Safety and Tolerability of Ziprasidone in Children and Adolescents With Bipolar I Disorder (Manic or Mixed)

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00265330
• Collaborator: (none)
• Enrollment: 169
• Locations: 41
• Arm: 1
• Duration (Months): 22
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and tolerability of ziprasidone during long-term open-label administration in children and adolescents (ages 10-17) with bipolar I disorder (manic or mixed)

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Ziprasidone oral capsules	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 169 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 26-Week Open-Label Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder (Manic Or Mixed)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open	Drug: Ziprasidone oral capsules; Study medications will include oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength. Subjects will be dosed daily for 26 weeks using a flexible dose design with a minimal dose range of 20mg bid to a maximum dose range of 80 mg bid .

Outcome Measures

Primary Outcome Measures

1. Young Mania Rating Scale (YMRS) Total Score Change From Baseline [baseline and 26 Weeks; 26 Weeks Last Observation Carried Forward (LOCF)]

   YMRS: 11-item instrument with scales 0 (normal) to 4 (highest abnormal)for 7 items and 0 (normal) to 8 (highest abnormal) for 4 items. Total possible 0 - 60. Baseline is from parent study A1281132.

2. Clinical Global Impression of Severity (CGI-S) Change From Baseline [baseline and 26 Weeks; 26 Weeks LOCF]

   CGI-S Scale:standardized assessment tool to rate severity of subject's illness; assesses investigator's impression of subject's current illness state. Change: score at observation minus score at baseline. Score: 1 (not ill at all) to 7 (among most extremely ill). Baseline = last available observation from parent double-blind study(A1281132).

3. Incidence of Lab Abnormalities [Week 26]

   number of subjects with an abnormal lab value for those parameters with 5% or greater incidence of abnormality.

4. Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol [Week 6, Week 26]

   Mean Change: lab value at observation minus lab value at baseline.

5. Change in Hormones [Week 6, Week 26]

   Mean Change: lab value at observation minus lab value at baseline

6. Mean Change From Baseline in Supine Systolic Blood Pressure [Week 1 through Week 26]

   Mean Change: vital sign value at observation minus vital sign value at baseline

7. Mean Change From Baseline in Supine Diastolic Blood Pressure [Week 1 through Week 26]

   Mean Change: vital sign value at observation minus vital sign value at baseline

8. Mean Change From Baseline in Supine Pulse Rates [Week 1 through Week 26]

   Mean Change: vital sign value at observation minus vital sign value at baseline

9. Mean Change From Baseline in Standing Systolic Blood Pressure [Week 1 through Week 26]

   Mean Change: vital sign value at observation minus vital sign value at baseline

10. Mean Change From Baseline in Standing Diastolic Blood Pressure [Week 1 through Week 26]

    Mean Change: vital sign value at observation minus vital sign value at baseline

11. Mean Change From Baseline in Standing Pulse Rates [Week 1 through Week 26]

    Mean Change: vital sign value at observation minus vital sign value at baseline

12. Mean Change From Baseline for Body Weight [Week 6, Week 26]

    Mean change; body weight value at observation minus body weight value at baseline.

13. Mean Change From Baseline for Body Mass Index (BMI) Z-Score [Week 6, 26, early termination]

    mean change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change

14. Body Mass Index (BMI) Z-score Frequency [Week 6]

    change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change

15. Body Mass Index (BMI) Z-score Frequency [Week 26]

    change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change

16. Mean Change From Baseline for QTcF Intervals [Baseline to Week 26 (end of study)]

    QT intervals (observed in an electrocardiogram)corrected using Fridericia's formula (QTcF). Mean change: mean change of observation minus baseline. Baseline: last available observation in the parent double-blind study.

17. Frequency of Largest Categorical Increases in QTcF for Males [Week 26 (end of study)]

    QT intervals (observed in an electrocardiogram) corrected with Fridericia's Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.

18. Frequency of Largest Categorical Increases in QTcF for Females [Week 26 (end of study)]

    QT interval (observed in an electrocardiogram) corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.

19. Frequency of Largest Categorical Increases in QTcF - All Subjects [Week 26 (end of study)]

    QT intervals (observed in an electrocardiogram)corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participation in double-blind treatment study A1281132, meeting specific criteria of duration and safety

Exclusion Criteria:

• Imminent risk of suicide or homicide, as judged by the site investigator;serious adverse event related to study medication in study A1281132; significant prolongation of QT interval in study A1281132.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Scottsdale	Arizona	United States	85251
2	Pfizer Investigational Site	San Diego	California	United States	92123
3	Pfizer Investigational Site	Aurora	Colorado	United States	80045
4	Pfizer Investigational Site	Altamonte Springs	Florida	United States	32701
5	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33301
6	Pfizer Investigational Site	North Miami	Florida	United States	33161
7	Pfizer Investigational Site	Orange City	Florida	United States	32763
8	Pfizer Investigational Site	Tavares	Florida	United States	32778
9	Pfizer Investigational Site	Decatur	Georgia	United States	30033
10	Pfizer Investigational Site	Honolulu	Hawaii	United States	96826
11	Pfizer Investigational Site	Terre Haute	Indiana	United States	47802
12	Pfizer Investigational Site	Lexington	Kentucky	United States	40509
13	Pfizer Investigational Site	Owensboro	Kentucky	United States	42301
14	Pfizer Investigational Site	Shreveport	Louisiana	United States	71103
15	Pfizer Investigational Site	Clinton Township	Michigan	United States	48038
16	Pfizer Investigational Site	Meridian	Mississippi	United States	39301
17	Pfizer Investigational Site	Saint Louis	Missouri	United States	63044-2588
18	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
19	Pfizer Investigational Site	Omaha	Nebraska	United States	68131
20	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87102
21	Pfizer Investigational Site	Rochester	New York	United States	14618
22	Pfizer Investigational Site	Cincinnati	Ohio	United States	45224
23	Pfizer Investigational Site	Cincinnati	Ohio	United States	45229
24	Pfizer Investigational Site	Cincinnati	Ohio	United States	45267-0559
25	Pfizer Investigational Site	Cleveland	Ohio	United States	44106-5080
26	Pfizer Investigational Site	Columbus	Ohio	United States	43210
27	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73101
28	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73107
29	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73112
30	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73116
31	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74114
32	Pfizer Investigational Site	Charleston	South Carolina	United States	29405
33	Pfizer Investigational Site	Arlington	Texas	United States	76011
34	Pfizer Investigational Site	DeSoto	Texas	United States	75115
35	Pfizer Investigational Site	Lake Jackson	Texas	United States	77566
36	Pfizer Investigational Site	Plano	Texas	United States	75093
37	Pfizer Investigational Site	San Antonio	Texas	United States	78229
38	Pfizer Investigational Site	Kirkland	Washington	United States	98033
39	Pfizer Investigational Site	Spokane	Washington	United States	99204
40	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53226
41	Pfizer Investigational Site	West Allis	Wisconsin	United States	53227

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: NCT00265330
• Other Study ID Numbers: A1281133
• First Posted: Dec 14, 2005
• Last Update Posted: Mar 25, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Children And Adolescents With Bipolar I Disorder (Manic Or Mixed)
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Ziprasidone

Study Results

Participant Flow

Recruitment Details	The number of subjects entering this trial was determined by the number of subjects electing to continue treatment after completing or withdrawing from the preceding double-blind study (A1281132: NCT00257166).
Pre-assignment Detail	A total of 169 subjects from the parent study were assigned to the extension study and 162 continued on and received study treatment in the extension study.

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Period Title: Overall Study
STARTED	162
COMPLETED	67
NOT COMPLETED	95

Baseline Characteristics

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Overall Participants	162
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (2.1)
Sex: Female, Male (Count of Participants)
Female	72 44.4%
Male	90 55.6%

Outcome Measures

1. Primary Outcome

Title	Young Mania Rating Scale (YMRS) Total Score Change From Baseline
Description	YMRS: 11-item instrument with scales 0 (normal) to 4 (highest abnormal)for 7 items and 0 (normal) to 8 (highest abnormal) for 4 items. Total possible 0 - 60. Baseline is from parent study A1281132.
Time Frame	baseline and 26 Weeks; 26 Weeks Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation)

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 2 (n=153)	-3.8 (9.0)
Week 6 (n=122)	-4.0 (9.1)
Week 18 (n=76)	-6.3 (12.7)
Week 26 (n=69)	-6.1 (11.6)
Early Termination (n=59)	1.5 (11.3)
Week 26-LOCF (n=153)	-3.3 (10.7)

2. Primary Outcome

Title	Clinical Global Impression of Severity (CGI-S) Change From Baseline
Description	CGI-S Scale:standardized assessment tool to rate severity of subject's illness; assesses investigator's impression of subject's current illness state. Change: score at observation minus score at baseline. Score: 1 (not ill at all) to 7 (among most extremely ill). Baseline = last available observation from parent double-blind study(A1281132).
Time Frame	baseline and 26 Weeks; 26 Weeks LOCF

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation)

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 1 (n=159)	-0.2 (0.9)
Week 2 (n=150)	-0.5 (1.2)
Week 6 (n=122)	-0.4 (1.1)
Week 10 (n=99)	-0.7 (1.3)
Week 14 (n=85)	-0.7 (1.2)
Week 18 (n=76)	-0.7 (1.5)
Week 22 (n=70)	-0.8 (1.3)
Week 26 (n=69)	-1.1 (1.4)
Early Termination (n=48)	0.4 (1.1)
Week 26-LOCF (n=160)	-0.4 (1.3)

3. Primary Outcome

Title	Incidence of Lab Abnormalities
Description	number of subjects with an abnormal lab value for those parameters with 5% or greater incidence of abnormality.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Total number of subjects with given laboratory test at given visit. Range: N=136-134, with the exception of Insulin (N=115)

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	136
Bicarbonate (N=136)	44 27.2%
Urine blood/Hemoglobin (N=136)	34 21%
Urine ketones (N=136)	32 19.8%
Testosterone (N=134)	22 13.6%
Urine specific gravity (N=136)	13 8%
Urine red blood cells (N=136)	13 8%
Monocytes (N=134)	9 5.6%
Triglycerides (N=136)	10 6.2%
Urine white blood cells (N=136)	10 6.2%
Insulin (N=115)	8 4.9%

4. Primary Outcome

Title	Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol
Description	Mean Change: lab value at observation minus lab value at baseline.
Time Frame	Week 6, Week 26

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test.)

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	134
LDL cholesterol Week 6 (n=113)	-7.5 (19.7)
LDL cholesterol Week 26 (n=59)	-8.9 (19.5)
LDL cholesterol Early Termination (n=44)	-7.6 (20.1)
Fasting cholesterol Week 6 (n=113)	-7.7 (21.8)
Fasting cholesterol Week 26 (n=59)	-10.3 (22.7)
Fasting cholesterol Early Termination (n=44)	-8.6 (24.9)

5. Primary Outcome

Title	Change in Hormones
Description	Mean Change: lab value at observation minus lab value at baseline
Time Frame	Week 6, Week 26

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test.)

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	131
Testosterone Week 6 (n=80)	0.9 (84.3)
Testosterone Week 26 (n=38)	-23.4 (112.9)
Testosterone Early Termination (n=32)	-0.4 (61.8)
Prolactin Week 6 (n=110)	2.7 (13.2)
Prolactin Week 26 (n=59)	1.9 (8.5)
Prolactin Early Termination (n=40)	1.0 (11.6)
Insulin-like growth factor Week 6 (n=95)	-19.9 (63.4)
Insulin-like growth factor Week 26 (n=47)	-9.2 (68.1)
Insulin-like growth factor Early Term (n=34)	-8.4 (66.5)

6. Primary Outcome

Title	Mean Change From Baseline in Supine Systolic Blood Pressure
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 1 (n=155)	0.4 (11.4)
Week 2 (n=142)	1.1 (10.4)
Week 6/pre-dose (n=115)	1.2 (9.5)
Week 6/5-7 hours post dose (n=108)	1.2 (9.9)
Week 10 (n=93)	1.4 (10.1)
Week 14 (n=82)	-0.7 (10.1)
Week 18 (n=74)	0.4 (11.7)
Week 22 (n=69)	1.7 (10.5)
Week 26 (n=68)	2.9 (11.4)
Early Termination (n=75)	1.3 (11.8)

7. Primary Outcome

Title	Mean Change From Baseline in Supine Diastolic Blood Pressure
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 1 (n=155)	-0.5 (8.8)
Week 2 (n=142)	0.5 (8.7)
Week 6/pre-dose (n=115)	0.6 (9.7)
Week 6/5-7 hours post dose (n=108)	0.5 (8.8)
Week 10 (n=93)	-0.4 (10.1)
Week 14 (n=82)	-2.4 (8.3)
Week 18 (n=74)	-0.6 (9.8)
Week 22 (n=69)	-0.7 (9.4)
Week 26 (n=68)	1.5 (10.4)
Early Termination (n=75)	1.3 (8.1)

8. Primary Outcome

Title	Mean Change From Baseline in Supine Pulse Rates
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 1 (n=155)	1.4 (12.4)
Week 2 (n=142)	2.0 (11.7)
Week 6/pre-dose (n=115)	-1.8 (11.6)
Week 6/5-7 hours post dose (n=108)	1.0 (12.3)
Week 10 (n=93)	1.4 (11.8)
Week 14 (n=82)	-3.0 (12.4)
Week 18 (n=74)	-3.5 (12.2)
Week 22 (n=69)	-2.1 (11.7)
Week 26 (n=68)	-3.0 (11.2)
Early Termination (n=75)	3.9 (13.9)

9. Primary Outcome

Title	Mean Change From Baseline in Standing Systolic Blood Pressure
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	161
Week 1 (n=154)	1.4 (10.5)
Week 2 (n=141)	3.7 (11.7)
Week 6/pre-dose (n=115)	1.6 (9.6)
Week 6/5-7 hours post dose (n=108)	2.0 (9.5)
Week 10 (n=93)	2.4 (11.0)
Week 14 (n=82)	0.5 (11.3)
Week 18 (n=74)	3.1 (10.5)
Week 22 (n=70)	3.2 (10.0)
Week 26 (n=68)	3.6 (10.9)
Early Termination (n=75)	3.0 (11.4)

10. Primary Outcome

Title	Mean Change From Baseline in Standing Diastolic Blood Pressure
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	161
Week 1 (n=154)	0.7 (9.1)
Week 2 (n=141)	2.0 (9.8)
Week 6/pre-dose (n=115)	1.4 (9.8)
Week 6/5-7 hours post dose (n=108)	1.2 (9.9)
Week 10 (n=93)	1.6 (10.8)
Week 14 (n=82)	-0.1 (9.8)
Week 18 (n=74)	1.1 (8.8)
Week 22 (n=70)	0.5 (8.5)
Week 26 (n=68)	2.8 (8.3)
Early Termination (n=75)	3.4 (10.8)

11. Primary Outcome

Title	Mean Change From Baseline in Standing Pulse Rates
Description	Mean Change: vital sign value at observation minus vital sign value at baseline
Time Frame	Week 1 through Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	161
Week 1 (n=154)	3.5 (14.0)
Week 2 (n=140)	2.9 (13.4)
Week 6/pre-dose (n=115)	0.3 (13.1)
Week 6/5-7 hours post dose (n=108)	3.8 (13.9)
Week 10 (n=93)	2.6 (14.5)
Week 14 (n=82)	0.5 (14.7)
Week 18 (n=74)	-0.3 (12.5)
Week 22 (n=70)	1.2 (14.7)
Week 26 (n=68)	-0.9 (12.9)
Early Termination (n=75)	4.8 (13.8)

12. Primary Outcome

Title	Mean Change From Baseline for Body Weight
Description	Mean change; body weight value at observation minus body weight value at baseline.
Time Frame	Week 6, Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 6 (n=119)	1.3 (3.0)
Week 26 (n=68)	3.9 (5.4)
Early Termination (n=74)	1.4 (2.8)

13. Primary Outcome

Title	Mean Change From Baseline for Body Mass Index (BMI) Z-Score
Description	mean change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change
Time Frame	Week 6, 26, early termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 6 (n=119)	0.0 (0.3)
Week 26 (n=68)	0.1 (0.5)
Early Termination (n=74)	0.0 (0.3)

14. Primary Outcome

Title	Body Mass Index (BMI) Z-score Frequency
Description	change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
<-4	0 0%
≥-4 to <-3	0 0%
≥-3 to <-2	0 0%
≥-2 to <-1	0 0%
≥-1 to <0	53 32.7%
≥0 to <1	61 37.7%
≥1 to <2	1 0.6%
≥2 to <3	0 0%
≥3 to <4	0 0%
≥4	0 0%

15. Primary Outcome

Title	Body Mass Index (BMI) Z-score Frequency
Description	change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
<-4	0 0%
≥-4 to <-3	0 0%
≥-3 to <-2	0 0%
≥-2 to <-1	1 0.6%
≥-1 to <0	27 16.7%
≥0 to <1	39 24.1%
≥1 to <2	1 0.6%
≥2 to <3	0 0%
≥3 to <4	0 0%
≥4	0 0%

16. Primary Outcome

Title	Mean Change From Baseline for QTcF Intervals
Description	QT intervals (observed in an electrocardiogram)corrected using Fridericia's formula (QTcF). Mean change: mean change of observation minus baseline. Baseline: last available observation in the parent double-blind study.
Time Frame	Baseline to Week 26 (end of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	162
Week 1 (n=152)	4.8 (18.5)
Week 2 (n=137)	3.5 (17.7)
Week 6/pre-dose (n=111)	7.6 (17.7)
Week 6/5-7 hours post dose (n=107)	7.0 (18.4)
Week 10 (n=91)	4.3 (18.8)
Week 14 (n=81)	6.2 (17.4)
Week 18 (n=73)	7.4 (15.4)
Week 22 (n=68)	8.1 (16.1)
Week 26 (n=64)	7.1 (15.2)
Early Termination (n=45)	2.7 (17.0)

17. Primary Outcome

Title	Frequency of Largest Categorical Increases in QTcF for Males
Description	QT intervals (observed in an electrocardiogram) corrected with Fridericia's Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
Time Frame	Week 26 (end of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	89
≥450 msec (millisecond )	0 0%
≥460 msec	0 0%
≥480 msec	0 0%
≥30 msec increase	28 17.3%
≥60 msec increase	0 0%

18. Primary Outcome

Title	Frequency of Largest Categorical Increases in QTcF for Females
Description	QT interval (observed in an electrocardiogram) corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
Time Frame	Week 26 (end of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	71
≥450 msec (millisecond)	3 1.9%
≥460 msec	0 0%
≥480 msec	0 0%
≥30 msec increase	10 6.2%
≥60 msec increase	2 1.2%

19. Primary Outcome

Title	Frequency of Largest Categorical Increases in QTcF - All Subjects
Description	QT intervals (observed in an electrocardiogram)corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
Time Frame	Week 26 (end of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
Measure Participants	160
≥450 msec (millisecond)	3 1.9%
≥460 msec	0 0%
≥480 msec	0 0%
≥30 msec increase	38 23.5%
≥60 msec increase	2 1.2%

Adverse Events

Time Frame	Treatment emergent adverse events are reported from time of first dose of study treatment up to 6 days after last dose of study treatment.
Adverse Event Reporting Description	Safety population = all randomized subjects with at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Arm/Group Title	Ziprasidone
Arm/Group Description	Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
All Cause Mortality
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	17/162 (10.5%)
General disorders
Disease progression	1/162 (0.6%)
Injury, poisoning and procedural complications
Overdose	1/162 (0.6%)
Psychiatric disorders
Aggression	1/162 (0.6%)
Bipolar disorder	3/162 (1.9%)
Conversion disorder	1/162 (0.6%)
Delusion	1/162 (0.6%)
Hallucinations, mixed	1/162 (0.6%)
Homicidal ideation	1/162 (0.6%)
Mania	1/162 (0.6%)
Negative thoughts	1/162 (0.6%)
Oppositional defiant disorder	2/162 (1.2%)
Self-injurious behavior	1/162 (0.6%)
Suicidal ideation	4/162 (2.5%)
Hallucination	1/162 (0.6%)
Other (Not Including Serious) Adverse Events
	Ziprasidone
	Affected / at Risk (%)	# Events
Total	123/162 (75.9%)
Gastrointestinal disorders
Abdominal pain upper	15/162 (9.3%)
Nausea	13/162 (8%)
Vomiting	12/162 (7.4%)
Abdominal discomfort	11/162 (6.8%)
General disorders
Fatigue	11/162 (6.8%)
Nervous system disorders
Dizziness	12/162 (7.4%)
Headache	36/162 (22.2%)
Sedation	43/162 (26.5%)
Somnolence	38/162 (23.5%)
Psychiatric disorders
Insomnia	22/162 (13.6%)
Respiratory, thoracic and mediastinal disorders
Cough	9/162 (5.6%)
Nasal congestion	12/162 (7.4%)

Limitations/Caveats

The AE tables were amended to incorporate previously unreported AEs that were found during an independent audit and verified by the investigators.

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.