Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia

Inclusion Criteria:

1. Subject is male or female, aged 18 to 65 years

2. Subject reads, understands, and signs an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved current ICF prior to performingany of the Screening procedures

3. Diagnosis schizophrenia

Exclusion Criteria:

1. Has a history of treatment resistance exhibited by any of the following:

2. No or minimal response to at least 2 periods of treatment lasting 28 days orlonger, with antipsychotic agents at the maximally tolerated dose.

3. Lifetime history of clozapine use

4. History of electroconvulsive therapy (ECT) for treatment of schizophreniawithin the past 5 years.

5. Is treatment-naïve for schizophrenia.

6. Primary current diagnosis other than schizophrenia or a comorbid diagnosis that isprimarily responsible for the current symptoms and functional impairment.

7. Has a current diagnosis of a psychotic disorder other than schizophrenia or abehavioral disturbance thought to be due to substance abuse disorder.

8. Meets criteria for moderate-to-severe substance use disorder within past 6 monthsprior to Screening (excluding those related to caffeine or nicotine).

9. Has a history of the following: (a) traumatic brain injury causing ongoing cognitivedifficulties, Alzheimer's disease, or another form of dementia, or any chronicorganic disease of the central nervous system (CNS) (b) intellectual disability of aseverity that would impact ability to participate in the study.

10. Subject has a current primary DSM-5 diagnosis other than schizophrenia, includingschizoaffective 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.

11. On antipsychotic within the Screening Period (minimum 3 days prior to Baseline andthroughout the study).

12. Within 28 days prior to Baseline: monoamine oxidase (MAO) inhibitors, CNSstimulants, potent CYP3A4/5 enzyme-inducing drugs including but not limited torifampin and carbamazepine and strong CYP3A4/5 inhibitors like ketoconazole,itraconazole, clarithromycin, etc. (see Appendix 20.1 for prohibited medications).

13. Antipsychotic depot medication within 5 half-lives prior to Baseline.

14. Positive Urine Drug Screen for drugs of abuse, including amphetamines, barbiturates,cocaine, ecstasy, phencyclidine or opiates meeting criteria of moderate-to-severeDSM-5 substance use disorder.