A Clinical Trial to Evaluate the Long-term Safety and Tolerability of SEP-363856 in Patients With Schizophrenia in Japan

A phase 3, 52-week, open-label study to evaluate the long-term safety and tolerability of SEP-363856 in patients with schizophrenia in Japan. Participants will take flexible dose of SEP-363856 (50 mg/day and 75 mg/day) every night at bedtime for 52 weeks in an open-label manner.

• SEP-363856 (Drug): SEP-363856 50 mg or 75 mg, flexibly dosed once daily tablet for 52 weeks

Primary outcomes

• The incidence of overall adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation. [Week 52]: Evaluate the long-term safety and tolerability of flexible dosed SEP-363856 (50 and 75 mg/day) in subjects with schizophrenia by the incidence of overall adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study related activities.
2. Male or female between 18 to 65 years of age (inclusive) at the time of consent.
3. Must meet DSM 5 criteria for schizophrenia as established by clinical interview at Screening
4. Must have a PANSS total score >=60 at Screening and Baseline.
5. Must have a CGI-S score >=3 at Screening and Baseline
6. Judged to be clinically stable (i.e., no evidence of an acute exacerbation) by the Investigator for at least 8 weeks prior to Baseline and has had no change in antipsychotic medication(s) (minor dose adjustments for tolerability purposes are permitted) for at least 6 weeks prior to Screening
7. In the opinion of the Investigator, subjects must be generally healthy based on Screening medical history, physical examination, vital signs, ECG, and clinical laboratory values (hematology, chemistry, and urinalysis).

Exclusion Criteria:

1. Have 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 or substance (other than nicotine or caffeine) use disorder within past 12 months or for a total of >= 10 years during the subject's lifetime, 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 have not been a focus of primary treatment
2. At significant risk of harming self, others, or objects based on Investigator's judgment.
3. Have 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 subjects who are pregnant or lactating.
5. Have any clinically significant abnormal laboratory value(s) at Screening (hematology, chemistry, and urinalysis) as determined by the Investigator.

• Results publication: Halff EF, Rutigliano G, Garcia-Hidalgo A, Howes OD. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010. Epub 2022 Nov 8. PMID 36369028