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

• ClinicalTrials.gov Identifier: NCT00748566
• Recruitment Status: Terminated
• First Posted: September 8, 2008
• Results First Posted: June 19, 2013
• Last Update Posted: March 3, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Schizophrenia and Disorders With Psychotic Features	Drug: Ziprasidone HCL (oral)	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 172 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: December 2008
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: May 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving at Least 1 Risk Factor Reduction From Baseline for Metabolic Syndrome (MS) [ Time Frame: Endpoint (premature discontinuation or Week 52) ]
   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 :

1. 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 ]
   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.
2. Percentage of Participants With Metabolic Syndrome (MS) [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
   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.
3. 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 ]
   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.
4. Percentage of Participants With Individual Risk Factors of Metabolic Syndrome (MS) [ Time Frame: Baseline, Week 4, 12, 28, 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.
5. Change From Baseline in Waist Circumference at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
   Waist circumference data is reported separately for male and female participants.
6. 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 ]
   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).
7. 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 ]
   Triglyceride data is reported for whole study population whereas HDL-C data is reported separately for male and female participants.
8. Change From Baseline in Fasting Glucose Level at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
9. 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 ]
   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.
10. 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 ]
11. Change From Baseline in Weight at Week 4,12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
12. Change From Baseline in Body Mass Index (BMI) at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
    Body mass index calculated as weight in kilograms (kg) divided by height in (meters) squared (m)^2 .
13. Change From Baseline in Glycosylated Hemoglobin (HbA1c) Concentration at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
14. Change From Baseline in Insulin Level at Week 4, 12, 28 and 52 [ Time Frame: Baseline, Week 4, 12, 28, 52 ]
15. Change From Baseline in the Physical Activity Index Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 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.
16. 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 ]
    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).
17. 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 ]
    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.
18. 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 ]
    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).
19. Clinical Global Impression-Improvement (CGI-I) Scale Score [ Time Frame: Endpoint (premature discontinuation or Week 52) ]
    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.
20. Change From Baseline in Drug-Attitude Inventory-30-Item Scale (DAI-30) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 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.
21. Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) Score at Week 28 and 52 [ Time Frame: Baseline, Week 28, 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.
22. 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 ]
    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.
23. 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 ]
    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.
24. 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 ]
    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").

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Canada, Alberta

Pfizer Investigational Site

Calgary, Alberta, Canada, T2N 2T9

Pfizer Investigational Site

Calgary, Alberta, Canada, T2N 4Z6

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, R3K 2E2

Pfizer Investigational Site

Winnipeg, Manitoba, Canada, R3P 0N5

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 1C6

Pfizer Investigational Site

Sydney, Nova Scotia, Canada, B1P 1E1

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, M5T 1R8

Pfizer Investigational Site

Toronto, Ontario, Canada, M6J 1H4

Pfizer Investigational Site

Windsor, Ontario, Canada, N9C 3Z4

Canada, Quebec

Pfizer Investigational Site

Montreal, Quebec, Canada, H1N 3M5

Pfizer Investigational Site

Montreal, Quebec, Canada, H1N 3V2

Pfizer Investigational Site

Montreal, Quebec, Canada, H3A 1A1

Pfizer Investigational Site

Verdun, Quebec, Canada, H4H 1R3

Canada, Saskatchewan

Pfizer Investigational Site

Saskatoon, Saskatchewan, Canada, S7K 3H3

Sponsors and Collaborators

Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chue P, Mandel FS, Therrien F. The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study. Curr Med Res Opin. 2014 Jun;30(6):997-1005. doi: 10.1185/03007995.2014.898139. Epub 2014 Mar 17.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00748566
• Other Study ID Numbers: A1281173
• First Posted: September 8, 2008
• Results First Posted: June 19, 2013
• Last Update Posted: March 3, 2021
• Last Verified: March 2021

Keywords provided by Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. ):

Ziprasidone; metabolic syndrome; risk factors; schizophrenia; psychotic disorders.

Additional relevant MeSH terms:

Metabolic Syndrome; Schizophrenia; Mental Disorders; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Ziprasidone; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents