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

• ClinicalTrials.gov Identifier: NCT03548584
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Last Update Posted: June 30, 2022
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborator: H. Lundbeck A/S
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

Brief Summary:

This study compares the efficacy of 2 doses of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type.

Condition or disease	Intervention/treatment	Phase
Agitation Associated With Alzheimer's Dementia; Alzheimer Dementia	Drug: Brexpiprazole; Other: Placebo	Phase 3

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 subjects 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 subject is not living alone. This trial will analyze data gathered from 330 subjects at multiple countries. Subjects may also be eligible to enter an active treatment extension trial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 345 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 16, 2018
• Actual Primary Completion Date: May 23, 2022
• Actual Study Completion Date: June 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose Brexpiprazole Arm; Tablet	Drug: Brexpiprazole; Tablet; Other Name: OPC-34712
Experimental: High Dose Brexpiprazole Arm; Tablet	Drug: Brexpiprazole; Tablet; Other Name: OPC-34712
Placebo Comparator: Placebo; Tablet	Other: Placebo; Tablet

Outcome Measures

Primary Outcome Measures :

1. Cohen-Mansfield Agitation Inventory (CMAI) total score [ Time Frame: From baseline to week 12 visit ]
   Change from baseline to Week 12; 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. The higher the value, the more frequent an agitated behavior has occurred.

Secondary Outcome Measures :

1. Clinical Global Impression Severity of Illness (CGI-S) score [ Time Frame: From baseline to week 12 visit ]
   Change from baseline to week 12, as related to agitation. CGI-S will be used to rate the severity of agitation. Score ranges from 0 (not assessed) to 7 (among the most extremely ill subjects). The higher the value, the more severe the agitation.

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects with a diagnosis of probable Alzheimer's disease.
• Subjects with a diagnosis of agitation
• Subjects with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.
• Subjects 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.
• Subjects 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 subjects with an identified caregiver who has sufficient contact (minimum of 2 hours per day for 4 days per week) to describe the subject's symptoms and has direct observation of the subject's behavior. Non-institutionalized subjects 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 subject's symptoms and has direct observation of the subject's behavior.
• Subjects with onset of symptoms of agitation at least 2 weeks prior to screening visit.
• Subjects will and able to discontinue all prohibited concomitant medications to meet protocol required washouts prior to and during the trial period.

Exclusion Criteria:

• Subjects with dementia or other memory impairment not due to Alzheimer's disease.
• Subjects with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
• Subjects who had an insufficient response, based on the investigator's judgment, to 2 or more previous antipsychotic medications.
• Subjects who have been diagnosed with an Axis I disorder.
• Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
• Subjects with uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension.
• Subjects with diabetes mellitus (insulin-dependent and non-insulin-dependent) may be eligible for the trial if their condition is stable and well-controlled.

Contacts and Locations

Locations

United States, California

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

Los Angeles, California, United States, 90036

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

H. Lundbeck A/S

More Information

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT03548584
• Other Study ID Numbers: 331-14-213
• First Posted: June 7, 2018
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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/
• URL: https://clinical-trials.otsuka.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Agitation

Additional relevant MeSH terms:

Dementia; Alzheimer Disease; Psychomotor Agitation; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Brexpiprazole; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Dopamine Agonists; Dopamine Agents