A Study of the Long-term Safety and Tolerability of an Investigational Drug in People With Schizophrenia.

Study Overview
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Brief Summary
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A clinical study to evaluate the long-term safety and tolerability of an investigational drug in people with schizophrenia. This study is accepting male and female participants between 18 years old -65 years old who have been diagnosed with schizophrenia. This study will be conducted in approximately 50 study centers worldwide. The study will last approximately 57 weeks.

Detailed Description
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This is a 52-week, multicenter, randomized, double-blind, parallel-group, flexible-dose study designed to evaluate the long-term safety and tolerability of SEP-363856 (50 to 100 mg/day) compared with quetiapine XR (400 to 800 mg/day) in clinically stable adult subjects with schizophrenia. This study is projected to randomize a least 300 subjects to two treatment groups (SEP-363856 50 to 100 mg/day or quetiapine XR 400 to 800 mg/day) in a 2:1 ratio. Study drug will be taken once a day and may be taken without food or with a light meal.

Official Title
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A Randomized, Double-blind, Active Comparator-Controlled Study to Evaluate the Long-term Safety and Tolerability of SEP-363856 in Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SEP363856
* Drug: quetiapine XR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: The main inclusion criteria include, but are not limited to the following: Male or female subject between 18 to 65 years of age (inclusive) at the time of consent. Subject meets DSM-5 criteria for a diagnosis of schizophrenia as established by clinical interview at screening (using the DSM-5 as a reference and confirmed using the SCID-CT). The time since the subject's diagnosis must be ≥ 1 year prior to Screening. Subject must have a CGI-S score ≤ 4 at Screening and Baseline. Subject must have a PANSS total score ≤ 80 at Screening and Baseline. Subject is judged to be clinically stable (i.e., no evidence of an acute exacerbation) by the Investigator for at least 8 weeks prior to Screening. Subject has had no change in antipsychotic medication(s) (minor dose adjustments for tolerability purposes are permitted) for at least 6 weeks prior to Screening. Subjects taking an antipsychotic agent at Screening may participate in this study only if there are signs of intolerability or lack of efficacy of the current antipsychotic (as determined by the Investigator). Subject is, in the opinion of the Investigator, generally healthy based on Screening medical history, PE, neurological examination, vital signs, electrocardiogram (ECG) and clinical laboratory values (hematology, chemistry and urinalysis). Exclusion criteria: Main exclusion criteria include, but are not limited to: Subject was hospitalized for a psychiatric illness within the 8 weeks prior to Screening. Subject has a current DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia. Exclusionary disorders include but are not limited to alcohol use disorder (within past 12 months), substance (other than nicotine or caffeine) use disorder within past 12 months, or lifetime history of significant substance abuse that, in the opinion of the Investigator or Sponsor, may have had a significant and potentially permanent impact on the brain or other body systems, major depressive disorder, schizoaffective disorder, ,bipolar I or II disorder, obsessive compulsive disorder, and posttraumatic stress disorder, symptoms of mild to moderate mood dysphoria or anxiety are allowed so long as theses symptoms are not the primary focus of treatment. Subject is judged to be resistant to antipsychotic treatment by the Investigator, based on failure to respond to 2 or more marketed antipsychotic agents within a 1-year period prior to Screening, given at adequate dose as per labeling, for at least 4 weeks. 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 assessment at Screening (i.e., in the past one month) or at Baseline (i.e., since last visit). Subject is at significant risk of harming self or others based on Investigator's judgment. Subject has attempted suicide within 6 months prior to Screening. Subject has received treatment with a psychotropic medication or herbal supplement within 3 days or 5 half-lives (whichever is longer) Subject has been treated with quetiapine or quetiapine XR within the 6 weeks prior to Screening or has a history of inadequate response or intolerability to quetiapine or quetiapine XR. 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. Subject has any clinically significant abnormal laboratory value(s) at Screening as determined by investigator.

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: A Randomized, Double-blind, Active Comparator-Controlled Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP363856<br>SEP363856 50mg, 75mg, 100mg, flexibly dosed once daily capsule | Drug: SEP363856<br>* SEP-363856, 50mg, 75mg, 100mg, flexibly dosed once daily capsule<br>|
| Active Comparator: quetiapine XR<br>quetiapine XR, 400, 600, 800 mg, flexibly dosed once daily capsule | Drug: quetiapine XR<br>* quetiapine XR, 400, 600, 800 mg, flexibly dosed once daily capsule<br>* Other names: Seroquel XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation |  | 52 Weeks | 

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