A Clinical Study to Investigate the Effect of an Investigational Drug as an Added Medication to an Antipsychotic, in Adults With Schizophrenia, as Measured Positron Emission Tomography (PET) Imaging

NCT04038957 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: SEP361-1182019-000568-65
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

A clinical study to investigate the effect of an investigational drug as an added medication to an antipsychotic, in adults with schizophrenia, as measured positron emission tomography (PET) imaging . This study is accepting male and female participants between 18 years old -45 years old who have been diagnosed with schizophrenia. This study will be conducted in 2 locations in the UK. The study will last approximately 14 months.

Conditions

Schizophrenia

Keywords

schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Dopamine Synthesis Capacity at Week 2 Using 18F-DOPA.

  Dopamine synthesis capacity was assessed using 18 F-DOPA PET(positron emission tomography) scans that were performed before (baseline) and after (Week 2 \[Day 14\]) administration of SEP-363856 adjunctive to an antipsychotic medication. A repeated measures ANOVA(analysis of variance) analysis was conducted. The dependent variable was Dopamine Synthesis Capacity (Ki Values). The independent variables were Time and Striatal Subregion. The covariance matrix was unstructured for each subject's Time and Striatal Subregion.

  baseline and week 2

Study Arms (1)

SEP-363856

EXPERIMENTAL

SEP-363856 50mg, 75mg flexible dosing, dosed once daily

Drug: SEP-363856

Interventions

SEP-363856 DRUG

SEP-363856 50mg, 75mg flexable dosing, dosed once daily capsule

SEP-363856

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must give written informed consent and privacy authorization prior to participation in the study.
• \. Subject must be willing and able to comply with the study procedures and visit schedule, including required minimum week in-clinic treatment period, and must be able to understand and follow verbal and written instructions
• Male or female subject between 18 to 45 years of age (inclusive) at the time of consent
• Subject meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a primary diagnosis of schizophrenia as established by clinical interview (using the DSM-5 as a reference and confirmed using the Structured Clinical Interview for DSM-V Clinical Trials Version \[SCID-CT\]). The duration of the subject's illness whether treated or untreated must be ≥ 6 months.
• Subject must be on a stable dose of a single antipsychotic medication, dosed within the labeled dose-range, for a minimum of 3 weeks prior to the PET scan at the screening visit. Patients taking clozapine are not eligible to participate
• Subject must have a Clinical Global Impression-Severity (CGI-S) score ≥ 3 (mild or greater)
• Subject must have a Positive and Negative Syndrome Scale (PANSS) total score ≥ 70.
• Subject's BMI must be at least 18 kg/m2 but no more than 35 kg/m2.
• Female subjects must have a negative serum pregnancy test at screening; as well as a negative urine pregnancy test prior to the PET scan on each day PET scans are performed, as well as prior to the MRI scan.
• Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to use an acceptable form of birth control from at least 30 days prior to administration of the first dose of study drug, during the treatment period, and 60 days after completion or premature discontinuation from the study drug. Male subjects must also refrain from semen/sperm donation 30 days prior to administration of the first dose of study drug, during the treatment period, and 60 days after completion or premature discontinuation from the study drug.
• Adequate contraception is defined as continuous use of either two barrier methods (eg, condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive. Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®) implanted at least 90 days prior to screening; b) injectable contraception (such as meroxyprogesterone acetate injection) given at least 14 days prior to screening; or c) oral contraception taken as directed for at least 30 days prior to screening. In the Investigator's judgment, the subject will adhere to this requirement.
• Female subjects who are of non-childbearing potential are not required to abide by birth control requirements.
• \- Non-childbearing potential is defined as subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone \[FSH\] concentrations within postmenopausal range as determined by laboratory analysis).
• Subject is, in the opinion of the Investigator, generally healthy based on screening medical history, PE, neurological examination, vital signs, clinical laboratory values (hematology, serum chemistry urinalysis, lipid panel, coagulation panel, thyroid panel, and serum prolactin).
• Subject has had a stable living arrangement at the time of screening and agrees to return to a similar living arrangement after discharge. This criterion is not meant to exclude subjects who have temporarily left a stable living arrangement (eg, due to psychosis). Such subjects remain eligible to participate in this study. Chronically homeless subjects should not be enrolled.

You may not qualify if:

• \. Subject answers "yes" to "Suicidal Ideation" Items 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 at or during the Screening period (ie, in the past one month) and/or Day 1 (ie, since last visit).
• \. Subject does not tolerate venipuncture or has poor venous access that would cause difficulty for administration of the radioisotope and for collecting blood samples.
• \. Subject is currently participating in, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent, or has participated in more than 2 studies of investigational compounds within 24 months prior to signing the informed consent.
• \. Subject has participated in a research and/or PET or radiological investigations with radiation exposure that, when combined with the dose from the present study, would exceed 10 mSv in addition to natural background radiation, in the previous 12 months.
• \. Subject has previously received SEP-363856.
• \. 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:
• Clinically significant hematological (including deep vein thrombosis) or bleeding disorder, renal, metabolic, endocrine, pulmonary, gastrointestinal, urological, cardiovascular, hepatic, neurologic, or allergic disease (except for untreated, asymptomatic, seasonal allergies at time of dosing).
• 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. Subject has a pituitary tumor of any duration.
• Disorder or history of a condition, or previous gastrointestinal surgery (eg, cholecystectomy, vagotomy, bowel resection) that may interfere with drug absorption, distribution, metabolism, excretion, gastrointestinal motility, or pH, or a history of clinically significant abnormality of the hepatic or renal system, or a history of malabsorption.
• Subject currently has or has had within the last 6 months a diagnosis of Alcohol or Substance Abuse Disorder (DSM-5 criteria). The only exceptions include caffeine or nicotine.
• Subject has a clinically significant abnormal 12-lead ECG that may jeopardize the subject's ability to complete the study as determined by the Investigator or a screening 12-lead ECG demonstrating any one of the following: heart rate \> 100 beats per minute, QRS \> 120 ms, QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 450 ms (males), QTcF \> 470 ms (females), or PR \> 220 ms.
• Subjects with known history of human immunodeficiency virus (HIV) seropositivity.
• Subject has a history of clinically significant hypotensive disorder, systolic blood pressure less than or equal to 80 mmHg or a diastolic blood pressure less than or equal to 40 mmHG at any measurement prior to dosing on Day 1, or any clinically significant symptoms associated with hypotension at any time during participation prior to dosing on day 1.
• \. Female subject who is pregnant or lactating.
• Subject has a presence or history of a medically diagnosed, clinically significant psychiatric disorder (including intellectual disability, major depressive disorder with psychosis, and bipolar disorder) other than schizophrenia (medically diagnosed schizoaffective disorder or schizophreniform disorder will be allowed).

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

SEP-363856

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: CNS Medical Director
• Organization: Sumitomo Pharma America Inc

clinicaltrialdisclosure@sunovion.com

1-866-503-6351

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-site, open-label, flexibly-dosed study

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: July 31, 2019
• Study Start: August 7, 2019
• Primary Completion: June 6, 2023
• Study Completion: June 6, 2023
• Last Updated: December 27, 2024
• Results First Posted: November 25, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

GB (1)