Study Assessing the Safety, Tolerability, and Pharmacokinetics of SEP-363856 in Male and Female Subjects With Schizophrenia

NCT01994473 | Completed Phase 1

• 1 other identifier: SEP361-106
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This is a study designed to evaluate the safety, tolerability, and PK of SEP-363856 and its metabolite SEP-363854 in male and female subjects with schizophrenia.

Conditions

Schizophrenia

Keywords

Schizophrenia

Outcome Measures

Primary Outcomes (3)

• Frequency of AEs, SAEs, and AEs resulting in study discontinuation in Parts 1 and 2.

  Up to 57 days

• Absolute values and changes from baseline in clinical laboratory tests, vital signs, 12-lead ECGs, and findings from neurological examinations in Parts 1 and 2

  Absolute values and changes from baseline in clinical laboratory tests (hematology, serum chemistry, urinalysis, lipid panel, coagulation panel, thyroid panel, and serum prolactin), vital signs (blood pressure \[supine and standing\], heart rate \[supine and standing\], respiration rate, and body temperature), 12-lead ECGs, and findings from neurological examinations in Parts 1 and 2

  Up to 57 days

• Frequency of subjects with suicidal ideation or suicidal behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS) in Parts 1 and 2.

  Up to 57 days

Secondary Outcomes (11)

• Plasma SEP-363856 and metabolite SEP-363854 maximum observed concentration (Cmax)

  Part 1, Day 1 (following first dose)

• Plasma metabolite to parent ratio for Cmax (MRCmax) and AUC0-24 (MRAUC0-24).

  Part 1, Day 1 (following first dose)

• Plasma SEP-363856 and metabolite SEP-363854 Cmax, tmax, AUC0-tau, terminal elimination half-life (t1/2), and accumulation ratios based on Cmax (RCmax), and AUC0-tau (RAUC0-tau).

  Part 1, Day 7 (following last dose)

• Plasma metabolite to parent ratio for Cmax (MRCmax) and AUC0-tau (MRAUC0-tau).

  Part 1, Day 7 (following last dose)

• Plasma SEP-363856 steady-state apparent volume of distribution (Vss/F).

  Day 7 (following last dose)

Study Arms (3)

SEP-363856

EXPERIMENTAL

Dosing will be initiated at 10 mg SEP-363856 as a single oral dose. Subsequent cohorts will be dosed at 25, 50, and 100 of SEP-363856.

Drug: SEP-363856

Placebo

PLACEBO COMPARATOR

An oral of matched placebo

Drug: Placebo

SEP-363856 Open Label

EXPERIMENTAL

75 mg SEP-363856 given once-daily

Drug: SEP-363856 Open Label

Interventions

SEP-363856 DRUG

SEP-36385625 as a single oral dose of 10, 25, 50, and 100 mcg

SEP-363856

Placebo DRUG

single oral dose placebo

Placebo

SEP-363856 Open Label DRUG

75 mg SEP-363856 given once-daily

SEP-363856 Open Label

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must give written informed consent and privacy authorization (Healthcare Insurance, Portability, and Accountability Act of 1996) prior to participation in the study. Female subjects of childbearing potential1 and male subjects must agree to contraceptive requirements outlined in the informed consent form.
• Subject must be willing and able to comply with the study procedures and visit schedules and must be able to follow verbal and written instructions.
• Male or female subject between 18 to 55 years of age (inclusive) at the time of consent.
• Subject's body mass index (BMI) must be at least 19.5 kg/m2 but no more than 37 kg/m2.
• Female subject must have a negative serum pregnancy test at screening.
• Female subjects of childbearing potential1 must agree to avoid pregnancy and use acceptable methods of birth control from at least 60 days prior to screening and for at least 90 days after the last study drug administration.
• Male subjects with female partner(s) of childbearing potential1 must agree to avoid fathering a child and use acceptable methods of birth control (see Section 24) from screening until at least 90 days after the last study drug administration.
• Subject must meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; Text Revision (DSM-IV-TR) criteria for a primary diagnosis of schizophrenia with the following subtypes: disorganized (295.10), catatonic type (295.20), paranoid (295.30), residual (295.60), or undifferentiated (295.90); and in the opinion of the Investigator has been clinically stable for the past 6 months.
• Subject must have a CGI-S score ≤ 4 (normal to moderately ill) at screening.
• Subject must have a PANSS total score ≤ 80 at screening.
• Subject must have a score of ≤ 4 (normal to moderate) on the following PANSS items at screening:
• P7 (hostility)
• G8 (uncooperativeness)
• Subject must be able and agree to remain off prior antipsychotic medication from clinic admission through Day 10
• Subject must have normal to mild symptoms on all individual items of the MSAS (\< 2) and AIMS (\< 3), and the clinical global assessment item of the BARS (\< 3).

You may not qualify if:

• Subject does not tolerate venipuncture or has poor venous access that would cause difficulty for collecting blood samples.
• Subject has participated in an investigational drug study and received investigational drug within 30 days (or longer if the half-life is known to be ≥ 150 hours) prior to the screening visit, or who is currently participating in another clinical study. Subject has previously received study drug.
• 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 (except for untreated, asymptomatic, seasonal allergies at time of dosing).
• History of cancer or significant neoplasm.
• 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.
• Known or suspected excessive alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of the screening visit or a positive breath alcohol test at screening.
• Subject has a clinically significant abnormal 12-lead ECG that may jeopardize the subject's ability to complete the study or a screening 12-lead ECG demonstrating any one of the following: heart rate \> 100 beats per minute, QRS \> 120 ms, QTinterval corrected for heart rate using Fridericia's formula (QTcF) \> 450 ms (males), QTcF \> 470 ms (females), or PR \> 220 ms.
• Female subject who is pregnant or lactating.
• Subject has a presence or history of a medically diagnosed, clinically significant psychiatric disorder (including mental retardation, schizoaffective disorder, schizophreniform disorder, psychotic depression, and bipolar disorder) other than schizophrenia.
• Subject experienced an acute exacerbation of psychosis within the last 3 months or experienced an acute exacerbation of psychosis requiring hospitalization within the last 6 months.
• Subject experienced an acute exacerbation of psychosis requiring change in antipsychotic medication (with reference to drug or dose) within the last 3 months.
• Subject has a diagnosis or history of substance dependence (except nicotine ≤ 1 pack/day) or substance abuse (except cannabis) according to DSM IV-TR criteria ≤ 3 months prior to screening or a positive urine drug screen (except benzodiazepines) at screening.
• Subject is at significant risk of harming him/herself or others according to the Investigator's judgment.
• Subject has had past episodes of significant extrapyramidal symptoms (EPS) under current medication that required dose modification or the addition of anti-Parkinson's treatment within the last 6 months.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (2)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

SEP-363856

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 25, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 26, 2024

Record last verified: 2024-06

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

US (2)