Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults With Schizophrenia (NCT NCT02969382)

Last Updated: 2024-07-05

Results Overview

PANSS 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. Higher PANSS total score means more severe outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

245 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2024-07-05

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo capsule once daily	SEP-363856 SEP-363856 capsule (50 mg or 75 mg) once daily
Overall Study STARTED	125	120
Overall Study Subjects Continued Into Extension Study	79	78
Overall Study COMPLETED	99	94
Overall Study NOT COMPLETED	26	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo capsule once daily	SEP-363856 SEP-363856 capsule (50 mg or 75 mg) once daily
Overall Study Adverse Event	8	10
Overall Study Lack of Efficacy	4	5
Overall Study Death	0	1
Overall Study PROTOCOL DEVIATION	0	1
Overall Study Withdrawal by Subject	14	9

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily	Total n=245 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	123 Participants n=5 Participants	120 Participants n=7 Participants	243 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	30.6 Years STANDARD_DEVIATION 6.07 • n=5 Participants	30.0 Years STANDARD_DEVIATION 5.76 • n=7 Participants	30.3 Years STANDARD_DEVIATION 5.91 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	43 Participants n=7 Participants	89 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	77 Participants n=7 Participants	156 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	119 Participants n=5 Participants	115 Participants n=7 Participants	234 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) White	104 Participants n=5 Participants	96 Participants n=7 Participants	200 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized >=18 - <25 years	29 Participants n=5 Participants	26 Participants n=7 Participants	55 Participants n=5 Participants
Age, Customized >=25 - <=40 years	96 Participants n=5 Participants	94 Participants n=7 Participants	190 Participants n=5 Participants
Baseline Height (cm)	172.7 cm STANDARD_DEVIATION 7.78 • n=5 Participants	173.0 cm STANDARD_DEVIATION 8.50 • n=7 Participants	172.8 cm STANDARD_DEVIATION 8.12 • n=5 Participants
Baseline Weight (kg)	73.74 kg STANDARD_DEVIATION 12.645 • n=5 Participants	75.23 kg STANDARD_DEVIATION 15.768 • n=7 Participants	74.47 kg STANDARD_DEVIATION 14.250 • n=5 Participants
Baseline Body Mass Index (kg/m^2)	24.71 kg/m^2 STANDARD_DEVIATION 3.727 • n=5 Participants	25.01 kg/m^2 STANDARD_DEVIATION 4.238 • n=7 Participants	24.86 kg/m^2 STANDARD_DEVIATION 3.981 • n=5 Participants
Baseline Body Mass Index (BMI) Group <18.5 kg/m^2	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Baseline Body Mass Index (BMI) Group >=18.5 - <25.0 kg/m^2	70 Participants n=5 Participants	59 Participants n=7 Participants	129 Participants n=5 Participants
Baseline Body Mass Index (BMI) Group >=25.0 - <30.0 kg/m^2	43 Participants n=5 Participants	41 Participants n=7 Participants	84 Participants n=5 Participants
Baseline Body Mass Index (BMI) Group >=30.0 kg/m^2	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Baseline Waist Circumference (cm)	84.18 cm STANDARD_DEVIATION 12.186 • n=5 Participants	85.21 cm STANDARD_DEVIATION 14.191 • n=7 Participants	84.68 cm STANDARD_DEVIATION 13.189 • n=5 Participants
Country Hungary	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Country Romania	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Country Russia	52 Participants n=5 Participants	46 Participants n=7 Participants	98 Participants n=5 Participants
Country Ukraine	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Country United States	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4	-9.7 Units on a scale Standard Error 1.61	-17.2 Units on a scale Standard Error 1.66

SECONDARY outcome

Timeframe: Baseline, Week 4

The CGI-S 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.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 4	-0.5 Units on a scale Standard Error 0.09	-1.0 Units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, Week 4

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. Higher PANSS Positive subscale score means more severe outcome.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score at Week 4	-3.9 Units on a scale Standard Error 0.51	-5.5 Units on a scale Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline, Week 4

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score at Week 4	-1.6 Units on a scale Standard Error 0.41	-3.1 Units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline, Week 4

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) General Psychopathology Subscale Score at Week 4	-4.7 Units on a scale Standard Error 0.84	-9.0 Units on a scale Standard Error 0.87

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Subjects who had BNSS total score data available are included in this analysis.

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. Higher BNSS total score means more severe outcome.

Outcome measures

Outcome measures
Measure	Placebo n=119 Participants Placebo capsule once daily	SEP-363856 n=113 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Brief Negative Symptom Scale (BNSS) Total Score at Week 4	-2.7 Units on a scale Standard Error 0.91	-7.1 Units on a scale Standard Error 0.95

SECONDARY outcome

Timeframe: Baseline, Week 4

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). Higher MADRS total score means more severe outcome.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 4	-1.6 Units on a scale Standard Error 0.57	-3.3 Units on a scale Standard Error 0.59

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Subjects who had PANSS total score data available at both Baseline and Week 4 are included in this analysis.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo capsule once daily	SEP-363856 n=96 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Positive and Negative Syndrome Scale (PANSS) Response at Week 4, Defined as a 20% or Greater Improvement From Baseline in PANSS Total Score	44 Participants	62 Participants

SECONDARY outcome

Timeframe: From first dose of study drug to last study visit, up to 5 weeks

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation Overall Adverse Events (AEs)	63 Participants	55 Participants
The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation Serious Adverse Events (SAEs)	3 Participants	2 Participants
The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation AEs/SAEs leading to discontinuation from study	8 Participants	11 Participants
The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation AEs/SAEs leading to discontinuation of study drug	8 Participants	10 Participants

SECONDARY outcome

Timeframe: Overall post-Baseline double-blind treatment period, up to 4 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.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Frequency of Subjects With Suicidal Ideation Using the Columbia - Suicide Severity Rating Scale (C-SSRS)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Overall post-Baseline double-blind treatment period, up to 4 weeks

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Frequency of Subjects With Suicidal Behavior Using the Columbia - Suicide Severity Rating Scale (C-SSRS)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Overall post-Baseline double-blind treatment period, up to 4 weeks

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Placebo capsule once daily	SEP-363856 n=120 Participants SEP-363856 capsule (50 mg or 75 mg) once daily
Frequency of Subjects With Suicidality Using the Columbia - Suicide Severity Rating Scale (C-SSRS)	2 Participants	0 Participants

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

SEP-363856

Serious events: 2 serious events

Other events: 35 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=125 participants at risk Placebo capsule once daily	SEP-363856 n=120 participants at risk SEP-363856 capsule (50 mg or 75 mg) once daily
Cardiac disorders Cardiovascular insufficiency	0.00% 0/125 • 5 weeks (from first dose of study drug to last study visit)	0.83% 1/120 • Number of events 1 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Schizophrenia	2.4% 3/125 • Number of events 3 • 5 weeks (from first dose of study drug to last study visit)	0.83% 1/120 • Number of events 1 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Suicide attempt	0.80% 1/125 • Number of events 1 • 5 weeks (from first dose of study drug to last study visit)	0.00% 0/120 • 5 weeks (from first dose of study drug to last study visit)

Other adverse events

Other adverse events
Measure	Placebo n=125 participants at risk Placebo capsule once daily	SEP-363856 n=120 participants at risk SEP-363856 capsule (50 mg or 75 mg) once daily
Nervous system disorders Headache	12.0% 15/125 • Number of events 18 • 5 weeks (from first dose of study drug to last study visit)	9.2% 11/120 • Number of events 15 • 5 weeks (from first dose of study drug to last study visit)
Nervous system disorders Somnolence	4.8% 6/125 • Number of events 6 • 5 weeks (from first dose of study drug to last study visit)	6.7% 8/120 • Number of events 8 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Anxiety	7.2% 9/125 • Number of events 12 • 5 weeks (from first dose of study drug to last study visit)	1.7% 2/120 • Number of events 2 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Insomnia	10.4% 13/125 • Number of events 20 • 5 weeks (from first dose of study drug to last study visit)	3.3% 4/120 • Number of events 5 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Schizophrenia	5.6% 7/125 • Number of events 8 • 5 weeks (from first dose of study drug to last study visit)	5.8% 7/120 • Number of events 7 • 5 weeks (from first dose of study drug to last study visit)
Gastrointestinal disorders Nausea	3.2% 4/125 • Number of events 4 • 5 weeks (from first dose of study drug to last study visit)	5.0% 6/120 • Number of events 7 • 5 weeks (from first dose of study drug to last study visit)
Psychiatric disorders Agitation	4.8% 6/125 • Number of events 6 • 5 weeks (from first dose of study drug to last study visit)	5.0% 6/120 • Number of events 6 • 5 weeks (from first dose of study drug to last study visit)

Additional Information

CNS Medical Director

Sunovion Pharmaceuticals, Inc.

Phone: 1-866-503-6351

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER