One-Year Trial of Oral Ziprasidone in Bipolar Patients With Metabolic Syndrome

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01113541
First received: April 28, 2010
Last updated: June 5, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to explore the impact of Ziprasidone HCl on the distribution of metabolic syndrome (MS) risk factors in a population of Bipolar patients presenting with glucose intolerance, dyslipidemia and/or elevated waist circumference associated with their current antipsychotic medication.


Condition Intervention Phase
Bipolar Disorder
Drug: Ziprasidone HCL (oral)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A One-year, Phase III, Open-label, Non-comparative Trial of the Effect of Ziprasidone HCl on Metabolic Syndrome Risk Factors in Patients With Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation [ Time Frame: Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated (el) waist circumference: ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm [men] and ≥80 cm [women]); el triglycerides: ≥1.7 millimoles per liter (mmol/L) (1≥50 milligrams per deciliter [mg/dL]); reduced high-density lipoprotein cholesterol (HDL-C): <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; el fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and el systolic/diastolic blood pressure: systolic ≥130 millimeters of mercury (mmHg) and/or diastolic ≥85 mmHg. Responder = at least 1 less risk factor at endpoint than baseline.


Secondary Outcome Measures:
  • Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm [men] and ≥80 cm [women]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.

  • Metabolic Syndrome (MS) Prevalence [ Time Frame: Baseline through Week 52 ] [ Designated as safety issue: Yes ]
    Percentage of participants at each visit defined as having metabolic syndrome (MS) based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. MS = 3 or more of 5 characteristics: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose.

  • Change From Baseline in the Percentage of Participants With Each Individual Metabolic Syndrome (MS) Risk Factor [ Time Frame: Baseline through Week 52 ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm [men] and ≥80 cm [women]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.

  • Percentage of Participants With Individual Metabolic Syndrome (MS) Risk Factors [ Time Frame: Baseline through Week 52 ] [ Designated as safety issue: Yes ]
    MS risks factors = elevated waist circumference: ≥102 cm in men and ≥88 cm in women (Asian origin: ≥90 cm [men] and ≥80 cm [women]); elevated triglycerides: ≥1.7 mmol/L (1≥50 mg/dL); reduced HDL-C: <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: ≥5.6 mmol/L (≥100 mg/dL); and elevated systolic/diastolic blood pressure: systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg.

  • Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Waist Circumference [ Time Frame: Baseline, Week 4, Week 12, Week 52 ] [ Designated as safety issue: Yes ]
    MS risk factor elevated waist circumference defined as ≥102 centimeters (cm) in men and ≥88 cm in women (Asian origin: ≥90 cm [men] and ≥80 cm [women]).

  • Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Systolic/Diastolic Blood Pressure [ Time Frame: Baseline, Week 4, Week 12, Week 52 ] [ Designated as safety issue: Yes ]
    MS risk factor elevated systolic/diastolic blood pressure defined as systolic blood pressure ≥130 millimeters of mercury (mm Hg) and/or diastolic blood pressure ≥85 mm Hg.

  • Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Fasting Glucose [ Time Frame: Baseline, Week 4, Week 12, Week 52 ] [ Designated as safety issue: Yes ]
    MS risk factor elevated fasting glucose defined as ≥5.6 millimoles per liter (mmol/L) (≥100 mg/dL).

  • Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Reduced High-density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline, Week 4, Week 12, Week 52 ] [ Designated as safety issue: Yes ]
    MS risk factor reduced HDL-C defined as <1.03 millimoles per liter (mmol/L) (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women.

  • Change From Baseline in Individual Risk Factors of Metabolic Syndrome (MS): Elevated Triglycerides [ Time Frame: Baseline, Week 4, Week 12, Week 52 ] [ Designated as safety issue: Yes ]
    MS risk factor elevated triglycerides defined as ≥1.7 millimoles per liter (mmol/L) (1≥50 mg/dL).

  • Change From Baseline in Ten-year Coronary Heart Disease (CHD) Risk According to Framingham Scoring System [ Time Frame: Baseline, Week 4, Week 52 ] [ Designated as safety issue: Yes ]
    Framingham scoring system risk factors: age (risk points range: -9 to 16), cholesterol (risk points range: 0 to 13), HDL cholesterol (risk points range: -1 to 2), smoking (risk points range: 0 to 9), and systolic blood pressure (risk points range: 0 to 6); total risk points range <0 to ≥25, higher score indicates higher 10 year risk (range <1% to ≥30% 10 year risk).

  • Change From Baseline in Total Cholesterol and Low-density Lipoprotein (LDL) Cholesterol Levels [ Time Frame: Baseline, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Weight [ Time Frame: Baseline, Week 4, Week 12, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline, Week 4, Week 12, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
    Body mass index = weight in kilograms (kg) / height in meters (m)^2 .

  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Insulin Levels [ Time Frame: Baseline, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Corrected QT Interval (QTc): Fridericia's Heart Rate Correction Formula (QTcF) [ Time Frame: Baseline, Week 4, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
    QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTc is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR^1/3, where RR=RR interval in seconds.

  • Change From Baseline in Apolipoprotein B (ApoB) Levels [ Time Frame: Baseline, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Leptin [ Time Frame: Baseline, Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Physical Activity Index [ Time Frame: Baseline, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    Physical activity (exercise) score derived for each participant based on the frequency and intensity of physical activities: regular walking, recreational activity, cycling, and sporting activity. Six categories of total score: inactive (range: 0-2), occasional (range: 3-5), light (range: 6-8), moderate (range: 9-12), moderately vigorous (range: 13-20), and vigorous (≥21). Higher score = higher frequency and intensity of physical activity.

  • Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score [ Time Frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

  • Change From Baseline in Young Mania Rating Scale (YMRS) [ Time Frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    11-item scale that measures the severity of manic episodes from subject reported symptoms over previous 48 hours and clinical observation during interview. Four items (irritability, speech, thought content, disruptive-aggressive behaviour) are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining 7 items (elevated mood, increased motor activity-energy, sexual interest, sleep, language-thought disorder, appearance, insight) are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). YMRS total score range = 0 to 60.

  • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Subscale [ Time Frame: Baseline, Week 4, Week 12, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.

  • Clinical Global Impression - Improvement (CGI-I) Subscale Score [ Time Frame: Week 52 or Early Termination ] [ Designated as safety issue: No ]
    CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.

  • Change From Baseline in Drug Attitude Inventory (DAI) [ Time Frame: Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    DAI, a 10-item scale to assess how the attitude of schizophrenia participants toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranged from -10 to 10, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance. Change: score at observation minus score at baseline.

  • Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) [ Time Frame: Baseline, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    0-100 single score scale focusing exclusively on participant's level of social and occupational functioning; not directly influenced by overall severity of participant's psychological symptoms; higher score = higher level of functioning. 1 to 10 = persistent inability to maintain minimal personal hygiene; unable to function without harming self or others or without considerable external support; 91 to 100 = superior functioning in a wide range of activities.

  • Change From Baseline in EuroQoL Index (EQ-I) [ Time Frame: Baseline, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  • Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score [ Time Frame: Baseline, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.

  • Change From Baseline in Impact of Weight on Quality of Life-Lite Version (IWQOL-Lite) Scale [ Time Frame: Baseline, Week 28, Week 52 or Early Termination ] [ Designated as safety issue: No ]
    31-item self report inventory to assess impact of weight on quality of life. Five subscales: physical functioning, self-esteem, sexual life, public distress, and work, with categories in each subscale scored 1 (no trouble or difficulty) to 5 (persistent trouble or difficulty). The rescaled IWQoL-Lite score is determined by the sum of scores on all 31 items and rescaling this sum to a 1 to 100 scoring with 0=the poorest and 100=the best quality of life.

  • Number of Participants With Suicidal Tendencies (Columbian-Suicide Severity Rating Scale, [C-SSRS], Mapped to C-CASA [Columbia Classification Algorithm For Suicide Assessment]) [ Time Frame: Baseline, Week 1 through Week 52 or Early Termination ] [ Designated as safety issue: Yes ]
    C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.


Enrollment: 13
Study Start Date: July 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active treatment (switch to oral Ziprasidone) Drug: Ziprasidone HCL (oral)
Ziprasidone Hydrochloride 20 to 80 mg administered orally twice a day (40-160 mg total daily dose) for up to 1 year.
Other Name: Zeldox, Geodon

Detailed Description:

The trial was terminated prematurely on December 14, 2010, due to inability to recruit the planned number of subjects and shifting organizational priorities. The decision to terminate the trial was not based on any safety or efficacy concerns.

  Eligibility

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

Inclusion Criteria:

  • Subject must present at least 2 of the following risk factors of MS at screening: Elevated waist circumference: >102 cm in men and >88 cm in women; Elevated triglycerides (TGs): ≥1.7 mmol/L (≥150 mg/dL); Reduced HDL-Cholesterol: <1.03 mmol/L (<40 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women; Elevated fasting glucose: ≥ 5.6 mmol/L.
  • According to the clinical judgment of the investigator, the risk factors for MS have developed in close temporal relationship to starting an antipsychotic medication.
  • Substitution to a less metabolically disruptive antipsychotic medication is considered

Exclusion Criteria:

  • Subjects with contraindication(s) to the use of Ziprasidone according to Canadian prescribing information.
  • Subjects with a history of treatment resistance.
  • Subjects with any medical condition (e.g. pre-existing diabetes, pre-existing dyslipidemia, thyroid pathology) or taking any concomitant medication (e.g. topiramate or other weight loss-promoting agents, hypoglycemic agents, hypolipemic agents), that may confound the evaluation of the study drug.
  • Body mass index ≥ 40 at baseline.
  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: NCT01113541

Locations
Canada, Alberta
Mental Health Centre for Research and Education
Calgary, Alberta, Canada, T2N 2T9
Foothills Medical Centre, Department of Psychiatry
Calgary, Alberta, Canada, T2N 2T9
Canada, British Columbia
Dr. Alexander McIntyre Inc.
Penticton, British Columbia, Canada, V2A 4M4
Canada, Manitoba
Country Club Plaza
Winnipeg, Manitoba, Canada, R3K 2E2
Edgeland Medical, Dr. Alla Kirshner Medical Corporation
Winnipeg, Manitoba, Canada, R3P 0N5
Canada, Nova Scotia
Capital, Health Authority, QE II Health Sciences Centre, Mood Disorder Clinic
Halifax, Nova Scotia, Canada, B3H 2E2
Office of Dr. A. K. Munshi
Sydney, Nova Scotia, Canada, B1S 2E8
Canada, Quebec
Clinique St-Leonard
Montreal, Quebec, Canada, H1P 3K2
Centre de recherche Fernand-Seguin de l'hopital Louis H. Lafontaine
Montreal, Quebec, Canada, H1N 3V2
Diex Research Sherbrooke Inc.
Sherbrooke, Quebec, Canada, J1H 1Z1
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01113541     History of Changes
Other Study ID Numbers: A1281190
Study First Received: April 28, 2010
Results First Received: October 12, 2011
Last Updated: June 5, 2012
Health Authority: Canada: Health Canada

Keywords provided by Pfizer:
Ziprasidone
Bipolar Disorder
Metabolic Syndrome

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Metabolic Syndrome X
Syndrome
Affective Disorders, Psychotic
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Mental Disorders
Metabolic Diseases
Mood Disorders
Pathologic Processes
Ziprasidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 21, 2014