Alzheimer's Disease
Conditions
Keywords
Agitation, Aggression, patients
Brief summary
The primary purpose of this study is to determine whether ELND005 is effective in treating symptoms of agitation and aggression in patients with Alzheimer's disease
Interventions
DRUGELND005
DRUGPlacebo
Sponsors
Elan Pharmaceuticals
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Probable AD according to the National Institute on Aging- Alzheimer's Association (NIA-AA) guidelines (McKhann et al 2011). * MMSE score of 5 to 24 (inclusive) at the Screening Visit. * Has clinically significant agitation/aggression defined as Neuropsychiatric Inventory (NPI)-agitation/aggression subscore of ≥4. * No response or suboptimal response to standard nonpharmacological interventions.
Exclusion criteria
* The agitation/aggression is attributable to concomitant medications, environmental conditions, or active medical or psychiatric condition. * Current diagnosis of major depressive disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM IV TR). * Has persistent and distressing psychotic symptoms (delusion and/or hallucinations) that require psychiatric hospitalization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A). | Week 12 | The NPI-C (de Medeiros et al 2010) is a validated and reliable behavioral measure that assesses psychopathology in dementia subjects. It evaluates 14 neuropsychiatric disturbances common in dementia.Higher scores on the NPI-C are associated with a greater clinical severity of symptoms. The NPI-C Agitation and Aggression score ranges from 0-63. The analysis of the NPI-C A+A score was performed on the mITT population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified-ADCS-CGIC Agitation Scores | Week 12 | The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) is a widely used scale for the global assessment of change in AD trials.It is a 7-point Likert scale that ranges from marked improvement scored as 1 to marked worsening scored as 7, with no change scored as 4. The range is from 1 to 7. Higher scores indicate worsening agitation. |
| Change From Baseline in NPI Total Scores | Week 12 | The NPI (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia subjects. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and appetite and eating abnormalities. Higher scores on the NPI are associated with greater frequency and severity of symptoms. The scale range is 0-144. |
| Change From Baseline in MMSE Scores | Week 12 | The Mini-Mental State Exam (MMSE) (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of products approved for the treatment of AD. The score can range from 0 to 30, with lower scores indicating greater impairment in function. |
| Change From Baseline in ADCS-ADL Scores | Week 12 | The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (Galasko et al 1997) is a functional assessment that measures instrumental and basic activities of daily living. The total score for the 23-item ADCS-ADL ranges from 0 to 78 points, with lower scores indicating greater impairment in function. |
Countries
Canada, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ELND005 ELND005 film coated tablets, BID for 12 weeks
ELND005 | 175 |
| Placebo Matched placebo BID for 12 weeks
Placebo | 175 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor Decision | 2 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 9 |
Baseline characteristics
| Characteristic | Placebo | ELND005 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 155 Participants | 162 Participants | 317 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 13 Participants | 33 Participants |
| Age, Continuous | 75.9 years STANDARD_DEVIATION 8.51 | 76.2 years STANDARD_DEVIATION 7.89 | 76.0 years STANDARD_DEVIATION 8.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 17 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 151 Participants | 155 Participants | 306 Participants |
| Region of Enrollment Canada | 10 participants | 7 participants | 17 participants |
| Region of Enrollment Spain | 10 participants | 13 participants | 23 participants |
| Region of Enrollment United Kingdom | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 152 participants | 153 participants | 305 participants |
| Sex: Female, Male Female | 100 Participants | 95 Participants | 195 Participants |
| Sex: Female, Male Male | 75 Participants | 80 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 97 / 175 | 82 / 175 |
| serious Total, serious adverse events | 17 / 175 | 5 / 175 |
Outcome results
Primary
Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A).
The NPI-C (de Medeiros et al 2010) is a validated and reliable behavioral measure that assesses psychopathology in dementia subjects. It evaluates 14 neuropsychiatric disturbances common in dementia.Higher scores on the NPI-C are associated with a greater clinical severity of symptoms. The NPI-C Agitation and Aggression score ranges from 0-63. The analysis of the NPI-C A+A score was performed on the mITT population.
Time frame: Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ELND005 | Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A). | -4.3 units on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A). | -4.2 units on a scale | Standard Error 0.7 |
Secondary
Change From Baseline in ADCS-ADL Scores
The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (Galasko et al 1997) is a functional assessment that measures instrumental and basic activities of daily living. The total score for the 23-item ADCS-ADL ranges from 0 to 78 points, with lower scores indicating greater impairment in function.
Time frame: Week 12
Population: mITT population with available data for ADCS-ADL Scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ELND005 | Change From Baseline in ADCS-ADL Scores | -1.458 units on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline in ADCS-ADL Scores | -2.229 units on a scale | Standard Error 0.7 |
Secondary
Change From Baseline in MMSE Scores
The Mini-Mental State Exam (MMSE) (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of products approved for the treatment of AD. The score can range from 0 to 30, with lower scores indicating greater impairment in function.
Time frame: Week 12
Population: mITT population with available data for MMSE Scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ELND005 | Change From Baseline in MMSE Scores | -0.3 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in MMSE Scores | -0.4 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in Modified-ADCS-CGIC Agitation Scores
The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) is a widely used scale for the global assessment of change in AD trials.It is a 7-point Likert scale that ranges from marked improvement scored as 1 to marked worsening scored as 7, with no change scored as 4. The range is from 1 to 7. Higher scores indicate worsening agitation.
Time frame: Week 12
Population: mITT population with available data for Modified-ADCS-CGIC Agitation Scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ELND005 | Change From Baseline in Modified-ADCS-CGIC Agitation Scores | 3.6 units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Modified-ADCS-CGIC Agitation Scores | 3.4 units on a scale | Standard Error 0.1 |
Secondary
Change From Baseline in NPI Total Scores
The NPI (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia subjects. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and appetite and eating abnormalities. Higher scores on the NPI are associated with greater frequency and severity of symptoms. The scale range is 0-144.
Time frame: Week 12
Population: mITT population with available data for NPI Total Scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ELND005 | Change From Baseline in NPI Total Scores | -14.38 units on a scale | Standard Error 1.69 |
| Placebo | Change From Baseline in NPI Total Scores | -15.12 units on a scale | Standard Error 1.71 |