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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Schizophrenia and Disorders With Psychotic Features

Intervention / Treatment
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* Drug: Ziprasidone HCL (oral)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment (switch to oral Ziprasidone)<br> | Drug: Ziprasidone HCL (oral)<br>* Ziprasidone Hydrochloride 20 to 80 mg administered orally twice a day (40 to 160 mg total daily dose) for up to 1 year.<br>* Other names: Zeldox, Geodon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving at Least 1 Risk Factor Reduction From Baseline for Metabolic Syndrome (MS) | 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. | Endpoint (premature discontinuation or Week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) at Week 4, 12, 28 and 52 | 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. | Baseline, Week 4, 12, 28, 52 | 
| Percentage of Participants With Metabolic Syndrome (MS) | 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. | Baseline, Week 4, 12, 28, 52 | 
| Number of Participants With Change From Baseline in Metabolic Syndrome (MS) Risk Factors at Week 4, 12, 28 and 52 | 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. | Week 4, 12, 28, 52 | 
| Percentage of Participants With Individual Risk Factors of Metabolic Syndrome (MS) | 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. | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Waist Circumference at Week 4, 12, 28 and 52 | Waist circumference data is reported separately for male and female participants. | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 4, 12, 28 and 52 | 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). | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Triglyceride and High Density Lipoprotein-Cholesterol (HDL-C) Levels at Week 4, 12, 28 and 52 | Triglyceride data is reported for whole study population whereas HDL-C data is reported separately for male and female participants. | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Fasting Glucose Level at Week 4, 12, 28 and 52 |  | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in 10-year Cardiovascular Heart Disease (CHD) Risk According to Framingham Scoring System at Week 4, 12, 28 and 52 | 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. | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Total Cholesterol (TC) and Low Density Lipoprotein-Cholesterol (LDL-C) Levels at Week 4, 12, 28 and 52 |  | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Weight at Week 4,12, 28 and 52 |  | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Body Mass Index (BMI) at Week 4, 12, 28 and 52 | Body mass index calculated as weight in kilograms (kg) divided by height in (meters) squared (m)^2 . | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) Concentration at Week 4, 12, 28 and 52 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Insulin Level at Week 4, 12, 28 and 52 |  | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in the Physical Activity Index Score at Week 28 and 52 | 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. | Baseline, Week 28, 52 | 
| Change From Baseline in QT Interval Corrected for Heart Rate (QTc) at Week 4, 12, 28 and 52 | 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). | Baseline, Week 4, 12, 28, 52 | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive and Negative Subscale Scores at Week 12, 28 and 52 | 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. | Baseline, Week 12, 28, 52 | 
| Change From Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score at Week 12, 28 and 52 | 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). | Baseline, Week 12, 28, 52 | 
| Clinical Global Impression-Improvement (CGI-I) Scale Score | 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. | Endpoint (premature discontinuation or Week 52) | 
| Change From Baseline in Drug-Attitude Inventory-30-Item Scale (DAI-30) Score at Week 28 and 52 | 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. | Baseline, Week 28, 52 | 
| Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) Score at Week 28 and 52 | 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. | Baseline, Week 28, 52 | 
| Change From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Index (EQ-I) Score at Week 28 and 52 | 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. | Baseline, Week 28, 52 | 
| Changes From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Visual Analog Scale (VAS) Score at Week 28 and 52 | 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. | Baseline, Week 28, 52 | 
| 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 | 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). | Baseline, Week 1, 2, 4, 8, 12, 20, 28, 36, 44 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ziprasidone, metabolic syndrome, risk factors, schizophrenia, psychotic disorders.