Trial Comparing the Effects of Aripiprazole With Those of... | NCT00857818

NCT00857818

Status Module

Label	Type	Description	Intervention Names
Aripiprazole	Experimental		Drug: Aripiprazole
Control group (Oanzapine, risperidone, or quetiapine)	Active Comparator		Drug: Oanzapine, risperidone, or quetiapine

Name	Type	Description	Arm Group Labels	Other Names
Aripiprazole	Drug	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

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility 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.

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution		Calgary	Alberta	T2N 2T9	Canada
Local Institution

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
FG001	Control Group (Olanzapine, Risperidone, or Quetiapine)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
BG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00014 BG00114 BG00228

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All randomized patients who took at least 1 dose of study medication during the treatment period. The Last Observation Carried Forward (LOCF) data set included data recorded at a given visit. If no observation was recorded at that visit, data was carried forward from the previous visit. .

Posted

Mean

Standard Error

Percentage of change

Baseline to Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG00013 OG00112

Title

Denominators

Categories

Week 4

Title	Measurements
	OG000-7.54± 3.22 OG0010.19± 3.60

Week 8

Title	Measurements
	OG000

Secondary

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.

All randomized subjects who took at least 1 dose of study medication during the treatment period.

Posted

Number

Participants

Baseline to Week 16, continuously

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts

Secondary

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

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Week 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Changes From Baseline in Fasting Glucose Levels

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Week 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Secondary

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

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline and Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Secondary

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.

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline and Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts

Secondary

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.

Due to low enrollment, this study was terminated early, and these data were not summarized.

Posted

Baseline and Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants

Secondary

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.

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Secondary

Mean Changes in Weight From Baseline

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Secondary

Median Changes in Body Mass Index From Baseline

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Weeks 4, 8, and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Changes in Serum Prolactin Levels From Baseline

Due to low enrollment, the study was terminated early. This endpoint was not analyzed because there were insufficient data to draw meaningful conclusions.

Posted

Baseline to Weeks 4, 8. and 16

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Primary

Mean Baseline Fasting Non-HDL Levels

All randomized patients who took at least 1 dose of study medication during the treatment period.

Posted

Mean

Standard Error

mg/dL

At baseline (Day 1)

ID	Title	Description
OG000	Aripiprazole	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 in a range of 10 to 30 mg daily.
OG001	Control Group (Olanzapine, Risperidone, or Quetiapine)	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
VISION BLURRED	Eye disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected14 at risk EG0010 affected12 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
ANXIETY	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected14 at risk EG0010 affected12 at risk
INSOMNIA	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0003 affected14 at risk EG0010 affected12 at risk
AGITATION	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
RESTLESSNESS	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
HALLUCINATION, AUDITORY	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
TREMOR	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0003 affected14 at risk EG0010 affected12 at risk
HEADACHE	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
AKATHISIA	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
SOMNOLENCE	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0011 affected12 at risk
PARAESTHESIA	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
EXTRAPYRAMIDAL DISORDER	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0011 affected12 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected14 at risk EG0011 affected12 at risk
INFLUENZA	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
TOOTH ABSCESS	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
PHARYNGITIS STREPTOCOCCAL	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected14 at risk EG0012 affected12 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
INCREASED APPETITE	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
WOUND	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected14 at risk EG0011 affected12 at risk
PAIN IN JAW	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected14 at risk EG0011 affected12 at risk
MUSCLE RIGIDITY	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
MUSCLE TWITCHING	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
RHINORRHOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
SPUTUM DISCOLOURED	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
FATIGUE	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0011 affected12 at risk
FEELING HOT	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
IRRITABILITY	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk

ID	Term
D012559	Schizophrenia
D011618	Psychotic Disorders
D024821	Metabolic Syndrome

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders
D007333	Insulin Resistance
D006946	Hyperinsulinism
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011744	Pyrimidinones
D011743	Pyrimidines
D003987	Dibenzothiazepines
D013841	Thiazepines
D013846	Thiepins
D013457	Sulfur Compounds
D009930	Organic Chemicals
D006575	Heterocyclic Compounds, 3-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ARIPIPRAZOLE	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 in a range of 10 to 30 mg daily.			2	14	11	14
EG001	CONTROL GROUP	Participants were to continue to receive the same dose of their current antipsychotic treatment (either olanzapine, risperidone, or quetiapine) for 16 weeks.			0	12	6	12

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
HALLUCINATION, VISUAL	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
HALLUCINATION, AUDITORY	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
PSYCHIATRIC DECOMPENSATION	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk
NEUROLEPTIC MALIGNANT SYNDROME	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected14 at risk EG0010 affected12 at risk

ID	Term
D000068180	Aripiprazole
D018967	Risperidone
D000069348	Quetiapine Fumarate