Agitation Associated with Dementia of the Alzheimer’s Type MedDRA version: 17.1 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Brexpiprazole
Product Code: OPC-34712
Pharmaceutical Form: Tablet
INN or Proposed INN: Brexpiprazole
CAS Number: 913611-97
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The subject population will include: 1. male and female subjects between 55 and 90 years of age (inclusive), 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, with a diagnosis of probable Alzheimer's disease according to the NINCDS-ADRDA criteria. 2. Subjects must have a previous magnetic resonance imaging (MRI) or computed tomography (CT). 3. Institutionalized subjects with an identified caregiver who has sufficient contact 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 settings or another individual (e.g., family member, family friend, hired professional caregiver) who meets the caregiver requirements. 4. Non-institutionalized subjects may not be living alone (see Section 3.3.1.1 for caretaker definition) and must have an identified caregiver who has sufficient contact to describe the subject's symptoms and has direct observation of the subject's behavior. 5. 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 a diagnosis of Alzheimer's disease. 6. Additionally, at both the screening and baseline visits, subjects must have a Mini-Mental State Examination (MMSE) score of 5 to 22, inclusive, and a score of = 4 on the agitation/aggression item of the NPI-NH. 7. The onset of the subject's symptoms of agitation must be at least 2 weeks prior to the screening visit. Subjects who require pharmacotherapy for the treatment of agitation per the investigator's judgment, after an evaluation for reversible factors (e.g., pain, infection, polypharmacy) and trial of nonpharmacological interventions. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 313 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 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, or any other specific non-Alzheimer’s-type dementia; subjects aged 55 years or older with a diagnosis of Down syndrome Subjects with a previous MRI or CT scan of the brain, which was performed after the onset of symptoms of dementia, with findings consistent with a clinically significant central nervous system disease other than Alzheimer’s disease, such as vascular changes (e.g., cortical stroke, multiple infarcts), space-occupying lesion (e.g., tumor), or other major structural brain disease. Subjects with a history of stroke, transient ischemic attack, or pulmonary or cerebral embolism. Subjects with a history of clinically relevant traumatic brain injury with neurological sequelae. Subjects with a history of a deep venous thrombosis within the 5 years prior to the screening visit. Subjects with delirium, unless resolved with no symptoms for at least 30 days prior to the screening visit. Subjects with evidence of serious risk of suicide based on the Sheehan Suicidality Tracking Scale (Sheehan-STS) or who, in the opinion of the investigator, present a serious risk of suicide. Subjects considered in poor general health based on the investigator’s judgment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of flexible dosing of brexpiprazole (dose range of 0.5 to 2 mg/day) with placebo in subjects with agitation associated with dementia of the Alzheimer’s type, as assessed by the Cohen Mansfield Agitation Inventory (CMAI) after 12 weeks of treatment;Secondary Objective: To evaluate the safety and tolerability of flexible dosing of brexpiprazole (dose range of 0.5 to 2 mg/day) compared with placebo in subjects with agitation associated with dementia of the Alzheimer’s type after 12 weeks of treatment.;Primary end point(s): The primary efficacy variable is the change from baseline to Week 12/ET in the CMAI total score;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy variable is the change from baseline to Week 12/ET in the Clinical Global Impression-Severity of Illness (CGI-S) score, as related to agitation Change from baseline to Week 12/ET in the following: - CMAI subscale scores (aggressive behavior, physically nonaggressive behavior, verbally agitated behavior) - NPI-NH total score, psychosis subscale score(delusions and hallucinations), individual item scores (eg, agitation/aggression, anxiety,irritability/lability), and occupational disruptiveness scores (individual item and total scores) for institutionalized subjects - Change from baseline to Week 12/ET in NPI-NH total score, psychosis subscale score (delusions and hallucinations), and individual item score (e.g., agitation/aggression, anxiety, irritability/lability), and in NPI distress scores (individual item and total scores), for noninstitutionalized subjects - CGI-Improvement (CGI-I) score, as related to agitation, at Week 12/ET -CGI-Efficacy index (CGI-E) score, which is defined as the ratio of current therapeutic effect (as related to agitation) and severity of side effects, at Week 12/ET Change from baseline to Week 12/ET in the following: - Modified Nursing Care Assessment Scale (M-NCAS) score ((for institutionalized subjects only)) - Quality of Life in Alzheimer’s Disease(QoL-AD) score - Nurses’ Observation Scale for Geriatric Patients (NOSGER) score ((for institutionalized subjects only)) - Change from baseline to Week 12/ET in the Resource Utilization in Dementia (RUD) score - Safety variables (adverse events, physical examinations, neurological examinations, vital signs, body weight, waist circumference, clinical laboratory tests and ECGs. Other safety variables will include the | — |
Countries
Bulgaria, Canada, Finland, France, Slovakia, Slovenia, Ukraine, United Kingdom, United States
Contacts
Public ContactCatherine Aurang
Otsuka Pharmaceutical Development & Commercialization, Inc.
Outcome results
None listed