A Clinical Study to Investigate the Effect of an Investigational Drug on Electrocardiogram Intervals in Adults With Schizophrenia.

A Randomized, Single-dose, Crossover Study of the Effects of SEP-363856 on Electrocardiogram (ECG) Intervals in Subjects With Schizophrenia

A clinical study to investigate the effect of an investigational drug in adults with schizophrenia by using Electrocardiogram (Picture of the electrical action of the heart). This study is accepting male and female participants between 18 years old -65 years old who have been diagnosed with schizophrenia. This study will be conducted in approximately 7 locations in the US. The study will last approximately 7 weeks.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: SEP363856 150 mg; Drug: moxifloxacin 400 mg

Detailed Description

This is a Phase 1, randomized, single-dose, active and placebo controlled, 3-period crossover study of the effect of SEP-363856 150 mg on electrocardiogram (ECG) intervals in subjects with schizophrenia. SEP-363856 and matching placebo will be utilized in a double-blind fashion. Moxifloxacin will be utilized as an active control in an open-label fashion.

The primary analysis will be based on concentration-QTc modeling of the relationship between plasma concentrations of SEP-363856 or its metabolite SEP-363854 and change-from baseline QTc.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC
    • Pico Rivera, California, United States, 90660
      • California Neuropsychopharmacology Clinical Research Institute-LA, LLC (CNRI-LA, LLC)
    • San Diego, California, United States, 92101
      • California Neuropsychopharmacology Clinical Research Institute-San Diego, LLC (CNRI-SD, LLC)
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Centers of America, LLC
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research Inc. Austin, TX 78754

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject between 18 and 65 years of age, inclusive, at the time of informed consent
• Subject must give written informed consent and privacy authorization prior to participation in the study
• Subject meets DSM-5 criteria for a primary diagnosis of schizophrenia as established by clinical interview
• Subject must have a CGI S score ≤ 4 at Screening
• Subject must have a PANSS total score ≤ 80 at Screening

• Subject must have a score of ≤ 4 on the following PANSS items at Screening:

  • P7 (hostility)
  • G8 (uncooperativeness)
• Subject must have normal to mild symptoms on all individual items of the SAS (< 2), AIMS (< 3) and BARS (< 3) at Screening
• Subject must be clinically stable for the past three months in the opinion of the Investigator
• Subject has been taking an antipsychotic for at least six weeks prior to Screening and has had no change in antipsychotic medication(s) for at least six weeks prior to Screening
• Subject is, in the opinion of the Investigator, generally healthy based on Screening medical history, physical examination, neurological examination, vital sign measurement, electrocardiogram and clinical laboratory values

Exclusion Criteria:

• 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), substance (other than nicotine or caffeine) use disorder within past 12 months, 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 tests positive for drugs of abuse or alcohol at Screening
• Subject is at significant risk of harming him/herself or others (passive or active) according to the Investigator's judgment.
• 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
• Female subject who is pregnant or lactating
• Subject has any clinically significant abnormal laboratory value(s) at Screening as judged by the Investigator
• Subject has an abnormal, clinically significant 12-lead ECG at screening
• Subject has experienced significant blood loss (≥ 473 mL) or donated blood within 60 days prior to first dose of study drug; has donated plasma within 72 hours prior to the first dose of study drug or intends to donate plasma or blood or undergo elective surgery during study participation or within 60 days after the last study visit.
• Subject has an abnormal, clinically significant 12-lead ECG at screening
• Subject has a history of sick sinus syndrome, first, second, or third-degree AV block,myocardial infarction, NYHA Class II-IV heart failure, cardiomyopathy, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, congenital long QT syndrome, family history of long QT, or moderate to severe hypokalemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SEP363856 150 mg; SEP363856 tablet 150 mg	Drug: SEP363856 150 mg; SEP363856 tablet 150 mg
Placebo Comparator: Placebo; matched placebo	Drug: Placebo; Placebo tablet
Active Comparator: moxifloxacin 400 mg; moxifloxacin tablet 400 mg	Drug: moxifloxacin 400 mg; moxifloxacin tablet 400 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-adjusted change-from-baseline QTc interval (ΔΔQTc)	24 Hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in heart rate, QTcF, pulse rate, and QRS intervals (∆HR, ΔQTcF, ΔPR, and ∆QRS)	24 Hours
If a substantial heart rate (HR) effect is observed: Change from baseline in QTcS, QTcI, and QTcP (ΔQTcS, ΔQTcI, and ΔQTcP)	24 Hours
Placebo-adjusted change from baseline in heart rate, pulse rate, and QRS intervals (ΔΔHR, ΔΔPR, and ΔΔQRS)	24 Hours
If a substantial heart rate (HR) effect is observed: Placebo-adjusted ΔQTcS, and/or ΔQTcI, and/or ΔQTcP, and/or ΔQTcF (ΔΔQTcS, ΔΔQTcI, ΔΔQTcP, ΔΔQTcF) if not selected as the primary endpoint	24 Hours
Categorical summary for QTcF, heart rate, pulse rate, and QRS intervals	24 Hours
If a substantial heart rate (HR) effect is observed: Categorical summary for QTcS, QTcI, and QTcP	24 Hours
Frequency of treatment-emergent changes of T-wave morphology and U-waves presence.	24 Hours

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): November 10, 2020

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: SEP361-114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study may be made available upon request via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available upon request within 12 months of posting the study results on ct.gov.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No