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

This study has been terminated.
(Slow Accrual)
Sponsor:
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00857818
First received: March 6, 2009
Last updated: November 7, 2013
Last verified: July 2011
  Purpose

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).


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Bipolar I Disorder
Metabolic Syndrome
Drug: Aripiprazole
Drug: Oanzapine, risperidone, or quetiapine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Mean Percent Change From Baseline in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Levels [ Time Frame: Baseline to Weeks 4, 8, and 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Baseline Fasting Non-HDL Levels [ Time Frame: At baseline (Day 1) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and 1 or More AEs [ Time Frame: Baseline to Week 16, continuously ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Fasting Glucose Levels [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Clinical Global Impression-Severity (CGI-S) Scale [ Time Frame: Baseline and Weeks 4, 8, and 16 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Weeks 4, 8, and 16 ] [ Designated as safety issue: Yes ]
    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.

  • Mean Change From Baseline in Impact of Weight on Quality of Life (IWQoL-Lite) Scores [ Time Frame: Baseline to Weeks 4, 8, and 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Changes in Weight From Baseline [ Time Frame: Baseline to Weeks 4, 8, and 16 ] [ Designated as safety issue: No ]
  • Median Changes in Body Mass Index From Baseline [ Time Frame: Baseline to Weeks 4, 8, and 16 ] [ Designated as safety issue: No ]
  • Mean Changes in Serum Prolactin Levels From Baseline [ Time Frame: Baseline to Weeks 4, 8. and 16 ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: April 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857818

Locations
Canada, Alberta
Local Institution
Calgary, Alberta, Canada, T2N 2T9
Canada, British Columbia
Local Institution
Pentincton, British Columbia, Canada, V2A 4M4
Local Institution
Vancouver, British Columbia, Canada, V6T 2A1
Canada, Ontario
Local Institution
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
Canada, Quebec
Local Institution
Montreal, Quebec, Canada, H4H 1R3
Local Institution
Montreal, Quebec, Canada, H3M 3A9
Local Institution
Montreal, Quebec, Canada, H3A 1A1
Local Institution
Montreal, Quebec, Canada, H1N 3M5
Canada
Local Institution
Quebec, Canada, G1R 2W8
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00857818     History of Changes
Other Study ID Numbers: CN138-564
Study First Received: March 6, 2009
Results First Received: May 17, 2011
Last Updated: November 7, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Metabolic Syndrome X
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Risperidone
Quetiapine
Aripiprazole
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on July 31, 2014