A 12-Week, Multicenter, Randomized, Double-blind, Placebo Trial to check how safe, effective and tolerable Brexpiprazole is in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer’s Type

Phase 1

Conditions: Agitation Associated With Dementia of the Alzheimer’s Type
MedDRA version: 20.0Level: PTClassification code 10012271Term: Dementia Alzheimer's typeSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2017-003940-19-HU

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 330

Inclusion Criteria

1.The investigator must assess the capacity of the subject to provide informed consent during the screening period and throughout the course of the trial.
2.Male and female subjects between 55 and 90 years of age, inclusive, at the time of informed consent.
3.Subjects with a diagnosis of probable Alzheimer’s disease according to the NINCDS-ADRDA criteria.
4.Subjects with a diagnosis of agitation that meets the IPA provisional definition of agitation
5.Subjects with a MMSE score of 5 to 22, inclusive, at the screening and baseline visits.
6.Subjects with a previous MRI or CT scan of the brain, that was performed after the onset of the symptoms of dementia, with findings consistent with a diagnosis of Alzheimer’s disease.
7.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.
8.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. The identified caregiver can be a staff member of the institutionalized setting or another individual (eg, family member, family friend, hired professional caregiver) who meets the caregiver requirements.
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.
9.Subjects with a total score (frequency × severity) of = 4 on the agitation/aggression item of the NPI NH (for institutionalized subjects) or the NPI/NPI-NH (for non-institutionalized subjects) at the screening and baseline visits.
10.Subjects with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
11.Subjects must meet additional predetermined blinded eligibility criteria according to the blinded addendum.
12.Subjects who require pharmacotherapy for the treatment of agitation per the investigator’s judgment, after:
•An evaluation for reversible factors (eg, pain, infection, or polypharmacy), and
•A trial of nonpharmacological interventions (eg, redirecting behavior, group activities, music therapy).
13.Subjects who are capable of self-locomotion or locomotion with an assistive device (eg, 4-point walker, wheelchair).
14.Subjects willing and able to discontinue all prohibited concomitant medications to meet protocol required washouts prior to and during the trial period.
15.Subjects able to satisfactorily comply with the protocol requirements.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 297

Exclusion Criteria

1) Subjects with dementia or other memory impairment not due to Alzheimer’s disease, such as mixed or vascular dementia, dementia with Lewy bodies, Parkinson’s disease dementia, frontotemporal dementia, substance-induced dementia, human immunodeficiency virus dementia, traumatic brain injury, normal pressure hydrocephalus, or any other specific non Alzheimer’s-type dementia; subjects with a diagnosis of Down syndrome.
2) Subjects with a previous magnetic resonance imaging (MRI)/computed tomography (CT) scan of the brain, which was performed after the onset of the symptoms of dementia, with findings consistent with a clinically significant central nervous system disease other than Alzheimer’s disease, such as vascular changes (eg, cortical stroke, multiple infarcts), space-occupying lesion (eg, tumor), or other major structural brain disease. Note that for subjects in Germany only, the MRI/CT scan can only be performed if it is standard of care.
3) Subjects with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
4) Subjects with delirium or history of delirium within the 30 days prior to the screening visit.
5) Subjects who have received high-dose antipsychotics exceeding the equivalent of = 3 mg of risperidone (eg, = 5 mg of haloperidol, = 375 mg quetiapine, = 10 mg olanzapine, or local equivalent) within 90 days prior to screening.
6) Subjects who have received multiple antipsychotic medications simultaneously for a period of > 7 days within 90 days prior to screening.
7) Subjects with evidence of serious risk of suicide based on the Sheehan Suicidality Tracking Scale (Sheehan-STS), ie, a score of 3 or 4 on any one question 2 through 6 or 11, or a score of 2 or higher on any one questions 1a, 7 through 10, or 12, or who, in the opinion of the investigator, present a serious risk of suicide.
8) Subjects considered in poor general health based on the investigator’s judgment. Examples include subjects who have a recent clinically significant weight loss, chronic dehydration or hypovolemia, poor fluid or nutritional intake, or a recent clinically significant infection, as per the investigator’s judgment.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To confirm the efficacy of brexpiprazole compared with placebo in subjects with Agitation in Alzheimer’s dementia;Secondary Objective: To evaluate the safety and tolerability of brexpiprazole compared with placebo in subjects with Agitation in Alzheimer’s dementia;Primary end point(s): The primary efficacy endpoint is the change from baseline to Week 12 in the CMAI total score.;Timepoint(s) of evaluation of this end point: Change from baseline to Week 12

Secondary Outcome Measures

Name	Time	Method

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