Agitation Associated With Dementia of the Alzheimer's TypePhase 2/3NCT03620981
Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type
A Phase 2/3 study testing Brexpiprazole in people with Agitation Associated With Dementia of the Alzheimer's Type, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.
Trial summary
To evaluate the superiority of brexpiprazole 1 mg or 2 mg over placebo after a 10-week treatment regimen for agitation associated with dementia of the Alzheimer's type in patients who require medication, and to investigate the safety of brexpiprazole and identify the optimum dose. Read more about this study
- Who is it for?
- Ages 55 to 90 years
- Conditions the study is for
- Agitation Associated With Dementia of the Alzheimer's Type
- 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
- 410 participants
- Where
- 1 siteJapan
- Study dates
- 20 Aug 2018to 15 May 2023
- Phase
- Phase 2/3
- 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
- Patients who satisfy both of the following diagnostic criteria:
- Diagnosis of "Dementia due to Alzheimer's Disease" according to DSM-5.
- Diagnosis of "Probable Alzheimer's Disease" according to NINCDS-ADRDA.
- Hospitalized patients or care facility patients or care at home patients
- Patients with an MMSE score of 1 to 22
- Patients who have the agitation defined according to the "Consensus provisional definition of agitation in cognitive disorders" from the International Psychogeriatric Association (IPA)
Who cannot join
- Patients who have dementia other than dementia of the Alzheimer's type
- Patients diagnosed with delirium between 30 days before the screening examination and baseline evaluation according to DSM-5.
- Patients diagnosed with any of the following disorders according to DSM-5:
- Schizophrenia spectrum and other psychotic disorders
- Bipolar and related disorders
- Major depressive disorder
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2/3 Multicenter, Placebo-controlled, Randomized, Double-blind, Parallel-group Comparison Trial to Evaluate the Efficacy and Safety of Brexpiprazole (OPC-34712) in the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type
To evaluate the superiority of brexpiprazole 1 mg or 2 mg over placebo after a 10-week treatment regimen for agitation associated with dementia of the Alzheimer's type in patients who require medication, and to investigate the safety of brexpiprazole and identify the optimum dose.
- Being tested
- Brexpiprazole, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Drug: 1 tablet /day Once daily for 10 weeks
PlaceboDrug
Placebo: 1 tablet /day Once daily for 10 weeks
| Study group | Role | What they receive |
|---|---|---|
| Brexpiprazole, 1mg/day | Experimental | Drug: 1mg/day Once daily for 10 weeks Receives: Drug: Brexpiprazole |
| Brexpiprazole, 2mg/day | Experimental | Drug: 2mg/day Once daily for 10 weeks Receives: Drug: Brexpiprazole |
| Placebo | Placebo comparator | Drug: Placebo (0mg/day) Once daily for 10 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Cohen-Manfield Agitation Inventory(CMAI) Score at 10 Weeks After Dosing.
The CMAI assessed the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consisted of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score was 29, and the maximum possible CMAI total score was 203. A decrease in score indicated improvement in symptoms.
Measured: Baseline and 10 weeks first dose, on average 10 weeks
Secondary outcomes (2)
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 10 Weeks After Dosing.
The CGI-S was used to rate the severity of agitation. Scores were: 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. A decrease in score indicated improvement in symptoms.
Measured: Baseline and 10 weeks first dose, on average 10 weeks
Clinical Global Impression of Improvement (CGI-I) Score at 10 Weeks After Dosing.
The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition.
Measured: Baseline and 10 weeks first dose, on average 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start20 Aug 2018
- Primary completion21 Apr 2023
- Study completion15 May 2023
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 (2)Papers the sponsor has linked to this study.
- Other trials for Agitation Associated With Dementia of the Alzheimer's TypeStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Co., Ltd.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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 410 participants (actual)
Sponsor and investigators
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03620981
- Sponsor's protocol ID
- 331-102-00088
- Status last verified
- Apr 2024
- First submitted
- 5 Aug 2018
- Last updated
- 14 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- 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.
Publications
Nakamura Y, Seiyama Y, Shimizu K, Shibasaki Y, Toda R, Nakamichi N, Adachi J, Hirota N, Nakai M, Takahashi K. Impact of dementia severity on efficacy of brexpiprazole for agitation in Alzheimer's dementia: A post hoc analysis of a randomized, double-blind, placebo-controlled study in Japan. J Alzheimers Dis. 2026 Oct 8:13872877261493010. doi: 10.1177/13872877261493010. Online ahead of print.
PubMed 42847294Nakamura Y, Adachi J, Hirota N, Iba K, Sasajima C, Shimizu K, Nakai M, Takahashi K. Brexpiprazole's impacts on patients and caregivers in agitation in Alzheimer's dementia. Alzheimers Dement. 2025 Jul;21(7):e70522. doi: 10.1002/alz.70522.
PubMed 40717666
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3 Multicenter, Placebo-controlled, Randomized, Double-blind, Parallel-group Comparison Trial to Evaluate the Efficacy and Safety of Brexpiprazole (OPC-34712) in the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type
- ClinicalTrials.gov ID
- NCT03620981
- Acronym / sponsor ID
- 331-102-00088
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 410 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 20 Aug 2018 (actual)
- Primary completion
- 21 Apr 2023 (actual)
- Study completion
- 15 May 2023 (actual)
- First posted
- 8 Aug 2018 (actual)
- Results
- Posted 14 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the superiority of brexpiprazole 1 mg or 2 mg over placebo after a 10-week treatment regimen for agitation associated with dementia of the Alzheimer's type in patients who require medication, and to investigate the safety of brexpiprazole and identify the optimum dose.
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, 1mg/day | Experimental | Drug: BrexpiprazoleDrug: 1mg/day Once daily for 10 weeks |
| Brexpiprazole, 2mg/day | Experimental | Drug: BrexpiprazoleDrug: 2mg/day Once daily for 10 weeks |
| Placebo | Placebo comparator | Drug: PlaceboDrug: Placebo (0mg/day) Once daily for 10 weeks |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients who satisfy both of the following diagnostic criteria:
- Hospitalized patients or care facility patients or care at home patients
- Patients with an MMSE score of 1 to 22
- Patients who have the agitation defined according to the "Consensus provisional definition of agitation in cognitive disorders" from the International Psychogeriatric Association (IPA)
Key exclusion criteria (6 listed)
- Patients who have dementia other than dementia of the Alzheimer's type
- Patients diagnosed with delirium between 30 days before the screening examination and baseline evaluation according to DSM-5.
- Patients diagnosed with any of the following disorders according to DSM-5:
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 |
|---|---|---|
| BrexpiprazoleDrug: 1 tablet /day Once daily for 10 weeks | Drug | Brexpiprazole, 1mg/day, Brexpiprazole, 2mg/day |
| PlaceboPlacebo: 1 tablet /day Once daily for 10 weeks | Drug | Placebo |
Primary outcome
Change From Baseline in Cohen-Manfield Agitation Inventory(CMAI) Score at 10 Weeks After Dosing.
Time frame: Baseline and 10 weeks first dose, on average 10 weeks
The CMAI assessed the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consisted of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score was 29, and the maximum possible CMAI total score was 203. A decrease in score indicated improvement in symptoms.
2 secondary outcomes
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 10 Weeks After Dosing.
Time frame: Baseline and 10 weeks first dose, on average 10 weeks
Clinical Global Impression of Improvement (CGI-I) Score at 10 Weeks After Dosing.
Time frame: Baseline and 10 weeks first dose, on average 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42847294Nakamura Y, Seiyama Y, Shimizu K, Shibasaki Y, Toda R, Nakamichi N, Adachi J, Hirota N, Nakai M, Takahashi K. Impact of dementia severity on efficacy of brexpiprazole for agitation in Alzheimer's dementia: A post hoc analysis of a randomized, double-blind, placebo-controlled study in Japan. J Alzheimers Dis. 2026 Oct 8:13872877261493010. doi: 10.1177/13872877261493010. Online ahead of print.
- Derived from this study: PubMed 40717666Nakamura Y, Adachi J, Hirota N, Iba K, Sasajima C, Shimizu K, Nakai M, Takahashi K. Brexpiprazole's impacts on patients and caregivers in agitation in Alzheimer's dementia. Alzheimers Dement. 2025 Jul;21(7):e70522. doi: 10.1002/alz.70522.
- 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.
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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 2/3 study testing Brexpiprazole in people with Agitation Associated With Dementia of the Alzheimer's Type, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.
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 6 inclusion and 6 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 14 Nov 2024. 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 Japan. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 14 Nov 2024). 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 in Cohen-Manfield Agitation Inventory(CMAI) Score at 10 Weeks After Dosing. (time frame: Baseline and 10 weeks first dose, on average 10 weeks). 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 NCT03620981, which also lists 2 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 14 Nov 2024.