A study to evaluate the safety and tolerability of SEP363856 in subjects with Parkinson's
- 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
7. Subject has a Mini-mental status examination (MMSE) score > 21 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 3 months before enrolment.
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.
- 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
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.
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
clinical study. 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
(except for untreated, asymptomatic, seasonal allergies at time of dosing).
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 a disorder or history of a condition, or previous gastrointestinal
surgery (eg, cholecystectomy, vagotomy, bowel resection, or any surgical procedure)
that may interfere with drug absorption, distribution, metabolism, excretion,
gastrointestinal motility, or pH, or a clinically significant abnormality of the
hepatic or renal system, or a history of malabsorption.
13. Subject has Alcohol or Substance Abuse Disorder (DSM 5 criteria). The only
exceptions are caffeine or nicotine.
14. Subject has a clinically significant abnormal 12 lead ECG that may jeopardize the
subject's ability to complete the study or a screening 12 lead ECG demonstrating any
one of the following: heart rate > 100 beats per minute, QRS > 120 ms, QT interval
corrected for heart rate using Fridericia's formula (QTcF) > 450 ms (males), QTcF >
470 ms (females), or PR > 220 ms.
15. Subjects with known human immunodeficiency virus (HIV) seropositivity will be
16. Female subject who is pregnant or lactating. 17. Subject has a presence or
history of a medically diagnosed, clinically significant psychiatric disorder.
18. Subject is at significant risk of harming him/herself or others according to the
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 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
23. Subjects with a random (non-fasting) blood glucose at screening ≥ 200 mg/dL (11.1
mmol/L) or HbA1c ≥ 6.5% will be excluded.
24. Subject has a prolactin concentration > 100 ng/mL at screening or has a history
of pituitary adenoma.
25. Subject's BMI is ≥ 30 mg/kg/m2. 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 or anticipates the need for
any disallowed medication during their participation in this study. Subject is a
staff member or the relative of a staff member.
29. Subject is in the opinion of the Investigator, unsuitable in any other way to
participate in this study.