To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type

Behavioral symptoms, such as agitation, are core features in subjects with Alzheimer's disease and related dementias and develop in the majority of dementia subjects. The presence of agitation in subjects with Alzheimer's disease places a significant burden not only on subjects and their caregivers but also on the healthcare system.

This is a trial designed to assess the safety and efficacy of flexible dosing of brexpiprazole in the treatment of subjects with agitation associated with dementia of the Alzheimer's type. 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.

Inclusion Criteria:

• Male and female subjects 55 to 90 years of age, inclusive, at the time of informed consent.
• Subjects who are residing at their current location for at least 14 days before screening and are expected to remain at the same location for the duration of the trial.
• Subjects with diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA criteria.
• Subjects with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.
• Subjects with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
• Subjects with a total score greater than or equal to 4 on the agitation aggression item of the NPI-NH or NPI/NPI-NH at the screening and baseline visits.
• Subjects who require pharmacotherapy for the treatment of agitation per the investigator's judgement, after an evaluation of reversible factors (eg, pain, infection, polypharmacy) and a trial of nonpharmacological interventions.
• Subjects must have a previous MRI or CT scan of the brain, which was performed after the onset of symptoms of dementia, with findings consistent with the diagnosis of Alzheimer's disease.

Exclusion Criteria:

• Subjects with dementia or other memory impairment not due to Alzheimer's disease.
• Subjects with history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
• Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
• Subjects who have been diagnosed with an Axis I disorder (DSM-IV-TR criteria).
• Subjects with uncontrolled hypertension.
• Subjects with uncontrolled insulin-dependent diabetes mellitus (IDDM)
• Subjects with epilepsy or a history of seizures.
• Subjects considered in poor general health based on the investigator's judgment.

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.

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.

Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com