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

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.

• SEP363856 (Drug): SEP-363856, 50mg, 75mg, 100mg, flexibly dosed once daily capsule
• quetiapine XR (Drug), also known as Seroquel XR: quetiapine XR, 400, 600, 800 mg, flexibly dosed once daily capsule

Primary outcomes

• 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.

Sex: All, ages: 18 Years to 65 Years

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 exclusion criteria include, but are not limited to:

* Participant was hospitalized for a psychiatric illness within the 8 weeks prior to Screening.
* Participant has a current 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, schizoaffective disorder, ,bipolar I or II disorder, obsessive compulsive disorder, and posttraumatic stress disorder, symptoms of mild to moderate mood dysphoria or anxiety are allowed so long as theses symptoms are not the primary focus of treatment.
* Participant is judged to be resistant to antipsychotic treatment by the Investigator, based on failure to respond to 2 or more marketed antipsychotic agents within a 1-year period prior to Screening, given at adequate dose as per labeling, for at least 4 weeks.
* Participant answers "yes" to "Suicidal Ideation" Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at Screening (i.e., in the past one month) or at Baseline (i.e., since last visit).
* Participant is at significant risk of harming self or others based on Investigator's judgment.
* Participant has attempted suicide within 6 months prior to Screening.
* Participant has received treatment with a psychotropic medication or herbal supplement within 3 days or 5 half-lives (whichever is longer)
* Participant has been treated with quetiapine or quetiapine XR within the 6 weeks prior to Screening or has a history of inadequate response or intolerability to quetiapine or quetiapine XR.
* 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.
* Participant has any clinically significant abnormal laboratory value(s) at Screening as determined by investigator.

Participant flow

Outcome results

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Study Discontinuation (Primary), Count of participants, Participants: SEP-363856 50 to 100 mg/Day 153; Quetiapine XR 400 to 800 mg/Day 77

Adverse events

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

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2021-01-14)
• Statistical Analysis Plan (PDF, 2023-01-30)

NIH grants: 2019