Schizophrenia
Conditions
Keywords
Schizophrenia
Brief summary
An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia
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.
Interventions
DRUGSEP-363856
One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
Countries
Hungary, Romania, Russia, Ukraine, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| SEP-363856 SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily | 156 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 18 |
| Overall Study | INVESTIGATOR CONSIDERS SUBJECT CLINICALLY UNSTABLE, NOT APPROPRIATE FOR DISCHARGE TO AN OUTPATIENT | 1 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | LOST TO FOLLOWUP | 6 |
| Overall Study | MOVED OUT OF STATE | 1 |
| Overall Study | NON-COMPLIANCE WITH STUDY DRUG | 1 |
| Overall Study | SPONSOR REQUEST THAT SUBJECT BE WITHDRAWN DUE TO POSITIVE DRUG RESULTS AND FOR THE SUBJECT'S SAFETY | 1 |
| Overall Study | Withdrawal by Subject | 16 |
Baseline characteristics
| Characteristic | SEP-363856 |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 154 Participants |
| Age, Continuous | 30.2 Years STANDARD_DEVIATION 6.03 |
| Age, Customized >=18 - <25 years | 38 Participants |
| Age, Customized >=25 - <=40 years | 118 Participants |
| Country Hungary | 8 Participants |
| Country Romania | 6 Participants |
| Country Russia | 68 Participants |
| Country Ukraine | 54 Participants |
| Country United States | 20 Participants |
| Double-blind Baseline BMI (Body Mass Index) Group >=18.5 - <25.0 kg/m^2 | 80 Participants |
| Double-blind Baseline BMI (Body Mass Index) Group <18.5 kg/m^2 | 2 Participants |
| Double-blind Baseline BMI (Body Mass Index) Group >=25.0 - <30.0 kg/m^2 | 55 Participants |
| Double-blind Baseline BMI (Body Mass Index) Group >=30.0 kg/m^2 | 19 Participants |
| Double-blind Baseline BMI (Body Mass Index) (kg/m^2) | 25.07 kg/m^2 STANDARD_DEVIATION 3.863 |
| Double-blind Baseline Height (cm) | 173.1 cm STANDARD_DEVIATION 7.73 |
| Double-blind Baseline Waist Circumference (cm) | 85.36 cm STANDARD_DEVIATION 13.508 |
| Double-blind Baseline Weight (kg) | 75.38 kg STANDARD_DEVIATION 13.873 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 151 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Open-label Baseline BMI (Body Mass Index) Group >=18.5 - <25.0 kg/m^2 | 82 Participants |
| Open-label Baseline BMI (Body Mass Index) Group <18.5 kg/m^2 | 3 Participants |
| Open-label Baseline BMI (Body Mass Index) Group >=25.0 - <30.0 kg/m^2 | 53 Participants |
| Open-label Baseline BMI (Body Mass Index) Group >=30.0 kg/m^2 | 18 Participants |
| Open-label Baseline BMI (Body Mass Index) (kg/m^2) | 25.05 kg/m^2 STANDARD_DEVIATION 3.89 |
| Open-label Baseline Height (cm) | 173.1 cm STANDARD_DEVIATION 7.73 |
| Open-label Baseline Waist Circumference (cm) | 85.20 cm STANDARD_DEVIATION 13.467 |
| Open-label Baseline Weight (kg) | 75.32 kg STANDARD_DEVIATION 13.987 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 136 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 156 |
| other Total, other adverse events | 39 / 156 |
| serious Total, serious adverse events | 15 / 156 |
Outcome results
Primary
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
Time frame: From first dose of study drug to last study visit (27 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SEP-363856 | The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation | Overall Adverse Events (AEs) | 88 Participants |
| SEP-363856 | The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation | Serious Adverse Events (SAEs) | 15 Participants |
| SEP-363856 | The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation | Adverse Events leading to discontinuation from study | 18 Participants |
| SEP-363856 | The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation | Adverse Events leading to discontinuation of study drug | 18 Participants |
Secondary
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.
Time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Population: Subjects with BNSS total score data missing at a particular time point did not contribute to the summary for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEP-363856 | 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 | Total Score: DB Baseline Observed | 38.4 Units on a scale | Standard Deviation 11.94 |
| SEP-363856 | 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 | Total Score: OL Baseline Observed | 33.0 Units on a scale | Standard Deviation 11.41 |
| SEP-363856 | 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 | Total Score: Week 26 Observed | 22.5 Units on a scale | Standard Deviation 11.83 |
| SEP-363856 | 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 | Total Score: Change from DB Baseline at Week 26 | -16.8 Units on a scale | Standard Deviation 12.42 |
| SEP-363856 | 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 | Total Score: Change from OL Baseline at Week 26 | -11.3 Units on a scale | Standard Deviation 9.69 |
Secondary
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.
Time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Population: Subjects with CGI-S score data missing at a particular time point did not contribute to the summary for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEP-363856 | 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 | CGI-S Score: DB Baseline Observed | 5.0 Units on a scale | Standard Deviation 0.42 |
| SEP-363856 | 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 | CGI-S Score: OL Baseline Observed | 4.0 Units on a scale | Standard Deviation 0.84 |
| SEP-363856 | 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 | CGI-S Score: Week 26 Observed | 3.0 Units on a scale | Standard Deviation 0.74 |
| SEP-363856 | 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 | CGI-S Score: Change from DB Baseline at Week 26 | -2.0 Units on a scale | Standard Deviation 0.82 |
| SEP-363856 | 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 | CGI-S Score: Change from OL Baseline at Week 26 | -1.0 Units on a scale | Standard Deviation 0.91 |
Secondary
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).
Time frame: Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Population: Subjects with MADRS total score data missing at a particular time point did not contribute to the summary for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEP-363856 | 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 | Total Score: DB Baseline Observed | 12.6 Units on a scale | Standard Deviation 7.25 |
| SEP-363856 | 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 | Total Score: OL Baseline Observed | 9.2 Units on a scale | Standard Deviation 6.33 |
| SEP-363856 | 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 | Total Score: Week 26 Observed | 4.4 Units on a scale | Standard Deviation 4.72 |
| SEP-363856 | 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 | Total Score: Change from DB Baseline at Week 26 | -8.1 Units on a scale | Standard Deviation 6.44 |
| SEP-363856 | 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 | Total Score: Change from OL Baseline at Week 26 | -4.5 Units on a scale | Standard Deviation 5.28 |
Secondary
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.
Time frame: Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)
Population: Subjects with PANSS data missing at a particular time point did not contribute to the summary for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEP-363856 | 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) | Total Score: DB BLN Observed | 101.5 Units on a scale | Standard Deviation 7.99 |
| SEP-363856 | 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) | Total Score: OL BLN Observed | 83.1 Units on a scale | Standard Deviation 15.03 |
| SEP-363856 | 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) | Total Score: Wk 26 Observed | 59.3 Units on a scale | Standard Deviation 12.45 |
| SEP-363856 | 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) | Total Score: Chg from DB BLN at Wk 26 | -41.8 Units on a scale | Standard Deviation 13.98 |
| SEP-363856 | 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) | Total Score: Chg from OL BLN at Wk 26 | -22.6 Units on a scale | Standard Deviation 15.48 |
| SEP-363856 | 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) | Positive SS: DB BLN Observed | 25.7 Units on a scale | Standard Deviation 3.22 |
| SEP-363856 | 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) | Positive SS: OL BLN Observed | 19.8 Units on a scale | Standard Deviation 4.96 |
| SEP-363856 | 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) | Positive SS: Wk 26 Observed | 12.2 Units on a scale | Standard Deviation 3.72 |
| SEP-363856 | 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) | Positive SS: Chg from DB BLN at Wk 26 | -13.5 Units on a scale | Standard Deviation 4.75 |
| SEP-363856 | 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) | Positive SS: Chg from OL BLN at Wk 26 | -7.3 Units on a scale | Standard Deviation 5.37 |
| SEP-363856 | 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) | Negative SS: DB BLN Observed | 25.4 Units on a scale | Standard Deviation 4.03 |
| SEP-363856 | 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) | Negative SS: OL BLN Observed | 22.3 Units on a scale | Standard Deviation 4.38 |
| SEP-363856 | 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) | Negative SS: Wk 26 Observed | 17.2 Units on a scale | Standard Deviation 4.1 |
| SEP-363856 | 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) | Negative SS: Chg from DB BLN at Wk 26 | -8.4 Units on a scale | Standard Deviation 4.48 |
| SEP-363856 | 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) | Negative SS: Chg from OL BLN at Wk 26 | -5.2 Units on a scale | Standard Deviation 4.2 |
| SEP-363856 | 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) | Gen-Psychopathology SS: DB BLN Observed | 50.4 Units on a scale | Standard Deviation 5.01 |
| SEP-363856 | 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) | Gen-Psychopathology SS: OL BLN Observed | 41.1 Units on a scale | Standard Deviation 7.93 |
| SEP-363856 | 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) | Gen-Psychopathology SS: Wk 26 Observed | 30.0 Units on a scale | Standard Deviation 6.77 |
| SEP-363856 | 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) | Gen-Psychopathology SS: Chg from DB BLN at Wk 26 | -19.9 Units on a scale | Standard Deviation 7.86 |
| SEP-363856 | 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) | Gen-Psychopathology SS: Chg from OL BLN at Wk 26 | -10.2 Units on a scale | Standard Deviation 8.31 |
Secondary
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.
Time frame: Overall post Open-label Baseline treatment period (26 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SEP-363856 | Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 3 Participants |
| SEP-363856 | Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 1 Participants |
| SEP-363856 | Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | Any suicidality | 3 Participants |
Secondary
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.
Time frame: Week 26
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEP-363856 | 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 | 52 Participants |
| SEP-SEP | 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 | 49 Participants |
Secondary
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.
Time frame: From the time of clinical response to relapse or censor (one day after the last study drug dose)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEP-363856 | 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 | 12 Participants |
| SEP-SEP | 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 | 11 Participants |
Secondary
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.
Time frame: Overall post Open-label Baseline treatment period (26 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SI: Wish to be dead | 2 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SI: Non-specific active suicidal thoughts | 2 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SI: Any methods (not plan) without intent to act | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SI: Some intent to act, without specific plan | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SI: Specific plan and intent | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SB: Preparatory acts or behavior | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SB: Aborted attempt | 1 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SB: Interrupted attempt | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SB: Actual attempt (non-fatal) | 0 Participants |
| SEP-363856 | Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) | SB: Completed suicide | 0 Participants |
Secondary
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.
Time frame: From the time of clinical response to relapse or censor (one day after the last study drug dose)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| SEP-363856 | 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 | NA Days |
| SEP-SEP | 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 | NA Days |