Trial Outcomes & Findings for A Study of the Long-term Safety and Tolerability of an Investigational Drug in People With Schizophrenia. (NCT NCT04115319)

Last Updated: 2025-12-31

Results Overview

An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Untoward medical occurrences that occured after first administration of study drug were considered AEs. A SAE is an AE that meets one or more criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

305 participants

Primary outcome timeframe

From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks)

Results posted on

2025-12-31

Participant Flow

Participants took part in the study at investigational sites in Russia, US, Romania and Ukraine from 21 Nov 2019 to 30 Dec 2022.

A total of 461 participants were screened, of which 305 participants were randomized and 303 participants received either SEP-363856 (N = 201) or quetiapine XR (N = 102).

Participant milestones

Participant milestones
Measure	SEP-363856 50 to 100 mg/Day Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.
Overall Study STARTED	203	102
Overall Study COMPLETED	105	57
Overall Study NOT COMPLETED	98	45

Reasons for withdrawal

Reasons for withdrawal
Measure	SEP-363856 50 to 100 mg/Day Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.
Overall Study Randomized, but Withdrawn From Study Prior to Treatment	2	0
Overall Study Withdrawal by participant	17	9
Overall Study Geopolitical Conflict Related	2	1
Overall Study COVID-19 Related	1	0
Overall Study Adverse Event	48	21
Overall Study Noncompliance with Study Drug	5	1
Overall Study Lack of Efficacy	6	2
Overall Study Lost to Follow-up	6	7
Overall Study Protocol Deviation	5	1
Overall Study Participant relocated	5	2
Overall Study Personal Reasons	0	1
Overall Study Deemed Unsuitable for Participation	1	0

Baseline Characteristics

A Study of the Long-term Safety and Tolerability of an Investigational Drug in People With Schizophrenia.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SEP-363856 50 to 100 mg/Day n=201 Participants Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day n=102 Participants Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.	Total n=303 Participants Total of all reporting groups
Age, Continuous	40.3 years STANDARD_DEVIATION 11.77 • n=1000 Participants	38.4 years STANDARD_DEVIATION 12.66 • n=1986 Participants	39.7 years STANDARD_DEVIATION 12.09 • n=2008 Participants
Sex: Female, Male Female	88 Participants n=1000 Participants	37 Participants n=1986 Participants	125 Participants n=2008 Participants
Sex: Female, Male Male	113 Participants n=1000 Participants	65 Participants n=1986 Participants	178 Participants n=2008 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=1000 Participants	4 Participants n=1986 Participants	12 Participants n=2008 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	193 Participants n=1000 Participants	98 Participants n=1986 Participants	291 Participants n=2008 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants	0 Participants n=1986 Participants	0 Participants n=2008 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=1000 Participants	0 Participants n=1986 Participants	2 Participants n=2008 Participants
Race (NIH/OMB) Asian	2 Participants n=1000 Participants	0 Participants n=1986 Participants	2 Participants n=2008 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=1000 Participants	0 Participants n=1986 Participants	0 Participants n=2008 Participants
Race (NIH/OMB) Black or African American	47 Participants n=1000 Participants	28 Participants n=1986 Participants	75 Participants n=2008 Participants
Race (NIH/OMB) White	150 Participants n=1000 Participants	73 Participants n=1986 Participants	223 Participants n=2008 Participants
Race (NIH/OMB) More than one race	0 Participants n=1000 Participants	0 Participants n=1986 Participants	0 Participants n=2008 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants	1 Participants n=1986 Participants	1 Participants n=2008 Participants
Region of Enrollment Romania	2 Participants n=1000 Participants	1 Participants n=1986 Participants	3 Participants n=2008 Participants
Region of Enrollment United States	74 Participants n=1000 Participants	39 Participants n=1986 Participants	113 Participants n=2008 Participants
Region of Enrollment Ukraine	42 Participants n=1000 Participants	21 Participants n=1986 Participants	63 Participants n=2008 Participants
Region of Enrollment Russia	83 Participants n=1000 Participants	41 Participants n=1986 Participants	124 Participants n=2008 Participants

PRIMARY outcome

Timeframe: From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks)

Population: Safety population included all participants that were enrolled and received at least 1 dose of study drug during the 52-week treatment period.

Outcome measures

Outcome measures
Measure	SEP-363856 50 to 100 mg/Day n=201 Participants Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day n=102 Participants Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation AEs	153 Participants	77 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation SAEs	16 Participants	0 Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation AEs Leading to Trial Discontinuation	48 Participants	21 Participants

Adverse Events

SEP-363856 50 to 100 mg/Day

Serious events: 16 serious events

Other events: 103 other events

Deaths: 0 deaths

Quetiapine XR 400 to 800 mg/Day

Serious events: 0 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SEP-363856 50 to 100 mg/Day n=201 participants at risk Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day n=102 participants at risk Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.
Psychiatric disorders Schizophrenia	5.0% 10/201 • Number of events 10 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Psychiatric disorders Anxiety	0.50% 1/201 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Psychiatric disorders Suicide attempt	1.00% 2/201 • Number of events 2 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Nervous system disorders Cerebrovascular accident	0.50% 1/201 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Injury, poisoning and procedural complications Multiple injuries	1.00% 2/201 • Number of events 2 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Injury, poisoning and procedural complications Fall	0.50% 1/201 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Injury, poisoning and procedural complications Limb injury	0.50% 1/201 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Infections and infestations Corona virus infection	0.50% 1/201 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.00% 0/102 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.

Other adverse events

Other adverse events
Measure	SEP-363856 50 to 100 mg/Day n=201 participants at risk Participants received flexible doses of SEP-363856 50 to 100 milligram per day (mg/day), orally, once daily (QD) up to Week 52. The dose was titrated up from 50 mg/day on Days 1 to 3, to 75 mg/day on Days 4 to 7. Beginning Day 8, the dose was adjusted within the range of 50 mg/day to 100 mg/day in 25 mg increments (i.e. 50, 75, or 100 mg/day) up to Week 52.	Quetiapine XR 400 to 800 mg/Day n=102 participants at risk Participants received flexible doses of quetiapine XR 300 to 800 mg/day, orally, QD up to Week 52. The dose was titrated up from 300 mg/day on Days 1 to 2, followed by 400 mg/day on Days 3 to 4, to 600 mg/day on Days 5 to 7. Beginning Day 8, the dose was adjusted within the range of 400 mg/day to 800 mg/day in 200 mg increments (i.e. 400, 600, or 800 mg/day) up to Week 52.
Nervous system disorders Dizziness	8.0% 16/201 • Number of events 18 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	4.9% 5/102 • Number of events 5 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Nervous system disorders Headache	10.0% 20/201 • Number of events 29 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	7.8% 8/102 • Number of events 8 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Nervous system disorders Somnolence	6.0% 12/201 • Number of events 13 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	20.6% 21/102 • Number of events 24 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Investigations Weight decreased	5.5% 11/201 • Number of events 11 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	0.98% 1/102 • Number of events 1 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Investigations Weight increased	4.5% 9/201 • Number of events 9 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	10.8% 11/102 • Number of events 11 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Nervous system disorders Akathisia	7.0% 14/201 • Number of events 15 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	2.0% 2/102 • Number of events 2 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
General disorders Asthenia	2.5% 5/201 • Number of events 6 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	8.8% 9/102 • Number of events 10 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Gastrointestinal disorders Constipation	3.5% 7/201 • Number of events 8 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	11.8% 12/102 • Number of events 16 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Gastrointestinal disorders Nausea	6.5% 13/201 • Number of events 13 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	3.9% 4/102 • Number of events 5 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Psychiatric disorders Anxiety	13.4% 27/201 • Number of events 41 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	9.8% 10/102 • Number of events 12 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Psychiatric disorders Insomnia	14.9% 30/201 • Number of events 38 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	10.8% 11/102 • Number of events 13 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.
Psychiatric disorders Schizophrenia	10.4% 21/201 • Number of events 23 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.	5.9% 6/102 • Number of events 6 • From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) Safety population included all participants that were enrolled and received at least 1 dose of the study drug during the 52-week treatment period.

Additional Information

Clinical Transparency

Otsuka

Phone: 1-800-441-6763

Email: [email protected],

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place