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

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

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 Overview

• Status: Terminated
• Conditions: Schizophrenia; Schizoaffective Disorder; Metabolic Syndrome; Bipolar I Disorder
• Intervention / Treatment: Drug: Aripiprazole; Drug: Oanzapine, risperidone, or quetiapine

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2W8
    • Local Institution
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Local Institution
  • British Columbia
    • Pentincton, British Columbia, Canada, V2A 4M4
      • Local Institution
    • Vancouver, British Columbia, Canada, V6T 2A1
      • Local Institution
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3K7
      • Local Institution
    • London, Ontario, Canada, N6H 4V1
      • Local Institution
    • Markham, Ontario, Canada, L6B 1A1
      • Local Institution
    • Mississauga, Ontario, Canada, L5M 4N4
      • Local Institution
    • Toronto, Ontario, Canada, M5T 2S8
      • Local Institution
    • Toronto, Ontario, Canada, M5T 1R8
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Local Institution
    • Montreal, Quebec, Canada, H1N 3M5
      • Local Institution
    • Montreal, Quebec, Canada, H3M 3A9
      • Local Institution
    • Montreal, Quebec, Canada, H4H 1R3
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole	Drug: Aripiprazole; 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; Other Names: Abilify; BMS-334039
Active Comparator: Control group (Oanzapine, risperidone, or quetiapine)	Drug: Oanzapine, risperidone, or quetiapine; Oanzapine, risperidone, or quetiapine administered orally as tablets at prior dosage for 16 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 6, 2009
• First Submitted That Met QC Criteria: March 6, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Estimate): December 2, 2013
• Last Update Submitted That Met QC Criteria: November 7, 2013
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Insulin Resistance; Hyperinsulinism; Syndrome; Schizophrenia; Disease; Psychotic Disorders; Metabolic Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Quetiapine Fumarate; Risperidone
• Other Study ID Numbers: CN138-564