An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia

A 26-Week Open-label Safety and Tolerability Extension Study of SEP-363856 in Adult Subjects With Schizophrenia

An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: SEP-363856

Detailed Description

This is a 26 week, multiregional, open-label extension study designed to evaluate the long-term safety and tolerability of SEP-363856 for the treatment of subjects with schizophrenia who have completed the 4 week double-blind treatment phase of Study SEP361-201 (NCT02969382) Subjects received open-label SEP-363856 50 mg/day from Day 1 through Day 3, and then received flexible dosing of SEP-363856 (25, 50, or 75 mg/day) for the rest of the trial.

No statistical hypothesis tests will be performed.

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Gyula, Hungary, 5700
    • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza, Pszichiatriai Osztaly
  • Dózsa György
    • Gyongyos, Dózsa György, Hungary, út 20-22
      • Bugát Pál Kórház-Rendelőintézet, Rehabilitációs Elmegyógyászati Osztály
• Romania
  • Bucuresti, Romania, 010825
    • Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
  • Bucuresti, Romania, 060222
    • Centrul de Evaluarea si Tratament al Toxicodependentelor pentru Tineri "Sf. Stelian", Sectia Psihiatrie
  • Craiova, Romania, 200473
    • spitalul Clinic de Neuropsihiatrie Craiova ,Clinica II Psihiatrie
  • Iasi, Romania, 700282
    • Institutul de Psihiatrie Socola Iasi, Sectia Psihiatrie III Acuti
• Russian Federation
  • Ekaterinburg, Russian Federation, 620030
    • Sverdlov Regional Psychiatric Clinical Hospital
  • Gatchina, Russian Federation, 188357
    • St-Petersburg SHI Psychiatrical hospital #1 n.a. Kaschenko
  • Saint-Petersburg, Russian Federation, 197341
    • SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
  • Saratov, Russian Federation, 410060
    • SHI Regional Clinical Psychiatry Hospital of St. Sofia
  • Smolensk, Russian Federation, 214019
    • FSBEI HE "Smolensk State Medical University" of the MoH of the RF
  • St. Petersburg, Russian Federation, 190121
    • City Psychiatric Hospital of St. Nikolay Chudotvorets
  • St. Petersburg, Russian Federation, 192019
    • FB=SBI"Saint Petersburg Scientific and Research Psychoneurological Institute n.a. V.M. Bekhterev"
  • St. Petersburg, Russian Federation, 198020
    • SPb SBIH "City Psychoneurological Dispensary #7 (with inpatient facilities)"
• Ukraine
  • Ivano Frankivsk, Ukraine, 76014
    • Regional Psychoneurological Hospital #3, Dept of Crisis Cond & Primary Psych Episode #1
  • Kharkiv, Ukraine, 61068
    • CHI Kharkiv RCPH#3 Center of Emerg PsychSI Inst of Neur, Psych & Narc of NAMSU, Unit of Emergency Psychiatry and Narcology
  • Kharkiv, Ukraine, 61068
    • CHI Kharkiv Regional Clinical Psychiatric Hospital #3, Psychiatric Department of Primary Psychotic Episod
  • Kherson, Ukraine, 73488
    • CI Kherson Regional Psychiatric Hospital of Kherson RC
  • Kyiv, Ukraine, 04080
    • TMA Psychiatry in Kyiv Center of NT & Rehabilitation of Psychotic Conditions
  • Odesa, Ukraine, 65006
    • CI Odesa Regional Medical Center of Mental Health
  • Smila, Ukraine, 20708
    • CI Cherkasy Regional Psychiatric Hospital of ChRC, Femail Dept #11, Male Dept #12
  • Ternopil, Ukraine, 46020
    • Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #6 Ternopil I.ya. Gorbachevskyi SMU
  • Uzhgorod, Ukraine, 88000
    • Transcarpathian Regional Narcological Dispensary
  • Vinnytsia, Ukraine, 21005
    • CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Pico Rivera, California, United States, 90660
      • CNRI-Los Angeles, LLC
    • San Diego, California, United States, 92103-8229
      • UCSD Medical Center UCSD Department of Psychiatry
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Kashinath Yadalam
  • Texas
    • Dallas, Texas, United States, 75243
      • Pillar Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subject must give written informed consent and privacy authorization prior to participation in the study and able to comply with the protocol, in the opinion of the investigator.

• Subject has completed Study SEP361 201 through Week 4
• Subject has not taken any medication other than the study drug for the purpose of controlling schizophrenia symptoms during Study SEP361 201.
• Female subject must have a negative urine pregnancy test at Visit 7 of Study SEP361 201; females who are post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will be exempted from the pregnancy test.
• Male subjects with female partner(s) of childbearing potential must agree to avoid fathering a child and use acceptable methods of birth control from screening until at least 30 days after the last study drug administration

Exclusion Criteria:

• 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 Visit 7 of Study SEP361 201. Subjects who answer "yes" to this question must be referred to the Investigator for follow up evaluation.
• Subject has a clinically significant abnormality including physical examination, vital signs, ECG, or laboratory test at Visit 7 of Study SEP361 201 that the investigator in consultation with the medical monitor considers to be inappropriate to allow participation in the study.
• Subject has a positive urine drug screen (UDS) or breath alcohol test at Visit 7 of Study SEP361 201.
• Subject is pregnant or lactating.
• Subject is at high risk of non-compliance in the Investigator's opinion.
• Subject is in the opinion of the Investigator, unsuitable in any other way to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SEP-363856; SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily	Drug: SEP-363856; One SEP-363856 capsule (25 mg, 50 mg or 75 mg (flex)) daily for 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation	Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation	From first dose of study drug to last study visit (27 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)	Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.	Overall post Open-label Baseline treatment period (26 weeks)
Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.	Overall post Open-label Baseline treatment period (26 weeks)
Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856	Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.	From the time of clinical response to relapse or censor (one day after the last study drug dose)
Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856	Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.	From the time of clinical response to relapse or censor (one day after the last study drug dose)
Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology)	PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.	Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score	The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score	The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms. Total score will be equal to the sum of the 10 items (range between 0 and 60).	Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26
Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201	PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.	Week 26

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): January 29, 2019
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimated): November 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: SEP361-202; 2016-001556-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No