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

NCT03594123 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 331-201-00182
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Alzheimer's Disease

Keywords

Agitation

Outcome Measures

Primary Outcomes (1)

• 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.

  From first dose through 30 days after last dose of study drug (Up to approximately Week 16)

Study Arms (2)

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.

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.

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

2 or 3 mg tablet

Prior Brexpiprazole

Eligibility Criteria

• Age: 55 Years - 91 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Participants with a substantial protocol violation during the course of their participation in the double-blind trial 331-14-213.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (1)

For additional information regarding sites, contact 844-687-8522

Miami, Florida, 33155, United States

Location

Related Publications (3)

• Shah 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. 2026 Jan 14:1-3. doi: 10.1080/03007995.2025.2608578. Online ahead of print.

  PMID: 41533472 DERIVED

• Shah 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.

  PMID: 40681915 DERIVED

• Behl 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.

  PMID: 39534972 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Psychomotor Agitation

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: July 20, 2018
• Study Start: October 11, 2018
• Primary Completion: September 19, 2022
• Study Completion: September 19, 2022
• Last Updated: November 14, 2023
• Results First Posted: November 14, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

US (1)