Alzheimer's DiseasePhase 3NCT03594123
A 12-week Extension Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
A Phase 3 study testing Brexpiprazole in people with Alzheimer's Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial summary
Active treatment extension study of the 331-14-213 trial, to assess the long-term safety and tolerability of oral brexpiprazole as treatment in adult participants with agitation associated with dementia of the Alzheimer's type (AAD). Read more about this study
- Who is it for?
- Ages 55 to 91 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Brexpiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Oct 2018to 19 Sep 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 91 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have participated in the 331-14-213 study.
- Participants must have an identified caregiver who has contact, at a minimum of 2 hours per day, 4 days per week to describe the participant's symptoms and can observe participant behavior.
Who cannot join
- Participants with a substantial protocol violation during the course of their participation in the double-blind trial 331-14-213.
Trial locations and contacts
1 site in 1 country.
United States1 site
For additional information regarding sites, contact 844-687-8522
Miami, Florida, 33155
About this study
Official title: A 12-week, Multicenter, Active-treatment Extension Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
Active treatment extension study of the 331-14-213 trial, to assess the long-term safety and tolerability of oral brexpiprazole as treatment in adult participants with agitation associated with dementia of the Alzheimer's type (AAD).
- Conditions
- Alzheimer's Disease
- Being tested
- Brexpiprazole
- 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
2 or 3 mg tablet
BrexpiprazoleDrug
0.5 to 3 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| Prior Brexpiprazole | Experimental | Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), received the same dose of brexpiprazole [2 or 3 milligrams (mg)], once daily (QD), orally, as they received during the previous study, for up to 12 weeks with dose adjustment. Receives: Drug: Brexpiprazole |
| Prior Placebo | Experimental | Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. Receives: Drug: Brexpiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs with an onset date on or after the first dose of brexpiprazole. They are all adverse events that started after start of brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy.
Adverse events were graded on a 3-point scale. The intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.
Measured: From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start11 Oct 2018
- Primary completion19 Sep 2022
- Study completion19 Sep 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 (5)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 259 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
- NCT03594123
- Sponsor's protocol ID
- 331-201-00182
- Status last verified
- Oct 2023
- First submitted
- 11 Jul 2018
- Last updated
- 14 Nov 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 42888370Porsteinsson 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 41961243Shah 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 41533472Shah 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 40681915Behl S, Slomkowski M, Chen D, Chang D, Hefting N, Lee D, Shah A, Estilo A, Kalu U, Hobart M. Brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease: A 12-week, active-treatment, extension trial. J Alzheimers Dis. 2024 Nov;102(2):520-529. doi: 10.3233/JAD-240491. Epub 2024 Nov 13.
PubMed 39534972
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-week, Multicenter, Active-treatment Extension Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
- ClinicalTrials.gov ID
- NCT03594123
- Acronym / sponsor ID
- 331-201-00182
- Conditions
- Alzheimer's Disease
- Keywords
- Agitation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- 11 Oct 2018 (actual)
- Primary completion
- 19 Sep 2022 (actual)
- Study completion
- 19 Sep 2022 (actual)
- First posted
- 20 Jul 2018 (actual)
- Results
- Posted 14 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Active treatment extension study of the 331-14-213 trial, to assess the long-term safety and tolerability of oral brexpiprazole as treatment in adult participants with agitation associated with dementia of the Alzheimer's type (AAD).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prior Brexpiprazole | Experimental | Drug: BrexpiprazoleParticipants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), received the same dose of brexpiprazole [2 or 3 milligrams (mg)], once daily (QD), orally, as they received during the previous study, for up to 12 weeks with dose adjustment. |
| Prior Placebo | Experimental | Drug: BrexpiprazoleParticipants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. |
Who may qualify
- Ages
- 55 to 91 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants must have participated in the 331-14-213 study.
- Participants must have an identified caregiver who has contact, at a minimum of 2 hours per day, 4 days per week to describe the participant's symptoms and can observe participant behavior.
Key exclusion criteria (1 listed)
- Participants with a substantial protocol violation during the course of their participation in the double-blind trial 331-14-213.
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 |
|---|---|---|
| Brexpiprazole2 or 3 mg tablet | Drug | Prior Brexpiprazole |
| Brexpiprazole0.5 to 3 mg tablet | Drug | Prior Placebo |
Primary outcome
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
Time frame: From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs with an onset date on or after the first dose of brexpiprazole. They are all adverse events that started after start of brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy. Adverse events were graded on a 3-point scale. The intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 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 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 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 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 39534972Behl S, Slomkowski M, Chen D, Chang D, Hefting N, Lee D, Shah A, Estilo A, Kalu U, Hobart M. Brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease: A 12-week, active-treatment, extension trial. J Alzheimers Dis. 2024 Nov;102(2):520-529. doi: 10.3233/JAD-240491. Epub 2024 Nov 13.
- 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 Alzheimer's Disease, 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 2 inclusion and 1 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 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. 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 14 Nov 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?
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity (time frame: From first dose through 30 days after last dose of study drug (Up to approximately Week 16)). 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 NCT03594123, which also lists 5 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 2023.