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

Phase 1
Completed
Conditions
Schizophrenia
Interventions
Drug: moxifloxacin 400 mg
Drug: SEP363856 150 mg
Drug: Placebo
Registration Number
NCT04369391
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
moxifloxacin 400 mgmoxifloxacin 400 mgmoxifloxacin tablet 400 mg
SEP363856 150 mgSEP363856 150 mgSEP363856 tablet 150 mg
PlaceboPlacebomatched placebo
Primary Outcome Measures
NameTimeMethod
Placebo-adjusted change-from-baseline QTc interval (ΔΔQTc)24 Hours
Secondary Outcome Measures
NameTimeMethod
If a substantial heart rate (HR) effect is observed: Change from baseline in QTcS, QTcI, and QTcP (ΔQTcS, ΔQTcI, and ΔQTcP)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 endpoint24 Hours
Change from baseline in heart rate, QTcF, pulse rate, and QRS intervals (∆HR, ΔQTcF, ΔPR, and ∆QRS)24 Hours
Placebo-adjusted change from baseline in heart rate, pulse rate, and QRS intervals (ΔΔHR, ΔΔPR, and ΔΔQRS)24 Hours
Categorical summary for QTcF, heart rate, pulse rate, and QRS intervals24 Hours
If a substantial heart rate (HR) effect is observed: Categorical summary for QTcS, QTcI, and QTcP24 Hours
Frequency of treatment-emergent changes of T-wave morphology and U-waves presence.24 Hours

Trial Locations

Locations (7)

Collaborative Neuroscience Research, LLC

🇺🇸

Long Beach, California, United States

Woodland International Research Group

🇺🇸

Little Rock, Arkansas, United States

Hassman Research Institute

🇺🇸

Marlton, New Jersey, United States

Community Clinical Research Inc. Austin, TX 78754

🇺🇸

Austin, Texas, United States

California Neuropsychopharmacology Clinical Research Institute-LA, LLC (CNRI-LA, LLC)

🇺🇸

Pico Rivera, California, United States

Research Centers of America, LLC

🇺🇸

Hollywood, Florida, United States

California Neuropsychopharmacology Clinical Research Institute-San Diego, LLC (CNRI-SD, LLC)

🇺🇸

San Diego, California, United States

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