A Clinical Trial to Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia

Study Overview
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Brief Summary
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A clinical trial to study the efficacy and safety of an investigational drug in acutely psychotic people with schizophrenia. Participants in the study will either receive the drug being studied or a placebo. This study is accepting male and female participants between 13 years old -65 years old who have been diagnosed with schizophrenia. This study will be conducted in 70 locations worldwide. The study will last up to 9 weeks total time.

Detailed Description
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This is a multicenter, randomized, double-blind, parallel-group, fixed-dosed study evaluating the efficacy and safety of two doses of SEP-363856 (50 and 75 mg/day) versus placebo over a 6-week Treatment Period in acutely psychotic subjects with schizophrenia. This study is projected to randomize approximately 435 subjects (18-65 years) to 3 treatment groups (SEP-363856 50 mg/day, SEP-363856 75 mg/day, or placebo) in a 1:1:1 ratio. In addition, the study will randomize approximately 90 adolescent subjects (13-17 years) in a 1:1:1 ratio to the 3 treatment groups (with approximately 30 subjects per group) in a separate cohort. Treatment assignment will be stratified by country. Study drug will be taken once a day and may be taken with or without food. This study is designed to test the hypothesis that, treatment with SEP-363856 in adult subjects with schizophrenia will result in significantly greater reduction (i.e. improvement) in PANSS total score and CGI-S score at Week 6 from Baseline when compared to placebo. The overall Type I error is controlled for two hierarchical families of hypotheses. The first family includes hypotheses about the testing of change from Baseline in PANSS total score at Week 6 between each of the SEP-363856 dose levels vs. placebo. The second family of hypotheses are about the testing of change from Baseline in CGI-S score at Week 6 between each of the SEP-363856 dose levels vs. placebo.

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose, Multicenter Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SEP-363856 50mg
* Drug: SEP-363856 75mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject between 13 to 65 years of age (inclusive) at the time of consent. Subject or subjects parent/legal guardian [adolescents] must give written informed consent and privacy authorization prior to participate in the study; adolescents must also provide informed assent.. Subject meets DSM-5 criteria for schizophrenia as established by clinical interview at screening Subject must have a CGI-S score ≥ 4 Subject must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 on 2 or more of the following PANSS items: delusions, conceptual disorganization, hallucinations, and unusual thought content Subject has an acute exacerbation of psychotic symptoms (persisting no longer than 2 months prior to providing informed consent). Subject has marked deterioration of functioning in one or more areas. Subject is, in the opinion of the Investigator, generally healthy based on screening medical history, PE, neurological examination, vital signs, ECG, and clinical laboratory values. Exclusion Criteria: Subject has a 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 of the brain or other body systems, major depressive disorder, bipolar I or II disorder, schizoaffective disorder, obsessive compulsive disorder, and posttraumatic stress disorder. Symptoms of mild to moderate mood dysphoria or anxiety are allowed so long as these symptoms are not the primary focus of treatment. Subject is at significant risk of harming self, others, or objects based on Investigator's judgment. 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: Female subject who is pregnant or lactating Subject has any clinically significant abnormal laboratory value(s) at Screening as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 13 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: randomized, double-blind, parallel-group, placebo controlled, fixed-dose multicenter study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP-363856 50mg<br>SEP-363856 50mg dosed once daily | Drug: SEP-363856 50mg<br>* SEP-363856 50mg tablet dosed once daily<br>|
| Experimental: SEP-363856 75mg<br>SEP-363856 75mg dosed once daily | Drug: SEP-363856 75mg<br>* SEP-363856 75mg tablet dosed once daily<br>|
| Placebo Comparator: Placebo<br>Placebo dosed once daily | Drug: Placebo<br>* Placebo tablet dosed once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Positive and negative syndrome scale (PANSS) total score at Endpoint (Week 6) | PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Clinical Global Impressions - Severity (CGI-S) score at Endpoint (Week 6) | The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity. | Baseline and Week 6 | 

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