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

Phase 3TerminatedNCT00857818

Otsuka Pharmaceutical Development & Commercialization, Inc.64 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Schizophrenia Schizoaffective Disorder Bipolar I Disorder Metabolic Syndrome

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (14)

Local Institution

Calgary, Alberta, Canada

Local Institution

Pentincton, British Columbia, Canada

Local Institution

Vancouver, British Columbia, Canada

Local Institution

Hamilton, Ontario, Canada

Local Institution

London, Ontario, Canada

Local Institution

Markham, Ontario, Canada

Local Institution

Mississauga, Ontario, Canada

Local Institution

Toronto, Ontario, Canada

Local Institution

Toronto, Ontario, Canada

Local Institution

Montreal, Quebec, Canada

...and 4 more locations

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Weeks 4, 8, and 16

Mean Baseline Fasting Non-HDL Levels

Time frame: At baseline (Day 1)

Secondary Outcomes

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.

Time frame: Baseline to Week 16, continuously

Mean Percent Changes From Baseline in Fasting Triglyceride and Total, High-Density Lipoprotein, and Low-Density Lipoprotein Cholesterol Levels

Time frame: Baseline to Week 16

Mean Changes From Baseline in Fasting Glucose Levels

Time frame: Baseline to Week 16

Percent of Participants Showing a Decrease or Increase in Body Weight of 7% or Greater From Baseline

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline to Weeks 4, 8, and 16

Mean Changes in Weight From Baseline

Time frame: Baseline to Weeks 4, 8, and 16

Median Changes in Body Mass Index From Baseline

Time frame: Baseline to Weeks 4, 8, and 16

Mean Changes in Serum Prolactin Levels From Baseline

Time frame: Baseline to Weeks 4, 8. and 16