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

This is a multicenter, randomized, parallel-group, double-blind, placebo-controlled study
evaluating the efficacy, safety, and tolerability of SEP-363856 flexibly dosed at 25, 50, or
75 mg/day for 6 weeks in male and female subjects ≥ 55 years of age with a clinical diagnosis
of PDP. The study will randomize approximately 36 subjects to 2 treatment groups in a 2:1
ratio (approximately 24 subjects to SEP-363856 and 12 to placebo).

The study will consist of 4 periods: Screening/washout Period (up to 14 days prior to
Lead-in), Lead-in Period (2 weeks prior to Baseline), Double-blind treatment Period (6
weeks), and Follow-up Period (1 week after last dose) as shown in the following figure. All
post-Baseline clinic visits will have a window of ± 2 days relative to the date of the
Baseline visit (Visit 3).

Inclusion Criteria:

- 1. Subject, caregiver, and/or legally authorized representative understands and is
willing to sign informed consent to participate in the study.

2. 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.

3. Subject is male or postmenopausal female ≥ 55 years of age. 4. Subject meets
established diagnostic criteria for Parkinson's disease of at least one year duration,
consistent with the UK Brain Bank criteria 5. 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.

6. 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 criterion must be met at visits 1 and 3.

7. Subject has a Mini-mental status examination (MMSE) score > 16 points out of 30.

8. 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
and Zarit 22 scale.

9. Subject is taking antiparkinsonian drugs or deep brain stimulation, with a stable
dose/dose regimen and settings for 1 month before screening.

10. Female subject must be postmenopausal defined as being amenorrheic for greater
than two years with an appropriate clinical profile.

11. 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.

12. 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).

13. Subject has had a stable living arrangement at the time of screening.

Exclusion Criteria:

- 1. Subject has psychosis secondary to other toxic or metabolic disorders. 2. Subject
has atypical Parkinson's disease, Parkinsonism secondary to medication or other
neurodegenerative disorders, such as progressive supranuclear palsy or multiple system
atrophy.

3. 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.

4. Subject failed 2 or more antipsychotic agents given at adequate doses for at least
4 weeks within 1 year before screening. Treatment failure is defined as a complete
lack of efficacy. Subjects who had a partial response or who discontinued treatment
for reasons of tolerability will be allowed.

5. Subject has had a stroke or other uncontrolled serious medical or neurological
illness within 6 months of baseline.

6. 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).

7. Subject does not tolerate venipuncture or has poor venous access that would cause
difficulty for collecting blood samples.

8. 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
interventional study. Observational studies are not exclusionary. Subject has
previously received SEP 363856.

9. 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: 10. Subject has
hematological (including deep vein thrombosis) or bleeding disorder, renal, metabolic,
endocrine, pulmonary, gastrointestinal, urological, cardiovascular, hepatic,
neurologic, or allergic disease that is clinically significant or unstable as judged
by the Investigator 11. Subject has a history of malignancy within 5 years prior to
the Screening visit, except for adequately treated basal cell or squamous cell skin
cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.

12. Subject has, in the opinion of the investigator, a disorder or history of a
condition such as a clinically significant abnormality of the hepatic or renal system
or a history of malabsorption, or previous gastrointestinal surgery (eg,
cholecystectomy, vagotomy, bowel resection, or any surgical procedure) that may
interfere with drug absorption, distribution, metabolism, excretion.

13. Subject has known or suspected Alcohol or Substance Use Disorder as defined by DSM
5. The only exceptions are caffeine or nicotine.

14. Subject has a clinically significant abnormal 12 lead ECG that may result in the
subject's inability to complete the study, as judged by the Investigator.

15. Subjects with known human immunodeficiency virus (HIV) seropositivity will be
excluded.

16. Female subject who is pregnant or lactating. 17. Subject has an active and
unstable psychiatric disorder as judged by the investigator 18. Subject is at
significant risk of harming him/herself or others according to the Investigator's
judgment.

19. Subject has attempted suicide within 3 months prior to screening. 20. Subject has
a history of allergic reaction or suspected sensitivity to any substance that is
contained in the study drug formulation.

21. Subject has any clinically significant abnormal laboratory values (hematology,
serum chemistry, urinalysis, lipid panel, coagulation panel, thyroid panel, serum
prolactin, and urine drug screen(Note: abnormal findings that may be clinically
significant or of questionable significance will be discussed with the Medical Monitor
prior to including subject).

22. Subjects with serum alanine transaminase (ALT) or aspartate transaminase (AST)
levels ≥ 3 times, serum blood urea nitrogen (BUN) or creatine ≥ 1.5 X the upper limit
of the reference ranges provided by the central laboratory require retesting. If on
retesting, the laboratory value remains equal to or above the ULN, the subject will be
excluded.

23. Subjects with a random (non-fasting) blood glucose at screening ≥ 200 mg/dL (11.1
mmol/L) or HbA1c ≥ 7% will be excluded.

24. Subject has a prolactin concentration > 100 ng/mL at screening or has a history of
pituitary adenoma.

25.. Subject has an abnormal BMI that may result in the subject's inability to
complete the study, as judged by the Investigator.

26. Subject has experienced significant blood loss (≥ 473 mL) or donated blood within
60 days prior to first dose of study drug; has donated plasma within 72 hours prior to
the first dose of study drug or intends to donate plasma or blood or undergo elective
surgery during study participation or within 60 days after the last study visit.

27. Subject consumes more than 300 mg of caffeine per day (5 cups of coffee or
equivalent in caffeinated beverages).

28. Subject has used disallowed prescription medications within 30 days of screening
or anticipates the need for any disallowed medication during their participation in
this study. 29. Subject is a staff member or the relative of a staff member.

30. Subject is in the opinion of the Investigator, unsuitable in any other way to
participate in this study.