Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Risperidone Extended Release Capsules in Patients with Schizophrenia, Schizoaffective Disorder or Bipolar 1 Disorder

Exclusion Criteria23

• Presence of an uncontrolled, unstable, clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, haematologic, immunologic or cerebrovascular disease, or malignancy) that in the opinion of the investigator could interfere with the interpretation of safety and PK evaluations;
• Individuals with a current DSM-5 diagnosis of major depressive episode, recent manic and hypomanic episode (excluding bipolar 1 disorder participants), panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalised anxiety disorder on the MINI, version 7.0.2, or in the judgment of the investigator;
• Receiving an antipsychotic drug other than risperidone;
• 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 patient's ability to complete the trial;
• Presence of a clinically significant abnormality on blood or urine safety tests, which do not improve on re-testing;
• If female, a positive serum pregnancy test, or planning to become pregnant during the trial, between signing informed consent and Day 28 (End of Study Visit), or is breastfeeding a child;
• History of Hepatitis B infection within the past year, or history of Hepatitis C infection that has not been adequately treated;
• History of neuroleptic malignant syndrome;
• Current or history of clinically significant tardive dyskinesia;
• Positive urine drug/alcohol screen finding, unless the positive finding can be accounted for by documented prescription use or is permitted at the investigator’s discretion.
• Fulfilment of the DSM-5 criteria for moderate or severe substance use disorder (excluding nicotine) within the past 6 months;
• 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 associated with actual intent and a method or plan in the past 6 months, as measured by the C-SSRS (i.e., “Yes” answers on items 4 or 5) at screening or baseline;
• Use of depot antipsychotics within the last 9 months;
• Use of moderate or strong cytochrome P450 3A4 (CYP3A4) p-glycoprotein (P-gp) enzyme inducers and inhibitors (carbamazepine, phenytoin, rifampicin, phenobarbital, itraconazole, verapamil) or moderate or strong cytochrome P450 2D6 (CYP2D6) inhibitors (e.g., fluoxetine, fluoxetine combinations, paroxetine) within 30 days prior to baseline;
• Use of any investigational drugs within the last 3 months;
• Current or past participation in any other clinical trial in the past 30 days;
• Known or suspected allergy or hypersensitivity to risperidone;
• Serious adverse reaction or serious hypersensitivity to components of the study formulations or patency capsule;
• Previous non-responder to risperidone treatment or treatment refractory schizophrenia, defined as failure of more than 2 adequate trials of second-generation atypical or typical antipsychotics;
• Individuals with clinically significant oesophageal or gastrointestinal disease (including irritable bowel syndrome) or have symptoms suggestive of functional constipation or diarrhoea;
• Individuals with gastrointestinal transit times, as assessed by administration of a patency pill, of either a) an Oesophageal Transit Time (ETT), defined as the time to reach the stomach, greater than 30 ±5 seconds, or b) a gastrointestinal transit time (GTT), defined as the time to reach the colon or exit the body, greater than 30 + 1 hours;
• CYP2D6 poor or undetermined metaboliser status based on genetic testing.
• Individuals who have made a suicide attempt within the last 5 years.