Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Risperidone; RBP-7000
Intervention description: Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.; RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.
Intervention MeSH terms: Risperidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizophrenia; Schizophrenic; Schizophrenias

Summary:

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

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