Alzheimer's Disease Psychosis
Conditions
Brief summary
This study will evaluate the safety and efficacy of pimavanserin 40 mg compared to placebo in patients with Alzheimer's disease psychosis.
Interventions
Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
DRUGPlacebo
Placebo, two tablets, once daily by mouth
Sponsors
ACADIA Pharmaceuticals 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must be 50 years of age or older with NINCDS-ADRDA defined possible or probable AD * Patient must have psychotic symptoms that developed after the diagnosis of AD was established. These symptoms must include visual and/or auditory hallucinations, and/or delusions * Patient must have been a nursing home resident for ≥ 4 weeks prior to randomization, not bedridden and expected to remain in the facility throughout the study * Patient must have actively experienced and verbally communicated psychotic symptoms during the month prior to the Screening visit and weekly during the previous 2 weeks prior to Baseline * If patient is on acetylcholinesterase inhibitor (AChEI) therapy and/or memantine, must be on stable doses for 3 months prior to the Baseline visit and during the study * Patient is willing and able to provide informed consent. If the subject is unable to provide written consent due to the severity of dementia, consent must be given by a legally authorized representative
Exclusion criteria
* Patient has a history of significant psychotic disorders prior to or concomitantly with the diagnosis of Alzheimer's disease including, but not limited to, schizophrenia or bipolar disorder * Patient is unable to communicate verbally * Patient has current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the study * Patient has had a myocardial infarction in the last six months * Patient has moderate to severe congestive heart failure * Patient has any surgery planned during the screening, treatment, or follow-up periods that could interfere with participation in the study per the protocol assessments Patients will be evaluated at screening to ensure that all criteria for study participation are met. These evaluations will include specific measures of psychosis severity, delirium, dementia, cardiovascular condition, and pregnancy status. Patients may be excluded from the study based on these assessments (and specifically if it is determined that their baseline health and psychiatric condition do not meet all protocol-specified entry criteria).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antipsychotic Efficacy | Day 43 | Change from Baseline to Day 43 in the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) psychosis score (Delusions \[Domain A\]+Hallucinations \[Domain B\]) in the Full Analysis Set (FAS). The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains. For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), The NPI-NH Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual domain scores, to yield a possible total score of 0 to 24. Lower scores correspond to less severity. A negative change score from baseline indicates improvement. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo, two tablets, once daily by mouth | 91 |
| Pimavanserin 40 mg Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin) | 90 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Death (See All-Cause Mortality Table) | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance with Study Drug | 0 | 1 |
| Overall Study | Other Reason | 0 | 4 |
| Overall Study | Physician Decision | 3 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Placebo | Pimavanserin 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 86.1 years STANDARD_DEVIATION 5.96 | 85.7 years STANDARD_DEVIATION 7.05 | 85.9 years STANDARD_DEVIATION 6.51 |
| Age, Customized Age <=85 | 41 Participants | 41 Participants | 82 Participants |
| Age, Customized Age >85 | 50 Participants | 49 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants | 90 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 89 Participants | 84 Participants | 173 Participants |
| Region of Enrollment United Kingdom | 91 participants | 90 participants | 181 participants |
| Sex: Female, Male Female | 73 Participants | 73 Participants | 146 Participants |
| Sex: Female, Male Male | 18 Participants | 17 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 91 | 4 / 90 |
| other Total, other adverse events | 70 / 91 | 67 / 90 |
| serious Total, serious adverse events | 10 / 91 | 15 / 90 |
Outcome results
Primary
Antipsychotic Efficacy
Change from Baseline to Day 43 in the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) psychosis score (Delusions \[Domain A\]+Hallucinations \[Domain B\]) in the Full Analysis Set (FAS). The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains. For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), The NPI-NH Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual domain scores, to yield a possible total score of 0 to 24. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.
Time frame: Day 43
Population: All randomized subjects who received at least one dose of study treatment and have both a Baseline and at least one post-Baseline NPI-NH psychosis score evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Antipsychotic Efficacy | -1.93 Score on the NPI-NH scale |
| Pimavanserin 40 mg | Antipsychotic Efficacy | -3.76 Score on the NPI-NH scale |
p-value: 0.045195% CI: [-3.64, -0.04]Mixed Models Analysis