Study to Evaluate the Efficacy and Safety of Risperidone in Situ Microparticle (ISM)® in Patients With Acute Schizophrenia

Inclusion Criteria

To be eligible for enrolment into the study, each patient must meet all of the following criteria at screening:

• Capable of providing informed consent
• A signed informed consent form must be provided before any study assessments are performed
• Patients must be fluent in the language that is spoken by the investigator and the study site staff (including raters) and must be able to read and understand the words in which the informed consent is written
• Age ≥ 18 and ≤ 65 years
• Body mass index 18.5 to 40.0 kg/m2 (inclusive)
• Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
• Currently experiencing an acute exacerbation or relapse with onset 4 months during the past year
• Has previously had a clinically significant beneficial response (improvement in schizophrenia symptoms), as determined by the investigator, to treatment with an antipsychotic medication other than clozapine
• Agrees to discontinue prohibited medications as applicable and as clinically indicated according to investigator instructions
• Dosages of all permitted medications are considered to have been stable (with the exception of medication to be used on an as-needed basis) for ≥ 2 weeks prior to the baseline visit and to remain stable during participation in this study
• Positive and Negative Syndrome Scale (PANSS) results at the screening and baseline visits meets the following criteria:

a. Total score between 80 and 120, inclusive b. Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale items: i. Item 1 (P1: delusions) ii. Item 2 (P2: conceptual disorganization) iii. Item 3 (P3: hallucinatory behavior) iv. Item 6 (P6: suspiciousness/persecution)

• Clinical Global Impression - Severity (CGI-S) score of ≥ 4 (moderately ill or worse)
• Resides in a stable living situation and is anticipated to return to that same stable living situation after discharge from the inpatient study unit, in the opinion of the investigator
• Has an identified reliable informant who is anticipated to remain the same after the patient is discharged from the inpatient study unit, in the opinion of the investigator
• Meets the following criteria:

a. If a sexually active, is using a medically accepted contraceptive method, and will continue to use such throughout participation in this study (and for ≥ 6 months after the last dose of IM study drug has been administered); acceptable methods include the following: i. Condoms (male or female) with or without a spermicidal agent ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device iv. Hormonal contraceptive b. If not currently sexually active, them meets the following criteria: i. Agrees that if sexually activity resumes while participating in this study, a medically accepted contraception method will be used

• Willing and able to be confined to an inpatient study unit for up to 2 weeks (or longer if clinically indicated), as applicable and as clinically indicated according to investigator instructions
• Agrees not to post any personal medical data related to the study or information related to the study on any website or social media site (eg, Facebook, Twitter, and others) during the study duration

Exclusion Criteria

An individual who meets any of the following criteria at screening will not be permitted to enroll in the study:

• History of proven inadequate clinical response to treatment with therapeutic doses (with good compliance) of risperidone or paliperidone
• History of treatment resistance, defined as failure to respond to 2 discrete adequate trials (≥ 4 weeks with an adequate dose) of 2 different antipsychotic medications; history of clozapine use (exception: use was not because of treatment resistance or refractory psychotic symptoms)
• Improvement in PANSS total score 20% or greater between the initial screening visit and first injection
• Known