Brexpiprazole in the Treatment of Subjects with Agitation Associated with Dementia of the Alzheimer’s Type
- Conditions
- Agitation Associated with Dementia of the Alzheimer’s TypeMedDRA version: 19.1Level: PTClassification code 10012271Term: Dementia Alzheimer's typeSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2013-000503-17-BG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 520
The subject population will include:
• Male and female subjects between 55 and 90 years of age, inclusive, at the time of informed consent.
• Subjects with a diagnosis of probable Alzheimer's disease according to the NINCDS-ADRDA criteria.
• Subjects with a MMSE score of 5 to 22, inclusive, at the screening and baseline visits.
• Subjects must have a previous MRI or CT scan of the brain, which was performed after the onset of the symptoms of dementia, with findings consistent with a diagnosis of Alzheimer's disease.
• 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.
• 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 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 (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.
• 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.
• Subjects with onset of symptoms of agitation 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 (eg, pain, infection, polypharmacy) and a trial of nonpharmacological interventions.
• Subjects who are capable of self-locomotion or locomotion with an assistive device (eg, 4-point walker, wheelchair).
• Subjects willing and able to discontinue all prohibited concomitant medications to meet protocol-required washouts prior to and during the trial period.
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 78
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 442
• 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, HIV-dementia, traumatic brain injury, normal pressure hydrocephalus, or any other specific non-Alzheimer'stype dementia; subjects with a diagnosis of Down syndrome.
• Subjects with a previous MRI or 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.
• Subjects with a history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
• Subjects who have an insufficient response, based on the investigator's judgment, to 2 or more previous antipsychotic medications for the treatment of agitation associated with Alzheimer's disease.
• Subjects with delirium or history of delirium within the 30 days prior to the screening visit.
• Subjects who have been diagnosed with an Axis I disorder (DSM-IV-TR criteria) including, but not limited to:
o Schizophrenia, schizoaffective disorder, or other psychotic disorder not related to dementia
o Bipolar I or II disorder, bipolar disorder not otherwise specified
o Current major depressive episode. Subjects with major depressive disorder are eligible provided that they have been on a stable dose(s) of antidepressant medication(s) for the 30 days prior to randomization. Please note: antidepressant medications that are CYP2D6 or CYP3A4 inhibitors are prohibited (see Table 4.1-2 for prohibited antidepressant medications).
• 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.
• Subjects who have a current medical condition that requires treatment with an anticoagulant.
• Subjects who have received bapineuzumab, solanezumab, or other immunotherapy, such as vaccines, for the treatment of Alzheimer's disease (through clinical trial or compassionate use program) in the 6 months preceding randomization.
• Subjects who would be likely to require prohibited concomitant therapy during the trial (see Table 4.1-1).
• Subjects who received brexpiprazole in any prior clinical trial or commercially available brexpiprazole (Rexulti®).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>Week 12/ET in the CMAI total score;Timepoint(s) of evaluation of this end point: 12 weeks
- Secondary Outcome Measures
Name Time Method 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.<br><br>• Change from baseline to Week 12/ET in CMAI subscale scores (aggressive behavior, physically nonaggressive behavior, verbally agitated behavior)<br><br>• Change from baseline to Week 12/ET in NPI-NH<br> o 12-item total score<br> o agitation/aggression score<br><br>• Clinical Global Impression-Improvement (CGI-I) score, as related to agitation, at Week 12/ET<br>;Timepoint(s) of evaluation of this end point: 12 weeks