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

A Phase 1, Two-part, Open-label, Randomized, Exploratory and Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Brexpiprazole Long-acting Injectable Administered Subcutaneously or Intramuscularly in Adult Subjects With Schizophrenia

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.

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.