A Clinical Trial That Will Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose, Multicenter Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Subjects With Schizophrenia

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 18 -65 years old who have been diagnosed with schizophrenia. This study will be conducted in 60 locations world wide. The study will last up to nine (9) weeks.

This is a multicenter, randomized, double-blind, parallel-group, fixed-dosed study evaluating the efficacy and safety of two doses of SEP-363856 (75 and 100 mg/day) versus placebo over a 6-week Treatment Period in acutely psychotic participants with schizophrenia. This study is projected to randomize approximately 462 participants to 3 treatment groups (SEP-363856 75 mg/day, SEP-363856 100 mg/day, or placebo) in a 1:1:1 ratio. 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 hypotheses that treatment with SEP-363856 in adult participants 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.

Inclusion Criteria:

1. Male or female participant between 18 to 65 years of age (inclusive) at the time of consent.
2. Participant must give written informed consent and privacy authorization prior to participation in the study.
3. Participant meets the Diagnostic and Statistical Manual of Mental Illnesses (DSM-5 )criteria for schizophrenia as established by clinical interview at screeing.
4. Participant must have a Clinical Global Impression - Severity (CGI-S) score ≥ 4.
5. Participant must have a Positive and Negative Syndrome Scale (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. Participant has an acute exacerbation of psychotic symptoms (persisting no longer than 2 months prior to providing informed consent).
7. Participant has marked deterioration of functioning in one or more areas.
8. Participant is, in the opinion of the Investigator, generally healthy based on screening medical history, physical examination (PE), neurological examination, vital signs, electrocardiogram (ECG) and clinical laboratory values.

Exclusion Criteria:

1. Participant 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 on 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. Participant is at significant risk of harming self, others, or objects based on Investigator's judgment.
3. Participant has any clinically significant unstable medical condition or any clinically significant chronic disease that in the opinion of the Investigator, would limit the participant's ability to complete and/or participate in the study
4. Female participant who is pregnant or lactating
5. Participant has any clinically significant abnormal laboratory value(s) at Screening as determined by investigator.