Trial Comparing the Effects of Aripiprazole With Those of Standard of Care on Non-HDL Cholesterol in Patients With Schizophrenia or Bipolar I Disorder Who Have Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of this study was to determine whether patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who also have metabolic syndrome have a larger decrease in fasting non-high density lipoprotein (non-HDL) cholesterol levels with aripiprazole than with their current atypical antipsychotic treatment (olanzapine, risperidone, or quetiapine).

Official Title
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A 16-Week, Randomized, Controlled Trial of the Effect of Aripiprazole Versus Standard of Care on Non-HDL Cholesterol Among Patients With Schizophrenia and Bipolar I Disorder Who Have Pre-existing Metabolic Syndrome

Conditions
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Schizophrenia, Schizoaffective Disorder, Bipolar I Disorder, Metabolic Syndrome

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: Oanzapine, risperidone, or quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Competency in understanding nature of study and ability to sign informed consent form A clinical diagnosis of schizophrenia, schizoaffective disorder, or bipolar I disorder (manic or mixed) that has been treated with antipsychotics (oral olanzapine, risperidone or quetiapine) for at least 3 months. Treatment with any of the antipsychotic medications olanzapine, risperidone, or quetiapine for at least 3 months A Clinical Global Impression-Severity Scale score of 4 or lower at baseline Confirmed diagnosis of metabolic syndrome Patients not receiving treatment specifically for any of the parameters related to metabolic syndrome at the time of randomization Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and up to 4 weeks after last dose of investigational product Patients for whom it is clinically appropriate to switch from their current atypical antipsychotic to aripiprazole (determined by the investigator) Exclusion Criteria: Risk of suicide (suicidal ideation or recently attempted suicide) Meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision criteria for any significant psychoactive substance use disorder within 3 months of screening Diagnosis of type 1 or 2 diabetes mellitus Current treatment for 1 of the components of metabolic syndrome Use of medication for the purpose of weight loss Diagnosis of bipolar disorders other than bipolar 1, depression with psychotic symptoms, or organic brain syndromes History of neuroleptic malignant syndrome Diagnosis of Parkinson's disease, Alzheimer's disease, multiple sclerosis, cerebral palsy, epilepsy, or mental retardation History of seizures Abnormal blood count for platelets, hemoglobin, absolute neutrophils, aspartate aminotransferase, alanine aminotransferase, creatinine, fasting glucose, and thyroid-stimulating hormone Electrocardiogram recording with QTc interval >475 msec Detectable levels of cocaine or positive screen for stimulants or other drugs considered (determined by the investigator) to be of abuse or dependence Blood alcohol levels superior or equal to 50 mg/dL [or 10.9 mmol/L] Prior participation in an aripiprazole clinical trial Treatment with aripiprazole within 1 month of enrollment Predefined exclusionary laboratory tests Patients with Bipolar Disorder treated with adjunctive therapy other than a stable dose of mood stabilizers (lithium or valproate) must undergo a 30-day washout period for adjunctive therapies, such as antidepressants, prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole<br> | Drug: Aripiprazole<br>* Aripiprazole administered orally as tablets, 5 mg once daily (QD) in Week 1; 10 mg QD in Week 2. Flexible dosing allowed after Week 2, adjusted in 5-mg increments every 7 days within a range of 10 to 30 mg daily, for 16 weeks<br>* Other names: BMS-334039;|
| Active Comparator: Control group (Oanzapine, risperidone, or quetiapine)<br> | Drug: Oanzapine, risperidone, or quetiapine<br>* Oanzapine, risperidone, or quetiapine administered orally as tablets at prior dosage for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Levels | Based on Last Observation Carried Forward data. Non-HDL cholesterol is defined as the difference between total cholesterol and high-density lipoprotein (HDL) cholesterol levels. Fasting non-HDL cholesterol is defined as the measured fasting HDL cholesterol level subtracted from the measured fasting total cholesterol level. | Baseline to Weeks 4, 8, and 16 | 
| Mean Baseline Fasting Non-HDL Levels |  | At baseline (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and 1 or More AEs | AE=any new untoward medical event or worsening of a preexisting medical condition that may or may not be causally related to treatment. SAE=any untoward medical occurrence that at any dose results in death; is life-threatening, a congenital anomaly/birth defect, or an important medical event; requires or prolongs inpatient hospitalization, or results in persistent or significant incapacity or drug dependency or abuse. | Baseline to Week 16, continuously | 
| Mean Percent Changes From Baseline in Fasting Triglyceride and Total, High-Density Lipoprotein, and Low-Density Lipoprotein Cholesterol Levels |  | Baseline to Week 16 | 
| Mean Changes From Baseline in Fasting Glucose Levels |  | Baseline to Week 16 | 
| Percent of Participants Showing a Decrease or Increase in Body Weight of 7% or Greater From Baseline |  | Baseline and Weeks 4, 8, and 16 | 
| Mean Changes From Baseline in Clinical Global Impression-Severity (CGI-S) Scale | The CGI-S scale is a 7-point scale that requires the clinician to rate the severity of a patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7=extremely ill. | Baseline and Weeks 4, 8, and 16 | 
| Number of Participants With Potentially Clinically Relevant Changes From Baseline in Blood Pressure, Heart Rate, Hemoglobin Levels, White Blood Cell Count, Differential Count, and Absolute Platelet Count | Any value falling outside of the normal range will be flagged for the attention of the investigator at the site. The investigator will indicate whether or not a flagged value is of clinical significance. | Baseline and Weeks 4, 8, and 16 | 
| Mean Change From Baseline in Impact of Weight on Quality of Life (IWQoL-Lite) Scores | The IWQoL-Lite is a 31-item self-report survey that assesses the impact of weight on quality of life (QoL) in obese patients. Total score=the sum of scores(ranging from 1-5 for each item) for all 31 items. The sum is then rescaled to a 0-100 scoring, with 0 representing the poorest and 100 the best QoL. The survey also assesses improvements in QoL that occur with weight losses of 5% or greater and deteriorations in QoL with weight gain of 5% or greater. A change of 7.8 to 12.0 points from baseline=meaningful improvement. A change of -4.5 to -7.6 points from baseline=meaningful deterioration. | Baseline to Weeks 4, 8, and 16 | 
| Mean Changes in Weight From Baseline |  | Baseline to Weeks 4, 8, and 16 | 
| Median Changes in Body Mass Index From Baseline |  | Baseline to Weeks 4, 8, and 16 | 
| Mean Changes in Serum Prolactin Levels From Baseline |  | Baseline to Weeks 4, 8. and 16 |