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    Clinical Trial Results:
    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.

    Summary
    EudraCT number
    		 2005-005501-28
    Trial protocol
    		 SE   DE  
    Global end of trial date
    26 Mar 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Apr 2016
    First version publication date
    16 Jul 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    A1281134
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00257192
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Sep 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Mar 2009
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1. To establish efficacy of oral ziprasidone compared to placebo in the treatment of adolescent subjects with schizophrenia, as measured by the change from baseline to Week 6 in Brief Psychiatric Rating Scale - Anchored (BPRS-A) total score. 2. To evaluate the safety and tolerability of oral ziprasidone over 6 weeks in the treatment of adolescent subjects with schizophrenia.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Apr 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Colombia: 8
    Country: Number of subjects enrolled
    Costa Rica: 5
    Country: Number of subjects enrolled
    India: 38
    Country: Number of subjects enrolled
    Malaysia: 14
    Country: Number of subjects enrolled
    Peru: 9
    Country: Number of subjects enrolled
    Russian Federation: 81
    Country: Number of subjects enrolled
    Singapore: 3
    Country: Number of subjects enrolled
    Ukraine: 56
    Country: Number of subjects enrolled
    United States: 69
    Worldwide total number of subjects
    283
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    283
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Data Safety Monitoring Board (DSMB) recommended to terminate study due to futility per interim analysis charter (p-value=0.9840). Only 1 active subject was affected by this decision. A total of 284 subjects randomized to study. Of these,193 took ziprasidone and 90 took placebo,while 1 subject assigned to placebo did not receive treatment.

    Pre-assignment
    Screening details
    		 Screening visit followed by a 1 to 10 day period to allow for wash-out of exclusionary medications.

    Period 1
    Period 1 title
    Overall study period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Carer, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ziprasidone
    Arm description
    		 Ziprasidone capsules administered twice daily (BID) with meals.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ziprasidone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Oral (PO) capsules administered twice daily (BID); titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increase of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight greater than or equal to (>=) 45 kilograms (kg); target dose for subjects with body weight less than (<) 45 kg is 60 to 80 mg/day. After titration dose was 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.

    Arm title
    		 Placebo
    Arm description
    		 Placebo capsules matched to ziprasidone twice daily (BID) with meals.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching ziprasidone administration; 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.

    Number of subjects in period 1
    		Ziprasidone Placebo
    Started
    193
    90
    Completed
    135
    52
    Not completed
    58
    38
         Consent withdrawn by subject
    14
    2
         Adverse Event
    21
    10
         Miscellaneous
    -
    4
         Study terminated by sponsor
    1
    -
         Laboratory abnormality
    1
    1
         Lost to follow-up
    3
    3
         Insufficient clinical response
    18
    18

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ziprasidone
    Reporting group description
    		 Ziprasidone capsules administered twice daily (BID) with meals.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo capsules matched to ziprasidone twice daily (BID) with meals.

    Reporting group values
    		 Ziprasidone Placebo Total
    Number of subjects
    		 193 90 283
    Age categorical
    Units: Subjects
        >12 years and <13 years at start of treatment
    		 4 0 4
        Between 13 and 17 years
    		 189 90 279
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 15.3 ( 1.4 ) 15.4 ( 1.4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 84 28 112
        Male
    		 109 62 171
    Ethnicity
    Units: Subjects
        Hispanic / Latino
    		 21 9 30
        Not Hispanic / Latino
    		 172 81 253
    Race
    Units: Subjects
        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)
    At baseline, subjects self-administer a gender appropriate Tanner Adolescent Pubertal Staging Questionnaire to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; males pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size).
    Units: Subjects
        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)
    At baseline, subjects self-administer a gender appropriate Tanner Adolescent Pubertal Staging Questionnaire to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; males pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size).
    Units: Subjects
        Stage 1
    		 0 1 1
        Stage 2
    		 9 3 12
        Stage 3
    		 25 16 41
        Stage 4
    		 57 26 83
        Stage 5
    		 18 16 34
        Not applicable
    		 82 28 110
        Missing (not answered)
    		 2 0 2
    Tanner adolescent pubertal self-assessment: Pubic hair (females and males)
    At baseline, subjects self-administer a gender appropriate Tanner Adolescent Pubertal Staging Questionnaire to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size; males pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size).
    Units: Subjects
        Stage 1
    		 0 3 3
        Stage 2
    		 13 7 20
        Stage 3
    		 36 13 49
        Stage 4
    		 90 43 133
        Stage 5
    		 52 24 76
        Missing (not answered)
    		 2 0 2
    Height
    Units: centimeters (cm)
        arithmetic mean (standard deviation)
    		 164.9 ( 10.1 ) 167.8 ( 10 ) -
    Weight
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    		 61.2 ( 15.5 ) 64.3 ( 15.7 ) -

    End points

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    End points reporting groups
    Reporting group title
    Ziprasidone
    Reporting group description
    		 Ziprasidone capsules administered twice daily (BID) with meals.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo capsules matched to ziprasidone twice daily (BID) with meals.

    Primary: Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6

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    End point title
    		 Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6
    End point 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. 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.
    End point type
    Primary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    189 [1]
    87 [2]
    Units: scores on a scale
        least squares mean (standard error)
    -14.16 ( 0.78 )
    -12.35 ( 1.05 )
    Notes
    [1] - N= number of subjects with analyzable data at post-baseline observation.
    [2] - N=number of subjects with analyzable data at post-baseline observation.
    Statistical analysis title
    		 Analysis of Change in BPRS-A at Week 6
    Statistical analysis description
    Sample size for 85 percent (%) 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% 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.
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.153 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.28
         upper limit
    		 0.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.26
    Notes
    [3] - P-value for final analysis is to be adjusted due to planned interim analysis (0.0462).
    [4] - 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.

    Secondary: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6

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    End point title
    		 Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6
    End point 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. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    190 [5]
    87 [6]
    Units: scores on a scale
        least squares mean (standard error)
    -1.05 ( 0.08 )
    -0.84 ( 0.12 )
    Notes
    [5] - N=number of subjects with analyzable data at post-baseline observation.
    [6] - N=number of subjects with analyzable data at post-baseline observation.
    Statistical analysis title
    		 Analysis of Change in CGI-S Score at Week 6
    Statistical analysis description
    Difference from placebo. Hochberg procedure was applied to p-value to preserve type I error in the analysis of key secondary endpoints (Positive and Negative Syndrome Scale (PANSS) total score and CGI-S).
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    277
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1289 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [7] - 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.

    Secondary: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6

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    End point title
    		 Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6
    End point 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. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    183 [8]
    86 [9]
    Units: scores on a scale
        least squares mean (standard error)
    -23.58 ( 1.42 )
    -21.01 ( 1.73 )
    Notes
    [8] - N=number of subjects with analyzable data at post-baseline observation.
    [9] - N=number of subjects with analyzable data at post-baseline observation.
    Statistical analysis title
    		 Analysis of Change in PANSS Total Score at Week 6
    Statistical analysis description
    Total score: difference from placebo. 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).
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1987 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -2.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.5
         upper limit
    		 1.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    2
    Notes
    [10] - 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.

    Secondary: Change From Baseline in PANSS: Positive and Negative Subscales at Week 6

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    End point title
    		 Change From Baseline in PANSS: Positive and Negative Subscales at Week 6
    End point 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. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    183 [11]
    86 [12]
    Units: scores on a scale
    least squares mean (standard error)
        Positive score
    -7.22 ( 0.44 )
    -5.88 ( 0.56 )
        Negative score
    -5.51 ( 0.43 )
    -5.09 ( 0.51 )
    Notes
    [11] - N=number of subjects with analyzable data at post-baseline observation.
    [12] - N=number of subjects with analyzable data at post-baseline observation.
    Statistical analysis title
    		 Change in Positive Subscale
    Statistical analysis description
    Positive Score: Difference From Placebo.
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0412 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -1.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.61
         upper limit
    		 -0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.65
    Notes
    [13] - 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.
    Statistical analysis title
    		 Change in Negative Subscales
    Statistical analysis description
    Negative Score: Difference From Placebo.
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4661 [14]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.57
         upper limit
    		 0.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [14] - 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.

    Secondary: Clinical Global Impression of Improvement (CGI-I) Score at Week 6

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    End point title
    		 Clinical Global Impression of Improvement (CGI-I) Score at Week 6
    End point 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. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    190 [15]
    87 [16]
    Units: scores on a scale
        least squares mean (standard error)
    2.66 ( 0.09 )
    2.85 ( 0.12 )
    Notes
    [15] - N=number of subjects with analyzable data at post-baseline observation.
    [16] - N=number of subjects with analyzable data at post-baseline observation.
    Statistical analysis title
    		 Analysis of CGI-I Score at Week 6
    Statistical analysis description
    Difference from placebo.
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    277
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.182 [17]
    Method
    		 ANOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 0.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [17] - Mixed effects MMRM with subject as random effect, treatment, region, visit and visit-by-treatment interaction as fixed effects.

    Secondary: Change From Baseline in Children's Global Assessment Scale (CGAS)

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    End point title
    		 Change From Baseline in Children's Global Assessment Scale (CGAS)
    End point 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. ITT population. Here, (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. ET (Early Termination) includes observations from visits not within windowing criteria. Last observation carried forward [LOCF] imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 4, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    193
    90
    Units: scores on a scale
    arithmetic mean (standard deviation)
        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 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Child Health Questionnaire (CHQ)

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    End point title
    		 Change From Baseline in Child Health Questionnaire (CHQ)
    End point 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. ITT. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    193
    90
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Global health: Week 6
    5 ( 18.2 )
    8.5 ( 24.7 )
        Global health: ET
    -5.4 ( 24 )
    -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 )
        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 ( 28 )
        Physical health: ET
    -6.5 ( 32.9 )
    3.2 ( 23.3 )
        Physical health: Week 6 [LOCF]
    1.4 ( 33.8 )
    4.8 ( 26 )
        Bodily pain: Week 6
    4.4 ( 21.6 )
    8 ( 19.4 )
        Bodily pain: ET
    4.7 ( 23 )
    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 ( 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 ( 25.8 )
    1.8 ( 21.7 )
        Time impact on parent: Week 6 [LOCF]
    7.4 ( 25.5 )
    8 ( 23.1 )
        Emotional impact on parent: Week 6
    8.9 ( 21.6 )
    10 ( 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 )
        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 ( 17.1 )
    9 ( 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 ( 17.5 )
    9 ( 22.9 )
        Self-esteem: ET
    1 ( 20.6 )
    1.3 ( 14 )
        Self-esteem: Week 6 [LOCF]
    5 ( 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 )
        Change in health: Week 6
    0.5 ( 1.1 )
    0.6 ( 1 )
        Change in health: ET
    -0.4 ( 1 )
    -0.1 ( 0.8 )
        Change in health: Week 6 [LOCF]
    0.3 ( 1.1 )
    0.3 ( 1 )
        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 )
        Psychosocial health global subscale: ET
    3.1 ( 10.4 )
    0 ( 5.7 )
        Psychosocial health global subscale: Week 6 [LOCF]
    5.9 ( 9.8 )
    4.8 ( 10 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score

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    End point title
    		 Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score
    End point 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. ITT; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    173 [18]
    74 [19]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=165, 69)
    -2.4 ( 7.1 )
    -1.3 ( 5.8 )
        Week 2 (n=161, 71)
    -2.5 ( 8 )
    -1 ( 6.2 )
        Week 3 (n=146, 64)
    -3 ( 6.7 )
    -0.7 ( 5.7 )
        Week 4 (n=138, 51)
    -2.7 ( 7.4 )
    -1 ( 6.5 )
        Week 5 (n=126, 44)
    -3.1 ( 7 )
    -0.8 ( 8.3 )
        Week 6 (n=119, 42)
    -3 ( 7.4 )
    -1.9 ( 6.7 )
        Week 6 [LOCF] (n=167, 71)
    -2.3 ( 8.2 )
    -0.3 ( 8.8 )
    Notes
    [18] - N=number of subjects with analyzable data at baseline.
    [19] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score

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    End point title
    		 Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score
    End point 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. ITT; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    180 [20]
    84 [21]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        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 ( 7.6 )
    -4.9 ( 6.6 )
        Week 5 (n=135, 49)
    -7 ( 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 ( 7.3 )
    Notes
    [20] - N=number of subjects with analyzable data at baseline
    [21] - N=number of subjects with analyzable data at baseline
    No statistical analyses for this end point

    Secondary: Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13

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    End point title
    		 Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13
    End point 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). ITT; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    192 [22]
    90 [23]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=188, 86)
    -0.1 ( 0.4 )
    0 ( 0.5 )
        Week 2 (n=182, 86)
    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 ( 0.5 )
    -0.1 ( 0.5 )
        Week 5 (n=141, 54)
    0 ( 0.4 )
    -0.1 ( 0.5 )
        Week 6 (n=134, 52)
    0 ( 0.3 )
    -0.1 ( 0.4 )
        Week 6 [LOCF] (n=189, 87)
    0 ( 0.6 )
    0 ( 0.5 )
    Notes
    [22] - N=number of subjects with analyzable data at baseline.
    [23] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1

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    End point title
    		 Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1
    End point 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). ITT; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    40 [24]
    15 [25]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        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 )
    -0.1 ( 1.1 )
    Notes
    [24] - N=number of subjects with analyzable data at baseline.
    [25] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Central Nervous System (CNS) Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales

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    End point title
    		 Change From Baseline in Central Nervous System (CNS) Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales
    End point 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). 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. LOCF imputation used for Week 6 LOCF timepoint (last post-baseline non-missing visit).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    174 [26]
    83 [27]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Sedation: Week 6 (n=124, 47)
    0 ( 1.7 )
    -0.4 ( 1.8 )
        Sedation: ET (n=23, 26)
    0 ( 2.3 )
    0.2 ( 1.3 )
        Sedation: Week 6 [LOCF] (n=147, 72)
    0 ( 1.8 )
    -0.2 ( 1.7 )
        Verbal Memory: Week 6 (n=124, 47)
    1.3 ( 12.1 )
    0.5 ( 14 )
        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 ( 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 ( 12 )
        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 )
    -0.7 ( 14.6 )
        Reasoning: ET (n=23, 25)
    1.3 ( 15.8 )
    3.3 ( 14 )
        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 )
        Working Memory: Week 6 [LOCF] (n=143, 68)
    2 ( 12.9 )
    1.3 ( 12.2 )
        Sustained Attention: Week 6 (n=120, 45)
    2 ( 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 )
    Notes
    [26] - N=number of subjects with analyzable data at baseline.
    [27] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index

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    End point title
    		 Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index
    End point 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). 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. LOCF imputation used for Week 6 LOCF timepoint (last post-baseline non-missing visit).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    168 [28]
    79 [29]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        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 ( 7.4 )
    1.1 ( 7.4 )
    Notes
    [28] - N=number of subjects with analyzable data at baseline.
    [29] - N=number of subjects with analyzable data at baseline.
    Statistical analysis title
    		 Change in Neurocognitive Index Score at Week 6
    Statistical analysis description
    Difference from placebo. Observed cases at Week 6.
    Comparison groups
    Ziprasidone v Placebo
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2613 [30]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.01
         upper limit
    		 3.69
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.19
    Notes
    [30] - SAS PROC MIXED to fit a mixed model analysis of covariance with treatment and region as fixed effects and baseline score as covariate.

    Secondary: Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS)

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    End point title
    		 Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS)
    End point 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. ITT; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    189 [31]
    87 [32]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=189, 85)
    0.5 ( 2.8 )
    0.1 ( 0.9 )
        Week 2 (n=182, 85)
    0.5 ( 2.4 )
    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 ( 0.6 )
        Week 5 (n=141, 54)
    0.2 ( 2.4 )
    0 ( 1 )
        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 )
    Notes
    [31] - N=number of subjects with analyzable data at baseline.
    [32] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item

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    End point title
    		 Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item
    End point 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. ITT; (n)= number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    190 [33]
    88 [34]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=190, 86)
    0.1 ( 0.6 )
    0.1 ( 0.4 )
        Week 2 (n=183, 86)
    0.1 ( 0.7 )
    0 ( 0.3 )
        Week 3 (n=166, 74)
    0.1 ( 0.6 )
    0 ( 0.3 )
        Week 4 (n=155, 63)
    0.1 ( 0.6 )
    0 ( 0.2 )
        Week 5 (n=142, 54)
    0.1 ( 0.5 )
    0 ( 0.2 )
        Week 6 (n=135, 52)
    0 ( 0.5 )
    0 ( 0.2 )
        Week 6 [LOCF] (n=190, 87)
    0 ( 0.6 )
    0 ( 0.2 )
    Notes
    [33] - N=number of subjects with analyzable data at baseline.
    [34] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score

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    End point title
    		 Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score
    End point 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. ITT; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1 through Week 6
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    190 [35]
    88 [36]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=190, 86)
    0.2 ( 1.6 )
    0 ( 0.4 )
        Week 2 (n=183, 86)
    0.1 ( 1.6 )
    0 ( 0.6 )
        Week 3 (n=166, 74)
    0.1 ( 1.3 )
    0.1 ( 1 )
        Week 4 (n=155, 63)
    0.1 ( 0.8 )
    0 ( 0.8 )
        Week 5 (n=142, 54)
    -0.1 ( 0.7 )
    0 ( 0.4 )
        Week 6 (n=135, 52)
    0 ( 0.6 )
    0 ( 0.5 )
        Week 6 [LOCF] (n=190, 87)
    0 ( 0.8 )
    0 ( 0.7 )
    Notes
    [35] - N=number of subjects with analyzable data at baseline.
    [36] - N=number of subjects with analyzable data at baseline.
    No statistical analyses for this end point

    Secondary: Number of Subjects Per Response on the School Placement Questionnaire: School Situation

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    End point title
    		 Number of Subjects Per Response on the School Placement Questionnaire: School Situation
    End point 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. ITT; (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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    189 [37]
    87 [38]
    Units: subjects
        Baseline: Enrolled or attend (n=185, 85)
    40
    15
        Baseline: Not attend or mental illness (n=185, 85)
    62
    26
        Baseline: Not attend or other (n=185, 85)
    2
    0
        Baseline: Enrolled or vacation (n=185, 85)
    20
    19
        Baseline: Not enrolled/mental illness
    36
    12
        Baseline: Not enrolled or other (n=185, 85)
    25
    13
        Week 2: Enrolled or attend (n=179, 84)
    38
    20
        Week 2: Not attend or mental illness (n=179, 84)
    59
    24
        Week 2: Not attend or other (n=179, 84)
    3
    2
        Week 2: Enrolled or vacation (n=179, 84)
    20
    11
        Week 2: Not enrolled or mental illness (n=179, 84)
    36
    15
        Week 2: Not enrolled or other (n=179, 84)
    23
    12
        Week 6: Enrolled or attend (n=134, 51)
    38
    18
        Week 6: Not attend or mental illness (n=134, 51)
    36
    7
        Week 6: Not attend or other (n=134, 51)
    3
    0
        Week 6: Enrolled or vacation (n=134, 51)
    14
    5
        Week 6: Not enrolled or mental illness (n=134, 51)
    23
    11
        Week 6: Not enrolled or other (n=134, 51)
    20
    10
        ET: Enrolled or attend (n=32, 25)
    5
    3
        ET: Not attend or mental illness (n=32, 25)
    8
    14
        ET: Not attend or other (n=32, 25)
    0
    0
        ET: Enrolled or vacation (n=32, 25)
    5
    4
        ET: Not enrolled or mental illness (n=32, 25)
    10
    3
        ET: Not enrolled or other (n=32, 25)
    4
    1
        Week 6 [LOCF]: Enrolled or attend (n=183, 86)
    47
    23
        Week 6 [LOCF]: Not attend/mental illness
    50
    23
        Week 6 [LOCF]: Not attend or other (n=183, 86)
    3
    1
        Week 6 [LOCF]: Enrolled or vacation (n=183, 86)
    21
    10
        Week 6 [LOCF]: Not enrolled or mental illness
    36
    17
        Week 6 [LOCF]: Not enrolled or other (n=183, 86)
    26
    12
    Notes
    [37] - N=number of subjects analyzable for School Placement Questionnaire.
    [38] - N=number of subjects analyzable for School Placement Questionnaire.
    No statistical analyses for this end point

    Secondary: Number of Subjects Per Response on the School Placement Questionnaire: School Attendance

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    End point title
    		 Number of Subjects Per Response on the School Placement Questionnaire: School Attendance
    End point 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. ITT; (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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    189 [39]
    87 [40]
    Units: subjects
        Baseline: No absences (n=88, 42)
    20
    7
        Baseline: Only a few absences (n=88, 42)
    16
    15
        Baseline: Frequent absences (n=88, 42)
    13
    2
        Baseline: Did not attend (n=88, 42)
    26
    7
        Baseline: Not applicable or vacation (n=88, 42)
    13
    11
        Week 2: No absences (n=82, 36)
    19
    8
        Week 2: Only a few absences (n=82, 36)
    14
    9
        Week 2: Frequent absences (n=82, 36)
    11
    4
        Week 2: Did not attend (n=82, 36)
    25
    8
        Week 2: Not applicable or vacation (n=82, 36)
    13
    7
        Week 6: No absences (n=67, 24)
    16
    8
        Week 6: Only a few absences (n=67, 24)
    22
    12
        Week 6: Frequent absences (n=67, 24)
    5
    0
        Week 6: Did not attend (n=67, 24)
    13
    0
        Week 6: Not applicable or vacation (n=67, 24)
    11
    4
        ET: No absences (n=12, 12)
    1
    0
        ET: Only a few absences (n=12, 12)
    4
    0
        ET: Frequent absences (n=12, 12)
    2
    5
        ET: Did not attend (n=12, 12)
    4
    4
        ET: Not applicable or vacation (n=12, 12)
    1
    3
        Week 6 [LOCF]: No absences (n=89, 37)
    18
    8
        Week 6 [LOCF]: Only a few absences (n=89, 37)
    26
    13
        Week 6 [LOCF]: Frequent absences (n=89, 37)
    11
    4
        Week 6 [LOCF]: Did not attend (n=89, 37)
    21
    4
        Week 6[LOCF]: Not applicable or vacation(n=89,37)
    13
    8
    Notes
    [39] - N=number of subjects analyzable for School Placement Questionnaire.
    [40] - N=number of subjects analyzable for School Placement Questionnaire.
    No statistical analyses for this end point

    Secondary: Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance

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    End point title
    		 Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance
    End point 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. ITT; (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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 6, ET
    End point values
    		 Ziprasidone Placebo
    Number of subjects analysed
    189 [41]
    87 [42]
    Units: subjects
        Baseline: Excellent (n=64, 29)
    4
    2
        Baseline: Good (n=64, 29)
    10
    6
        Baseline: Fair (n=64, 29)
    25
    14
        Baseline: Poor (n=64, 29)
    19
    3
        Baseline: Very poor (n=64, 29)
    6
    4
        Week 2: Excellent (n=60, 26)
    5
    1
        Week 2: Good (n=60, 26)
    12
    8
        Week 2: Fair (n=60, 26)
    20
    10
        Week 2: Poor (n=60, 26)
    17
    5
        Week 2: Very poor (n=60, 26)
    6
    2
        Week 6: Excellent (n=52, 21)
    4
    1
        Week 6: Good (n=52, 21)
    16
    8
        Week 6: Fair (n=52, 21)
    17
    11
        Week 6: Poor (n=52, 21)
    12
    1
        Week 6: Very poor (n=52, 21)
    3
    0
        ET: Excellent (n=8, 7)
    0
    0
        ET: Good (n=8, 7)
    0
    1
        ET: Fair (n=8, 7)
    5
    3
        ET: Poor (n=8, 7)
    2
    1
        ET: Very poor (n=8, 7)
    1
    2
        Week 6 [LOCF]: Excellent (n=68, 28)
    4
    1
        Week 6 [LOCF]: Good (n=68, 28)
    18
    9
        Week 6 [LOCF]: Fair (n=68, 28)
    24
    14
        Week 6 [LOCF]: Poor (n=68, 28)
    16
    2
        Week 6 [LOCF]: Very poor (n=68, 28)
    6
    2
    Notes
    [41] - N=number of subjects analyzable for School Placement Questionnaire.
    [42] - N=number of subjects analyzable for School Placement Questionnaire.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    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 additional 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.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Ziprasidone
    Reporting group description
    		 Ziprasidone capsules administered twice daily (BID) with meals.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo matching ziprasidone administration.

    Serious adverse events
    		 Ziprasidone Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 193 (4.66%)
    1 / 90 (1.11%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Laceration
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 193 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination, auditory
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hostility
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impulsive behaviour
         subjects affected / exposed
    1 / 193 (0.52%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 193 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    2 / 193 (1.04%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    2 / 193 (1.04%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ziprasidone Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    110 / 193 (56.99%)
    27 / 90 (30.00%)
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    11 / 193 (5.70%)
    4 / 90 (4.44%)
         occurrences all number
    11
    4
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    13 / 193 (6.74%)
    3 / 90 (3.33%)
         occurrences all number
    15
    3
    Dizziness
         subjects affected / exposed
    18 / 193 (9.33%)
    1 / 90 (1.11%)
         occurrences all number
    18
    1
    Extrapyramidal disorder
         subjects affected / exposed
    22 / 193 (11.40%)
    1 / 90 (1.11%)
         occurrences all number
    23
    1
    Headache
         subjects affected / exposed
    15 / 193 (7.77%)
    2 / 90 (2.22%)
         occurrences all number
    23
    2
    Somnolence
         subjects affected / exposed
    38 / 193 (19.69%)
    6 / 90 (6.67%)
         occurrences all number
    50
    6
    Tremor
         subjects affected / exposed
    15 / 193 (7.77%)
    1 / 90 (1.11%)
         occurrences all number
    19
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    17 / 193 (8.81%)
    4 / 90 (4.44%)
         occurrences all number
    19
    4
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    19 / 193 (9.84%)
    2 / 90 (2.22%)
         occurrences all number
    19
    2
    Vomiting
         subjects affected / exposed
    12 / 193 (6.22%)
    3 / 90 (3.33%)
         occurrences all number
    13
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    18 / 193 (9.33%)
    13 / 90 (14.44%)
         occurrences all number
    30
    19

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Dec 2006
    1. A physical exam including body temperature was completed at week 6 or end of treatment. 2. Extensive electrocardiogram (ECG) monitoring was performed throughout the study, including triplicate ECGs at baseline and excluding Week 4. 3. Subjects who could not tolerate a dose of 120 mg/day were allowed to have a dose reduction and to continue study treatment at 100 mg/day or as low as 80 mg/day. Subjects weighing <45 kilograms (kg) were to be allowed a minimum dose of 40 mg/day. Subjects who could not tolerate the dose range of 80 to 160 mg/day for children above 45 kg or 40-80 mg/day for children <45 kg, discontinue and might be eligible to enter the extension trial. 4. ECGs showing a Fridericia corrected QT (QTcF) of >=460 milliseconds (msec) or a suspected increase from baseline of 60 msec or greater was to be repeated within the same visit. If the QTcF value persisted at >=460 msec and/or the change from baseline persisted at >=60 msec, the study drug was to be discontinued immediately and a pediatric cardiologist or a pediatric intensive care specialist should be contacted to discuss the ECG result. 5. Exposure In Utero definition was amended to include paternal exposure. 6. It was recommended that subjects should complete the CNS Vital Signs battery before any intrusive assessments such as blood draws, if at all possible. 7. Possibly Suicide-Related Adverse Events (PSRAEs) were included in adverse event reporting.
    09 Nov 2007
    1. Subjects who could not tolerate a dose of 120 mg/day were allowed to have a reduction and to continue study treatment at 100 mg/day or as low as 80 mg/day. Subjects weighing <45 kg were to be allowed a minimum dose of 40 mg/day. Subjects who could not tolerate the dose range of 80 to 160 mg/day for children above 45 kg or 40-80 mg/day for children <45 kg, should discontinue and might be eligible to enter the extension trial. This statement was added in section summary, Trial Design, Trial Treatments. 2. Concominant medication section amended to include lorazepam(up to 2 mg/day) or (if lorazepam is not available in the country diazepam up to 5 mg/day) for anxiety or agitation. 3. Protocol amended to provide subject status information on supplemental analysis addressing “pre-pause” and "post-pause” study enrollment, general clarifications and consistencies, and redesign of the study drug blister card to decrease the chance for dosing errors (usually overdosing beyond protocol specified dose). Subjects enrolled prior to the pause used the original blister card packaging, while subjects entering after the pause, used the improved blister card packaging. A sensitivity analysis was performed to assess the effect, if any, of this change.
    24 Jan 2008
    1. The scheduling of post-dose sampling paired to ECG measurement was changed from within 10 minutes of ECG to immediately after ECG.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    09 Nov 2007
    During the conduct of the trial, the study was “paused” to improve the blister card packaging. The original card provided for mulitiple dose levels. The replacement card provided a single dose level for each specific card, while still preserving the flexible dosing capability. The blister card design was changed after approximately 1/3 of the subjects had enrolled. The study was interrupted (paused) for approximately 4 months pending re-packaging of the drug.
    26 Feb 2008

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The AE tables were amended to incorporate previously unreported AEs that were found during an independent audit and verified by the investigators.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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