A Clinical Study That Will Assess How Food Moves Through the Stomach and Effects Blood Glucose Levels in Subjects With Schizophrenia Taking SEP-363856 or and Prior Antipsychotic (PA) Standard

Study Overview
=================
Brief Summary
-----------------
A clinical study to determine whether an investigational medication (SEP363856) changes how long it takes for food to move through the stomach into the small intestine in patients with schizophrenia. This study is accepting both male and female subjects. It will be conducted in approximately 6 study sites in the United States. The duration of participation will be approximtely 10 weeks.

Detailed Description
-----------------
This is a randomized, open-label, single dose two-period crossover study with two treatment sequences. For each treatment sequence, subjects will receive a single-dose of SEP-363856 and prior antipsychotic (PA) standard of care (PA) in random order. Up to 3 separate cohorts of subjects will be randomized to determine the final dose of SEP-363856.

Official Title
-----------------
A Randomized, Open-Label, Single Dose, Cross-over Study of Gastric Emptying Rate: SEP-363856 vs Prior Antipsychotic Standard of Care in Subjects With Schizophrenia

Conditions
-----------------
Schizophrenia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: (this list is not all inclusive) 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 CGI-S score ≤ 4 (normal to moderately ill) at Screening Subject must have a PANSS total score ≤ 80 at Screening and a score of ≤ 4 on the following PANSS items at Screening: P7 (hostility) and G8 (uncooperativeness) Subjects' antipsychotic medication at screening must have had no dose change (minor dose adjustments for tolerability purposes are permitted) for at least eight weeks prior to the Screening visit. Exclusion Criteria: (this list is not all inclusive) 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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP-363856<br> | Drug: SEP-363856<br>* SEP-363856 will be supplied by 25 mg and 50 mg tablets. Multiple tablets may be required to achieve a single dose.<br>|
| 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>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying T 1/2 (gastric emptying scintigraphy (GES) imaging) | Gastric emptying T 1/2 (gastric emptying scintigraphy (GES) imaging) is gastric emptying half life (T1/2), which is a time needed for the half of the ingested gastric solids to leave the stomach. | multiple time-points post-radiolabelled meal on dosing day 1 and 2 | 
| Gastric retention at 4 hr post-radiolabeled meal (gastric emptying scintigraphy (GES) imaging) | Gastric retention at 4 hr post-radiolabeled meal is gastric retention 4h post meal, which estimates a percentage of remaining gastric solids in the stomach 4 hours after the meal. | 4 hours post-radiolabel meal on dosing Day 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric retention (proportion retained or % retained) at 1 hr and 2 hr post-radiolabeled meal | Gastric retention (proportion retained or % retained) at 1h and 2h post meal. | 1 and 2 hours post-radiolabel meal | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
schizophrenia