A 4-Week, Randomized, Double-blind, Parallel-group, Placebo-controlled, Flexibly-dosed, Multicenter Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adult Subjects With Schizophrenia

Otsuka Pharmaceutical Development & Commercialization, Inc.32 sites in 5 countries245 target enrollmentDecember 5, 2016

ConditionsSchizophrenia

InterventionsSEP-363856 Placebo - Cap

DrugsSEP-363856 Placebo - Cap

Overview

Phase: Phase 2
Intervention: SEP-363856
Conditions: Schizophrenia
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Enrollment: 245
Locations: 32
Primary Endpoint: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A study to evaluate the efficacy and safety of an experimental drug (SEP-363856) in acutely psychotic adults with schizophrenia

Detailed Description

This is a multicenter, randomized, double-blind, parallel-group, flexibly-dosed, study evaluating the efficacy and safety of SEP-363856 in acutely psychotic adult subjects with schizophrenia using SEP-363856 (50 or 75 mg/day \[ie, once daily\]) versus placebo over a 4-week treatment period. Primary hypoathesis to be tested: H0: μSEP = μPBO versus H1: μSEP ≠ μPBO, where μSEP and μPBO are the mean changes from Baseline at Week 4 in PANSS total score for the SEP-363856 and placebo arms, respectively. Subjects who complete study SEP361-201 may be eligible to enroll in the open-label extension study SEP361-202.

Registry

clinicaltrials.gov

Start Date

December 5, 2016

End Date

July 31, 2018

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject must give written informed consent and privacy authorization prior to participation in the study. Separate consent will be obtained from a caregiver or legal guardian if required by local law.
•Subject must be willing and able to comply with the study procedures and visit schedules, including required hospitalization for the washout period and the double-blind treatment period, and must be able to understand and follow verbal and written instructions.
•Male or female subject between 18 to 40 years of age (inclusive) at the time of consent.
•Subject meets DSM-5 criteria for schizophrenia as established by clinical interview (using the DSM-5 as a reference and confirmed using the SCID-CT). The duration of the subject's illness whether treated or untreated must be ≥ 6 months.
•Subject must have a CGI-S score ≥ 4 (moderate or greater) at screening and Baseline (Day 1).
•Subject must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 (moderate) on 2 or more of the following PANSS items: delusions, conceptual disorganization, hallucinations, and unusual thought content at screening and Baseline (Day 1).
•Subject has an acute exacerbation of psychotic symptoms (no longer than 2 months).
•Subject has marked deterioration of functioning in one or more areas, such as occupational, social, or personal care or hygiene.
•Subject requires hospitalization for an acute psychotic exacerbation at the time of screening or has been hospitalized for the purpose of treating an acute psychotic exacerbation for no more than 2 consecutive weeks immediately before screening.
•Subjects who have been hospitalized for more than 2 weeks for reasons unrelated to an acute psychotic exacerbation may be included if such a hospitalization was for a condition other than an acute psychotic relapse. For example, subjects in a long-term hospital setting who have an acute exacerbation and are transferred to an acute unit are eligible for the study.

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 or during the Screening period (ie, in the past one month) and/or at Baseline (ie, since last visit).
•Subject does not tolerate venipuncture or has poor venous access that would cause difficulty for collecting blood samples.
•Subject is currently participating, or has participated in, a study with an investigational or marketed compound or device within 6 months prior to signing the informed consent, or has participated in 2 or more studies within 24 months prior to signing informed consent.
•Subject has previously received SEP-
•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:
•Hematological (including deep vein thrombosis) or bleeding disorder, renal, metabolic, endocrine, pulmonary, gastrointestinal, urological, cardiovascular, hepatic, neurologic, or allergic disease that is clinically significant or unstable (except for untreated, asymptomatic, seasonal allergies at time of dosing).
•Subject has a history of neuroleptic malignant syndrome. Protocol SEP361-201, Version 3.01 SEP-363856 Confidential and Proprietary 37 17 August 2017
•Subject has a history of malignancy within 5 years prior to the Screening visit, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.
•Disorder or history of a condition, or previous gastrointestinal surgery (eg, cholecystectomy, vagotomy, bowel resection, or any surgical procedure) that may interfere with drug absorption, distribution, metabolism, excretion, gastrointestinal motility, or pH, or a clinically significant abnormality of the hepatic or renal system, or a history of malabsorption.
•Subject has Alcohol or Substance Abuse Disorder (DSM-5 criteria). The only exceptions include caffeine or nicotine.

Arms & Interventions

SEP-363856

SEP-363856 capsule (50 mg or 75 mg) once daily

Intervention: SEP-363856

Placebo

Placebo capsule once daily

Intervention: Placebo - Cap

Outcomes

Primary Outcomes

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4

Time Frame: Baseline, Week 4

PANSS 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. Higher PANSS total score means more severe outcome.

Secondary Outcomes

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 4(Baseline, Week 4)
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score at Week 4(Baseline, Week 4)
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 4(Baseline, Week 4)
Frequency of Subjects With Suicidal Ideation Using the Columbia - Suicide Severity Rating Scale (C-SSRS)(Overall post-Baseline double-blind treatment period, up to 4 weeks)
Frequency of Subjects With Suicidal Behavior Using the Columbia - Suicide Severity Rating Scale (C-SSRS)(Overall post-Baseline double-blind treatment period, up to 4 weeks)
Frequency of Subjects With Suicidality Using the Columbia - Suicide Severity Rating Scale (C-SSRS)(Overall post-Baseline double-blind treatment period, up to 4 weeks)
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score at Week 4(Baseline, Week 4)
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) General Psychopathology Subscale Score at Week 4(Baseline, Week 4)
Change From Baseline in Brief Negative Symptom Scale (BNSS) Total Score at Week 4(Baseline, Week 4)
Positive and Negative Syndrome Scale (PANSS) Response at Week 4, Defined as a 20% or Greater Improvement From Baseline in PANSS Total Score(Baseline, Week 4)
The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation(From first dose of study drug to last study visit, up to 5 weeks)