Neuropsychiatric Symptoms Related to Neurodegenerative Disease
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety and tolerability of pimavanserin in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease exposed to open-label pimavanserin for up to 52 weeks.
Interventions
DRUGPimavanserin
• Pimavanserin 34 mg is provided as 2×17 mg tablets as single dose, once daily by mouth. Dose adjustments of pimavanserin down to 20 mg (provided as 2×10 mg tablets as a single dose, once daily by mouth) and up to 34 mg are permitted based on Investigator assessment of clinical response.
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject satisfied all entry criteria for the antecedent pimavanserin study 2. Subject completed the antecedent study; or was participating in a pimavanserin study that the Sponsor ended early 3. Has a designated study partner/caregiver who meets the following requirements: 1. In the Investigator's opinion, is in contact with the subject frequently enough to accurately report on the subject's symptoms and whether or not the subject is taking the study drug 2. In the Investigator's opinion, is considered reliable in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures 3. Is fluent in the local language in which study assessments will be administered 4. Agrees to participate in study assessments, has the capacity to provide informed consent, and provides written consent to participate in the study 4. Subject is willing and able to provide informed consent. 5. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception or be abstinent during the study and 1 month following completion of the study.
Exclusion criteria
1. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study, due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study, or is judged to be a danger to self or others 2. Is in hospice, is receiving end-of-life palliative care, or has become bedridden 3. Has any of the following ECG results at the EOT/ET visit of the antecedent study: a. If the subject is not on citalopram, escitalopram, or venlafaxine: i. QTcF \>450 ms, if QRS duration \<120 ms ii. QTcF \>470 ms, if QRS duration ≥120 ms b. If the subject is on citalopram, escitalopram, or venlafaxine: i. QTcF \>425 ms, if QRS duration \<120 ms ii. QTcF \>450 ms, if QRS duration ≥120 ms 4. Has a heart rate \<50 beats per minute. If bradycardia is secondary to iatrogenic or treatable causes and these causes are treated, a heart rate assessment can be repeated at the EOT/ET visit of the antecedent study. 5. Has clinically significant laboratory abnormalities in the antecedent study that, in the judgment of the Investigator or Medical Monitor, would either: 1. jeopardize the safe participation of the subject in the study; OR 2. would interfere with the conduct or interpretation of safety or efficacy evaluations in the study 6. Is suicidal at Visit 1 (Baseline) 7. Has developed a medical condition that in the judgment of the Investigator, would increase the risk associated with taking study medication or significantly interfere with the conduct or interpretation of the study 8. Requires treatment with a medication or other substance that is prohibited by the protocol 9. Has a significant sensitivity or allergic reaction to pimavanserin or its excipients 10. Is an employee of ACADIA, or has a family member who is an employee of ACADIA Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events (TEAEs) | Treatment period and Follow-up period: 56 weeks | Number (%) of patients experiencing at least one TEAE |
Countries
Bulgaria, Colombia, Czechia, Georgia, Mexico, Poland, Romania, Russia, Serbia, South Africa, Ukraine, United States
Participant flow
Recruitment details
This was an open-label extension study to evaluate the long-term safety and tolerability of pimavanserin in patients with neuropsychiatric symptoms related to neurodegenerative disease, who had completed an antecedent study (ACP-103-046) or had participated in a pimavanserin study that the sponsor terminated early.
Participants by arm
| Arm | Count |
|---|---|
| Pimavanserin Pimavanserin 34 mg once daily (QD). Dose reductions to pimavanserin 20 mg and subsequent dose increases to 34 mg were allowed at any time, based on investigator assessment of clinical response of the patient. | 595 |
| Total | 595 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 32 |
| Overall Study | Consent withdrawn by patient or legally accepted representative | 29 |
| Overall Study | Death | 9 |
| Overall Study | Lack of Efficacy | 9 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Noncompliance with study drug | 6 |
| Overall Study | Not further specified | 43 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Use of prohibited medication | 3 |
Baseline characteristics
| Characteristic | Pimavanserin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 508 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants |
| Age, Continuous | 72.2 years STANDARD_DEVIATION 6.69 |
| Mini Mental State Examination total score | 20.0 units on a scale STANDARD_DEVIATION 5.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) White | 561 Participants |
| Region of Enrollment Bulgaria | 29 participants |
| Region of Enrollment Colombia | 16 participants |
| Region of Enrollment Czechia | 30 participants |
| Region of Enrollment Georgia | 25 participants |
| Region of Enrollment Mexico | 9 participants |
| Region of Enrollment Poland | 90 participants |
| Region of Enrollment Romania | 3 participants |
| Region of Enrollment Russia | 68 participants |
| Region of Enrollment Serbia | 36 participants |
| Region of Enrollment South Africa | 11 participants |
| Region of Enrollment Ukraine | 81 participants |
| Region of Enrollment United States | 197 participants |
| Sex: Female, Male Female | 348 Participants |
| Sex: Female, Male Male | 247 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 595 |
| other Total, other adverse events | 0 / 595 |
| serious Total, serious adverse events | 37 / 595 |
Outcome results
Primary
Treatment-emergent Adverse Events (TEAEs)
Number (%) of patients experiencing at least one TEAE
Time frame: Treatment period and Follow-up period: 56 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimavanserin | Treatment-emergent Adverse Events (TEAEs) | 238 Participants |