Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia

Prior treatment

• Meets criteria for moderate-to-severe substance use disorder within past 6 months prior to Screening (excluding those related to caffeine or nicotine).
• On antipsychotic within the Screening Period (minimum 3 days prior to Baseline and throughout the study).
• Within 28 days prior to Baseline: monoamine oxidase (MAO) inhibitors, CNS stimulants, potent CYP3A4/5 enzyme-inducing drugs including but not limited to rifampin and carbamazepine and strong CYP3A4/5 inhibitors like ketoconazole, itraconazole, clarithromycin, etc. (see Appendix 20.1 for prohibited medications).
• Antipsychotic depot medication within 5 half-lives prior to Baseline.

Other illness

• Has a history of treatment resistance exhibited by any of the following:
  • No or minimal response to at least 2 periods of treatment lasting 28 days or longer, with antipsychotic agents at the maximally tolerated dose.
  • Lifetime history of clozapine use
  • History of electroconvulsive therapy (ECT) for treatment of schizophrenia within the past 5 years.
• Primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment.
• Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse disorder.
• Has a history of the following: (a) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's disease, or another form of dementia, or any chronic organic disease of the central nervous system (CNS) (b) intellectual disability of a severity that would impact ability to participate in the study.
• Subject has a current primary DSM-5 diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, post-traumatic stress disorder, obsessive-compulsive disorder, manic episode, hypomania, panic disorder, delirium, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
• Positive Urine Drug Screen for drugs of abuse, including amphetamines, barbiturates, cocaine, ecstasy, phencyclidine or opiates meeting criteria of moderate-to-severe DSM-5 substance use disorder.

Other

• Is treatment-naïve for schizophrenia.

• Subject is male or female, aged 18 to 65 years
• Subject reads, understands, and signs an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved current ICF prior to performing any of the Screening procedures
• Diagnosis schizophrenia