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

• Status: Completed
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Indivior Inc.
• Treatments: Risperidone

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