Schizophrenia
Conditions
Keywords
acute psychosis, schizophrenia
Brief summary
A clinical trial to study the efficacy and safety of an investigational drug in acutely psychotic people with schizophrenia. Participants in the study will either receive the drug being studied or a placebo. This study is accepting male and female participants between 13 years old -65 years old who have been diagnosed with schizophrenia.
Detailed description
This is a multicenter, randomized, double-blind, parallel-group, fixed-dosed study evaluating the efficacy and safety of two doses of SEP-363856 (50 and 75 mg/day) versus placebo over a 6-week Treatment Period in acutely psychotic subjects with schizophrenia. This study is projected to randomize approximately 435 subjects (18-65 years) to 3 treatment groups (SEP-363856 50 mg/day, SEP-363856 75 mg/day, or placebo) in a 1:1:1 ratio. In addition, the study will randomize approximately 90 adolescent subjects (13-17 years) in a 1:1:1 ratio to the 3 treatment groups (with approximately 30 subjects per group) in a separate cohort. Treatment assignment will be stratified by country. Study drug will be taken once a day and may be taken with or without food. This study is designed to test the hypothesis that, treatment with SEP-363856 in adult subjects with schizophrenia will result in significantly greater reduction (i.e. improvement) in PANSS total score and CGI-S score at Week 6 from Baseline when compared to placebo. The overall Type I error is controlled for two hierarchical families of hypotheses. The first family includes hypotheses about the testing of change from Baseline in PANSS total score at Week 6 between each of the SEP-363856 dose levels vs. placebo. The second family of hypotheses are about the testing of change from Baseline in CGI-S score at Week 6 between each of the SEP-363856 dose levels vs. placebo. 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
DRUGSEP-363856 50mg
SEP-363856 50mg tablet dosed once daily
DRUGSEP-363856 75mg
SEP-363856 75mg tablet dosed once daily
DRUGPlacebo
Placebo tablet dosed once daily
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
randomized, double-blind, parallel-group, placebo controlled, fixed-dose multicenter study
Eligibility
Sex/Gender
ALL
Age
13 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subject between 13 to 65 years of age (inclusive) at the time of consent. 2. Subject or subjects parent/legal guardian \[adolescents\] must give written informed consent and privacy authorization prior to participate in the study; adolescents must also provide informed assent.. 3. Subject meets DSM-5 criteria for schizophrenia as established by clinical interview at screening 4. Subject must have a CGI-S score ≥ 4 5. Subject must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 on 2 or more of the following PANSS items: delusions, conceptual disorganization, hallucinations, and unusual thought content 6. Subject has an acute exacerbation of psychotic symptoms (persisting no longer than 2 months prior to providing informed consent). 7. Subject has marked deterioration of functioning in one or more areas. 8. Subject is, in the opinion of the Investigator, generally healthy based on screening medical history, PE, neurological examination, vital signs, ECG, and clinical laboratory values.
Exclusion criteria
1. Subject has a DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia. Exclusionary disorders include but are not limited to alcohol use disorder (within past 12 months), substance (other than nicotine or caffeine) use disorder within past 12 months or lifetime history of significant substance abuse that in the opinion of the Investigator or Sponsor, may have had a significant and potentially permanent impact of the brain or other body systems, major depressive disorder, bipolar I or II disorder, schizoaffective disorder, obsessive compulsive disorder, and posttraumatic stress disorder. Symptoms of mild to moderate mood dysphoria or anxiety are allowed so long as these symptoms are not the primary focus of treatment. 2. Subject is at significant risk of harming self, others, or objects based on Investigator's judgment. 3. Subject has any clinically significant unstable medical condition or any clinically significant chronic disease that in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in the study: 4. Female subject who is pregnant or lactating 5. Subject has any clinically significant abnormal laboratory value(s) at Screening as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PANSS Total Score at Week 6 | Baseline, Week 6 | PANSS was an interview-based assessment comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). The Positive subscale assessed hallucinations, delusions, and related symptoms; the Negative subscale assessed emotional withdrawal, lack of motivation, and similar symptoms; and the General Psychopathology subscale addressed other symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1 - 7, where values of 2 and above indicated the presence of progressively more severe symptoms, was used to score each item. Individual items were then summed to determine scores for the 3 subscales, as well as a total score. PANSS total score ranges from: 30-210, where a higher score indicates greater severity. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CGI-S Total Score at Week 6 | Baseline, Week 6 | The CGI-S was a single-item clinician-rated assessment of the participant's current illness state on a 7-point scale (score range: 1-7), where a higher score was associated with greater illness severity. |
Countries
Bulgaria, Colombia, Russia, Serbia, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at investigational sites in the United States, Russia, Ukraine, Bulgaria, and Serbia from 17 September 2019 to 12 September 2023.
Pre-assignment details
A total of 628 participants were screened, of which 463 participants (435 adults and 28 adolescents) were randomized to receive SEP-363856 50mg, 75 mg or placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.0 years STANDARD_DEVIATION 10.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| PANSS Total Score | 101.9 units on a scale STANDARD_DEVIATION 10.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 109 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 114 Participants |
| Region of Enrollment Bulgaria | 18 participants |
| Region of Enrollment Russia | 0 participants |
| Region of Enrollment Serbia | 136 participants |
| Region of Enrollment Ukraine | 78 participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 190 Participants |
| Sex: Female, Male Male | 273 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 146 | 0 / 144 | 0 / 145 | 0 / 10 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 41 / 146 | 55 / 144 | 50 / 145 | 3 / 10 | 5 / 9 | 6 / 9 |
| serious Total, serious adverse events | 4 / 146 | 11 / 144 | 12 / 145 | 0 / 10 | 0 / 9 | 0 / 9 |
Outcome results
None listed