An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia
- Registration Number
- NCT02970929
- Brief Summary
An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 157
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SEP-363856 SEP-363856 SEP-363856 capsule (25 mg, 50 mg, or 75 mg) once daily
- Primary Outcome Measures
Name Time Method The Incidence of 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) Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation
- Secondary Outcome Measures
Name Time Method 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 From the time of clinical response to relapse or censor (one day after the last study drug dose) 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.
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) Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26) 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.
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 Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 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).Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Overall post Open-label Baseline treatment period (26 weeks) 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.
Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Overall post Open-label Baseline treatment period (26 weeks) 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.
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 From the time of clinical response to relapse or censor (one day after the last study drug dose) 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.
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 Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 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.
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 Week 26 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.
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 Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26 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.
Trial Locations
- Locations (30)
CNRI-Los Angeles, LLC
🇺🇸Pico Rivera, California, United States
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
UCSD Medical Center UCSD Department of Psychiatry
🇺🇸San Diego, California, United States
Pillar Clinical Research, LLC
🇺🇸Dallas, Texas, United States
FB=SBI"Saint Petersburg Scientific and Research Psychoneurological Institute n.a. V.M. Bekhterev"
🇷🇺St. Petersburg, Russian Federation
SPb SBIH "City Psychoneurological Dispensary #7 (with inpatient facilities)"
🇷🇺St. Petersburg, Russian Federation
CHI Kharkiv RCPH#3 Center of Emerg PsychSI Inst of Neur, Psych & Narc of NAMSU, Unit of Emergency Psychiatry and Narcology
🇺🇦Kharkiv, Ukraine
CI Kherson Regional Psychiatric Hospital of Kherson RC
🇺🇦Kherson, Ukraine
CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU
🇺🇦Vinnytsia, Ukraine
Bugát Pál Kórház-Rendelőintézet, Rehabilitációs Elmegyógyászati Osztály
🇭🇺Gyongyos, Dózsa György, Hungary
CI Odesa Regional Medical Center of Mental Health
🇺🇦Odesa, Ukraine
Woodland International research Group
🇺🇸Little Rock, Arkansas, United States
Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
🇷🇴Bucuresti, Romania
TMA Psychiatry in Kyiv Center of NT & Rehabilitation of Psychotic Conditions
🇺🇦Kyiv, Ukraine
CI Cherkasy Regional Psychiatric Hospital of ChRC, Femail Dept #11, Male Dept #12
🇺🇦Smila, Ukraine
Institutul de Psihiatrie Socola Iasi, Sectia Psihiatrie III Acuti
🇷🇴Iasi, Romania
St-Petersburg SHI Psychiatrical hospital #1 n.a. Kaschenko
🇷🇺Gatchina, Russian Federation
City Psychiatric Hospital of St. Nikolay Chudotvorets
🇷🇺St. Petersburg, Russian Federation
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza, Pszichiatriai Osztaly
🇭🇺Gyula, Hungary
spitalul Clinic de Neuropsihiatrie Craiova ,Clinica II Psihiatrie
🇷🇴Craiova, Romania
FSBEI HE "Smolensk State Medical University" of the MoH of the RF
🇷🇺Smolensk, Russian Federation
Regional Psychoneurological Hospital #3, Dept of Crisis Cond & Primary Psych Episode #1
🇺🇦Ivano Frankivsk, Ukraine
CHI Kharkiv Regional Clinical Psychiatric Hospital #3, Psychiatric Department of Primary Psychotic Episod
🇺🇦Kharkiv, Ukraine
Centrul de Evaluarea si Tratament al Toxicodependentelor pentru Tineri "Sf. Stelian", Sectia Psihiatrie
🇷🇴Bucuresti, Romania
Sverdlov Regional Psychiatric Clinical Hospital
🇷🇺Ekaterinburg, Russian Federation
SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"
🇷🇺Saint-Petersburg, Russian Federation
SHI Regional Clinical Psychiatry Hospital of St. Sofia
🇷🇺Saratov, Russian Federation
Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #6 Ternopil I.ya. Gorbachevskyi SMU
🇺🇦Ternopil, Ukraine
Transcarpathian Regional Narcological Dispensary
🇺🇦Uzhgorod, Ukraine
Kashinath Yadalam
🇺🇸Lake Charles, Louisiana, United States