E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Schizophrenia is a psychotic disorder (or group of disorders) marked by severely impaired thinking, emotions, and behaviours. |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001064 |
E.1.2 | Term | Acute schizophrenia |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008525 |
E.1.2 | Term | Childhood schizophrenia |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of fixed doses of SEP-363856 (50 and 75 mg/day) compared with placebo in acutely psychotic adult subjects with schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) total score.
Adolescent subjects are included in order to evaluate the consistency of treatment effects between adult and adolescent subjects and for the characterization of safety profile in this age group. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of fixed doses of SEP-363856 (50 and 75 mg/day) compared with placebo in acutely psychotic adult subjects with schizophrenia as measured by the Clinical Global Impression-Severity (CGI-S) score. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female subject between 13 to 65 years of age (inclusive) at the time of consent. • Subject meets DSM-5 criteria for schizophrenia as established by clinical interview at Screening (using the DSM-5 as a reference and confirmed using the Structured Clinical Interview for DSM-5, Clinical Trials Version [SCID-CT] and using the Schedule for Affective Disorders and Schizophrenia for School-age Children [K-SADS-PL] for adolescents) at Screening. • Information supporting a diagnosis of schizophrenia must be obtained from additional sources to confirm the Screening evaluation of schizophrenia diagnosis. This should include medical records and/or documented correspondence with a treating psychiatrist or mental healthcare provider/staff but can also include information from a reliable informant who is familiar with the subject's psychiatric history (eg, family member, caregiver, case worker, etc.). The adequacy of the information will be assessed by the Sponsor or designee during the eligibility adjudication process. Exception: For adult subjects experiencing their first psychotic episode or who have not previously been seen by a psychiatrist or mental healthcare provider, documentation of schizophrenia diagnosis by a psychiatrist or mental healthcare provider other than the trial Investigator or Sub-Investigator is required. • Subject must have a CGI-S score ≥ 4 at Screening and Baseline. • 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 at Screening and Baseline. • Subject has an acute exacerbation of psychotic symptoms (persisting no longer than 2 months prior to providing informed consent for this study). • Subject has marked deterioration of functioning (or has not attained expected level of functioning for adolescents) in one or more areas, such as occupational, social, or personal care or hygiene. • Subject has had no more than 2 prior lifetime inpatient hospitalizations for the treatment of an acute psychotic episode or exacerbation of schizophrenia(not including hospitalization at the time of Screening, during Screening or at Baseline).Hospitalization history must be informed by sources other than the subject's own report. This should include medical records and/or documented correspondence with a treating psychiatrist or mental healthcare provider/staff but can also include information from a reliable informant who is familiar with the subject's psychiatric history (eg, family member, caregiver, case worker, etc.). The adequacy of the information will be assessed by the Sponsor or designee during the eligibility adjudication process. |
|
E.4 | Principal exclusion criteria |
• Subject has had a decrease (improvement of symptoms) of ≥ 20% on the PANSS total score between Screening and Baseline. • Subject has been hospitalized for more than 2 consecutive weeks immediately before screening, unless the hospitalization was for reasons unrelated to acute psychotic exacerbation. • 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 or for a total of ≥ 10 years during the subject's lifetime), 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 are not the primary focus of treatment. • Subject 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 an adequate dose as per labeling, for at least 4 weeks. • Subject 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 Baseline (i.e., since last visit). • Subject is at significant risk of harming self, others, or objects based on Investigator’s judgment. • Subject has attempted suicide within 6 months prior to Screening. • Subject is involuntarily hospitalized. • 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in PANSS total score at Endpoint (Week 6) in adult subjects. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Change from Baseline in CGI-S score at Endpoint (Week 6) in adult subjects. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Colombia |
United States |
Russian Federation |
Ukraine |
Serbia |
Bulgaria |
Croatia |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 15 |