Safety and Tolerability Study of Single-dose Administration of Brexpiprazole in Adult Subjects With Schizophrenia

Phase 1TerminatedNCT02968121

Otsuka Pharmaceutical Development & Commercialization, Inc.22 enrolled

Overview

To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia.

This trial is designed to assess the pharmacokinetics, safety and tolerability of brexpiprazole in the treatment of subjects with schizophrenia. The trial will consist of two parts across 13-36 months. The trial population will include approximately 110 male \& female subjects between 18 and 64 years of age (inclusive) with a diagnosis of schizophrenia as defined by DSM-V criteria.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Enrollment

Conditions

Schizophrenia

Interventions

Brexpiprazole, OPDC-34712DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females between 18 and 64 years of age, inclusive, at the screening visit with a diagnosis of schizophrenia as defined by DSM-V criteria. * Body mass index between 18 and 35 kg/m\^2 at the screening visit. * Good physical health as determined by no clinically significant deviation from normal. * Ability to provide informed consent and/or consent obtained from a legally acceptable representative (as required by IRB), prior to the initiation of any protocol-required procedures. * Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male subjects/female subjects (of childbearing potential) who agree to remain abstinent or to practice 2 of the approved birth control methods from the screening visit and for at least 150 days after the dose of IMP for a female subject or 180 days after the dose of IMP for a male subject. Exclusion Criteria: * Subjects who have: * Met DSM-V criteria for substance use disorder within the past 180 days; including alcohol and benzodiazepines, excluding caffeine/nicotine. * A positive drug screen for drugs of abuse (excluding stimulants, other prescribed medications, and marijuana \[if in investigator's documented opinion the subject does not meet DSM-V criteria for substance use disorder\]). * Use of more than 1 psychotropic medication at the screening or baseline visit, except for oral brexpiprazole administered during the brexpiprazole tolerability testing (if applicable) and current oral antipsychotic medication. * Use of varenicline beyond screening. * Subjects who have participated in any clinical trial involving a psychotropic medication within 1 month prior to the administration of IMP or 5 half-lives from last IMP administration whichever is longer. * Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 on the Baseline Version of the C-SSRS. * Subjects currently in an acute relapse of schizophrenia as assessed by the investigator. * Subjects with a current DSM-V diagnosis other than schizophrenia. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

Locations (2)

Collaborative Neuro Science (CNS)

Garden Grove, California, United States

CNRI

San Diego, California, United States

Outcomes

Primary Outcomes

Change in Suicidality via Columbia-Suicide Severity Rating Scale

Baseline version and Since Last Visit version of CSSRS will be completed by trained trial center staff

Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126

Number of reported Adverse Events (AE)

Time frame: Part A: 182 days; Part B: 126 days

Clinical Laboratory Tests

Hematology, serum chemistry, urinalysis, drug screen, etc. will be performed.

Time frame: Part A: 182 days; Part B: 126 days

Change in physical exam results

Investigator or designee will perform complete physical exam and document any clinically significant conditions. Body height and weight will also be measured for BMI calculation and weight will be measured as part of all subsequent physical exams.

Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126

Change in Systolic/Diastolic blood pressure from screening to end of study

Heart rate and body temperature will also be obtained prior to PK blood draws and ECG.

Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126

ECG Reading

12-lead ECG will be collected in triplicate (5 minutes apart). heart rate, ventricular rate, RR interval, PR interval, QRS duration and QT intervals will be recorded. QTcF and corrected QT interval using Bazett's formula will be calculated.

Time frame: Part A: 182 days; Part B: 126 days

Extrapyramidal Symptoms (EPS) Rating Scale

SAS, AIMS \& BARS will be assess by trained trial center staff

Time frame: Part A: 182 days; Part B: 126 days

Data from ClinicalTrials.gov

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Secondary Outcomes

Maximum peak plasma concentration (Cmax) [Pharmacokinetics]

Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded. PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411.