multiple ascending dose study of the safety, tolerability, pharmacokinetic/efficacy

Conditions: Schizophrenia

Summary: 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

Keywords: schizophrenia schizophrenic schizophrenias