Schizophrenia
Conditions
Keywords
schizophrenia
Brief summary
A clinical study to evaluate the long-term safety and tolerability of an investigational drug in people with schizophrenia. This study is accepting male and female participants between 18 years old -65 years old who have been diagnosed with schizophrenia. This study will be conducted in approximately 50 study centers worldwide. The study will last approximately 57 weeks.
Detailed description
This is a 52-week, multicenter, randomized, double-blind, parallel-group, flexible-dose study designed to evaluate the long-term safety and tolerability of SEP-363856 (50 to 100 mg/day) compared with quetiapine XR (400 to 800 mg/day) in clinically stable adult participants with schizophrenia. This study is projected to randomize a least 300 participants to two treatment groups (SEP-363856 50 to 100 mg/day or quetiapine XR 400 to 800 mg/day) in a 2:1 ratio. Study drug will be taken once a day and may be taken without food or with a light meal. Sumitomo Pharma America Inc. was the former Sponsor and conducted this study. Sumitomo was responsible for analysis and clinical study report (CSR) completion. Otsuka took over study after IND was transferred and is concluding activities with registry postings.
Interventions
DRUGSEP363856
SEP-363856, 50mg, 75mg, 100mg, flexibly dosed once daily capsule
DRUGquetiapine XR
quetiapine XR, 400, 600, 800 mg, flexibly dosed once daily capsule
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
A Randomized, Double-blind, Active Comparator-Controlled Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include, but are not limited to the following: * Male or female participant between 18 to 65 years of age (inclusive) at the time of consent. * Participant meets DSM-5 criteria for a diagnosis of schizophrenia as established by clinical interview at screening (using the DSM-5 as a reference and confirmed using the SCID-CT). The time since the participant's diagnosis must be ≥ 1 year prior to Screening. * Participant must have a CGI-S score ≤ 4 at Screening and Baseline. * Participant must have a PANSS total score ≤ 80 at Screening and Baseline. * Participant is judged to be clinically stable (i.e., no evidence of an acute exacerbation) by the Investigator for at least 8 weeks prior to Screening. * Participant has had no change in antipsychotic medication(s) (minor dose adjustments for tolerability purposes are permitted) for at least 6 weeks prior to Screening. * Participants taking an antipsychotic agent at Screening may participate in this study only if there are signs of intolerability or lack of efficacy of the current antipsychotic (as determined by the Investigator). * Participant is, in the opinion of the Investigator, generally healthy based on Screening medical history, PE, neurological examination, vital signs, electrocardiogram (ECG) and clinical laboratory values (hematology, chemistry and urinalysis).
Exclusion criteria
Main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | From first dose of the study drug up to 7 days after last dose of study drug (Up to 53 weeks) | 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. |
Countries
Romania, Russia, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at investigational sites in Russia, US, Romania and Ukraine from 21 Nov 2019 to 30 Dec 2022.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 201 |
| 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. | 102 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 48 | 21 |
| Overall Study | COVID-19 Related | 1 | 0 |
| Overall Study | Deemed Unsuitable for Participation | 1 | 0 |
| Overall Study | Geopolitical Conflict Related | 2 | 1 |
| Overall Study | Lack of Efficacy | 6 | 2 |
| Overall Study | Lost to Follow-up | 6 | 7 |
| Overall Study | Noncompliance with Study Drug | 5 | 1 |
| Overall Study | Participant relocated | 5 | 2 |
| Overall Study | Personal Reasons | 0 | 1 |
| Overall Study | Protocol Deviation | 5 | 1 |
| Overall Study | Randomized, but Withdrawn From Study Prior to Treatment | 2 | 0 |
| Overall Study | Withdrawal by participant | 17 | 9 |
Baseline characteristics
| Characteristic | Quetiapine XR 400 to 800 mg/Day | Total | SEP-363856 50 to 100 mg/Day |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 12.66 | 39.7 years STANDARD_DEVIATION 12.09 | 40.3 years STANDARD_DEVIATION 11.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 12 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants | 291 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 75 Participants | 47 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 73 Participants | 223 Participants | 150 Participants |
| Region of Enrollment Romania | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Russia | 41 Participants | 124 Participants | 83 Participants |
| Region of Enrollment Ukraine | 21 Participants | 63 Participants | 42 Participants |
| Region of Enrollment United States | 39 Participants | 113 Participants | 74 Participants |
| Sex: Female, Male Female | 37 Participants | 125 Participants | 88 Participants |
| Sex: Female, Male Male | 65 Participants | 178 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 201 | 0 / 102 |
| other Total, other adverse events | 103 / 201 | 55 / 102 |
| serious Total, serious adverse events | 16 / 201 | 0 / 102 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SEP-363856 50 to 100 mg/Day | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | SAEs | 16 Participants |
| SEP-363856 50 to 100 mg/Day | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | AEs | 153 Participants |
| SEP-363856 50 to 100 mg/Day | 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 |
| Quetiapine XR 400 to 800 mg/Day | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | AEs | 77 Participants |
| Quetiapine XR 400 to 800 mg/Day | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | SAEs | 0 Participants |
| Quetiapine XR 400 to 800 mg/Day | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation | AEs Leading to Trial Discontinuation | 21 Participants |