Agitation Associated With Dementia of the Alzheimer's Type
Conditions
Brief summary
To evaluate the safety of brexpiprazole 1 mg or 2 mg after a 14 week treatment regimen for agitation associated with dementia of the Alzheimer's type patients who completed in a double-blind trial, and to investigate the efficacy of brexpiprazole.
Interventions
DRUGBrexpiprazole
Brexpiprazole 1mg or 2mg will be orally once daily for 14 weeks
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Patients who completed the double-blind treatment period for 10 weeks and all observation, examination and evaluation at Week 10 of the double-blind trial. * Patients whose caregiver can properly collect the necessary information.
Exclusion criteria
* Patients who had a serious adverse event which the principal investigator or sub-investigator assessed as related to the investigator product during the double-blind trial. * Patients who had delirium during the double-blind trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | From baseline to week 14 | This trial enrolled subjects rolled over from Trial 331-102-00088, and the safety of brexpiprazole when administered for a maximum of 24 weeks (including the treatment period of Trial 331-102-00088) was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Cohen-Mansfield Agitation Inventory (CMAI) Score at 14 Weeks After Dosing | Baseline and 14 weeks after dosing | The CMAI assessed the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consisted of 29 items all rated on a 1 to 7 scale with 1 being the best rating and 7 being the worst rating. The minimum possible CMAI total score was 29, and the maximum possible CMAI total score was 203. A decrease in score indicated improvement in symptoms. |
| Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 14 Weeks After Dosing. | Baseline and 14 weeks after dosing. | The CGI-S was used to rate the severity of agitation. Scores were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A decrease in score indicated improvement in symptoms. |
| Clinical Global Impression of Improvement (CGI-I) Score at 14 Weeks After Dosing | 14 weeks after dosing. | The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ROLLOVER BREX Rollover subjects from the brexpiprazole group in Trial 331-102-00088 | 102 |
| ROLLOVER PLACEBO Rollover subjects from the placebo group in Trial 331-102-00088 | 62 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 14 |
| Overall Study | Bedridden All Day and Required Full Assistance for Excretion, Meals and Change of Clothes | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Physician Decision | 5 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Legal Representative | 3 | 0 |
Baseline characteristics
| Characteristic | ROLLOVER BREX | ROLLOVER PLACEBO | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 96 Participants | 60 Participants | 156 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 8 Participants |
| Age, Continuous | 79.0 years STANDARD_DEVIATION 6.8 | 80.2 years STANDARD_DEVIATION 6.9 | 79.5 years STANDARD_DEVIATION 6.8 |
| Race/Ethnicity, Customized Asian | 102 Participants | 62 Participants | 164 Participants |
| Region of Enrollment Japan | 102 participants | 62 participants | 164 participants |
| Sex: Female, Male Female | 65 Participants | 36 Participants | 101 Participants |
| Sex: Female, Male Male | 37 Participants | 26 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 1 / 62 |
| other Total, other adverse events | 90 / 102 | 55 / 62 |
| serious Total, serious adverse events | 7 / 102 | 4 / 62 |
Outcome results
Primary
The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs)
This trial enrolled subjects rolled over from Trial 331-102-00088, and the safety of brexpiprazole when administered for a maximum of 24 weeks (including the treatment period of Trial 331-102-00088) was evaluated.
Time frame: From baseline to week 14
Population: The safety analysis set comprised subjects who have received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ROLLOVER BREX | The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | 90.2 Percentage of percipitante |
| ROLLOVER PLACEBO | The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | 90.3 Percentage of percipitante |
Secondary
Clinical Global Impression of Improvement (CGI-I) Score at 14 Weeks After Dosing
The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition.
Time frame: 14 weeks after dosing.
Population: The efficacy analysis set will comprise subjects who have received at least 1 dose of the IMP and from whom CMAI total scores have been obtained at baseline and at least 1 time point after initiation of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ROLLOVER BREX | Clinical Global Impression of Improvement (CGI-I) Score at 14 Weeks After Dosing | 3.1 Units on a scale | Standard Deviation 1.2 |
| ROLLOVER PLACEBO | Clinical Global Impression of Improvement (CGI-I) Score at 14 Weeks After Dosing | 2.7 Units on a scale | Standard Deviation 1.1 |
Secondary
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 14 Weeks After Dosing.
The CGI-S was used to rate the severity of agitation. Scores were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A decrease in score indicated improvement in symptoms.
Time frame: Baseline and 14 weeks after dosing.
Population: The efficacy analysis set will comprise subjects who have received at least 1 dose of the IMP and from whom CMAI total scores have been obtained at baseline and at least 1 time point after initiation of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ROLLOVER BREX | Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 14 Weeks After Dosing. | -0.2 Units on a scale | Standard Deviation 0.8 |
| ROLLOVER PLACEBO | Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 14 Weeks After Dosing. | -0.4 Units on a scale | Standard Deviation 1.1 |
Secondary
Mean Change From Baseline in Cohen-Mansfield Agitation Inventory (CMAI) Score at 14 Weeks After Dosing
The CMAI assessed the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consisted of 29 items all rated on a 1 to 7 scale with 1 being the best rating and 7 being the worst rating. The minimum possible CMAI total score was 29, and the maximum possible CMAI total score was 203. A decrease in score indicated improvement in symptoms.
Time frame: Baseline and 14 weeks after dosing
Population: The efficacy analysis set will comprise subjects who have received at least 1 dose of the IMP and from whom CMAI total scores have been obtained at baseline and at least 1 time point after initiation of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ROLLOVER BREX | Mean Change From Baseline in Cohen-Mansfield Agitation Inventory (CMAI) Score at 14 Weeks After Dosing | -2.5 Units on a scale | Standard Deviation 9.9 |
| ROLLOVER PLACEBO | Mean Change From Baseline in Cohen-Mansfield Agitation Inventory (CMAI) Score at 14 Weeks After Dosing | -6.4 Units on a scale | Standard Deviation 9.3 |