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

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00748566
• Collaborator: (none)
• Enrollment: 172
• Locations: 32
• Arm: 1
• Duration (Months): 41
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Dec 1, 2008
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 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 Names: Zeldox, Geodon

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving at Least 1 Risk Factor Reduction From Baseline for Metabolic Syndrome (MS) [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 [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) [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 [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) [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 [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 [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 [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 [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 [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 [Baseline, Week 4, 12, 28, 52]

11. Change From Baseline in Weight at Week 4,12, 28 and 52 [Baseline, Week 4, 12, 28, 52]

12. Change From Baseline in Body Mass Index (BMI) at Week 4, 12, 28 and 52 [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 [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 [Baseline, Week 4, 12, 28, 52]

15. Change From Baseline in the Physical Activity Index Score at Week 28 and 52 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Calgary	Alberta	Canada	T2N 2T9
2	Pfizer Investigational Site	Calgary	Alberta	Canada	T2N 4Z6
3	Pfizer Investigational Site	Medicine Hat	Alberta	Canada	T1A 4C2
4	Pfizer Investigational Site	Medicine Hat	Alberta	Canada	T1B 4E7
5	Pfizer Investigational Site	Red Deer	Alberta	Canada	T4N 1T6
6	Pfizer Investigational Site	Penticton	British Columbia	Canada	V2A 4M4
7	Pfizer Investigational Site	Victoria	British Columbia	Canada	V8R 4Z3
8	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3A 1R9
9	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3E 3N4
10	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3K 2E2
11	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3P 0N5
12	Pfizer Investigational Site	Bathurst	New Brunswick	Canada	E2A 2Z6
13	Pfizer Investigational Site	St. John's	Newfoundland and Labrador	Canada	A1E 4J8
14	Pfizer Investigational Site	Halifax	Nova Scotia	Canada	B3H 2E2
15	Pfizer Investigational Site	Sydney	Nova Scotia	Canada	B1P 1C6
16	Pfizer Investigational Site	Sydney	Nova Scotia	Canada	B1P 1E1
17	Pfizer Investigational Site	Burlington	Ontario	Canada	L7R 4E2
18	Pfizer Investigational Site	Chatham	Ontario	Canada	N7L 1B7
19	Pfizer Investigational Site	Kingston	Ontario	Canada	K7L 4X3
20	Pfizer Investigational Site	London	Ontario	Canada	N6A 4G5
21	Pfizer Investigational Site	Markham	Ontario	Canada	L6B 1A1
22	Pfizer Investigational Site	Mississauga	Ontario	Canada	L5M 4N4
23	Pfizer Investigational Site	Ottawa	Ontario	Canada	K1H 8K7
24	Pfizer Investigational Site	Sudbury	Ontario	Canada	P3E 1X3
25	Pfizer Investigational Site	Toronto	Ontario	Canada	M5T 1R8
26	Pfizer Investigational Site	Toronto	Ontario	Canada	M6J 1H4
27	Pfizer Investigational Site	Windsor	Ontario	Canada	N9C 3Z4
28	Pfizer Investigational Site	Montreal	Quebec	Canada	H1N 3M5
29	Pfizer Investigational Site	Montreal	Quebec	Canada	H1N 3V2
30	Pfizer Investigational Site	Montreal	Quebec	Canada	H3A 1A1
31	Pfizer Investigational Site	Verdun	Quebec	Canada	H4H 1R3
32	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00748566
• Other Study ID Numbers: A1281173
• First Posted: Sep 8, 2008
• Last Update Posted: Mar 3, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by 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; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 milligram (mg) capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Period Title: Overall Study
STARTED	172
COMPLETED	60
NOT COMPLETED	112

Baseline Characteristics

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Overall Participants	172
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.9 (12.2)
Sex: Female, Male (Count of Participants)
Female	52 30.2%
Male	120 69.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol (PP) population included all enrolled participants who received at least 1 dose of study medication, had baseline and at least 1 post-baseline MS measure, and remained in the study for at least 16 weeks. Missing values were imputed using last observation carried forward (LOCF).

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Number (95% Confidence Interval) [percentage of participants]	58.77 34.2%

2. Secondary Outcome

Title	Mean Change From Baseline in the Number of Risk Factors of Metabolic Syndrome (MS) at Week 4, 12, 28 and 52
Description	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.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	3.4 (1.0)
Change at Week 4 (n=113)	-0.3 (1.0)
Change at Week 12 (n=112)	-0.4 (1.1)
Change at Week 28 (n=98)	-0.7 (1.3)
Change at Week 52 (n=114)	-0.8 (1.2)

3. Secondary Outcome

Title	Percentage of Participants With Metabolic Syndrome (MS)
Description	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.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	79.82 46.4%
Week 4 (n=113)	70.80 41.2%
Week 12 (n=112)	72.32 42%
Week 28 (n=98)	58.16 33.8%
Week 52 (n=114)	52.63 30.6%

4. Secondary Outcome

Title	Number of Participants With Change From Baseline in Metabolic Syndrome (MS) Risk Factors at Week 4, 12, 28 and 52
Description	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.
Time Frame	Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Week 4: Decrease by at least 1 risk factor (n=113)	46 26.7%
Week 4: No change in risk factor (n=113)	46 26.7%
Week 4: Increase by at least 1 risk factor (n=113)	21 12.2%
Week 12:Decrease by at least 1 risk factor (n=112)	44 25.6%
Week 12: No change in risk factor (n=112)	51 29.7%
Week 12:Increase by at least 1 risk factor (n=112)	17 9.9%
Week 28: Decrease by at least 1 risk factor (n=98)	45 26.2%
Week 28: No change in risk factor (n=98)	39 22.7%
Week 28: Increase by at least 1 risk factor (n=98)	14 8.1%
Week 52:Decrease by at least 1 risk factor (n=114)	67 39%
Week 52: No change in risk factor (n=114)	35 20.3%
Week 52:Increase by at least 1 risk factor (n=114)	12 7%

5. Secondary Outcome

Title	Percentage of Participants With Individual Risk Factors of Metabolic Syndrome (MS)
Description	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.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline: Elevated waist circumference (n=114)	93.86 54.6%
Baseline: Elevated triglycerides (n=114)	83.33 48.4%
Baseline: Reduced HDL-C (n=114)	78.07 45.4%
Baseline: Elevated SBP (n=114)	32.46 18.9%
Baseline: Elevated DBP (n=114)	26.32 15.3%
Baseline: Elevated fasting glucose (n=114)	44.74 26%
Week 4: Elevated waist circumference (n=113)	88.50 51.5%
Week 4: Elevated triglycerides (n=111)	60.36 35.1%
Week 4: Reduced HDL-C (n=113)	71.68 41.7%
Week 4: Elevated SBP (n=113)	31.86 18.5%
Week 4: Elevated DBP (n=113)	29.20 17%
Week 4: Elevated fasting glucose (n=113)	46.02 26.8%
Week 12: Elevated waist circumference (n=112)	83.93 48.8%
Week 12: Elevated triglycerides (n=112)	61.61 35.8%
Week 12: Reduced HDL-C (n=112)	72.32 42%
Week 12: Elevated SBP (n=112)	29.46 17.1%
Week 12: Elevated DBP (n=112)	31.25 18.2%
Week 12: Elevated fasting glucose (n=112)	36.61 21.3%
Week 28: Elevated waist circumference (n=100)	76.00 44.2%
Week 28: Elevated triglycerides (n=99)	56.57 32.9%
Week 28: Reduced HDL-C (n=99)	61.62 35.8%
Week 28: Elevated SBP (n=100)	29.00 16.9%
Week 28: Elevated DBP (n=100)	35.00 20.3%
Week 28: Elevated fasting glucose (n=99)	37.37 21.7%
Week 52: Elevated waist circumference (n=114)	72.81 42.3%
Week 52: Elevated triglycerides (n=114)	52.63 30.6%
Week 52: Reduced HDL-C (n=114)	63.16 36.7%
Week 52: Elevated SBP (n=114)	28.95 16.8%
Week 52: Elevated DBP (n=114)	28.95 16.8%
Week 52: Elevated fasting glucose (n=114)	32.46 18.9%

6. Secondary Outcome

Title	Change From Baseline in Waist Circumference at Week 4, 12, 28 and 52
Description	Waist circumference data is reported separately for male and female participants.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline: Male (n=79)	110.8 (10.0)
Baseline: Female (n=35)	108.9 (10.5)
Change at Week 4: Male (n=78)	-1.0 (3.1)
Change at Week 4: Female (n=35)	0.4 (3.0)
Change at Week 12: Male (n=77)	-2.1 (4.9)
Change at Week 12: Female (n=35)	-2.4 (6.8)
Change at Week 28: Male (n=70)	-3.7 (7.2)
Change at Week 28: Female (n=30)	-2.5 (5.8)
Change at Week 52: Male (n=79)	-3.6 (7.5)
Change at Week 52: Female (n=35)	-4.0 (8.9)

7. Secondary Outcome

Title	Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Week 4, 12, 28 and 52
Description	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).
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline: SBP (n=114)	124.3 (13.3)
Baseline: DBP (n=114)	80.7 (9.5)
Change at Week 4: SBP (n=113)	-1.0 (10.0)
Change at Week 4: DBP (n=113)	-0.4 (7.6)
Change at Week 12: SBP (n=112)	-1.0 (11.8)
Change at Week 12: DBP (n=112)	-0.1 (8.0)
Change at Week 28: SBP (n=100)	-1.0 (11.9)
Change at Week 28: DBP (n=100)	0.0 (9.5)
Change at Week 52: SBP (n=114)	-1.0 (11.2)
Change at Week 52: DBP (n=114)	-1.1 (8.8)

8. Secondary Outcome

Title	Change From Baseline in Triglyceride and High Density Lipoprotein-Cholesterol (HDL-C) Levels at Week 4, 12, 28 and 52
Description	Triglyceride data is reported for whole study population whereas HDL-C data is reported separately for male and female participants.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline: Triglyceride (n=114)	242.8 (115.1)
Baseline: HDL-C, Male (n=79)	35.8 (7.2)
Baseline: HDL-C, Female (n=35)	41.9 (9.0)
Change at Week 4: Triglyceride (n=111)	-37.3 (103.8)
Change at Week 4: HDL-C, Male (n=78)	1.2 (5.1)
Change at Week 4: HDL-C, Female (n=35)	2.1 (7.8)
Change at Week 12: Triglyceride (n=112)	-39.5 (93.9)
Change at Week 12: HDL-C, Male (n=77)	2.1 (6.0)
Change at Week 12: HDL-C, Female (n=35)	1.8 (5.8)
Change at Week 28: Triglyceride (n=99)	-52.3 (103.8)
Change at Week 28: HDL-C, Male (n=69)	3.1 (5.4)
Change at Week 28: HDL-C, Female (n=30)	4.5 (8.0)
Change at Week 52: Triglyceride (n=114)	-60.0 (100.7)
Change at Week 52: HDL-C, Male (n=79)	3.9 (7.0)
Change at Week 52: HDL-C, Female (n=35)	5.0 (8.8)

9. Secondary Outcome

Title	Change From Baseline in Fasting Glucose Level at Week 4, 12, 28 and 52
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	104.5 (25.7)
Change at Week 4 (n=113)	-0.8 (19.7)
Change at Week 12 (n=112)	-4.0 (20.3)
Change at Week 28 (n=99)	-5.0 (19.1)
Change at Week 52 (n=114)	-3.0 (31.0)

10. Secondary Outcome

Title	Change From Baseline in 10-year Cardiovascular Heart Disease (CHD) Risk According to Framingham Scoring System at Week 4, 12, 28 and 52
Description	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.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	113
Baseline (n=113)	9.3 (5.9)
Change at Week 4 (n=112)	-0.7 (2.5)
Change at Week 12 (n=111)	-0.9 (2.1)
Change at Week 28 (n=97)	-1.2 (2.3)
Change at Week 52 (n=113)	-1.3 (2.4)

11. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline: TC (n=114)	5.5 (1.1)
Baseline: LDL-C (n=114)	3.3 (1.1)
Change at Week 4: TC (n=113)	-0.3 (0.8)
Change at Week 4: LDL-C (n=110)	-0.1 (0.8)
Change at Week 12: TC (n=112)	-0.4 (0.8)
Change at Week 12: LDL-C (n=112)	-0.2 (0.8)
Change at Week 28: TC (n=99)	-0.4 (0.8)
Change at Week 28: LDL-C (n=97)	-0.2 (0.7)
Change at Week 52: TC (n=114)	-0.5 (0.7)
Change at Week 52: LDL-C (n=114)	-0.3 (0.8)

12. Secondary Outcome

Title	Change From Baseline in Weight at Week 4,12, 28 and 52
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	96.5 (16.9)
Change at Week 4 (n=113)	-0.9 (3.9)
Change at Week 12 (n=112)	-2.4 (5.1)
Change at Week 28 (n=100)	-3.8 (7.4)
Change at Week 52 (n=114)	-4.4 (8.4)

13. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI) at Week 4, 12, 28 and 52
Description	Body mass index calculated as weight in kilograms (kg) divided by height in (meters) squared (m)^2 .
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	32.4 (4.3)
Change at Week 4 (n=113)	-0.3 (1.2)
Change at Week 12 (n=112)	-0.8 (1.6)
Change at Week 28 (n=100)	-1.2 (2.3)
Change at Week 52 (n=114)	-1.5 (2.8)

14. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) Concentration at Week 4, 12, 28 and 52
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	114
Baseline (n=114)	5.7 (0.8)
Change at Week 4 (n=111)	-0.0 (0.2)
Change at Week 12 (n=112)	-0.0 (0.3)
Change at Week 28 (n=99)	-0.1 (0.4)
Change at Week 52 (n=114)	-0.1 (0.4)

15. Secondary Outcome

Title	Change From Baseline in Insulin Level at Week 4, 12, 28 and 52
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values were imputed using LOCF at Week 52. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	107
Baseline (n=107)	22.4 (27.1)
Change at Week 4 (n=102)	-0.3 (28.9)
Change at Week 12 (n=104)	-4.6 (20.9)
Change at Week 28 (n=92)	-7.8 (23.5)
Change at Week 52 (n=107)	-5.6 (31.0)

16. Secondary Outcome

Title	Change From Baseline in the Physical Activity Index Score at Week 28 and 52
Description	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.
Time Frame	Baseline, Week 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	112
Baseline	7.3 (6.8)
Change at Week 28	0.6 (6.5)
Change at Week 52	0.5 (6.3)

17. Secondary Outcome

Title	Change From Baseline in QT Interval Corrected for Heart Rate (QTc) at Week 4, 12, 28 and 52
Description	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).
Time Frame	Baseline, Week 4, 12, 28, 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study medication, had baseline and at least 1 post-baseline MS measure. Missing values at Week 52 were imputed using LOCF. N (number of participants analyzed)=participants evaluable for this measure. n=evaluable participants at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	56
Baseline (n=56)	413.2 (24.1)
Change at Week 4 (n=4)	0.9 (22.0)
Change at Week 12 (n=14)	3.4 (27.7)
Change at Week 28 (n=38)	6.6 (23.7)
Change at Week 52 (n=56)	7.6 (22.8)

18. Secondary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score, Positive and Negative Subscale Scores at Week 12, 28 and 52
Description	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.
Time Frame	Baseline, Week 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	113
Baseline: Total Score (n=112)	64.1 (17.8)
Baseline: Positive Subscale Score (n=113)	13.6 (4.6)
Baseline: Negative Subscale Score (n=112)	17.9 (6.6)
Change at Week 12: Total Score (n=110)	-5.7 (11.6)
Change at Week 12: Positive Subscale Score (n=112)	-1.0 (3.2)
Change at Week 12: Negative Subscale Score (n=111)	-1.9 (4.5)
Change at Week 28: Total Score (n=98)	-4.4 (14.3)
Change at Week 28: Positive Subscale Score (n=100)	-0.9 (4.5)
Change at Week 28: Negative Subscale Score (n=98)	-1.6 (5.3)
Change at Week 52: Total Score (n=112)	-3.2 (17.0)
Change at Week 52: Positive Subscale Score (n=113)	-0.2 (5.6)
Change at Week 52: Negative Subscale Score (n=112)	-1.7 (5.5)

19. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score at Week 12, 28 and 52
Description	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).
Time Frame	Baseline, Week 12, 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	113
Baseline (n=113)	3.3 (0.9)
Change at Week 12 (n=112)	-0.3 (0.7)
Change at Week 28 (n=100)	-0.2 (0.8)
Change at Week 52 (n=113)	-0.2 (1.1)

20. Secondary Outcome

Title	Clinical Global Impression-Improvement (CGI-I) Scale Score
Description	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.
Time Frame	Endpoint (premature discontinuation or Week 52)

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	107
Mean (Standard Deviation) [units on a scale]	3.2 (1.4)

21. Secondary Outcome

Title	Change From Baseline in Drug-Attitude Inventory-30-Item Scale (DAI-30) Score at Week 28 and 52
Description	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.
Time Frame	Baseline, Week 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	105
Baseline (n=105)	-1.3 (5.8)
Change at Week 28 (n=104)	0.4 (6.5)
Change at Week 52 (n=105)	-0.1 (6.1)

22. Secondary Outcome

Title	Change From Baseline in Social and Occupational Functioning Assessment Scale (SOFAS) Score at Week 28 and 52
Description	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.
Time Frame	Baseline, Week 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	111
Baseline	57.2 (11.5)
Change at Week 28	1.6 (11.3)
Change at Week 52	1.1 (11.4)

23. Secondary Outcome

Title	Change From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Index (EQ-I) Score at Week 28 and 52
Description	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.
Time Frame	Baseline, Week 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	111
Baseline	0.8 (0.3)
Change at Week 28	0.0 (0.2)
Change at Week 52	0.0 (0.2)

24. Secondary Outcome

Title	Changes From Baseline in European Quality of Life (EuroQoL) - 5 Dimensions Visual Analog Scale (VAS) Score at Week 28 and 52
Description	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.
Time Frame	Baseline, Week 28, 52

Outcome Measure Data

Analysis Population Description

PP population. Missing values at Week 52 were imputed using LOCF. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable for this measure at specified time points.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	112
Baseline (n=112)	58.8 (27.4)
Change at Week 28 (n=111)	4.7 (30.5)
Change at Week 52 (n=112)	5.7 (30.4)

25. Secondary Outcome

Title	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
Description	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").
Time Frame	Baseline, Week 1, 2, 4, 8, 12, 20, 28, 36, 44 and 52

Outcome Measure Data

Analysis Population Description

Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Ziprasidone
Arm/Group Description	Ziprasidone 40 mg capsule orally twice daily from Day 1 to 3, followed by ziprasidone 60 mg capsule orally twice daily from Day 4 to 7, then ziprasidone 80 mg capsule orally twice daily from Day 8 to 15 and thereafter ziprasidone 20 to 80 mg capsule orally twice daily as per investigator's discretion from Day 16 to 365.
All Cause Mortality
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	20/172 (11.6%)
Infections and infestations
Appendicitis	1/172 (0.6%)
Sepsis	1/172 (0.6%)
Injury, poisoning and procedural complications
Overdose	1/172 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/172 (0.6%)
Nervous system disorders
Convulsion	1/172 (0.6%)
Sedation	1/172 (0.6%)
Psychiatric disorders
Adjustment disorder with mixed anxiety and depressed mood	1/172 (0.6%)
Agitation	1/172 (0.6%)
Attention-seeking behaviour	1/172 (0.6%)
Depressed mood	1/172 (0.6%)
Depression	1/172 (0.6%)
Hallucinations, mixed	1/172 (0.6%)
Psychotic disorder	3/172 (1.7%)
Schizophrenia	5/172 (2.9%)
Suicidal ideation	1/172 (0.6%)
Suicide attempt	1/172 (0.6%)
Other (Not Including Serious) Adverse Events
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	122/172 (70.9%)
Gastrointestinal disorders
Diarrhoea	11/172 (6.4%)
Nausea	28/172 (16.3%)
Vomiting	11/172 (6.4%)
General disorders
Fatigue	21/172 (12.2%)
Infections and infestations
Nasopharyngitis	13/172 (7.6%)
Nervous system disorders
Akathisia	11/172 (6.4%)
Dizziness	15/172 (8.7%)
Headache	22/172 (12.8%)
Somnolence	17/172 (9.9%)
Psychiatric disorders
Anxiety	33/172 (19.2%)
Depression	9/172 (5.2%)
Insomnia	50/172 (29.1%)
Restlessness	10/172 (5.8%)

Limitations/Caveats

The study was prematurely terminated by sponsor due to changes in organizational strategy and resources, not due to safety concerns.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.