Safety and Efficacy 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: NCT00257166
• Collaborator: (none)
• Enrollment: 238
• Locations: 50
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if flexibly-dosed ziprasidone is safe and effective for the treatment of 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; Drug: placebo oral capsules	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 238 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Four Week, Double-Blind, Placebo Controlled Phase III Trial Evaluating The Efficacy, Safety And Pharmacokinetics Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder (Manic Or Mixed)
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jul 1, 2007
• Actual Study Completion Date: Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ziprasidone oral capsules	Drug: Ziprasidone oral capsules; Oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength administered BID.
Placebo Comparator: Placebo	Drug: placebo oral capsules; Oral placebo capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength administered BID.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4 [Baseline, Week 4]

   YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.

Secondary Outcome Measures

1. Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3 [Baseline, Week 1, 2, 3]

   YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.

2. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4 [Baseline, Week 1, 2, 3, 4]

   CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill).

3. Clinical Global Impression - Improvement (CGI-I) Score [Week 1, 2, 3, 4]

   CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• DSM-IV criteria for Bipolar I disorder (manic or mixed); age 10 - 17 years

Exclusion Criteria:

• Imminent risk of suicide or homicide, as judged by the site investigator; any history of serious or unstable medical illness, including risk for QT prolongation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Scottsdale	Arizona	United States	85251
2	Pfizer Investigational Site	Orange	California	United States	92868
3	Pfizer Investigational Site	San Diego	California	United States	92123
4	Pfizer Investigational Site	Denver	Colorado	United States	80218
5	Pfizer Investigational Site	Altamonte Springs	Florida	United States	32701
6	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33301
7	Pfizer Investigational Site	North Miami	Florida	United States	33161
8	Pfizer Investigational Site	Orange City	Florida	United States	32763
9	Pfizer Investigational Site	Tavares	Florida	United States	32778
10	Pfizer Investigational Site	Decatur	Georgia	United States	30033
11	Pfizer Investigational Site	Honolulu	Hawaii	United States	96826
12	Pfizer Investigational Site	Des Plaines	Illinois	United States	60016
13	Pfizer Investigational Site	Schaumburg	Illinois	United States	60194
14	Pfizer Investigational Site	Terre Haute	Indiana	United States	47802
15	Pfizer Investigational Site	Lexington	Kentucky	United States	40509
16	Pfizer Investigational Site	Owensboro	Kentucky	United States	42301
17	Pfizer Investigational Site	Baton Rouge	Louisiana	United States	70809
18	Pfizer Investigational Site	Shreveport	Louisiana	United States	71103
19	Pfizer Investigational Site	Pikesville	Maryland	United States	21208
20	Pfizer Investigational Site	Towson	Maryland	United States	21204
21	Pfizer Investigational Site	Towson	Maryland	United States	21286
22	Pfizer Investigational Site	Clinton Township	Michigan	United States	48038
23	Pfizer Investigational Site	Meridian	Mississippi	United States	39301
24	Pfizer Investigational Site	Saint Louis	Missouri	United States	63044-2588
25	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
26	Pfizer Investigational Site	Omaha	Nebraska	United States	68131
27	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87102
28	Pfizer Investigational Site	Buffalo	New York	United States	14215
29	Pfizer Investigational Site	Rochester	New York	United States	14618
30	Pfizer Investigational Site	Cincinnati	Ohio	United States	45224
31	Pfizer Investigational Site	Cincinnati	Ohio	United States	45229
32	Pfizer Investigational Site	Cincinnati	Ohio	United States	45267-0559
33	Pfizer Investigational Site	Cleveland	Ohio	United States	44106-5080
34	Pfizer Investigational Site	Columbus	Ohio	United States	43210
35	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73101
36	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73107
37	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73112
38	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73116
39	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74114
40	Pfizer Investigational Site	Charleston	South Carolina	United States	29405
41	Pfizer Investigational Site	Arlington	Texas	United States	76011
42	Pfizer Investigational Site	DeSoto	Texas	United States	75115
43	Pfizer Investigational Site	Fort Worth	Texas	United States	76102
44	Pfizer Investigational Site	Lake Jackson	Texas	United States	77566
45	Pfizer Investigational Site	Plano	Texas	United States	75093
46	Pfizer Investigational Site	San Antonio	Texas	United States	78229
47	Pfizer Investigational Site	Kirkland	Washington	United States	98033
48	Pfizer Investigational Site	Spokane	Washington	United States	99204
49	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53226
50	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: NCT00257166
• Other Study ID Numbers: A1281132
• First Posted: Nov 22, 2005
• Last Update Posted: Mar 3, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Bipolar Disorder; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Period Title: Overall Study
STARTED	150	88
Treated	149	88
COMPLETED	97	51
NOT COMPLETED	53	37

Baseline Characteristics

Arm/Group Title	Ziprasidone	Placebo	Total
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.	Total of all reporting groups
Overall Participants	149	88	237
Age, Customized (participants) [Number]
10 to 13 years	74 49.7%	35 39.8%	109 46%
14 to 17 years	74 49.7%	53 60.2%	127 53.6%
>=18 years	1 0.7%	0 0%	1 0.4%
Sex: Female, Male (Count of Participants)
Female	65 43.6%	41 46.6%	106 44.7%
Male	84 56.4%	47 53.4%	131 55.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 4
Description	YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT): all randomized participants who had baseline measurements, took at least (>=) 1 dose of study medication (ziprasidone or placebo) and had >=1 post-baseline visit. Here, 'n' signifies those participants who were available for this measure at given time points for each group.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Measure Participants	143	86
Baseline (n=143,86)	26.2 (6.6)	27.0 (6.6)
Change at Week 4 (n=97,51)	-13.8 (7.8)	-9.9 (7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 4: Mixed effects repeated measures Analysis of Covariance (ANCOVA) model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean difference
	Estimated Value	-5.22
	Confidence Interval	(2-Sided) 95%; -8.12 to -2.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.48
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Young Mania Rating Scale (YMRS) Score at Week 1, 2 and 3
Description	YMRS: an 11-item scale that measured the severity of manic episodes. Four items were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score ranged from 0 to 60, higher score indicated higher severity of mania.
Time Frame	Baseline, Week 1, 2, 3

Outcome Measure Data

Analysis Population Description

ITT population. 'N' (number of participants analyzed) signifies those participants who were available for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Measure Participants	131	85
Change at Week 1 (n=131,85)	-9.3 (7.5)	-6.3 (7.1)
Change at Week 2 (n=120,81)	-11.5 (8.7)	-8.1 (7.9)
Change at Week 3 (n=108,65)	-13.0 (8.1)	-9.0 (7.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 1: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-3.2545
	Confidence Interval	(2-Sided) 95%; -5.1045 to -1.4046
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.9422
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 2: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0117
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-3.5857
	Confidence Interval	(2-Sided) 95%; -6.3705 to -0.8009
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4184
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 3: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0047
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-4.8665
	Confidence Interval	(2-Sided) 95%; -8.2345 to -1.4985
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7154
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 1, 2, 3 and 4
Description	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill).
Time Frame	Baseline, Week 1, 2, 3, 4

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'n' signifies those participants who were available for this measure at given time points for each group respectively.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Measure Participants	143	86
Baseline (n=143,86)	4.5 (0.7)	4.5 (0.7)
Change at Week 1 (n=131,85)	-0.9 (0.8)	-0.5 (0.9)
Change at Week 2 (n=120,82)	-1.1 (1.0)	-0.6 (0.9)
Change at Week 3 (n=108,65)	-1.3 (1.0)	-0.7 (1.0)
Change at Week 4 (n=96,51)	-1.4 (1.1)	-0.9 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 1: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.3754
	Confidence Interval	(2-Sided) 95%; -0.5696 to -0.1812
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0989
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 2: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.5596
	Confidence Interval	(2-Sided) 95%; -0.8256 to -0.2936
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1355
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 3: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.6798
	Confidence Interval	(2-Sided) 95%; -1.0024 to -0.3572
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1643
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Change at Week 4: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.6884
	Confidence Interval	(2-Sided) 95%; -1.0342 to -0.3426
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1761
	Estimation Comments

4. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I) Score
Description	CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.
Time Frame	Week 1, 2, 3, 4

Outcome Measure Data

Analysis Population Description

ITT population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' signifies those participants who were available for this measure at given time points for each group respectively.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.	Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
Measure Participants	132	85
Week 1 (n=132,85)	2.8 (0.9)	3.4 (0.9)
Week 2 (n=120,82)	2.5 (1.1)	3.2 (1.1)
Week 3 (n=108,65)	2.4 (1.0)	3.1 (1.3)
Week 4 (n=96,51)	2.3 (1.0)	2.8 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Week 4: Mixed effects repeated measures ANCOVA model with center and participant within center as random effects, treatment, visit and visit-by-treatment interaction as fixed effects was used for the analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.18 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

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		Placebo
Arm/Group Description	Ziprasidone capsule administered orally in 2 divided doses daily in the morning and evening with a starting dose of ziprasidone 20 milligram per day (mg/day) as an evening dose on Day 1. This was followed by dose escalation of 20 mg/day every other day up to a target dose of ziprasidone 120 to 160 mg/day for participants with greater than or equal to [>=] 45 kilogram [kg] weight and ziprasidone 60 to 80 mg/day for participants with less than [<] 45 kg weight over 2 weeks, as per investigator's discretion. Flexible dosing of ziprasidone capsule 80 to 160 mg/day for participants with >= 45 kg weight and ziprasidone capsule 40 to 80 mg/day for participants with <45 kg weight orally in 2 divided doses daily in the morning and evening up to Week 4, as per investigator's discretion.		Placebo matched to ziprasidone capsule orally twice daily up to Week 4.
All Cause Mortality
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/149 (4%)		7/88 (8%)
Infections and infestations
Viral infection	1/149 (0.7%)		0/88 (0%)
Injury, poisoning and procedural complications
Overdose	1/149 (0.7%)		0/88 (0%)
Investigations
Liver function test abnormal	1/149 (0.7%)		0/88 (0%)
Nervous system disorders
Dystonia	1/149 (0.7%)		0/88 (0%)
Psychiatric disorders
Suicidal ideation	1/149 (0.7%)		3/88 (3.4%)
Mania	1/149 (0.7%)		0/88 (0%)
Aggression	1/149 (0.7%)		2/88 (2.3%)
Hypersexuality	1/149 (0.7%)		0/88 (0%)
Bipolar I disorder	0/149 (0%)		1/88 (1.1%)
Bipolar disorder	0/149 (0%)		1/88 (1.1%)
Hallucination	0/149 (0%)		1/88 (1.1%)
Paranoia	0/149 (0%)		1/88 (1.1%)
Other (Not Including Serious) Adverse Events
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/149 (85.9%)		42/88 (47.7%)
Eye disorders
Vision blurred	9/149 (6%)		1/88 (1.1%)
Gastrointestinal disorders
Abdominal pain upper	8/149 (5.4%)		3/88 (3.4%)
Nausea	21/149 (14.1%)		6/88 (6.8%)
Vomiting	12/149 (8.1%)		1/88 (1.1%)
General disorders
Fatigue	23/149 (15.4%)		6/88 (6.8%)
Infections and infestations
Upper respiratory tract infection	8/149 (5.4%)		0/88 (0%)
Injury, poisoning and procedural complications
Overdose	6/149 (4%)		5/88 (5.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	8/149 (5.4%)		0/88 (0%)
Nervous system disorders
Akathisia	8/149 (5.4%)		1/88 (1.1%)
Dizziness	19/149 (12.8%)		2/88 (2.3%)
Headache	33/149 (22.1%)		19/88 (21.6%)
Sedation	49/149 (32.9%)		5/88 (5.7%)
Somnolence	37/149 (24.8%)		7/88 (8%)
Tremor	9/149 (6%)		0/88 (0%)
Psychiatric disorders
Insomnia	14/149 (9.4%)		3/88 (3.4%)
Restlessness	8/149 (5.4%)		1/88 (1.1%)

Limitations/Caveats

[Not Specified]

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.