Parkinson's Disease
Conditions
Brief summary
This is a pilot study to explore the effects of pimavanserin and low-dose quetiapine in subjects with Parkinson's disease with neuropsychiatric symptoms.
Interventions
DRUGPimavanserin
Pimavanserin 34 mg (provided as 2×17 mg encapsulated tablets) administered orally as a single dose once daily
OTHERPlacebo
Placebo (provided as 2 × placebo encapsulated tablets) administered orally as a single dose once daily
DRUGQuetiapine
Quetiapine 25 mg (provided as 1×25 mg quetiapine encapsulated tablet and 1 × placebo encapsulated tablet), OR 50 mg (provided as 2×25 mg quetiapine encapsulated tablets), OR 100 mg (provided as 2×50 mg quetiapine encapsulated tablets) administered orally as a single dose once daily
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 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects 50 to 85 years of age, inclusive 2. Able to understand the protocol requirements and provide written informed consent 3. Able to complete questions on a handheld device / tablet, is willing to wear an actigraph and can be reliably rated on assessment scales 4. Able to designate an 'informant' (relative, housemate, friend) who can provide information about the subject's well being and attend clinic visits with the subject 5. Is able to swallow the test capsule without difficulty during the Screening visit 6. Has a Mini-Mental State Examination (MMSE) score ≥19 7. Has a diagnosis of idiopathic Parkinson's disease, without any other known or suspected cause of parkinsonism. Initial diagnosis of PD must have been made more than 1 year prior to Screening. 8. Has non-motor neuropsychiatric symptoms severe enough to warrant treatment with an antipsychotic agent based on investigator judgement and CGI-S score 9. If the subject is on anti-Parkinsonian medication, they must be on a stable regimen for 1 month prior to Baseline and not planning (at the time of the Baseline visit) to make a major change in dose(s) 10. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential or must agree to use a clinically acceptable method of contraception or be abstinent for at least 1 month prior to the Baseline visit, during the study, and 41 days following completion of double-blind treatment.
Exclusion criteria
1. Has atypical parkinsonism or secondary parkinsonism variants such as tardive or medication induced parkinsonism 2. Is in hospice, is receiving end-of-life palliative care, or is bedridden or confined to a wheelchair 3. Has neuropsychiatric symptoms that are primarily attributable to current delirium or substance abuse 4. Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or psychiatric disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study 5. Has a known personal or family history of long QT syndrome or family history of sudden cardiac death 6. Has orthostatic hypotension as judged by the investigator and medical monitor 7. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason, including if the subject is judged to be a danger to self or others Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events (TEAEs) | 4-week treatment duration, plus 30 days treatment-free safety follow-up | Assess the safety and tolerability of pimavanserin in patients with PD in terms of treatment-emergent adverse events. |
Countries
United States
Participant flow
Recruitment details
The study was performed in patients aged 50-85 years with a diagnosis of idiopathic Parkinson's disease (PD) with a minimum duration of \>1 year at screening and with no other known or suspected cause of parkinsonism.
Pre-assignment details
During the screening period, patients were assessed for study eligibility, and prohibited medications were discontinued when medically appropriate.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Two encapsulated placebo tablets, taken once daily | 4 |
| Quetiapine Quetiapine starting dose 25 mg once daily (provided as 1 × 25 mg quetiapine immediate release encapsulated tablet plus 1 placebo encapsulated tablet), with the possibility to increase the dose to 50 mg (2 × 25 mg quetiapine immediate release encapsulated tablets) or 100 mg (2 × 50 mg quetiapine immediate release encapsulated tablets) taken once daily, based on clinical response. | 4 |
| Pimavanserin 34 mg Pimavanserin provided as 2 × 17 mg encapsulated tablets, taken once daily | 3 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | COVID-19 withdrawal of consent | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Pimavanserin 34 mg | Quetiapine |
|---|---|---|---|---|
| Age, Continuous | 69.8 years STANDARD_DEVIATION 5.74 | 67.0 years STANDARD_DEVIATION 6.65 | 62.0 years STANDARD_DEVIATION 3 | 68.0 years STANDARD_DEVIATION 8.49 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 10 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 4 participants | 11 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 1 / 4 | 3 / 4 | 1 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Treatment-emergent Adverse Events (TEAEs)
Assess the safety and tolerability of pimavanserin in patients with PD in terms of treatment-emergent adverse events.
Time frame: 4-week treatment duration, plus 30 days treatment-free safety follow-up
Population: Safety Analysis set, i.e. all patients who had received at least one dose of study medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Quetiapine | Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Pimavanserin 34 mg | Treatment-emergent Adverse Events (TEAEs) | 1 Participants |