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

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02970929
• Collaborator: (none)
• Enrollment: 157
• Locations: 30
• Arm: 1
• Actual Duration (Months): 23.9
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: SEP-363856	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-Week Open-label Safety and Tolerability Extension Study of SEP-363856 in Adult Subjects With Schizophrenia
• Actual Study Start Date: Jan 31, 2017
• Actual Primary Completion Date: Jan 29, 2019
• Actual Study Completion Date: Jan 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SEP-363856 SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily	Drug: SEP-363856; One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks

Outcome Measures

Primary Outcome Measures

1. The Incidence of 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)]

   Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation

Secondary Outcome Measures

1. Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) [Overall post Open-label Baseline treatment period (26 weeks)]

   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.

2. Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) [Overall post Open-label Baseline treatment period (26 weeks)]

   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.

3. 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 [From the time of clinical response to relapse or censor (one day after the last study drug dose)]

   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.

4. 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 [From the time of clinical response to relapse or censor (one day after the last study drug dose)]

   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.

5. 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) [Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)]

   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.

6. 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 [Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26]

   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.

7. 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 [Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26]

   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.

8. 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 [Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26]

   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).

9. 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 [Week 26]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland International research Group	Little Rock	Arkansas	United States	72211
2	CNRI-Los Angeles, LLC	Pico Rivera	California	United States	90660
3	UCSD Medical Center UCSD Department of Psychiatry	San Diego	California	United States	92103-8229
4	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
5	Kashinath Yadalam	Lake Charles	Louisiana	United States	70629
6	Pillar Clinical Research, LLC	Dallas	Texas	United States	75243
7	Bugát Pál Kórház-Rendelőintézet, Rehabilitációs Elmegyógyászati Osztály	Gyongyos	Dózsa György	Hungary	út 20-22
8	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza, Pszichiatriai Osztaly	Gyula		Hungary	5700
9	Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"	Bucuresti		Romania	010825
10	Centrul de Evaluarea si Tratament al Toxicodependentelor pentru Tineri "Sf. Stelian", Sectia Psihiatrie	Bucuresti		Romania	060222
11	spitalul Clinic de Neuropsihiatrie Craiova ,Clinica II Psihiatrie	Craiova		Romania	200473
12	Institutul de Psihiatrie Socola Iasi, Sectia Psihiatrie III Acuti	Iasi		Romania	700282
13	Sverdlov Regional Psychiatric Clinical Hospital	Ekaterinburg		Russian Federation	620030
14	St-Petersburg SHI Psychiatrical hospital #1 n.a. Kaschenko	Gatchina		Russian Federation	188357
15	SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"	Saint-Petersburg		Russian Federation	197341
16	SHI Regional Clinical Psychiatry Hospital of St. Sofia	Saratov		Russian Federation	410060
17	FSBEI HE "Smolensk State Medical University" of the MoH of the RF	Smolensk		Russian Federation	214019
18	City Psychiatric Hospital of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation	190121
19	FB=SBI"Saint Petersburg Scientific and Research Psychoneurological Institute n.a. V.M. Bekhterev"	St. Petersburg		Russian Federation	192019
20	SPb SBIH "City Psychoneurological Dispensary #7 (with inpatient facilities)"	St. Petersburg		Russian Federation	198020
21	Regional Psychoneurological Hospital #3, Dept of Crisis Cond & Primary Psych Episode #1	Ivano Frankivsk		Ukraine	76014
22	CHI Kharkiv RCPH#3 Center of Emerg PsychSI Inst of Neur, Psych & Narc of NAMSU, Unit of Emergency Psychiatry and Narcology	Kharkiv		Ukraine	61068
23	CHI Kharkiv Regional Clinical Psychiatric Hospital #3, Psychiatric Department of Primary Psychotic Episod	Kharkiv		Ukraine	61068
24	CI Kherson Regional Psychiatric Hospital of Kherson RC	Kherson, Vil Stepanivka		Ukraine	73488
25	TMA Psychiatry in Kyiv Center of NT & Rehabilitation of Psychotic Conditions	Kyiv		Ukraine	04080
26	CI Odesa Regional Medical Center of Mental Health	Odesa		Ukraine	65006
27	CI Cherkasy Regional Psychiatric Hospital of ChRC, Femail Dept #11, Male Dept #12	Smila		Ukraine	20708
28	Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #6 Ternopil I.ya. Gorbachevskyi SMU	Ternopil		Ukraine	46020
29	Transcarpathian Regional Narcological Dispensary	Uzhgorod		Ukraine	88000
30	CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU	Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• Sunovion

Investigators

• Study Chair: CNS Medical Director, Sunovion

Study Documents (Full-Text)

• Study Protocol - Oct 13, 2017
• Statistical Analysis Plan - Feb 27, 2019

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT02970929
• Other Study ID Numbers: SEP361-202; 2016-001556-21
• First Posted: Nov 22, 2016
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sunovion: Schizophrenia
• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Period Title: Overall Study
STARTED	157
Subjects Who Received Study Medication	156
COMPLETED	105
NOT COMPLETED	52

Baseline Characteristics

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Overall Participants	156
Age (Count of Participants)
<=18 years	2 1.3%
Between 18 and 65 years	154 98.7%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.2 (6.03)
Sex: Female, Male (Count of Participants)
Female	54 34.6%
Male	102 65.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 3.2%
Not Hispanic or Latino	151 96.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 2.6%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	15 9.6%
White	136 87.2%
More than one race	1 0.6%
Unknown or Not Reported	0 0%
Age, Customized (Count of Participants)
>=18 - <25 years	38 24.4%
>=25 - <=40 years	118 75.6%
Country (Count of Participants)
Hungary	8 5.1%
Romania	6 3.8%
Russia	68 43.6%
Ukraine	54 34.6%
United States	20 12.8%
Double-blind Baseline BMI (Body Mass Index) Group (Count of Participants)
<18.5 kg/m^2	2 1.3%
>=18.5 - <25.0 kg/m^2	80 51.3%
>=25.0 - <30.0 kg/m^2	55 35.3%
>=30.0 kg/m^2	19 12.2%
Open-label Baseline BMI (Body Mass Index) Group (Count of Participants)
<18.5 kg/m^2	3 1.9%
>=18.5 - <25.0 kg/m^2	82 52.6%
>=25.0 - <30.0 kg/m^2	53 34%
>=30.0 kg/m^2	18 11.5%
Open-label Baseline Waist Circumference (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	85.20 (13.467)
Open-label Baseline BMI (Body Mass Index) (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.05 (3.890)
Open-label Baseline Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.32 (13.987)
Open-label Baseline Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.1 (7.73)
Double-blind Baseline Waist Circumference (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	85.36 (13.508)
Double-blind Baseline BMI (Body Mass Index) (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.07 (3.863)
Double-blind Baseline Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.38 (13.873)
Double-blind Baseline Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.1 (7.73)

Outcome Measures

1. Primary Outcome

Title	The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation
Description	Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation
Time Frame	From first dose of study drug to last study visit (27 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
Overall Adverse Events (AEs)	88 56.4%
Serious Adverse Events (SAEs)	15 9.6%
Adverse Events leading to discontinuation from study	18 11.5%
Adverse Events leading to discontinuation of study drug	18 11.5%

2. Secondary Outcome

Title	Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	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.
Time Frame	Overall post Open-label Baseline treatment period (26 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
Any suicidal ideation	3 1.9%
Any suicidal behavior	1 0.6%
Any suicidality	3 1.9%

3. Secondary Outcome

Title	Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	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.
Time Frame	Overall post Open-label Baseline treatment period (26 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
SI: Wish to be dead	2 1.3%
SI: Non-specific active suicidal thoughts	2 1.3%
SI: Any methods (not plan) without intent to act	0 0%
SI: Some intent to act, without specific plan	0 0%
SI: Specific plan and intent	0 0%
SB: Preparatory acts or behavior	0 0%
SB: Aborted attempt	1 0.6%
SB: Interrupted attempt	0 0%
SB: Actual attempt (non-fatal)	0 0%
SB: Completed suicide	0 0%

4. Secondary Outcome

Title	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
Description	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.
Time Frame	From the time of clinical response to relapse or censor (one day after the last study drug dose)

Outcome Measure Data

Analysis Population Description

Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.

Arm/Group Title	PBO-SEP	SEP-SEP
Arm/Group Description	Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202	Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202
Measure Participants	59	51
Median (95% Confidence Interval) [Days]	NA	NA

5. Secondary Outcome

Title	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
Description	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.
Time Frame	From the time of clinical response to relapse or censor (one day after the last study drug dose)

Outcome Measure Data

Analysis Population Description

Relapse population, which includes subjects who received at least one dose of open-label treatment and demonstrated a clinical response to 4 weeks of treatment with SEP-363856. Clinical response is defined as meeting (1) a decrease in PANSS total score of ≥ 20% from double-blind Baseline, AND (2) a CGI-S score ≤ 4. For PBO-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-201. For SEP-SEP subjects, clinical response was evaluated at Week 4 of study SEP361-202.

Arm/Group Title	PBO-SEP	SEP-SEP
Arm/Group Description	Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202	Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202
Measure Participants	59	51
Count of Participants [Participants]	12 7.7%	11 NaN

6. Secondary Outcome

Title	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)
Description	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.
Time Frame	Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)

Outcome Measure Data

Analysis Population Description

Subjects with PANSS data missing at a particular time point did not contribute to the summary for that time point.

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
Total Score: DB BLN Observed	101.5 (7.99)
Total Score: OL BLN Observed	83.1 (15.03)
Total Score: Wk 26 Observed	59.3 (12.45)
Total Score: Chg from DB BLN at Wk 26	-41.8 (13.98)
Total Score: Chg from OL BLN at Wk 26	-22.6 (15.48)
Positive SS: DB BLN Observed	25.7 (3.22)
Positive SS: OL BLN Observed	19.8 (4.96)
Positive SS: Wk 26 Observed	12.2 (3.72)
Positive SS: Chg from DB BLN at Wk 26	-13.5 (4.75)
Positive SS: Chg from OL BLN at Wk 26	-7.3 (5.37)
Negative SS: DB BLN Observed	25.4 (4.03)
Negative SS: OL BLN Observed	22.3 (4.38)
Negative SS: Wk 26 Observed	17.2 (4.10)
Negative SS: Chg from DB BLN at Wk 26	-8.4 (4.48)
Negative SS: Chg from OL BLN at Wk 26	-5.2 (4.20)
Gen-Psychopathology SS: DB BLN Observed	50.4 (5.01)
Gen-Psychopathology SS: OL BLN Observed	41.1 (7.93)
Gen-Psychopathology SS: Wk 26 Observed	30.0 (6.77)
Gen-Psychopathology SS: Chg from DB BLN at Wk 26	-19.9 (7.86)
Gen-Psychopathology SS: Chg from OL BLN at Wk 26	-10.2 (8.31)

7. Secondary Outcome

Title	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
Description	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.
Time Frame	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Subjects with CGI-S score data missing at a particular time point did not contribute to the summary for that time point.

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
CGI-S Score: DB Baseline Observed	5.0 (0.42)
CGI-S Score: OL Baseline Observed	4.0 (0.84)
CGI-S Score: Week 26 Observed	3.0 (0.74)
CGI-S Score: Change from DB Baseline at Week 26	-2.0 (0.82)
CGI-S Score: Change from OL Baseline at Week 26	-1.0 (0.91)

8. Secondary Outcome

Title	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
Description	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.
Time Frame	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Subjects with BNSS total score data missing at a particular time point did not contribute to the summary for that time point.

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
Total Score: DB Baseline Observed	38.4 (11.94)
Total Score: OL Baseline Observed	33.0 (11.41)
Total Score: Week 26 Observed	22.5 (11.83)
Total Score: Change from DB Baseline at Week 26	-16.8 (12.42)
Total Score: Change from OL Baseline at Week 26	-11.3 (9.69)

9. Secondary Outcome

Title	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
Description	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).
Time Frame	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Subjects with MADRS total score data missing at a particular time point did not contribute to the summary for that time point.

Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
Measure Participants	156
Total Score: DB Baseline Observed	12.6 (7.25)
Total Score: OL Baseline Observed	9.2 (6.33)
Total Score: Week 26 Observed	4.4 (4.72)
Total Score: Change from DB Baseline at Week 26	-8.1 (6.44)
Total Score: Change from OL Baseline at Week 26	-4.5 (5.28)

10. Secondary Outcome

Title	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
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Subjects who received at least one dose of open-label treatment and had PANSS total score data available at Double-blind Baseline and Week 26 are included in analysis.

Arm/Group Title	PBO-SEP	SEP-SEP
Arm/Group Description	Subjects who received Placebo in study SEP361-201 and SEP-363856 in study SEP361-202	Subjects who received SEP-363856 in study SEP361-201 and SEP-363856 in study SEP361-202
Measure Participants	53	51
Count of Participants [Participants]	52 33.3%	49 NaN

Adverse Events

Time Frame	From first dose of study drug to last study visit (27 weeks)
Arm/Group Title	SEP-363856
Arm/Group Description	SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
All Cause Mortality
	SEP-363856
	Affected / at Risk (%)	# Events
Total	0/156 (0%)
Serious Adverse Events
	SEP-363856
	Affected / at Risk (%)	# Events
Total	15/156 (9.6%)
Psychiatric disorders
Acute psychosis	1/156 (0.6%)	1
Depression	1/156 (0.6%)	1
Psychotic disorder	1/156 (0.6%)	1
Schizophrenia	11/156 (7.1%)	11
Suicidal ideation	1/156 (0.6%)	1
Reproductive system and breast disorders
Uterine haemorrhage	1/156 (0.6%)	1
Other (Not Including Serious) Adverse Events
	SEP-363856
	Affected / at Risk (%)	# Events
Total	39/156 (25%)
Nervous system disorders
Headache	18/156 (11.5%)	36
Psychiatric disorders
Anxiety	8/156 (5.1%)	36
Insomnia	13/156 (8.3%)	24
Schizophrenia	10/156 (6.4%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.