Comparative Bioavailability of Risperidone

Exclusion Criteria

• •1. Presence of an uncontrolled, unstable, clinically significant medical condition (eg, renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy) that in the opinion of the investigator could have interfered with the interpretation of safety and PK evaluations
• •2. Presence of a clinically significant vital sign or physical examination finding that in the opinion of the investigator could potentially interfere with the ability to evaluate safety and tolerability of the trial medication or could impair the subject's ability to complete the trial
• •3. Presence of a clinically significant abnormality on blood or urine safety tests, which do not improve on retesting. In particular, laboratory and/or clinical evidence of clinically significant hepatic conditions, such as:
• •* alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) and total bilirubin \> 2 × ULN; or
• •* ALT or AST \> 3 × ULN with the appearance of jaundice, worsening of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia
• •4. Corrected QT interval, Fridericia's correction (QTcF) interval greater than 450 msec for males and 470 msec for females, or other clinically significant ECG abnormality on screening or baseline
• •5. If female, a positive serum pregnancy test, or planning to become pregnant between signing informed consent and 1 month after the last dose of trial medication, or is breastfeeding a child
• •6. Uncontrolled or unstable diabetes, or a clinically significant abnormal Hba1c blood level
• •7. Known or suspected (non-febrile) seizure disorder
• •8. Known serological evidence of human immunodeficiency (HIV) antibody
• •9. History of hepatitis B infection within the past year, or history of hepatitis C infection that has not been adequately treated and abnormal Liver Functional Tests (LFT) values
• •10. History of neuroleptic malignant syndrome
• •11. Current or past history of clinically significant tardive dyskinesia
• •12. Primary diagnosis other than schizophrenia diagnosis that is primarily responsible for current symptoms and functional impairment
• •13. Known or suspected diagnosis of mental retardation or organic brain disorder
• •14. Positive urine drug/alcohol (ethanol breathalyzer is also acceptable) screen finding, unless the positive finding can be accounted for by documented prescription use. Individuals who have positive results for alcohol, cannabis, or other psychotropic substances but are not dependent on or abusing these substances may be included at the investigator's discretion, following a discussion between the investigator and the medical monitor
• •15. Heavy smoker (consumption of \>40 cigarettes daily)
• •16. Fulfillment of the DSM-5 criteria for moderate or severe substance use disorder (excluding nicotine) within the past 6 months
• •17. Diagnosis of a psychotic disorder or a behavioral disturbance that is thought to be substance-induced or due to substance abuse
• •18. In the investigator's opinion, at imminent risk of committing self-harm or harm to others, based on clinical interview and responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS). Individuals will be excluded if they report having suicidal ideation of Type 4 or 5 in the past 2 months, or suicidal behavior in the past 6 months, as measured by the C-SSRS at screening or baseline
• •19. On more than 1 antidepressant; or if on just one, a change in dose within the last 4 weeks prior to screen
• •20. Use of depot antipsychotics within the last 6 to 9 months
• •21. Use of electroconvulsive therapy (ECT) within the last 3 months
• •22. Use of moderate or strong cytochrome P450 3A4 (CYP3A4)enzyme inducers and inhibitors (carbamazepine, phenytoin, rifampicin, phenobarbital) or moderate or strong cytochrome P450 2D6 (CYP2D6) inhibitors (fluoxetine, paroxetine) (see Appendix 11.2) within 3 days or a time period of 5 half lives of the concerning drug, whichever is longer, prior to baseline
• •23. Unwilling to discontinue any of prohibited medications prior to the baseline visit; or, in the opinion of the investigator, is unable to safely taper off such medication without significant destabilization or increased risk of self-harm (suicide). Prohibited medications may include antipsychotics, phenobarbital, fluoxetine, fluoxetine combinations, paroxetine, benzodiazepines except lorazepam, diazepam, oxazepam, psychotropics, herbal drugs/dietary supplements for depression, anxiety, insomnia, rifampicin, and quinidine
• •24. Receipt of any investigational drugs within the last 3 months
• •25. Current participation in any other clinical trial
• •26. In the investigator's opinion, medically non-compliant in the management of his or her disease
• •27. Known or suspected allergy or hypersensitivity to risperidone or any of the ISM® excipients
• •28. Previous non-responder to risperidone treatment
• •29. Currently under involuntary in-patient commitment