We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02969369
Recruitment Status : Completed
First Posted : November 21, 2016
Last Update Posted : August 4, 2021
Information provided by (Responsible Party):

Brief Summary:
A study to evaluate the safety and tolerability of SEP363856 in subjects with Parkinson's Disease Psychosis. This study is accepting male and female participants 55 years of age and older who have been diagnosed with Parkinson's Disease. This study will be conducted in 24 study centers in the United States. The study will last approximately 21 weeks

Condition or disease Intervention/treatment Phase
Parkinson Disease Psychosis Drug: SEP-363856 Drug: Placebo capsule Phase 2

Detailed Description:

This is a multicenter, randomized, parallel-group, placebo-controlled study evaluating the efficacy, safety, and tolerability of double-blind SEP-363856 flexibly dosed at 25, 50, or 75 mg/day for 6 weeks followed by 12 weeks of open-label extension of SEP-363856 flexibly-dosed at 25, 50, or 75 mg/day 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 Double-blind Treatment), Double-blind Treatment Period (6 weeks), Open-label SEP-363856 Treatment Period (12 weeks), and Follow-up Period (1 week after last dose) as shown in the following figure. All postBaseline clinic visits will have a window of ± 2 days relative to the date of the Baseline visit (Visit 3).

Treatment with SEP-363856 in subjects with PDP will result in a significant reduction in the Scale for Assessment of Positive Symptoms - Parkinson's Disease (SAPS-PD) total score at Week 6 when compared to placebo. Let μSEP and μPBO represent the mean changes from Baseline at Week 6 in SAPS-PD total score for the SEP-363856 and placebo arms, respectively. The following hypothesis will be tested to compare the mean change values between the SEP-363856 group and placebo group at Week 6: H0: μSEP = μPBO versus H1: μSEP ≠ μPBO

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter Randomized Double-blind Followed by an Open-label Extension Study to Evaluate the Efficacy, Safety, and Tolerability of SEP-363856 in Subjects With Parkinson's Disease Psychosis
Actual Study Start Date : December 31, 2016
Actual Primary Completion Date : April 20, 2020
Actual Study Completion Date : April 20, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: SEP-363856
SEP-363856 (25, 50, or 75mg/day), once daily
Drug: SEP-363856
SEP-363856 (25, 50, or 75mg/day)

Placebo Comparator: Placebo Capsule
Placebo once daily
Drug: Placebo capsule
Placebo once daily

Primary Outcome Measures :
  1. Change from Double Blind (DB) Baseline in total Scale for Assessment of Positive Symptoms - Parkinson's Disease ( SAPS-PD) Score at Week 6 [ Time Frame: week 0-week 6 ]

    There are seven items assessing individual symptoms (four items for hallucinations and three items for delusions), a global hallucinations item and a global delusions item. Separate items are rated from 0 (absent) to 5 (severe). Total score will be equal to the sum of the seven items plus the global hallucinations, plus the global delusions. Therefore a total possible score on the SAPS-PD ranges from 0 to 45.

    Higher values represent a worse outcome: 0 (absent) to 5 (severe).

    Ttotal score will be equal to the sum of the seven items plus the global hallucinations, plus the global delusions.

Secondary Outcome Measures :
  1. Change from from Double Blind (DB) Baseline in the Clinical Global Impression-Severity of Illness (CGI S) at Week 6. [ Time Frame: week 0-week 6 ]
    The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.

  2. Change from from Double Blind (DB) Baseline in Neuropsychiatric Inventory (NPI) at Week 6 [ Time Frame: week 0-week 6 ]
    The Neuropsychiatric Inventory (NPI) is a 12-item behavior rating scale composed of a structured interview of the caregiver, which assess psychiatric disturbance. Both the frequency and the severity of each behavior are determined. NPI score is obtained by summing all the 12 sub-domain scores.

  3. Change from Double-blind (DB) Baseline in Mini Mental State Evaluation (MMSE) at Week 6 [ Time Frame: Week 0-Week 6 ]
    The Mini Mental State Examination (MMSE) for Cognition is a brief instrument, used to assess cognitive function, consisting of 11 tests including orientation, memory (recent and immediate), concentration, language, and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. MMSE, the total score will also be summing scores of all 11 tests.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   55 Years to 105 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 crieterion must be met at Visit 1 and Visit 3.
  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.
  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.

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.
  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 cancer or significant neoplasm.
  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 excluded.
  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 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 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) and 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.

Continuation into Open-label Extension Cirteria

  • Subject must have completed the 6-week double-blind treatment.
  • Subject has not taken any medication other than the study drug for the purpose of controlling PDD symptoms

    . • There has been no clinically significant change in the subject's medical condition or Parkinson's disease, in the opinion of the investigator.

  • Subject has not answered "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 assessment at any time during the DB treatment period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02969369

Show Show 24 study locations
Sponsors and Collaborators
Layout table for investigator information
Study Chair: CNS Medical Director Sunovion
Layout table for additonal information
Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02969369    
Other Study ID Numbers: SEP361-203
First Posted: November 21, 2016    Key Record Dates
Last Update Posted: August 4, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study may be made available upon request via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: IPD will be made available upon request within 12 months of posting the study results on ct.gov.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Keywords provided by Sunovion:
Parkinson's Disease Psychosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Psychotic Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Schizophrenia Spectrum and Other Psychotic Disorders