Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone

Inclusion Criteria

• Diagnosis of schizophrenia
• Clinically stable as defined as no hospitalizations for acute exacerbations within 3 months of screening and Screening PANSS score ≤70
• Total body mass index (BMI) between 18 and 35 kg/m2
• Given written informed consent

Exclusion Criteria

• Received a once-monthly long-acting injectable (LAI) antipsychotic within 60 days of screening and a once every 3 month LAI antipsychotic within 120 days of screening
• Taking the following concurrent or over the counter (OTC) products:
• Inducers or inhibitors of CYP2D6 within 14 days or 5 half-lives whichever is greater prior to study screening
• Bupropion, chlorpheniramine, cimetidine, clomipramine, doxepin or quinidine within 30 days prior to study screening
• Clozapine, phenothiazines, aripiprazole, haloperidol or any other antipsychotic other than oral risperidone within 14 days prior to study screening
• Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) within 30 days prior to study screening
• Opioids or opioid-containing analgesics within 14 days prior to study screening
• Medications, in the addition to those listed above which in the opinion of the Investigator in conjunction with the medical monitor, may be expected to significantly interfere with the metabolism or excretion of risperidone and/or 9-hydroxyrisperidone, that may be associated with a significant drug interaction with risperidone, or that may pose a significant risk to subjects' participation in the study. The medical monitor should be contacted with any questions regarding the use of CYP2D6 or 3A4 inducers or inhibitors in particular.
• History of cancer (with the exception of resected basal cell or squamous cell carcinoma of the skin) unless they have been disease free for ≥5 years.
• Another active medical condition or organ disease that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug.
• Evidence or history of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug. Individuals with acute or chronic hepatitis (including but not limited to hepatitis B or C); or individuals with 1) total bilirubin >1.5x the upper limit of normal (ULN) and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x ULN will be excluded.
• A history of renal disease, or a creatinine clearance of less than 60 mL/min (as determined by the Cockcroft-Gault formula).
• A history of orthostatic hypotension, syncope, significant low white blood cell (WBC) count (i.e., based on absolute neutrophil count or drug-induced leukopenia or other medical conditions including, but not limited to, history of heart attack (i.e., myocardial infarction) or brain injury (i.e., traumatic with loss of consciousness and/or cardiovascular accident) within a year of Screening and clinically significant low blood pressure or arrhythmias as interpreted by the principal investigator (PI).
• Corrected QT interval [Fridericia's calculation (QTcF)] >450 msec (male) or >470 msec (female) at screening or prior to administration of the 1st dose of PERSERIS, or with a known history of Torsades de Points, or family member with sudden unexplained cardiac death.
• Known to have AIDS (acquired immunodeficiency syndrome) or to be HIV (human immunodeficiency virus) positive.
• Suicidal ideation with intent and plan, as assessed by affirmative answers to C-SSRS questions 4 and 5 of the ideation section,or suicide attempts within the last 6 months as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the Investigator.
• Known diagnosis of type 1 diabetes or subjects with Haemoglobin A1c (HbA1c) >8.0% at screening.
• Participated in a clinical trial within 30 days prior to study screening.
• Significant traumatic injury, major surgery or open biopsy within 30 days prio