A Study to Evaluate the Efficacy, Safety and Tolerability of SEP-363856 in Subjects With Parkinson's Disease Psychosis

Inclusion Criteria

• Subject, caregiver, and/or legally authorized representative understands and is willing to sign informed consent to participate in the study.
• Subject must be willing and able to comply with the study procedures and visit schedules and must be able to follow verbal and written instructions.
• Subject is male or postmenopausal female ≥ 55 years of age.
• Subject meets established diagnostic criteria for Parkinson's disease of at least one year duration, consistent with the UK Brain Bank criteria
• Subject has psychotic symptoms that began after the diagnosis of PD for at least one month, occurring at least weekly in the month prior to screening (according to subject or caregiver), and severe enough to warrant treatment with antipsychotics.
• Subject has a combined score of at least 6 or an individual score of at least 4 on the neuropsychiatric inventory (NPI) Item A (delusions) and/or Item B (hallucinations). This crieterion must be met at Visit 1 and Visit 3.
• Subject has a Mini-mental status examination (MMSE) score > 21 points out of 30.
• Subject has a caregiver (spouse or family member) who will be required to attend all visits and is able to provide study information on various scales such as the NPI.
• Subject is taking antiparkinsonian drugs or deep brain stimulation, with a stable dose/dose regimen and settings for 3 months before enrolment.
• Female subject must be postmenopausal defined as being amenorrheic for greater than two years with an appropriate clinical profile.
• Male subjects with female partner(s) of childbearing potential must agree to avoid fathering a child and use acceptable methods of birth control from screening until at least 30 days after the last study drug administration.
• Subject is, in the opinion of the Investigator, medically stable based on screening medical history, PE, neurological examination, vital signs, clinical laboratory values (hematology, serum chemistry, urinalysis, lipid panel, coagulation panel, thyroid panel, and serum prolactin).
• Subject has had a stable living arrangement at the time of screening.

Exclusion Criteria

• Subject has psychosis secondary to other toxic or metabolic disorders.
• Subject has atypical Parkinson's disease, Parkinsonism secondary to medication or other neurodegenerative disorders, such as progressive supranuclear palsy or multiple system atrophy.
• Subject has dementia diagnosed concurrent with or before Parkinson's disease, motor symptoms that began less than one year before the onset of dementia or symptoms consistent with the diagnosis of lewy body dementia (LBD), or if the psychosis occurred after ablative stereotaxic surgery.
• Subject failed 2 or more antipsychotic agents given at adequate doses for at least 4 weeks within 1 year before screening.
• Subject has had a stroke or other uncontrolled serious medical or neurological illness within 6 months of baseline.
• Subject answers "yes" to "Suicidal Ideation" Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C SSRS at Screening (ie, in the past one month), or baseline (ie, since last visit).
• Subject does not tolerate venipuncture or has poor venous access that would cause difficulty for collecting blood samples.
• Subject has participated in an investigational drug study and received investigational drug within 30 days (or longer if the half-life is known to be ≥ 150 hours) prior to the screening visit, or who is currently participating in another clinical study. Subject has previously received SEP 363856.
• Subject has any clinically significant unstable medical condition or any clinically significant chronic disease that in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in the study:
• Subject has hematological (including deep vein thrombosis) or bleeding disorder, renal, metabolic, endocrine, pulmonary, gas