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

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.

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