E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Agitation Associated with Dementia of the Alzheimer's Type |
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E.1.1.1 | Medical condition in easily understood language |
Dementia of the Alzheimer's Type |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of subjects with agitation associated with dementia of the Alzheimer’s type who were previously treated with brexpiprazole (0.5, 1, or 2 mg/day) or placebo during Trial 331-12-283 or Trial 331-12-284 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The investigator must assess the capacity of the subject to provide informed consent prior to enrollment and throughout the course of the trial. Once this determination is made by the investigator, the options for obtaining informed consent from and/or on behalf of the subject must be followed accordingly:
- If the subject is deemed capable by the investigator, written informed consent will be obtained from the subject prior to the initiation of any trial protocol-required procedures. In such cases, acknowledgement from the subject’s legally acceptable representative (an individual, or judicial or other body, authorized under applicable law to consent to the subject’s participation in the clinical trial on behalf of that prospective subject) will also be obtained, if required, in accordance with state and/or local regulations prior to initiation of any trial protocol-required procedures.
- If the subject is deemed incapable by the investigator of providing consent (eg, subjects with severe dementia), written informed consent will be obtained from the subject’s legally acceptable representative prior to initiation of any trial protocol-required procedures. In such cases, assent from the subject, if possible, will be confirmed in accordance with state and/or local regulations prior to the initiation of any trial protocol-required procedures.
- If the subject cannot provide assent, and does not dissent, then the consent of the legally acceptable representative is sufficient unless otherwise required by the governing ethics body and/or applicable state and/or local regulations.
- If the subject dissents, then the subject is not eligible for participation in the trial.
- If the subject initially provided assent at trial entry, but subsequently dissents to participate in the trial, then the subject will be early terminated from the trial.
- If the subject was initially deemed capable of providing informed consent but is no longer deemed so, informed consent must be obtained from the subject’s legally acceptable representative, and assent from the subject, if possible, will be confirmed in accordance with state and/or local regulations prior to the initiation of any trial protocol-required procedures.
- Male and female subjects who completed all the visits of the double-blind treatment period and the 30-day safety follow-up visit of a previous phase 3 brexpiprazole trial of subjects with agitation associated with dementia of the Alzheimer’s type.
- 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 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 able to satisfactorily comply with the protocol requirements. |
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E.4 | Principal exclusion criteria |
Key exclusion criteria include the following: - Subjects who, in the opinion of the investigator, medical monitor, or sponsor should not participate in the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following safety endpoints will be evaluated during this trial. - Frequency and severity of AEs, serious AEs, and discontinuations from the trial due to AEs. - Frequency and severity of AEs related to the worsening of agitation associated with Alzheimer’s disease. - Frequency and severity of AEs related to the worsening of cognition associated with Alzheimer’s disease. - Frequency and severity of other AEs of interest (eg, falls, sedation, weight changes, or deaths). - Newly initiated concomitant medications for the treatment of agitation associated with Alzheimer’s disease. - Newly initiated concomitant medications for the treatment of cognitive symptoms associated with Alzheimer’s disease. - Mean change in the MMSE score from baseline (Week 12 MMSE from Trials 283/284) to Month 2/ET. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Observational rollover trial |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Croatia |
Finland |
France |
Germany |
Russian Federation |
Serbia |
Slovenia |
Spain |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The End of Trial Date is defined as the date for the Month 2/ET visit, or the last Date of Contact or the Date of Final Contact Attempt if the Month 2/ET visit does not occur as a clinic visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |