Safety And Efficacy Of Ziprasidone In Adolescents With Schizophrenia

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00257192
• Collaborator: (none)
• Enrollment: 284
• Locations: 92
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

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 adolescents (ages 13-17) with schizophrenia

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: placebo; Drug: Ziprasidone oral capsules	Phase 3

Detailed Description

Termination Reason: On March 24, 2009, Pfizer Inc. stopped late stage Geodon pediatric clinical trials in schizophrenia (A1281134 - placebo controlled; A1281135 - open label). As recommended by the DSMB, these studies were stopped due to lack of efficacy. No safety concerns were identified.

Study Design

• Study Type: Interventional
• Actual Enrollment: 284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Six Week, Double-Blind, Placebo Controlled Phase III Trial Evaluating The Efficacy, Safety And Pharmacokinetics Of Flexible Doses Of Oral Ziprasidone In Adolescent Subjects With Schizophrenia
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 2.0	Drug: placebo; Placebo matching the oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength or matching placebo. Subjects will be dosed daily for 6 weeks using a flexible dose design with a minimal dose range of 40mg twice a day (BID) to a maximum dose range of 80 mg BID. For subjects weighing <45 kg, the doses will range from 20 mg BID to 40 mg BID.
Active Comparator: 1.0	Drug: Ziprasidone oral capsules; Oral ziprasidone capsules of 20 mg, 40 mg, 60 mg, and 80 mg strength or matching placebo. Subjects will be dosed daily for 6 weeks using a flexible dose design with a minimal dose range of 40mg BID to a maximum dose range of 80 mg BID. For subjects weighing <45 kg, the doses will range from 20 mg BID to 40 mg BID.; Other Names: Geodon, Zeldox

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6 [Baseline, Week 6]

   BPRS-A: 18-item clinician rated scale to assess somatic concern, anxiety, emotional withdrawal, disorganization, hallucinatory behavior, guilt feelings, suspiciousness, disorientation, tension, mannerisms, posturing, grandiosity, depressive mood, hostility, motor retardation, uncooperativeness, unusual thought content, blunted affect, and excitement. Ratings anchored to improve consistency for a single rater over time or between raters. Items rated on 7-point scale 0 (not present) to 6 (extremely severe). Total score=sum of items (range 0 to 108); higher scores indicate increased pathology.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6 [Baseline, Week 6]

   CGI-S: single-item clinician rated scale to rate the severity of a subject's illness over time. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score indicates more affected.

2. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6 [Baseline, Week 6]

   PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.

3. Change From Baseline in PANSS: Positive and Negative Subscales at Week 6 [Baseline, Week 6]

   PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.

4. Clinical Global Impression of Improvement (CGI-I) Score at Week 6 [Baseline, Week 6]

   CGI-I: single-item clinician rated scale used to assess the subject's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.

5. Change From Baseline in Children's Global Assessment Scale (CGAS) [Baseline, Week 2, Week 4, Week 6, Early termination (ET)]

   CGAS: clinician-rated global assessment item for children based on symptoms and social functioning in home, school, and community settings. Scores on this single item range from 1 to 100 (higher levels indicate greater health) with descriptive anchors for every 10-point interval. Scores above 70 on this scale are considered within the "normal" range; lower score indicates need for increased supervision.

6. Change From Baseline in Child Health Questionnaire (CHQ) [Baseline, Week 6, ET]

   CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.

7. Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score [Baseline, Week 1 through Week 6]

   CPBAQ: 19-item parent or legal guardian completed questionnaire to rate the child's verbal (such as yelling or cursing) and physical aggression (such a fighting with peers or being cruel to an animal) during the past week. Behavior was rated on a 4-point scale; range 0 (behavior did not occur or was not a problem) to 3 (behavior occurred a lot or was severe problem). Total score range 0 to 57; higher scores indicate a greater frequency and severity of aggression.

8. Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score [Baseline, Week 1 through Week 6]

   CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment). Total score calculated as sum of the 17 items (range 1 to 119); higher score indicates greater impairment.

9. Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13 [Baseline, Week 1 through Week 6]

   CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Suicide Ideation (Item 13) detects changes in suicidality over time. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).

10. Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1 [Baseline, Week 2, Week 6]

    Clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses resolved by using most impaired rating given by valid informant. Impaired Schoolwork (Item 1) assesses school function for the subgroup of subjects reported to be in school. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).

11. Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales [Baseline, Week 6, ET]

    A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score >109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).

12. Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index [Baseline, Week 6, ET]

    A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score >109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).

13. Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS) [Baseline, Week 1 through Week 6]

    SARS: 10-item clinician rated instrument to assess parkinsonian symptoms (7 items) and related extrapyramidal side effects (3 items): gait, arm dropping, shoulder shaking, elbow rigidity, leg pendulousness, glabellar tap, tremor, and salivation. Head dropping (modified SARS item 7) substituted for head rotation. Anchored 5-point scale: range 0 (absence of condition, normal) to 4 (most extreme form of condition). Total score is sum of individual item scores (range 0 to 40); higher score indicates more affected.

14. Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item [Baseline, Week 1 through Week 6]

    BAS: clinician rated scale to assess akathisia to determine the degree of subjective restlessness and distress associated with restlessness. First 3 items (Objective, Subjective, and Distress related to restlessness) rated on a 4-point scale with range 0 (no symptoms) to 3 (increased severity of symptoms). Item 4 Global Clinical Assessment of Akathisia rated on a 6-point scale range 0 (no symptoms) to 5 (increased severity of symptoms); higher score indicates increased severity. All rating are anchored. Only the Global Clinical Assessment of Akathisia was to be analyzed.

15. Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score [Baseline, Week 1 through Week 6]

    AIMS: clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe) (total possible score 0 to 40; higher score indicates greater severity); items 11 to 14 are No or Yes response to dental status and sleep movements. Only the sum of the first 7 items to be analyzed (AIMS Movement Cluster score). Total score 0 to 28; higher score indicates greater severity.

16. Number of Subjects Per Response on the School Placement Questionnaire: School Situation [Baseline, Week 2, Week 6, ET]

    School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

17. Number of Subjects Per Response on the School Placement Questionnaire: School Attendance [Baseline, Week 2, Week 6, ET]

    School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

18. Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance [Baseline, Week 2, Week 6, ET]

    School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia: Current symptoms were to be present for at least 7 days before screening.

• At the Screening and Baseline visits, subjects must have had a Brief Psychiatric Rating Scale - Anchored score ≥35 and a score of ≥4 on at least 1 of the following items: unusual thought content (i.e., delusions), hallucinations, suspiciousness, or conceptual disorganization.

• Age 13 - 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	Birmingham	Alabama	United States	35205
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35294-4400
3	Pfizer Investigational Site	Birmingham	Alabama	United States	35294
4	Pfizer Investigational Site	San Diego	California	United States	92123
5	Pfizer Investigational Site	Stanford	California	United States	94305
6	Pfizer Investigational Site	Aurora	Colorado	United States	80045
7	Pfizer Investigational Site	Washington	District of Columbia	United States	20010
8	Pfizer Investigational Site	Altamonte Springs	Florida	United States	32701
9	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33301
10	Pfizer Investigational Site	North Miami	Florida	United States	33161
11	Pfizer Investigational Site	Orange City	Florida	United States	32763
12	Pfizer Investigational Site	Tampa	Florida	United States	33613
13	Pfizer Investigational Site	Tavares	Florida	United States	32778
14	Pfizer Investigational Site	Smyrna	Georgia	United States	30080
15	Pfizer Investigational Site	Tucker	Georgia	United States	30084
16	Pfizer Investigational Site	Honolulu	Hawaii	United States	96813
17	Pfizer Investigational Site	Des Plaines	Illinois	United States	60016
18	Pfizer Investigational Site	Oakbrook Terrace	Illinois	United States	60181
19	Pfizer Investigational Site	Schaumburg	Illinois	United States	60194
20	Pfizer Investigational Site	Pikesville	Maryland	United States	21208
21	Pfizer Investigational Site	Towson	Maryland	United States	21204
22	Pfizer Investigational Site	Towson	Maryland	United States	21286
23	Pfizer Investigational Site	Clinton Township	Michigan	United States	48038
24	Pfizer Investigational Site	Meridian	Mississippi	United States	39301
25	Pfizer Investigational Site	Bridgeton	Missouri	United States	63044-2588
26	Pfizer Investigational Site	Saint Louis	Missouri	United States	63141
27	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
28	Pfizer Investigational Site	Omaha	Nebraska	United States	68131
29	Pfizer Investigational Site	Buffalo	New York	United States	14209
30	Pfizer Investigational Site	Buffalo	New York	United States	14215
31	Pfizer Investigational Site	Rochester	New York	United States	14618
32	Pfizer Investigational Site	Cincinnati	Ohio	United States	45219
33	Pfizer Investigational Site	Cincinnati	Ohio	United States	45224
34	Pfizer Investigational Site	Cincinnati	Ohio	United States	45229
35	Pfizer Investigational Site	Cleveland	Ohio	United States	44106
36	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73101
37	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73107
38	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73116
39	Pfizer Investigational Site	Arlington	Texas	United States	76011
40	Pfizer Investigational Site	DeSoto	Texas	United States	75115
41	Pfizer Investigational Site	Plano	Texas	United States	75093
42	Pfizer Investigational Site	Bothell	Washington	United States	98011
43	Pfizer Investigational Site	Spokane	Washington	United States	99204
44	Pfizer Investigational Site	Spokane	Washington	United States	99216
45	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53226
46	Pfizer Investigational Site	West Allis	Wisconsin	United States	53227
47	Pfizer Investigational Site	Medellin	Antioquia	Colombia
48	Pfizer Investigational Site	Bogota	Cundinamarca	Colombia
49	Pfizer Investigational Site	San Jose		Costa Rica
50	Pfizer Investigational Site	Vijaywada	Andhra Pradesh	India	520 002
51	Pfizer Investigational Site	Visakhapatnam	Andra Pradesh/India	India	530 017
52	Pfizer Investigational Site	Ahmedabad	Guj	India	380015
53	Pfizer Investigational Site	Mangalore	Karnataka	India	575001
54	Pfizer Investigational Site	Aurangabad	Maharashtra	India	431 005
55	Pfizer Investigational Site	Mumbai	Maharashtra	India	400 058
56	Pfizer Investigational Site	Pune	Maharashtra	India	411 001
57	Pfizer Investigational Site	Pune	Maharashtra	India	411 046
58	Pfizer Investigational Site	Ludhiana	Punjab	India	141001
59	Pfizer Investigational Site	Chennai	Tamil Nadu	India	600 003
60	Pfizer Investigational Site	Kubang Kerian	Kelantan	Malaysia	16150
61	Pfizer Investigational Site	Kuala Lumpur		Malaysia	50586
62	Pfizer Investigational Site	Kuala Lumpur		Malaysia	50603
63	Pfizer Investigational Site	Kuala Lumpur		Malaysia	55100
64	Pfizer Investigational Site	Lima		Peru	L13
65	Pfizer Investigational Site	Lima		Peru	L41
66	Pfizer Investigational Site	Kazan		Russian Federation	420012
67	Pfizer Investigational Site	Khotkovo, Moscow Region		Russian Federation	142601
68	Pfizer Investigational Site	Lipetsk Region		Russian Federation	399313
69	Pfizer Investigational Site	Moscow		Russian Federation	107076
70	Pfizer Investigational Site	Moscow		Russian Federation	115522
71	Pfizer Investigational Site	Moscow		Russian Federation	117152
72	Pfizer Investigational Site	Moscow		Russian Federation	127473
73	Pfizer Investigational Site	Moscow		Russian Federation	143300
74	Pfizer Investigational Site	Nizhniy Novgorod		Russian Federation	603155
75	Pfizer Investigational Site	Saratov		Russian Federation	410012
76	Pfizer Investigational Site	Saratov		Russian Federation	410060
77	Pfizer Investigational Site	St. Petersburg		Russian Federation	192019
78	Pfizer Investigational Site	Tver		Russian Federation	170005
79	Pfizer Investigational Site	Yaroslavl		Russian Federation	150003
80	Pfizer Investigational Site	Singapore		Singapore	229899
81	Pfizer Investigational Site	Singapore		Singapore	539747
82	Pfizer Investigational Site	Simferopol	Crimea	Ukraine	95006
83	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49005
84	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49115
85	Pfizer Investigational Site	Donetsk		Ukraine	83037
86	Pfizer Investigational Site	Kharkiv		Ukraine	61068
87	Pfizer Investigational Site	Kyiv		Ukraine	04655
88	Pfizer Investigational Site	Lugansk		Ukraine	91045
89	Pfizer Investigational Site	Lviv		Ukraine	79021
90	Pfizer Investigational Site	Odessa		Ukraine	65006
91	Pfizer Investigational Site	Poltava		Ukraine	36006
92	Pfizer Investigational Site	Vinnytsya		Ukraine	21005

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: NCT00257192
• Other Study ID Numbers: A1281134
• First Posted: Nov 22, 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.: Adolescent Subjects With Schizophrenia
• Additional relevant MeSH terms: Schizophrenia; Ziprasidone

Study Results

Participant Flow

Recruitment Details	A planned interim analysis resulted in recommendation from Data Safety Monitoring Board (DSMB) to terminate study due to futility per the interim analysis charter (p-value = 0.9840). Only one active subject in the study was affected by this decision.
Pre-assignment Detail	Screening visit followed by a 1 to 10 day period to allow for wash-out of exclusionary medications.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Period Title: Overall Study
STARTED	193	91
Received Study Treatment	193	90
COMPLETED	135	52
NOT COMPLETED	58	39

Baseline Characteristics

Arm/Group Title	Ziprasidone	Placebo	Total
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Total of all reporting groups
Overall Participants	193	90	283
Age, Customized (participants) [Number]
>12 years and <13 years at start of treatment	4 2.1%	0 0%	4 1.4%
Between 13 and 17 years	189 97.9%	90 100%	279 98.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.3 (1.4)	15.4 (1.4)	15.3 (1.4)
Sex: Female, Male (Count of Participants)
Female	84 43.5%	28 31.1%	112 39.6%
Male	109 56.5%	62 68.9%	171 60.4%
Ethnicity (participants) [Number]
Hispanic / Latino	21 10.9%	9 10%	30 10.6%
Not Hispanic / Latino	172 89.1%	81 90%	253 89.4%
Race (particpants) [Number]
White	116	60	176
Black	17	2	19
Asian	38	17	55
Hispanic	9	3	12
Other	13	8	21
Tanner adolescent pubertal self-assessment: Breast (females) (particpants) [Number]
Stage 1	0	1	1
Stage 2	6	3	9
Stage 3	16	4	20
Stage 4	35	11	46
Stage 5	25	9	34
Not applicable	109	62	171
Missing (not answered)	2	0	2
Tanner adolescent pubertal self-assessment: Genitalia (males) (participants) [Number]
Stage 1	0 0%	1 1.1%	1 0.4%
Stage 2	9 4.7%	3 3.3%	12 4.2%
Stage 3	25 13%	16 17.8%	41 14.5%
Stage 4	57 29.5%	26 28.9%	83 29.3%
Stage 5	18 9.3%	16 17.8%	34 12%
Not applicable	82 42.5%	28 31.1%	110 38.9%
Missing (not answered)	2 1%	0 0%	2 0.7%
Tanner adolescent pubertal self-assessment: Pubic hair (females and males) (participants) [Number]
Stage 1	0 0%	3 3.3%	3 1.1%
Stage 2	13 6.7%	7 7.8%	20 7.1%
Stage 3	36 18.7%	13 14.4%	49 17.3%
Stage 4	90 46.6%	43 47.8%	133 47%
Stage 5	52 26.9%	24 26.7%	76 26.9%
Missing (not answered)	2 1%	0 0%	2 0.7%
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	164.9 (10.1)	167.8 (10.0)	165.8 (10.1)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	61.2 (15.5)	64.3 (15.7)	62.2 (15.6)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6
Description	BPRS-A: 18-item clinician rated scale to assess somatic concern, anxiety, emotional withdrawal, disorganization, hallucinatory behavior, guilt feelings, suspiciousness, disorientation, tension, mannerisms, posturing, grandiosity, depressive mood, hostility, motor retardation, uncooperativeness, unusual thought content, blunted affect, and excitement. Ratings anchored to improve consistency for a single rater over time or between raters. Items rated on 7-point scale 0 (not present) to 6 (extremely severe). Total score=sum of items (range 0 to 108); higher scores indicate increased pathology.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT): all randomized subjects who had baseline measurements, took at least 1 dose of study medication, and had at least 1 post-baseline visit. N=number of subjects with analyzable data at post-baseline observation.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	189	87
Least Squares Mean (Standard Error) [scores on a scale]	-14.16 (0.78)	-12.35 (1.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Sample size for 85% power 2-tailed 0.05 significance level based on expected difference of -5 with average within-group standard deviation=13 was 276 subjects (2 to 1 ratio of enrollment: 184 ziprasidone, 92 placebo). Interim analysis at 60 percent (%) enrollment (ITT population): may stop trial early for efficacy (2-sided p-value less than (<) 0.0124) or for futility (2-sided p-value greater than (>) 0.4772; The final analysis is to employ a 2-sided p-value <0.0462.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1530
	Comments	Mixed effects repeated measures (MMRM) analysis of covariance model with subject as random effect, treatment, region, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate.
	Method	ANCOVA
	Comments	P-value for final analysis is to be adjusted due to planned interim analysis (0.0462).
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.80
	Confidence Interval	(2-Sided) 95%; -4.28 to 0.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.26
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6
Description	CGI-S: single-item clinician rated scale to rate the severity of a subject's illness over time. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score indicates more affected.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at post-baseline observation.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	190	87
Least Squares Mean (Standard Error) [scores on a scale]	-1.05 (0.08)	-0.84 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1289
	Comments	Mixed effects repeated measures (MMRM) analysis of covariance model with subject as random effect, treatment, region, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate.
	Method	ANCOVA
	Comments	Hochberg procedure was applied to p-value to preserve type I error in the analysis of key secondary endpoints (PANSS total score and CGI-S).
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.48 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6
Description	PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at post-baseline observation.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	183	86
Least Squares Mean (Standard Error) [scores on a scale]	-23.58 (1.42)	-21.01 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Total score: difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1987
	Comments	Mixed effects repeated measures (MMRM) analysis of covariance model with subject as random effect, treatment, region, visit and visit-by-treatment interaction as fixed effects and baseline score as a covariate.
	Method	ANCOVA
	Comments	Hochberg procedure was applied to p-value to preserve type I error in the analysis of key secondary endpoints (PANSS total score and CGI-S).
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-2.57
	Confidence Interval	() 95%; -6.50 to 1.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.00
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in PANSS: Positive and Negative Subscales at Week 6
Description	PANSS: 30-item clinician-rated scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Items scored on anchored Likert scale rated 1 (absent symptoms) to 7 (extreme); scores above 1 indicate clinical symptom is present; scores from 2 to 7 indicate increased severity. Total score range 30 to 210: higher score indicates greater severity.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at post-baseline observation.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	183	86
Positive score	-7.22 (0.44)	-5.88 (0.56)
Negative score	-5.51 (0.43)	-5.09 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Positive score: difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0412
	Comments	Mixed effects repeated measures (MMRM) analysis of covariance model with subject as random effect, treatment, region, visit, and visit-by-treatment interaction as fixed effects and baseline score as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.33
	Confidence Interval	(2-Sided) 95%; -2.61 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.65
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Negative score: difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4661
	Comments	Mixed effects repeated measures (MMRM) analysis of covariance model with subject as random effect, treatment, region, visit, and visit-by-treatment interaction as fixed effects and baseline score as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.57 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.58
	Estimation Comments

5. Secondary Outcome

Title	Clinical Global Impression of Improvement (CGI-I) Score at Week 6
Description	CGI-I: single-item clinician rated scale used to assess the subject's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at post-baseline observation.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	190	87
Least Squares Mean (Standard Error) [scores on a scale]	2.66 (0.09)	2.85 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1820
	Comments	Mixed effects MMRM with subject as random effect, treatment, region, visit and visit-by-treatment interaction as fixed effects.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Children's Global Assessment Scale (CGAS)
Description	CGAS: clinician-rated global assessment item for children based on symptoms and social functioning in home, school, and community settings. Scores on this single item range from 1 to 100 (higher levels indicate greater health) with descriptive anchors for every 10-point interval. Scores above 70 on this scale are considered within the "normal" range; lower score indicates need for increased supervision.
Time Frame	Baseline, Week 2, Week 4, Week 6, Early termination (ET)

Outcome Measure Data

Analysis Population Description

ITT; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. Last observation carried forward [LOCF] imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	193	90
Week 2 (n=183, 86)	4.7 (8.7)	2.6 (5.8)
Week 4 (n=155, 63)	7.9 (10.4)	6.2 (8.9)
Week 6 (n=135, 52)	10.9 (11.8)	10.8 (9.9)
ET (n=20, 15)	1.3 (10.1)	1.7 (8.9)
Week 6 [LOCF] (n=185, 87)	8.4 (11.8)	6.4 (10.6)

7. Secondary Outcome

Title	Change From Baseline in Child Health Questionnaire (CHQ)
Description	CHQ: 50-item, 15 subscale parent or legal guardian assessed instrument of child's physical, emotional, social well-being, and relative burden of disease on the parents; rated on Likert-type scale: range 0 to 100; higher scores indicate a more positive health status. Global indicators for Physical Health and Psychosocial Health are weighted composites derived from subscale items using scoring algorithms (transformed scores); range 0 to 100: higher scores indicate more positive health status.
Time Frame	Baseline, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	193	90
Global health: Week 6	5.0 (18.2)	8.5 (24.7)
Global health: ET	-5.4 (24.0)	-9.1 (17.4)
Global health: Week 6 [LOCF]	2.8 (19.9)	1.4 (23.7)
Global behavior: Week 6	9.4 (23.6)	10.9 (22.1)
Global behavior: ET	6.4 (21.4)	-0.5 (23.0)
Global behavior: Week 6 [LOCF]	8.8 (23.1)	6.5 (23.1)
Family cohesion: Week 6	1.9 (21.3)	-0.8 (19.7)
Family cohesion: ET	-1.8 (18.4)	-2.6 (16.1)
Family cohesion: Week 6 [LOCF]	1.2 (20.8)	-1.1 (18.1)
Physical health: Week 6	3.5 (33.9)	5.0 (28.0)
Physical health: ET	-6.5 (32.9)	3.2 (23.3)
Physical health: Week 6 [LOCF]	1.4 (33.8)	4.8 (26.0)
Bodily pain: Week 6	4.4 (21.6)	8.0 (19.4)
Bodily pain: ET	4.7 (23.0)	0.0 (14.6)
Bodily pain: Week 6 [LOCF]	4.5 (21.9)	4.9 (18.1)
Emotion, behavior: Week 6	16.2 (29.8)	13.8 (31.1)
Emotion, behavior: ET	4.0 (43.1)	-2.5 (22.7)
Emotion, behavior: Week 6 [LOCF]	13.6 (33.4)	7.8 (29.2)
Time impact on parent: Week 6	8.8 (25.4)	11.8 (23.1)
Time impact on parent: ET	2.0 (25.8)	1.8 (21.7)
Time impact on parent: Week 6 [LOCF]	7.4 (25.5)	8.0 (23.1)
Emotional impact on parent: Week 6	8.9 (21.6)	10.0 (22.3)
Emotional impact on parent: ET	3.5 (21.2)	2.7 (12.6)
Emotional impact on parent: Week 6 [LOCF]	7.7 (21.6)	7.4 (19.4)
Mental health: Week 6	8.1 (15.3)	12.6 (18.2)
Mental health: ET	1.3 (17.9)	-0.8 (12.0)
Mental health: Week 6 [LOCF]	6.7 (16.1)	7.5 (17.4)
Physical function: Week 6	5.6 (19.7)	5.9 (25.2)
Physical function: ET	-5.4 (22.5)	-0.2 (17.7)
Physical function: Week 6 [LOCF]	3.3 (20.8)	3.7 (22.8)
Behavior scale: Week 6	9.0 (17.1)	9.0 (16.8)
Behavior scale: ET	7.6 (15.2)	0.6 (17.1)
Behavior scale: Week 6 [LOCF]	8.7 (16.7)	5.8 (17.4)
Self-esteem: Week 6	6.0 (17.5)	9.0 (22.9)
Self-esteem: ET	1.0 (20.6)	1.3 (14.0)
Self-esteem: Week 6 [LOCF]	5.0 (18.2)	6.4 (20.2)
General health perception: Week 6	1.1 (11.6)	3.3 (11.7)
General health perception: ET	-2.2 (12.3)	-0.6 (10.8)
General health perception: Week 6 [LOCF]	0.4 (11.8)	1.8 (11.5)
Family activities: Week 6	9.2 (22.6)	14.6 (22.5)
Family activities: ET	1.3 (16.8)	-4.6 (16.5)
Family activities: Week 6 [LOCF]	7.5 (21.7)	7.8 (22.0)
Change in health: Week 6	0.5 (1.1)	0.6 (1.0)
Change in health: ET	-0.4 (1.0)	-0.1 (0.8)
Change in health: Week 6 [LOCF]	0.3 (1.1)	0.3 (1.0)
Physical health global subscale: Week 6	1.8 (9.7)	2.4 (9.8)
Physical health global subscale: ET	-2.8 (11.8)	0.1 (4.4)
Physical health global subscale: Week 6 [LOCF]	0.9 (10.3)	1.6 (8.2)
Psychosocial health global subscale: Week 6	6.6 (9.5)	7.7 (11.0)
Psychosocial health global subscale: ET	3.1 (10.4)	0.0 (5.7)
Psychosocial health global subscale: Week 6 [LOCF]	5.9 (9.8)	4.8 (10.0)

8. Secondary Outcome

Title	Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score
Description	CPBAQ: 19-item parent or legal guardian completed questionnaire to rate the child's verbal (such as yelling or cursing) and physical aggression (such a fighting with peers or being cruel to an animal) during the past week. Behavior was rated on a 4-point scale; range 0 (behavior did not occur or was not a problem) to 3 (behavior occurred a lot or was severe problem). Total score range 0 to 57; higher scores indicate a greater frequency and severity of aggression.
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	173	74
Week 1 (n=165, 69)	-2.4 (7.1)	-1.3 (5.8)
Week 2 (n=161, 71)	-2.5 (8.0)	-1.0 (6.2)
Week 3 (n=146, 64)	-3.0 (6.7)	-0.7 (5.7)
Week 4 (n=138, 51)	-2.7 (7.4)	-1.0 (6.5)
Week 5 (n=126, 44)	-3.1 (7.0)	-0.8 (8.3)
Week 6 (n=119, 42)	-3.0 (7.4)	-1.9 (6.7)
Week 6 [LOCF] (n=167, 71)	-2.3 (8.2)	-0.3 (8.8)

9. Secondary Outcome

Title	Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score
Description	CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment). Total score calculated as sum of the 17 items (range 1 to 119); higher score indicates greater impairment.
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	180	84
Week 1 (n=179, 82)	-2.8 (6.6)	-1.4 (5.7)
Week 2 (n=174, 80)	-4.2 (7.3)	-2.5 (5.6)
Week 3 (n=157, 69)	-5.5 (7.4)	-3.2 (5.4)
Week 4 (n=148, 59)	-6.0 (7.6)	-4.9 (6.6)
Week 5 (n=135, 49)	-7.0 (8.5)	-5.6 (5.9)
Week 6 (n=126, 47)	-7.9 (7.9)	-6.5 (5.5)
Week 6 [LOCF] (n=178, 82)	-5.8 (8.7)	-4.0 (7.3)

10. Secondary Outcome

Title	Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13
Description	CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Suicide Ideation (Item 13) detects changes in suicidality over time. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	192	90
Week 1 (n=188, 86)	-0.1 (0.4)	-0.0 (0.5)
Week 2 (n=182, 86)	-0.0 (0.5)	-0.1 (0.5)
Week 3 (n=165, 74)	-0.1 (0.5)	-0.1 (0.3)
Week 4 (n=154, 63)	0.0 (0.5)	-0.1 (0.5)
Week 5 (n=141, 54)	0.0 (0.4)	-0.1 (0.5)
Week 6 (n=134, 52)	-0.0 (0.3)	-0.1 (0.4)
Week 6 [LOCF] (n=189, 87)	0.0 (0.6)	-0.0 (0.5)

11. Secondary Outcome

Title	Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1
Description	Clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses resolved by using most impaired rating given by valid informant. Impaired Schoolwork (Item 1) assesses school function for the subgroup of subjects reported to be in school. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).
Time Frame	Baseline, Week 2, Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	40	15
Week 2 (n=38, 15)	-0.3 (0.9)	-0.2 (0.7)
Week 6 (n=30, 8)	-0.6 (1.1)	-0.1 (1.4)
Week 6 [LOCF] (n=39, 15)	-0.6 (1.0)	-0.1 (1.1)

12. Secondary Outcome

Title	Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales
Description	A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score >109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).
Time Frame	Baseline, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint (last post-baseline non-missing visit).

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	174	83
Sedation: Week 6 (n=124, 47)	0.0 (1.7)	-0.4 (1.8)
Sedation: ET (n=23, 26)	0.0 (2.3)	0.2 (1.3)
Sedation: Week 6 [LOCF] (n=147, 72)	0.0 (1.8)	-0.2 (1.7)
Verbal Memory: Week 6 (n=124, 47)	1.3 (12.1)	0.5 (14.0)
Verbal Memory: ET (n=24, 25)	-2.3 (13.9)	-2.6 (15.1)
Verbal Memory: Week 6 [LOCF] (n=148, 71)	0.7 (12.4)	-0.5 (14.4)
Visual Memory: Week 6 (n=124, 46)	0.5 (13.3)	2.0 (14.5)
Visual Memory: ET (n=24, 26)	-3.8 (10.2)	0.4 (14.2)
Visual Memory: Week 6 [LOCF] (n=148, 71)	-0.2 (12.9)	1.2 (14.3)
Processing Speed: Week 6 (n=124, 46)	1.3 (13.5)	1.0 (12.0)
Processing Speed: ET (n=24, 25)	-10.6 (34.5)	0.5 (5.4)
Processing Speed: Week 6 [LOCF] (n=148, 70)	-0.6 (18.9)	0.6 (10.1)
Reasoning: Week 6 (n=122, 46)	2.2 (12.0)	-0.7 (14.6)
Reasoning: ET (n=23, 25)	1.3 (15.8)	3.3 (14.0)
Reasoning: Week 6 [LOCF] (n=145, 70)	1.9 (12.7)	0.7 (14.1)
Executive Functioning: Week 6 (n=123, 46)	2.9 (15.4)	2.7 (18.2)
Executive Functioning: ET (n=23, 26)	-6.7 (9.1)	4.6 (13.2)
Executive Functioning: Week 6 [LOCF] (n=146, 71)	1.4 (14.9)	3.2 (16.6)
Working Memory: Week 6 (n=120, 45)	1.9 (12.9)	0.5 (12.9)
Working Memory: ET (n=23, 24)	3.2 (13.5)	3.7 (11.0)
Working Memory: Week 6 [LOCF] (n=143, 68)	2.0 (12.9)	1.3 (12.2)
Sustained Attention: Week 6 (n=120, 45)	2.0 (12.3)	-1.6 (13.1)
Sustained Attention: ET (n=23, 24)	0.5 (13.5)	1.5 (11.6)
Sustained Attention: Week 6 [LOCF] (n=143, 68)	1.7 (12.4)	-0.9 (12.6)

13. Secondary Outcome

Title	Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index
Description	A computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, and sustained attention. A computerized 7-point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. The Neurocognitive index score was derived from subtest scores per an algorithm. The index score and subtest scores assessed the subject's changes in cognition. Scores were rated as above average (score >109), average (90 to 109), below average (80 to 89), or well below average (70 to 79).
Time Frame	Baseline, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint (last post-baseline non-missing visit).

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	168	79
Neurocognitive Index: Week 6 (n=120, 45)	1.8 (7.1)	0.8 (7.5)
Neurocognitive Index: ET (n=23, 23)	-2.7 (7.6)	2.2 (7.2)
Neurocognitive Index: Week 6 [LOCF] (n=143, 67)	1.0 (7.4)	1.1 (7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone, Placebo
	Comments	Neurocognitive Index score at Week 6: difference from placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2613
	Comments	SAS PROC MIXED to fit a mixed model analysis of covariance with treatment and region as fixed effects and baseline score as covariate.
	Method	ANCOVA
	Comments	Observed cases at Week 6.
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; -1.01 to 3.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.19
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS)
Description	SARS: 10-item clinician rated instrument to assess parkinsonian symptoms (7 items) and related extrapyramidal side effects (3 items): gait, arm dropping, shoulder shaking, elbow rigidity, leg pendulousness, glabellar tap, tremor, and salivation. Head dropping (modified SARS item 7) substituted for head rotation. Anchored 5-point scale: range 0 (absence of condition, normal) to 4 (most extreme form of condition). Total score is sum of individual item scores (range 0 to 40); higher score indicates more affected.
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	189	87
Week 1 (n=189, 85)	0.5 (2.8)	0.1 (0.9)
Week 2 (n=182, 85)	0.5 (2.4)	-0.0 (0.5)
Week 3 (n=165, 74)	0.7 (3.1)	0.3 (1.6)
Week 4 (n=154, 62)	0.4 (2.6)	-0.0 (0.6)
Week 5 (n=141, 54)	0.2 (2.4)	-0.0 (1.0)
Week 6 (n=134, 52)	0.2 (2.5)	-0.2 (0.8)
Week 6 [LOCF] (n=189, 86)	0.3 (2.5)	-0.1 (0.6)

15. Secondary Outcome

Title	Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item
Description	BAS: clinician rated scale to assess akathisia to determine the degree of subjective restlessness and distress associated with restlessness. First 3 items (Objective, Subjective, and Distress related to restlessness) rated on a 4-point scale with range 0 (no symptoms) to 3 (increased severity of symptoms). Item 4 Global Clinical Assessment of Akathisia rated on a 6-point scale range 0 (no symptoms) to 5 (increased severity of symptoms); higher score indicates increased severity. All rating are anchored. Only the Global Clinical Assessment of Akathisia was to be analyzed.
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	190	88
Week 1 (n=190, 86)	0.1 (0.6)	0.1 (0.4)
Week 2 (n=183, 86)	0.1 (0.7)	0.0 (0.3)
Week 3 (n=166, 74)	0.1 (0.6)	0.0 (0.3)
Week 4 (n=155, 63)	0.1 (0.6)	-0.0 (0.2)
Week 5 (n=142, 54)	0.1 (0.5)	0.0 (0.2)
Week 6 (n=135, 52)	0.0 (0.5)	0.0 (0.2)
Week 6 [LOCF] (n=190, 87)	0.0 (0.6)	0.0 (0.2)

16. Secondary Outcome

Title	Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score
Description	AIMS: clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe) (total possible score 0 to 40; higher score indicates greater severity); items 11 to 14 are No or Yes response to dental status and sleep movements. Only the sum of the first 7 items to be analyzed (AIMS Movement Cluster score). Total score 0 to 28; higher score indicates greater severity.
Time Frame	Baseline, Week 1 through Week 6

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects with analyzable data at baseline; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	190	88
Week 1 (n=190, 86)	0.2 (1.6)	-0.0 (0.4)
Week 2 (n=183, 86)	0.1 (1.6)	0.0 (0.6)
Week 3 (n=166, 74)	0.1 (1.3)	0.1 (1.0)
Week 4 (n=155, 63)	0.1 (0.8)	-0.0 (0.8)
Week 5 (n=142, 54)	-0.1 (0.7)	0.0 (0.4)
Week 6 (n=135, 52)	0.0 (0.6)	0.0 (0.5)
Week 6 [LOCF] (n=190, 87)	0.0 (0.8)	-0.0 (0.7)

17. Secondary Outcome

Title	Number of Subjects Per Response on the School Placement Questionnaire: School Situation
Description	School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.
Time Frame	Baseline, Week 2, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects analyzable for School Placement Questionnaire; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	189	87
Baseline: Enrolled or attend (n=185, 85)	40 20.7%	15 16.7%
Baseline: Not attend or mental illness (n=185, 85)	62 32.1%	26 28.9%
Baseline: Not attend or other (n=185, 85)	2 1%	0 0%
Baseline: Enrolled or vacation (n=185, 85)	20 10.4%	19 21.1%
Baseline: Not enrolled or mental illness	36 18.7%	12 13.3%
Baseline: Not enrolled or other (n=185, 85)	25 13%	13 14.4%
Week 2: Enrolled or attend (n=179, 84)	38 19.7%	20 22.2%
Week 2: Not attend or mental illness (n=179, 84)	59 30.6%	24 26.7%
Week 2: Not attend or other (n=179, 84)	3 1.6%	2 2.2%
Week 2: Enrolled or vacation (n=179, 84)	20 10.4%	11 12.2%
Week 2: Not enrolled or mental illness (n=179, 84)	36 18.7%	15 16.7%
Week 2: Not enrolled or other (n=179, 84)	23 11.9%	12 13.3%
Week 6: Enrolled or attend (n=134, 51)	38 19.7%	18 20%
Week 6: Not attend or mental illness (n=134, 51)	36 18.7%	7 7.8%
Week 6: Not attend or other (n=134, 51)	3 1.6%	0 0%
Week 6: Enrolled or vacation (n=134, 51)	14 7.3%	5 5.6%
Week 6: Not enrolled or mental illness (n=134, 51)	23 11.9%	11 12.2%
Week 6: Not enrolled or other (n=134, 51)	20 10.4%	10 11.1%
ET: Enrolled or attend (n=32, 25)	5 2.6%	3 3.3%
ET: Not attend or mental illness (n=32, 25)	8 4.1%	14 15.6%
ET: Not attend or other (n=32, 25)	0 0%	0 0%
ET: Enrolled or vacation (n=32, 25)	5 2.6%	4 4.4%
ET: Not enrolled or mental illness (n=32, 25)	10 5.2%	3 3.3%
ET: Not enrolled or other (n=32, 25)	4 2.1%	1 1.1%
Week 6 [LOCF]: Enrolled or attend (n=183, 86)	47 24.4%	23 25.6%
Week 6 [LOCF]: Not attend or mental illness	50 25.9%	86 95.6%
Week 6 [LOCF]: Not attend or other (n=183, 86)	3 1.6%	1 1.1%
Week 6 [LOCF]: Enrolled or vacation (n=183, 86)	21 10.9%	10 11.1%
Week 6 [LOCF]: Not enrolled or mental illness	36 18.7%	17 18.9%
Week 6 [LOCF]: Not enrolled or other (n=183, 86)	26 13.5%	12 13.3%

18. Secondary Outcome

Title	Number of Subjects Per Response on the School Placement Questionnaire: School Attendance
Description	School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.
Time Frame	Baseline, Week 2, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects analyzable for School Placement Questionnaire; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	189	87
Baseline: No absences (n=88, 42)	20 10.4%	7 7.8%
Baseline: Only a few absences (n=88, 42)	16 8.3%	15 16.7%
Baseline: Frequent absences (n=88, 42)	13 6.7%	2 2.2%
Baseline: Did not attend (n=88, 42)	26 13.5%	7 7.8%
Baseline: Not applicable or vacation (n=88, 42)	13 6.7%	11 12.2%
Week 2: No absences (n=82, 36)	19 9.8%	8 8.9%
Week 2: Only a few absences (n=82, 36)	14 7.3%	9 10%
Week 2: Frequent absences (n=82, 36)	11 5.7%	4 4.4%
Week 2: Did not attend (n=82, 36)	25 13%	8 8.9%
Week 2: Not applicable or vacation (n=82, 36)	13 6.7%	7 7.8%
Week 6: No absences (n=67, 24)	16 8.3%	8 8.9%
Week 6: Only a few absences (n=67, 24)	22 11.4%	12 13.3%
Week 6: Frequent absences (n=67, 24)	5 2.6%	0 0%
Week 6: Did not attend (n=67, 24)	13 6.7%	0 0%
Week 6: Not applicable or vacation (n=67, 24)	11 5.7%	4 4.4%
ET: No absences (n=12, 12)	1 0.5%	0 0%
ET: Only a few absences (n=12, 12)	4 2.1%	0 0%
ET: Frequent absences (n=12, 12)	2 1%	5 5.6%
ET: Did not attend (n=12, 12)	4 2.1%	4 4.4%
ET: Not applicable or vacation (n=12, 12)	1 0.5%	3 3.3%
Week 6 [LOCF]: No absences (n=89, 37)	18 9.3%	8 8.9%
Week 6 [LOCF]: Only a few absences (n=89, 37)	26 13.5%	13 14.4%
Week 6 [LOCF]: Frequent absences (n=89, 37)	11 5.7%	4 4.4%
Week 6 [LOCF]: Did not attend (n=89, 37)	21 10.9%	4 4.4%
Week 6[LOCF]: Not applicable or vacation(n=89,37)	13 6.7%	8 8.9%

19. Secondary Outcome

Title	Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance
Description	School placement questionnaire: parent or legal guardian assessed questionnaire to determine whether the child is currently enrolled in school (or planned to be enrolled if on school holiday like summer break), whether attending regularly if enrolled, and how well the child is doing overall in school. Questions were modified from those used in the National Institute of Mental Health (NIMH) funded Treatment of Early Onset Schizophrenia Spectrum (TEOSS) study. Results determine whether subjects are currently attending school and qualitatively describe how well they are doing in school.
Time Frame	Baseline, Week 2, Week 6, ET

Outcome Measure Data

Analysis Population Description

ITT; N=number of subjects analyzable for School Placement Questionnaire; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.

Arm/Group Title	Ziprasidone	Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.	Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Measure Participants	189	87
Baseline: Excellent (n=64, 29)	4 2.1%	2 2.2%
Baseline: Good (n=64, 29)	10 5.2%	6 6.7%
Baseline: Fair (n=64, 29)	25 13%	14 15.6%
Baseline: Poor (n=64, 29)	19 9.8%	3 3.3%
Baseline: Very poor (n=64, 29)	6 3.1%	4 4.4%
Week 2: Excellent (n=60, 26)	5 2.6%	1 1.1%
Week 2: Good (n=60, 26)	12 6.2%	8 8.9%
Week 2: Fair (n=60, 26)	20 10.4%	10 11.1%
Week 2: Poor (n=60, 26)	17 8.8%	5 5.6%
Week 2: Very poor (n=60, 26)	6 3.1%	2 2.2%
Week 6: Excellent (n=52, 21)	4 2.1%	1 1.1%
Week 6: Good (n=52, 21)	16 8.3%	8 8.9%
Week 6: Fair (n=52, 21)	17 8.8%	11 12.2%
Week 6: Poor (n=52, 21)	12 6.2%	1 1.1%
Week 6: Very poor (n=52, 21)	3 1.6%	0 0%
ET: Excellent (n=8, 7)	0 0%	0 0%
ET: Good (n=8, 7)	0 0%	1 1.1%
ET: Fair (n=8, 7)	5 2.6%	3 3.3%
ET: Poor (n=8, 7)	2 1%	1 1.1%
ET: Very poor (n=8, 7)	1 0.5%	2 2.2%
Week 6 [LOCF]: Excellent (n=68, 28)	4 2.1%	1 1.1%
Week 6 [LOCF]: Good (n=68, 28)	18 9.3%	9 10%
Week 6 [LOCF]: Fair (n=68, 28)	24 12.4%	14 15.6%
Week 6 [LOCF]: Poor (n=68, 28)	16 8.3%	2 2.2%
Week 6 [LOCF]: Very poor (n=68, 28)	6 3.1%	2 2.2%

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		Placebo
Arm/Group Description	Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.		Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
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	9/193 (4.7%)		1/90 (1.1%)
Injury, poisoning and procedural complications
Overdose	1/193 (0.5%)		0/90 (0%)
Skin laceration	1/193 (0.5%)		0/90 (0%)
Psychiatric disorders
Aggression	0/193 (0%)		1/90 (1.1%)
Anxiety	1/193 (0.5%)		0/90 (0%)
Depression	1/193 (0.5%)		0/90 (0%)
Hallucination, auditory	1/193 (0.5%)		0/90 (0%)
Hostility	1/193 (0.5%)		0/90 (0%)
Impulsive behaviour	1/193 (0.5%)		0/90 (0%)
Psychotic disorder	0/193 (0%)		1/90 (1.1%)
Schizophrenia	2/193 (1%)		0/90 (0%)
Suicidal ideation	2/193 (1%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/193 (57%)		27/90 (30%)
Gastrointestinal disorders
Nausea	19/193 (9.8%)		2/90 (2.2%)
Vomiting	12/193 (6.2%)		3/90 (3.3%)
General disorders
Fatigue	17/193 (8.8%)		4/90 (4.4%)
Injury, poisoning and procedural complications
Overdose	11/193 (5.7%)		4/90 (4.4%)
Nervous system disorders
Akathisia	13/193 (6.7%)		3/90 (3.3%)
Dizziness	18/193 (9.3%)		1/90 (1.1%)
Extrapyramidal disorder	22/193 (11.4%)		1/90 (1.1%)
Headache	15/193 (7.8%)		2/90 (2.2%)
Somnolence	38/193 (19.7%)		6/90 (6.7%)
Tremor	15/193 (7.8%)		1/90 (1.1%)
Psychiatric disorders
Insomnia	18/193 (9.3%)		13/90 (14.4%)

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.