Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy

Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia

This will be an open-label, Phase 2A, multiple ascending dose study in 1 to 3 sites, designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple subcutaneous injections of 60mg, 90mg, and 120mg doses of risperidone in the RBP-7000 formulation, in subjects with clinically-stable schizophrenia who are on a once daily stable dose of 2mg, 3mg, or 4mg of oral risperidone.

Eligibility Criteria:
Inclusion Criteria:

* Male and female
* \> 18 to \< 65 years
* Diagnosis of paranoid, residual, or undifferentiated schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) criteria

  * Status: clinically stable subjects defined as subjects with no hospitalizations for acute exacerbations within 3 months of screening and screening total Positive and Negative Syndrome Scale (PANSS) score \< 60
* Subjects who have given written informed consent

Exclusion Criteria:

* Subjects taking any risperidone sustained release formulation within the 60 days prior to study screening
* Subjects taking the following concurrent medication/over-the-counter products:
* Inducers or inhibitors of cytochrome P450 2D6 (CYP-2D6) within 14 days or 7 half - lives (whichever occurs last) 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 (e.g., fluoxetine, paroxetine) or serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine, desvenlafaxine, duloxetine) within 30 days prior to study screening
* Opioids or opioid-containing analgesics within 14 days prior to study screening
* Medications, in addition to those listed above, which 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
* Subjects with a 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
* Subjects with another active medical condition or organ disease that may either compromise subject safety and/or outcome evaluation of the study drug
* Subjects with 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 hepatitis (including but not limited to B or C); or individuals with 1) total bilirubin \>1.5x the upper limit of normal and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2x upper limit of normal (ULN) will be excluded
* Subjects with hepatitis C antibody and AST, ALT, or alkaline phosphatase \>2x and total bilirubin \>1.3 mg/dL will be excluded
* Subjects with a history of renal disease, or a creatinine clearance of less than 80 mL/min (as determined by the Cockcroft Gault formula)
* Subjects with an international normalized ratio \>2.0 at screening
* Subjects with corrected QT interval (Bazett's - QTcB) \>450 msec (male) or \>470 msec (female) at screening. Subjects with a QTc above these levels due to a benign right bundle branch block can be included in the study at the discretion of the PI
* Subjects who are known to have AIDS or to be HIV positive
* Subjects with suicidal ideation with intent and plan (Columbia-Suicide Severity Rating Scale (C-SSRS) affirmative answers to questions 4 and 5 of the ideation section) or suicide attempts within the last six months as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the investigator
* Subjects with known diagnosis of type 1 or 2 diabetes or subjects with Hemoglobin A1c \>7.0 at screening
* Subjects who have participated in a clinical trial within 30 days prior to study screening
* Subjects who meet the DSM-IV-TR criteria for alcohol abuse or dependence within the last six months of screening