517-9. Epub 2026 Jan 27.
PubMed 41591746Shah A, Kalu U, Chen D, Slomkowski M, Hobart M, Such P, Grossberg GT. Brexpiprazole side-effect profile in people with agitation in Alzheimer's dementia: a plain language summary. Curr Med Res Opin. 2025 Dec;41(12):2369-2377. doi: 10.1080/03007995.2025.2608578. Epub 2026 Jan 14.
PubMed 41533472Grossberg GT, Sabbagh MN, Chumki SR, Wang D, Such P, Zhang Z, Palma AM, Cummings JL. Efficacy of Brexpiprazole on Neuropsychiatric Symptoms and Impact on Caregivers: Pooled Neuropsychiatric Inventory (NPI) Analysis in Patients With Agitation Associated With Dementia due to Alzheimer's Disease. J Geriatr Psychiatry Neurol. 2026 Sep;39(5):589-601. doi: 10.1177/08919887251407124. Epub 2025 Dec 24.
PubMed 41439450Stroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Brubaker M, Grossberg GT. Brexpiprazole for agitation in clinically relevant patient subgroups: a post hoc analysis of efficacy and safety in patients with agitation associated with dementia due to Alzheimer's disease. Curr Med Res Opin. 2025 Aug;41(8):1523-1534. doi: 10.1080/03007995.2025.2552278. Epub 2025 Sep 5.
PubMed 40847656Shah A, Estilo A, Sheridan PL, Kalu U, Chen D, Chang D, Slomkowski M, Lee D, Hefting N, Hobart M, Behl S, Such P, Brubaker M, Grossberg GT. Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial. CNS Drugs. 2025 Oct;39(10):1011-1023. doi: 10.1007/s40263-025-01200-9. Epub 2025 Jul 19.
PubMed 40681915Meunier J, Creel K, Loubert A, Larsen KG, Aggarwal J, Hefting N, Oberdhan D. Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer's dementia. Front Neurol. 2024 Jul 23;15:1379062. doi: 10.3389/fneur.2024.1379062. eCollection 2024.
PubMed 39108660Lee D, Slomkowski M, Hefting N, Chen D, Larsen KG, Kohegyi E, Hobart M, Cummings JL, Grossberg GT. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. 2023 Dec 1;80(12):1307-1316. doi: 10.1001/jamaneurol.2023.3810.
PubMed 37930669
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03548584
- Acronym / sponsor ID
- 331-14-213
- Keywords
- Agitation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 345 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- 16 May 2018 (actual)
- Primary completion
- 23 May 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 7 Jun 2018 (actual)
- Results
- Posted 18 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Brexpiprazole 2 mg | Experimental | Drug: BrexpiprazoleParticipants followed a titration schedule, to gradually increase their dose from 0.5 milligrams per day (mg/day) in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 milligrams (mg), once daily until Week 12. |
| Brexpiprazole 3 mg | Experimental | Drug: BrexpiprazoleParticipants 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. |
| Placebo | Placebo comparator | Other: PlaceboParticipants received matching placebo, once daily for 12 weeks. |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrexpiprazoleAlso: OPC-34712Oral tablets | Drug | Brexpiprazole 2 mg, Brexpiprazole 3 mg |
| PlaceboOral tablets | Other | Placebo |
Primary outcome
Change From Baseline to Week 12 in the CMAI Total Score
Time frame: 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.
8 secondary outcomes
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 to Week 12 in CMAI Subscale Scores
Time frame: Baseline and Week 12
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 in CGI-S for Each Trial Visit During the Double-Blind Treatment Period
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42888370Porsteinsson AP, Chumki SR, Palma AM, Zhang Z, Wang D, Such P, Montano CB. Brexpiprazole for Individual Agitation Symptoms in Alzheimer's Dementia: A Caregiver-Centered Post Hoc Analysis. Neurol Ther. 2026 Oct 16. doi: 10.1007/s40120-026-01037-4. Online ahead of print.
- Derived from this study: PubMed 42502037Montano CB, Chumki SR, Wang D, Palma AM, Zhang Z, Porsteinsson AP. Brexpiprazole With Antidepressants for Agitation in Alzheimer's Dementia: Post Hoc Analysis. Am J Geriatr Psychiatry. 2026 Jun 30:S1064-7481(26)00450-1. doi: 10.1016/j.jagp.2026.06.015. Online ahead of print.
- Derived from this study: PubMed 42052145Tariot PN, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Montano CB. Brexpiprazole for Agitation in Patients with Alzheimer's Dementia with and without Co-Occurring Psychosis: Post Hoc Analysis of Short- and Long-Term Trials. Neuropsychiatr Dis Treat. 2026 Apr 21;22:586701. doi: 10.2147/NDT.S586701. eCollection 2026.
- Derived from this study: PubMed 41961243Porsteinsson AP, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Shah A, Kalu U, Montano CB. Short-Term and Long-Term Safety Analyses of Brexpiprazole for Agitation Associated with Dementia due to Alzheimer's Disease: Timing and Duration of Adverse Events. Drug Saf. 2026 Aug;49(8):969-983. doi: 10.1007/s40264-026-01670-w. Epub 2026 Apr 10.
- Derived from this study: PubMed 41689409Stroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Grossberg GT. Brexpiprazole for treating agitation in different groups of people with Alzheimer's dementia: a plain language summary. Neurodegener Dis Manag. 2026 Apr;16(2):113-121. doi: 10.1080/17582024.2026.2623968. Epub 2026 Feb 14.
- Derived from this study: PubMed 41591746Cummings JL, Chumki SR, Chang D, Zhang Z, Brubaker M, Hefting N, Such P, Wang D, Grossberg GT. Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials. Clin Drug Investig. 2026 Mar;46(3):281-292. doi: 10.1007/s40261-025-01517-9. Epub 2026 Jan 27.
- Derived from this study: PubMed 41533472Shah A, Kalu U, Chen D, Slomkowski M, Hobart M, Such P, Grossberg GT. Brexpiprazole side-effect profile in people with agitation in Alzheimer's dementia: a plain language summary. Curr Med Res Opin. 2025 Dec;41(12):2369-2377. doi: 10.1080/03007995.2025.2608578. Epub 2026 Jan 14.
- Derived from this study: PubMed 41439450Grossberg GT, Sabbagh MN, Chumki SR, Wang D, Such P, Zhang Z, Palma AM, Cummings JL. Efficacy of Brexpiprazole on Neuropsychiatric Symptoms and Impact on Caregivers: Pooled Neuropsychiatric Inventory (NPI) Analysis in Patients With Agitation Associated With Dementia due to Alzheimer's Disease. J Geriatr Psychiatry Neurol. 2026 Sep;39(5):589-601. doi: 10.1177/08919887251407124. Epub 2025 Dec 24.
- Derived from this study: PubMed 40847656Stroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Brubaker M, Grossberg GT. Brexpiprazole for agitation in clinically relevant patient subgroups: a post hoc analysis of efficacy and safety in patients with agitation associated with dementia due to Alzheimer's disease. Curr Med Res Opin. 2025 Aug;41(8):1523-1534. doi: 10.1080/03007995.2025.2552278. Epub 2025 Sep 5.
- Derived from this study: PubMed 40681915Shah A, Estilo A, Sheridan PL, Kalu U, Chen D, Chang D, Slomkowski M, Lee D, Hefting N, Hobart M, Behl S, Such P, Brubaker M, Grossberg GT. Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial. CNS Drugs. 2025 Oct;39(10):1011-1023. doi: 10.1007/s40263-025-01200-9. Epub 2025 Jul 19.
- Derived from this study: PubMed 39108660Meunier J, Creel K, Loubert A, Larsen KG, Aggarwal J, Hefting N, Oberdhan D. Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer's dementia. Front Neurol. 2024 Jul 23;15:1379062. doi: 10.3389/fneur.2024.1379062. eCollection 2024.
- Derived from this study: PubMed 37930669Lee D, Slomkowski M, Hefting N, Chen D, Larsen KG, Kohegyi E, Hobart M, Cummings JL, Grossberg GT. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. 2023 Dec 1;80(12):1307-1316. doi: 10.1001/jamaneurol.2023.3810.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brexpiprazole in people with Agitation Associated With Alzheimer's Dementia and Alzheimer Dementia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 12 in the CMAI Total Score (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03548584, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2023.