One-Year Trial Of Oral Ziprasidone In Patients With Metabolic Syndrome

This study has been terminated.
(See Detailed Description)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00748566
First received: September 5, 2008
Last updated: April 29, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Schizophrenia and Disorders With Psychotic Features
Drug: Ziprasidone HCL (oral)
Phase 4

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 IV, Open-Label, Non-Comparative Trial Of The Effect Of Ziprasidone HCL On Metabolic Syndrome Risk Factors In Patients With Psychotic Disorders

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Achieving at Least 1 Risk Factor Reduction From Baseline for Metabolic Syndrome (MS) [ Time Frame: Endpoint (premature discontinuation or Week 52) ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated (el) waist, men:>=102 centimeters(cm), women:>=88 cm (Asian origin:>=90 cm in men, >=80 cm in women); el triglycerides: >=1.7 millimoles per liter (mmol/L) (>=150 milligram per deciliter [mg/dL]); reduced high-density lipoprotein cholesterol (HDL-C), men:<1.03 mmol/L (<40 mg/dL), women:<1.3 mmol/L (<50 mg/dL); el fasting glucose: >=5.6 mmol/L (>=100 mg/dL); el systolic/diastolic blood pressure (SBP/DBP): SBP>=130 millimeters of mercury (mmHg) and/or DBP>=85 mmHg. Responder=at least 1 less risk factor at endpoint (premature discontinuation or Week 52) than baseline.


Secondary Outcome Measures:
  • Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated waist circumference: greater than or equal to (>=)102 cm in men, >=88 cm in women (Asian origin: >=90 cm [men], >=80 cm [women]); elevated triglycerides: >=1.7 mmol/L (>=150 mg/dL); reduced high-density lipoprotein cholesterol (HDL-C): less than (<)1.03 mmol/L (<40 mg/dL) in men, <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: >=5.6 mmol/L (>=100 mg/dL); elevated SBP/DBP: SBP >=130 mmHg and/or DBP >=85 mmHg.

  • Percentage of Participants With Metabolic Syndrome (MS) [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    According to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII), metabolic syndrome is defined as a condition that includes 3 or more of 5 characteristics: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose.

  • Number of Participants With Change From Baseline in Metabolic Syndrome (MS) Risk Factors at Week 4, 12, 28 and 52 [ Time Frame: Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated waist circumference: >=102 cm in men, >=88 cm in women (Asian origin: >=90 cm [men], >=80 cm [women]); elevated triglycerides: >=1.7 mmol/L (>=150 mg/dL); reduced high-density lipoprotein cholesterol (HDL-C): <1.03 mmol/L (<40 mg/dL) in men, <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: >=5.6 mmol/L (>=100 mg/dL); elevated SBP/DBP: SBP >=130 mmHg and/or DBP >=85 mmHg.

  • Percentage of Participants With Individual Risk Factors of Metabolic Syndrome (MS) [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    MS risks factors: elevated waist circumference: >=102 cm in men, >=88 cm in women (Asian origin: >=90 cm [men], >=80 cm [women]); elevated triglycerides: >=1.7 mmol/L (>=150 mg/dL); reduced high-density lipoprotein cholesterol (HDL-C): <1.03 mmol/L (<40 mg/dL) in men, <1.3 mmol/L (<50 mg/dL) in women; elevated fasting glucose: >=5.6 mmol/L (>=100 mg/dL); elevated SBP/DBP: SBP >=130 mmHg and/or DBP >=85 mmHg.

  • Change From Baseline in Waist Circumference at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    Waist circumference data is reported separately for male and female participants.

  • Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    BP measurement is recorded as systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles).

  • Change From Baseline in Triglyceride and High Density Lipoprotein-Cholesterol (HDL-C) Levels at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    Triglyceride data is reported for whole study population whereas HDL-C data is reported separately for male and female participants.

  • Change From Baseline in Fasting Glucose Level at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in 10-year Cardiovascular Heart Disease (CHD) Risk According to Framingham Scoring System at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 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 CHD risk. The risk points are transformed to 10-year risk percentage for CHD which ranges from <1% to >=30%, where higher percent indicates greater risk for CHD.

  • Change From Baseline in Total Cholesterol (TC) and Low Density Lipoprotein-Cholesterol (LDL-C) Levels at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Weight at Week 4,12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Body Mass Index (BMI) at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    Body mass index calculated as weight in kilograms (kg) divided by height in (meters) squared (m)^2 .

  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) Concentration at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

  • Change From Baseline in Insulin Level at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in the Physical Activity Index Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 52 ] [ 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 total score = higher frequency and intensity of physical activity.

  • Change From Baseline in QT Interval Corrected for Heart Rate (QTc) at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ] [ 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 (60 divided by heart rate).

  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive and Negative Subscale Scores at Week 12, 28 and 52 [ Time Frame: Baseline, Week 12, 28, 52 ] [ Designated as safety issue: No ]
    Assesses positive and negative symptoms, general psychopathology specifically associated with schizophrenia. Scale consists of 30 items, each rated on scale from 1 (symptom not present) - 7 (symptoms extremely severe). Sum of 30 items is defined as PANSS total score, range:30-210. 7 items make up positive scale (delusions, conceptual disorganization, hallucinatory behavior); total range: 7-49. 7 items make up negative scale (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); total range: 7-49. For each subscale, total score: higher score=greater severity.

  • Change From Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score at Week 12, 28 and 52 [ Time Frame: Baseline, Week 12, 28, 52 ] [ Designated as safety issue: No ]
    CGI-S is a single-item, clinician-rated scale that assesses the global severity of the participants overall illness. CGI-S ratings range from 1 (normal, not at all ill) to 7 (among the most severely ill participants).

  • Clinical Global Impression-Improvement (CGI-I) Scale Score [ Time Frame: Endpoint (premature discontinuation or Week 52) ] [ Designated as safety issue: No ]
    CGI-I is a single-item, clinician-rated scale that assesses global improvement in the participants clinical state in response to study treatment, and as compared to their status at pre-treatment baseline. Possible CGI-I scores range from 1 to 7, where 1=very much improved, 4=no change and 7=very much worse.

  • Change From Baseline in Drug-Attitude Inventory-30-Item Scale (DAI-30) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 52 ] [ Designated as safety issue: No ]
    DAI, a 30-item scale measuring subjective responses to medication (including acceptability and tolerability which aims to understand the factors influencing treatment adherence). Scale has 15 items (statements) scored as true and 15 items scored as false. An overall calculated score ranged from -15 to 15, where a positive score indicated a positive subjective response (compliant), a negative score indicated non-compliance.

  • Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 52 ] [ Designated as safety issue: No ]
    SOFAS: a 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.

  • Change From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Index (EQ-I) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 52 ] [ Designated as safety issue: No ]
    EQ-5D: participant 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.

  • Changes From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Visual Analog Scale (VAS) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 52 ] [ Designated as safety issue: No ]
    EQ-5D: participant 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 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.

  • Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at Week 1, 2, 4, 8, 12, 20, 28, 36, 44 and 52 [ Time Frame: Baseline, Week 1, 2, 4, 8, 12, 20, 28, 36, 44 and 52 ] [ Designated as safety issue: Yes ]
    C-SSRS assessed whether participant experienced following: completed suicide(1), suicide attempt(2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior(3)("Yes" on "preparatory acts or behavior"), suicidal ideation(4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior(7)("Yes" on "Has subject engaged in non-suicidal self-injurious behavior").


Enrollment: 172
Study Start Date: December 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (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 to 160 mg total daily dose) for up to 1 year.
Other Name: Zeldox, Geodon

Detailed Description:

The trial was terminated prematurely on May 24, 2012, due to changes in organizational strategy and resources. 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: NCT00748566

Locations
Canada, Alberta
Pfizer Investigational Site
Calgary, Alberta, Canada, T2N 4Z6
Pfizer Investigational Site
Calgary, Alberta, Canada, T2N 2T9
Pfizer Investigational Site
Medicine Hat, Alberta, Canada, T1A 4C2
Pfizer Investigational Site
Medicine Hat, Alberta, Canada, T1B 4E7
Pfizer Investigational Site
Red Deer, Alberta, Canada, T4N 1T6
Canada, British Columbia
Pfizer Investigational Site
Penticton, British Columbia, Canada, V2A 4M4
Pfizer Investigational Site
Victoria, British Columbia, Canada, V8R 4Z3
Canada, Manitoba
Pfizer Investigational Site
Winnipeg, Manitoba, Canada, R3A 1R9
Pfizer Investigational Site
Winnipeg, Manitoba, Canada, R3E 3N4
Pfizer Investigational Site
Winnipeg, Manitoba, Canada, R3P 0N5
Pfizer Investigational Site
Winnipeg, Manitoba, Canada, R3K 2E2
Canada, New Brunswick
Pfizer Investigational Site
Bathurst, New Brunswick, Canada, E2A 2Z6
Canada, Newfoundland and Labrador
Pfizer Investigational Site
St. John's, Newfoundland and Labrador, Canada, A1E 4J8
Canada, Nova Scotia
Pfizer Investigational Site
Halifax, Nova Scotia, Canada, B3H 2E2
Pfizer Investigational Site
Sydney, Nova Scotia, Canada, B1P 1E1
Pfizer Investigational Site
Sydney, Nova Scotia, Canada, B1P 1C6
Canada, Ontario
Pfizer Investigational Site
Burlington, Ontario, Canada, L7R 4E2
Pfizer Investigational Site
Chatham, Ontario, Canada, N7L 1B7
Pfizer Investigational Site
Kingston, Ontario, Canada, K7L 4X3
Pfizer Investigational Site
London, Ontario, Canada, N6A 4G5
Pfizer Investigational Site
Markham, Ontario, Canada, L6B 1A1
Pfizer Investigational Site
Mississauga, Ontario, Canada, L5M 4N4
Pfizer Investigational Site
Ottawa, Ontario, Canada, K1H 8K7
Pfizer Investigational Site
Sudbury, Ontario, Canada, P3E 1X3
Pfizer Investigational Site
Toronto, Ontario, Canada, M6J 1H4
Pfizer Investigational Site
Toronto, Ontario, Canada, M5T 1R8
Pfizer Investigational Site
Windsor, Ontario, Canada, N9C 3Z4
Canada, Quebec
Pfizer Investigational Site
Montreal, Quebec, Canada, H3A 1A1
Pfizer Investigational Site
Montreal, Quebec, Canada, H1N 3V2
Pfizer Investigational Site
Montreal, Quebec, Canada, H1N 3M5
Pfizer Investigational Site
Verdun, Quebec, Canada, H4H 1R3
Canada, Saskatchewan
Pfizer Investigational Site
Saskatoon, Saskatchewan, Canada, S7K 3H3
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00748566     History of Changes
Other Study ID Numbers: A1281173
Study First Received: September 5, 2008
Results First Received: April 29, 2013
Last Updated: April 29, 2013
Health Authority: Canada: Health Canada

Keywords provided by Pfizer:
Ziprasidone
metabolic syndrome
risk factors
schizophrenia
psychotic disorders.

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia
Metabolic Syndrome X
Schizophrenia and Disorders with Psychotic Features
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ziprasidone
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 August 26, 2014