A Clinical Study That Will Assess the Effect of SEP-363856 or Prior Antipsychotic (PA) Standard of Care on Body-weight Associated Parameters in Subjects With Schizophrenia

Study Overview
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Brief Summary
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A Clinical Study that will look at an investigational medication, SEP-363856 (called study medication) in patients with schizophrenia, and assess wether it affectsbody-weight associated parameters. This study is accepting male and female participants age 18 years to 65 years. This study will be conducted in approximately 6 study sites in the United States. Participation could last up to 13 weeks.

Detailed Description
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This is a double-blind, randomized, multiple dose study in male and female adult subjects with schizophrenia. Subjects will undergo structural magnetic resonance abdominal imaging (MRI) scans as well as hyperinsulinemic euglycemic clamp (HEC) also known as glucose clamp, after the check-in and towards the end of the treatment phase. Subjects will be randomized to SEP-363856 or their prior antipsychotic (PA). Subjects randomized to SEP-363856 will undergo blinded wash out of their PA, subsequent SEP-363856 blinded titration and 15 day of well tolerated SEP-363856 exposure. Subjects randomized to their prior antipsychotic (PA), will undergo pseudo PA washout, followed by pseudo-titration and 15 day of well tolerated PA exposure. Subjects will be discharged after subject is stable. All subjects will return to the clinic 7 + 2 days post discharge for follow-up assessments.

Official Title
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A Double-Blind, Randomized, Multiple Dose Study of Weight Associated Parameters: SEP-363856 vs Prior Antipsychotic (PA) Standard of Care in Subjects With Schizophrenia Suffering From Metabolic Dysregulation

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SEP-363856
* Drug: Prior antipsychotic (risperidone, olanzapine, quetiapine or aripiprazole)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: This is not an all inclusive list Male or female subjects between 18 and 65 years of age, inclusive at time of consent. Subject meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a primary diagnosis of schizophrenia as established by clinical interview, using the DSM-5 as a reference and confirmed using the Structured Clinical Interview for DSM-5, Clinical Trials Version [SCID-CT]). Subject must have a Positive and negative symptoms scale (PANSS) total score ≤ 80 at Screening and a score of ≤ 4 on the following PANSS items at Screening: P7 (hostility) and G8 (uncooperativeness) Subject must have a Clinical Global Impressions - Severity (CGI-S) score ≤ 4 (normal to moderately ill) at Screening. Subject must be receiving risperidone, olanzapine, quetiapine or aripiprazole as treatment for schizophrenia at the time of Screening. Exclusion Criteria: This is not an all inclusive list Subject has a DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia or intellectual disability (IQ < 70). Subject has attempted suicide within 12 months prior to Screening. Subject answers yes to Suicidal Ideation Items 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 1 month) or at any subsequent C-SSRS assessment prior to dosing (ie, since last visit). Subject is at risk of harming him/herself or others according to the Investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-Blind, Randomized, Multiple Dose
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prior antipsychotic (risperidone, olanzapine, quetiapine or aripiprazole)<br> | Drug: Prior antipsychotic (risperidone, olanzapine, quetiapine or aripiprazole)<br>* PA will be prepared by the pharmacy staff according to the patient's prescribed treatment and will be orally administered. Multiple tablets or capsules may be required to achieve a single dose.<br>|
| Experimental: SEP-363856<br> | Drug: SEP-363856<br>* SEP-363856 will be supplied as over-encapsulated tablets. Multiple tablets may be required to achieve a single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin stimulated change in glucose disposal rate during the steady state of the low dose hyperinsulinemic euglycemic clamp (HEC), baseline to end of the treatment |  | up to 8 weeks | 
| Insulin stimulated change in glucose disposal rate during the steady state of the high dose hyperinsulinemic euglycemic clamp (HEC) baseline to end of the treatment. |  | up to 8 weeks | 
| Change in liver proton density fat fraction (PDFF), baseline to end of the treatment |  | up to 8 weeks | 
| Change in fat content in muscles of interest, baseline to end of the treatment |  | up to 8 weeks | 
| Change in Liver Fibroinflammation, baseline to end of the treatment |  | up to 8 weeks | 
| Change in Liver Volume from baseline to end of treatment |  | up to 8 weeks |