An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia

Study Overview
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Brief Summary
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An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia

Detailed Description
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This is a 26 week, multiregional, open-label extension study designed to evaluate the long-term safety and tolerability of SEP-363856 for the treatment of subjects with schizophrenia who have completed the 4 week double-blind treatment phase of Study SEP361-201 (NCT02969382) Subjects received open-label SEP-363856 50 mg/day from Day 1 through Day 3, and then received flexible dosing of SEP-363856 (25, 50, or 75 mg/day) for the rest of the trial. No statistical hypothesis tests will be performed.

Official Title
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A 26-Week Open-label Safety and Tolerability Extension Study of SEP-363856 in Adult Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SEP-363856


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must give written informed consent and privacy authorization prior to participation in the study and able to comply with the protocol, in the opinion of the investigator. Subject has completed Study SEP361 201 through Week 4 Subject has not taken any medication other than the study drug for the purpose of controlling schizophrenia symptoms during Study SEP361 201. Female subject must have a negative urine pregnancy test at Visit 7 of Study SEP361 201; females who are post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will be exempted from the pregnancy test. 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 Exclusion Criteria: 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 Visit 7 of Study SEP361 201. Subjects who answer yes to this question must be referred to the Investigator for follow up evaluation. Subject has a clinically significant abnormality including physical examination, vital signs, ECG, or laboratory test at Visit 7 of Study SEP361 201 that the investigator in consultation with the medical monitor considers to be inappropriate to allow participation in the study. Subject has a positive urine drug screen (UDS) or breath alcohol test at Visit 7 of Study SEP361 201. Subject is pregnant or lactating. Subject is at high risk of non-compliance in the Investigator's opinion. Subject is in the opinion of the Investigator, unsuitable in any other way to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP-363856<br>SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily | Drug: SEP-363856<br>* One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks<br>|

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 | Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation | From first dose of study drug to last study visit (27 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior. | Overall post Open-label Baseline treatment period (26 weeks) | 
| Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior. | Overall post Open-label Baseline treatment period (26 weeks) | 
| Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856 | Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others. | From the time of clinical response to relapse or censor (one day after the last study drug dose) | 
| Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856 | Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others. | From the time of clinical response to relapse or censor (one day after the last study drug dose) | 
| Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology) | 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. | Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26) | 
| Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score | 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. | Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 | 
| Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score | The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form. | Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 | 
| Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms. Total score will be equal to the sum of the 10 items (range between 0 and 60). | Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 | 
| Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201 | 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. | Week 26 | 

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