Agitation in Dementia, Including Alzheimer's Disease
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled study comparing the efficacy and safety of ITI-007 versus placebo administered orally once daily in the treatment of agitation in patients with dementia, including Alzheimer's disease.
Interventions
DRUGITI-007
DRUGPlacebo
Sponsors
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of probable Alzheimer's disease * Clinically significant symptoms of agitation secondary to probable Alzheimer's disease * Able to attend outpatient clinic visits with primary caregiver
Exclusion criteria
* Unable to comply with study procedures * Considered medically inappropriate for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | 4 weeks (28 Days) | The Cohen-Mansfield Agitation Inventory-Community Version is a 37-item scale for identifying and quantifying agitated behaviors in elderly persons in a community setting. Each item is rated from 1='Never' to 7='Several Times Per Hour'. Each category contains a pre-specified subset of the CMAI-C items. The score of each category is the sum of the CMAI-C items included in that category: Aggressive Behavior-Sum of 9 CMAI-C items, ranges from 9 to 63; Non-Aggressive Agitated Behavior-Sum of 6 CMAI-C items, ranges from 6 to 42; Verbally Agitated Behavior-Sum of 4 CMAI-C items, ranges from 4 to 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S) | 4 weeks (28 Days) | The CGI scale for Severity of Illness is a standardized assessment tool to rate the overall severity of illness and efficacy of medication. CGI-S of Agitation and CGI-S of Aggression will be used in this study as a measure of efficacy. Scores on the CGI-S range from 1 (not ill at all) to 7 (among the most extremely ill). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 9 mg ITI-007 9 mg ITI-007 administered as a solid oral dose formulation once daily for 4 weeks | 86 |
| Placebo Placebo administered as a visually-matched solid oral dose formulation once daily for 4 weeks | 89 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Study Terminated by Sponsor | 2 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 0 |
Baseline characteristics
| Characteristic | 9 mg ITI-007 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 75.6 years STANDARD_DEVIATION 8.64 | 74.1 years STANDARD_DEVIATION 8.61 | 74.8 years STANDARD_DEVIATION 8.63 |
| CMAI-C CMAI-C Aggressive Behavior | 13.28 units on a scale STANDARD_DEVIATION 4.51 | 14.08 units on a scale STANDARD_DEVIATION 5.92 | 13.69 units on a scale STANDARD_DEVIATION 5.27 |
| CMAI-C CMAI-C Non-Aggressive Agitated Behavior | 17.20 units on a scale STANDARD_DEVIATION 7.42 | 17.46 units on a scale STANDARD_DEVIATION 7.05 | 17.33 units on a scale STANDARD_DEVIATION 7.22 |
| CMAI-C CMAI-C Verbally Agitated Behavior | 15.37 units on a scale STANDARD_DEVIATION 4.95 | 15.65 units on a scale STANDARD_DEVIATION 5.02 | 15.51 units on a scale STANDARD_DEVIATION 4.98 |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 10 Participants | 20 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 73 Participants | 75 Participants | 148 Participants |
| Sex: Female, Male Female | 44 Participants | 57 Participants | 101 Participants |
| Sex: Female, Male Male | 42 Participants | 32 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 89 |
| other Total, other adverse events | 13 / 86 | 8 / 89 |
| serious Total, serious adverse events | 2 / 86 | 1 / 89 |
Outcome results
Primary
Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C)
The Cohen-Mansfield Agitation Inventory-Community Version is a 37-item scale for identifying and quantifying agitated behaviors in elderly persons in a community setting. Each item is rated from 1='Never' to 7='Several Times Per Hour'. Each category contains a pre-specified subset of the CMAI-C items. The score of each category is the sum of the CMAI-C items included in that category: Aggressive Behavior-Sum of 9 CMAI-C items, ranges from 9 to 63; Non-Aggressive Agitated Behavior-Sum of 6 CMAI-C items, ranges from 6 to 42; Verbally Agitated Behavior-Sum of 4 CMAI-C items, ranges from 4 to 28.
Time frame: 4 weeks (28 Days)
Population: Intent-to-Treat Set (Study stopped for futility)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 9 mg ITI-007 | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Aggressive Agitated Behavior | -1.0 score on a scale | Standard Error 0.37 |
| 9 mg ITI-007 | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Non-Aggressive Agitated Behavior | -4.1 score on a scale | Standard Error 0.72 |
| 9 mg ITI-007 | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Verbally Agitated Behavior | -2.9 score on a scale | Standard Error 0.49 |
| Placebo | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Aggressive Agitated Behavior | -2.3 score on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Non-Aggressive Agitated Behavior | -3.9 score on a scale | Standard Error 0.65 |
| Placebo | Change From Baseline in the Cohen-Mansfield Agitation Inventory - Community Version (CMAI-C) | Verbally Agitated Behavior | -2.3 score on a scale | Standard Error 0.45 |
Secondary
Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S)
The CGI scale for Severity of Illness is a standardized assessment tool to rate the overall severity of illness and efficacy of medication. CGI-S of Agitation and CGI-S of Aggression will be used in this study as a measure of efficacy. Scores on the CGI-S range from 1 (not ill at all) to 7 (among the most extremely ill).
Time frame: 4 weeks (28 Days)
Population: Intent-to Treat Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 9 mg ITI-007 | Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S) | CGI-S Aggression | -0.4 score on a scale | Standard Error 0.12 |
| 9 mg ITI-007 | Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S) | CGI-S Agitation | -0.8 score on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S) | CGI-S Aggression | -0.6 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale for Severity of Illness (CGI-S) | CGI-S Agitation | -0.9 score on a scale | Standard Error 0.1 |