PK, Safety, and Tolerability Study of RBP-7000 of Different Molecular Weight Polymer in Subjects With Schizophrenia

Exclusion Criteria

• •Subjects taking any oral risperidone product (except the test doses of 0.25 mg of risperidone); or subjects taking any risperidone or 9-hydroxyrisperidone sustained-release or depot formulation within 120 days prior to study screening; or subjects who have received the 3-month depot formulation of 9-hydroxyrisperidone within 2 years of study screening.
• •Subjects taking a clinically relevant inducer or inhibitor of cytochrome P450 (CYP) 2D6, or CYP3A4, who have not undergone proper washout (minimum of 5 half-lives of the medication) of this prohibited medication prior to Day 1.
• •Medications, which in the opinion of the Investigator in conjunction with the medical monitor, may be expected to significantly interfere with metabolism or excretion of risperidone and/or 9-hydroxyrisperidone; may be associated with a significant drug interaction with risperidone; or may pose a significant risk to a subject's participation in the study.
• •Any natural products or herbal preparations including all vitamins and supplements throughout the study.
• •Subjects with a history of cancer unless disease-free for ≥5 years (with the exception of resected basal cell or squamous cell carcinoma of the skin).
• •Subjects with any other active medical condition/disorder/disease that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug.
• •Subjects that had an exacerbation of schizophrenia in the last 30 days.
• •Subjects with evidence or history (in the past 6 months prior to screening) of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug, including:
• •Acute or chronic hepatitis, including but not limited to hepatitis B or C.
• •Total bilirubin \>1.5 x the upper limit of normal (ULN), or
• •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2x ULN.
• •Subjects with a history of severe renal disease, or creatinine clearance \<60 mL/min
• •Subjects with evidence or history of orthostatic hypotension within 6 months of screening.
• •Subjects with absolute neutrophil count \<1.5x 10\^9/L (African and African/American \<1.2x 10\^9/L).
• •Subjects with a history of drug-induced leucopenia.
• •Subjects who have acquired immune deficiency syndrome (AIDS) or to be human immunodeficiency virus (HIV)-positive.
• •Subjects with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), or clinically significant low blood pressure or arrhythmias as interpreted by the Principal Investigator or medically qualified sub-investigator.
• •Subjects with congenital long QT syndrome, history of prolonged QT in the 3 months prior to screening, or a corrected QT interval (Fridericia - QTcF) \>450 msec (male) or \>470 msec (female) at screening (Visit 1).
• •Subjects with suicidal ideation with intent or plan
• •Subjects with uncontrolled depression, in the opinion of the Investigator.
• •Subjects with a diagnosis of insulin-dependent diabetes, or who have a hemoglobin A1c (HbA1c) ≥8.0% at screening, or have had changes in diabetic medication regimen in the 28 days prior to signing the informed consent document.
• •Subjects with prior allergic reactions, sensitivities or other known contraindications to any component of RBP-7000 (e.g., risperidone, PLGH or NMP).
• •Women of childbearing potential who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study.
• •Subjects with the presence of opioids, cocaine, amphetamines, methadone, barbiturates, benzodiazepines, methamphetamines, cannabinoids, or phencyclidine in the urine as assessed by a urine drug screen.
• •Subjects with epilepsy or other seizure disorders, Parkinson's disease or dementia.