Safety And Tolerability Of Ziprasidone In Adolescents With Schizophrenia

This study has been terminated.
(Please see Detailed Description for termination reason.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00265382
First received: December 12, 2005
Last updated: December 2, 2011
Last verified: December 2011
Results First Received: April 16, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Schizophrenia
Intervention: Drug: Ziprasidone oral capsules

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study enrolled adolescent subjects with schizophrenia, ages 13-17 years, who participated in the double-blind placebo controlled Study A1281134 (NCT00257192) who met qualification criteria and wished to receive treatment with open-label ziprasidone.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 milligrams (mg)/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kilograms (kg). For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg twice a day [BID]). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Participant Flow:   Overall Study
    Ziprasidone  
STARTED     221  
COMPLETED     76  
NOT COMPLETED     145  
Adverse Event                 21  
Laboratory Abnormality                 1  
Lost to Follow-up                 3  
Lack of Efficacy                 6  
Miscellaneous                 6  
Withdrawal by Subject                 13  
Study terminated by sponsor                 94  
Death                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Baseline Measures
    Ziprasidone  
Number of Participants  
[units: participants]
  221  
Age, Customized [1]
[units: Participants]
 
>12 years and <13 years at start of treatment     3  
13 to 17 years     218  
Gender  
[units: Participants]
 
Female     90  
Male     131  
[1] Baseline data are from the preceding Study A1281134 (NCT00257192).



  Outcome Measures
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1.  Primary:   Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: 26 weeks ]

Measure Type Primary
Measure Title Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measure Description All observed or volunteered treatment-emergent AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Time Frame 26 weeks  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set = all subjects who took at least one dose of study medication. In this table, the number of subjects with AEs is based on a 0% AE threshold whereas the number of subjects with AEs reported in the AE section are based on a 5% AE threshold.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)  
[units: participants]
 
AEs     137  
SAEs     16  

No statistical analysis provided for Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)



2.  Secondary:   Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self Assessment   [ Time Frame: Baseline, Week 26, Early Termination (ET) ]

Measure Type Secondary
Measure Title Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self Assessment
Measure Description Tanner Adolescent Pubertal Staging Questionnaire: used 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).
Time Frame Baseline, Week 26, Early Termination (ET)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline. Baseline data from Study A1281134 (NCT00257192) served as the baseline for A1281135.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  73  
Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self Assessment  
[units: participants]
 
Pubic Hair, Week 26 (Stage 1)     1  
Pubic Hair, Week 26 (Stage 2)     1  
Pubic Hair, Week 26 (Stage 3)     11  
Pubic Hair, Week 26 (Stage 4)     39  
Pubic Hair, Week 26 (Stage 5)     21  
Pubic Hair, ET (Stage 1)     0  
Pubic Hair, ET (Stage 2)     10  
Pubic Hair, ET (Stage 3)     22  
Pubic Hair, ET (Stage 4)     59  
Pubic Hair, ET (Stage 5)     30  

No statistical analysis provided for Number of Subjects With Change From Baseline to Each Pubertal Stage of Development as Assessed by the Tanner Adolescent Pubertal Self Assessment



3.  Secondary:   Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score   [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score
Measure 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, Weeks 2, 6, 18, 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). Last Observation Carried Forward (LOCF) imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  208  
Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 2 (n=178)     -0.3  ± 4.8  
Week 6 (n=153)     -0.8  ± 6.1  
Week 18 (n=93)     -0.5  ± 6.5  
Week 26 (n=68)     0.7  ± 7.7  
ET (n=113)     0.5  ± 7.1  
Week 26 LOCF (n=177)     -0.5  ± 7.0  

No statistical analysis provided for Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score



4.  Secondary:   Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score   [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score
Measure 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, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  214  
Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 1 (n=198)     -1.4  ± 4.8  
Week 2 (n=188)     -2.2  ± 6.1  
Week 6 (n=160)     -3.5  ± 6.3  
Week 10 (n=129)     -4.6  ± 7.3  
Week 14 (n=105)     -5.0  ± 7.4  
Week 18 (n=94)     -4.9  ± 8.1  
Week 22 (n=78)     -5.1  ± 7.9  
Week 26 (n=72)     -5.3  ± 7.8  
ET (n=122)     -2.7  ± 7.3  
Week 26 LOCF (n=197)     -4.5  ± 7.0  

No statistical analysis provided for Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score



5.  Secondary:   Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales
Measure Description Computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, sustained attention. Computerized 7- point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. Neurocognitive index score was derived from subtest scores per an algorithm. 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, Weeks 6 and 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  212  
Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales  
[units: scores on a scale]
Mean ± Standard Deviation
 
Sedation: Week 6 (n=149)     0.1  ± 1.7  
Sedation: Week 26 (n=70)     -0.2  ± 1.5  
Sedation: ET (n=102)     -0.1  ± 2.0  
Sedation: Week 26 LOCF (n=153)     -0.2  ± 1.7  
Verbal Memory: Week 6 (n=150)     -1.3  ± 13.7  
Verbal Memory: Week 26 (n=71)     0.6  ± 14.0  
Verbal Memory: ET (n=103)     -0.7  ± 14.6  
Verbal Memory: Week 26 LOCF (n=155)     0.3  ± 14.5  
Visual Memory: Week 6 (n=148)     -3.6  ± 13.7  
Visual Memory: Week 26 (n=71)     -2.1  ± 15.5  
Visual Memory: ET (n=103)     -1.9  ± 12.7  
Visual Memory: Week 26 LOCF (n=154)     -1.5  ± 14.4  
Processing Speed: Week 6 (n=148)     -1.2  ± 11.4  
Processing Speed: Week 26 (n=71)     2.1  ± 10.2  
Processing Speed: ET (n=103)     -1.4  ± 19.0  
Processing Speed: Week 26 LOCF (n=153)     0.5  ± 12.0  
Reasoning: Week 6 (n=145)     -0.3  ± 14.1  
Reasoning: Week 26 (n=71)     3.0  ± 11.3  
Reasoning: ET (n=100)     1.9  ± 14.9  
Reasoning: Week 26 LOCF (n=151)     1.5  ± 14.3  
Executive Functioning: Week 6 (n=145)     2.0  ± 16.7  
Executive Functioning: Week 26 (n=71)     2.0  ± 16.8  
Executive Functioning: ET (n=100)     2.4  ± 15.7  
Executive Functioning: Week 26 LOCF (n=151)     2.4  ± 16.9  
Working Memory: Week 6 (n=145)     -0.5  ± 12.6  
Working Memory: Week 26 (n=68)     0.8  ± 16.4  
Working Memory: ET (n=99)     0.3  ± 12.1  
Working Memory: Week 26 LOCF (n=150)     0.7  ± 14.2  
Sustained Attention: Week 6 (n=145)     0.2  ± 12.0  
Sustained Attention: Week 26 (n=68)     1.9  ± 14.0  
Sustained Attention: ET (n=99)     -0.6  ± 12.2  
Sustained Attention: Week 26 LOCF (n=150)     1.2  ± 12.7  

No statistical analysis provided for Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales



6.  Secondary:   Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index
Measure Description Computerized subject-administered test battery with subtests for verbal and visual memory, processing speed, nonverbal reasoning, executive functioning, working memory, sustained attention. Computerized 7- point sedation item (0 [not sleepy] to 10 [very sleepy]) was completed prior to test battery. Neurocognitive index score was derived from subtest scores per an algorithm. 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, Weeks 6 and 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  208  
Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index  
[units: scores on a scale]
Mean ± Standard Deviation
 
Neurocognitive Index: Week 6 (n=144)     -0.6  ± 7.2  
Neurocognitive Index: Week 26 (n=68)     1.3  ± 7.3  
Neurocognitive Index: ET (n=99)     0.5  ± 6.3  
Neurocognitive Index: Week 26 LOCF (n=150)     0.7  ± 7.7  

No statistical analysis provided for Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index



7.  Secondary:   Change From Baseline in Simpson-Angus Rating Scale (SARS)   [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Simpson-Angus Rating Scale (SARS)
Measure 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, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Change From Baseline in Simpson-Angus Rating Scale (SARS)  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 1 (n=206)     -0.05  ± 1.4  
Week 2 (n=197)     -0.11  ± 1.3  
Week 6 (n=168)     -0.04  ± 1.7  
Week 10 (n=135)     -0.10  ± 1.6  
Week 14 (n=110)     -0.02  ± 1.9  
Week 18 (n=99)     0.02  ± 1.4  
Week 22 (n=82)     -0.04  ± 1.7  
Week 26 (n=76)     -0.32  ± 1.4  
ET (n=127)     -0.31  ± 2.0  
Week 26 LOCF (n=206)     -0.15  ± 1.5  

No statistical analysis provided for Change From Baseline in Simpson-Angus Rating Scale (SARS)



8.  Secondary:   Change From Baseline in Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item   [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item
Measure 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, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Change From Baseline in Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 1 (n=206)     0.0  ± 0.4  
Week 2 (n=197)     0.0  ± 0.4  
Week 6 (n=168)     0.0  ± 0.4  
Week 10 (n=135)     0.0  ± 0.5  
Week 14 (n=110)     0.1  ± 0.6  
Week 18 (n=99)     0.0  ± 0.4  
Week 22 (n=82)     0.0  ± 0.6  
Week 26 (n=76)     0.0  ± 0.6  
ET (n=127)     0.0  ± 0.5  
Week 26 LOCF (n=206)     0.1  ± 0.5  

No statistical analysis provided for Change From Baseline in Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item



9.  Secondary:   Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score   [ Time Frame: Baseline, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score
Measure 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, Weeks 1, 2, 6, 10, 14, 18, 22, 26, ET  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 1 (n=206)     0.06  ± 1.3  
Week 2 (n=197)     -0.05  ± 0.7  
Week 6 (n=168)     -0.04  ± 0.9  
Week 10 (n=135)     0.02  ± 1.4  
Week 14 (n=110)     0.01  ± 0.9  
Week 18 (n=99)     0.01  ± 0.6  
Week 22 (n=82)     0.10  ± 1.2  
Week 26 (n=76)     0.08  ± 1.2  
ET (n=127)     -0.12  ± 1.5  
Week 26 LOCF (n=206)     0.00  ± 1.0  

No statistical analysis provided for Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score



10.  Secondary:   Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score   [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score
Measure 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, excitement. Ratings anchored to improve consistency for 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, Weeks 2, 6, 18, 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  220  
Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 2 (n=196)     -3.8  ± 7.8  
Week 6 (n=167)     -6.1  ± 8.8  
Week 18 (n=98)     -7.8  ± 11.0  
Week 26 (n=75)     -8.5  ± 9.9  
ET (n=127)     -4.0  ± 9.1  
Week 26 LOCF (n=196)     -6.9  ± 8.9  

No statistical analysis provided for Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score



11.  Secondary:   Change From Baseline in Children's Global Assessment Scale (CGAS)   [ Time Frame: Baseline, Weeks 2, 6, 18, 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Children's Global Assessment Scale (CGAS)
Measure 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, Weeks 2, 6, 18, 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Change From Baseline in Children's Global Assessment Scale (CGAS)  
[units: scores on a scale]
Mean ± Standard Deviation
 
Week 2 (n=197)     55.5  ± 12.9  
Week 6 (n=168)     59.2  ± 12.5  
Week 18 (n=99)     62.3  ± 11.4  
Week 26 (n=76)     65.6  ± 12.4  
ET (n=127)     56.6  ± 15.1  
Week 26 LOCF (n=197)     60.5  ± 14.2  

No statistical analysis provided for Change From Baseline in Children's Global Assessment Scale (CGAS)



12.  Secondary:   Change From Baseline in Child Health Questionnaire (CHQ)   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Change From Baseline in Child Health Questionnaire (CHQ)
Measure 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, Weeks 6 and 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects with analyzable data at baseline; n=number of subjects with analyzable data at post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  220  
Change From Baseline in Child Health Questionnaire (CHQ)  
[units: scores on a scale]
Mean ± Standard Deviation
 
Global Health: Week 6 (n=163)     44.2  ± 23.9  
Global Health: Week 26 (n=75)     50.3  ± 22.1  
Global Health: ET (n=124)     40.5  ± 25.8  
Global Health: Week 26 LOCF (n=164)     44.9  ± 22.9  
Global Behavior: Week 6 (n=163)     44.9  ± 23.6  
Global Behavior: Week 26 (n=75)     47.0  ± 24.2  
Global Behavior: ET (n=124)     38.7  ± 25.8  
Global Behavior: Week 26 LOCF (n=164)     43.8  ± 24.4  
Family Cohesion: Week 6 (n=163)     53.0  ± 23.9  
Family Cohesion: Week 26 (n=75)     54.4  ± 24.7  
Family Cohesion: ET (n=124)     50.0  ± 23.9  
Family Cohesion: Week 26 LOCF (n=164)     53.4  ± 23.7  
Physical Health: Week 6 (n=163)     76.4  ± 30.8  
Physical Health: Week 26 (n=74)     80.2  ± 28.8  
Physical Health: ET (n=123)     75.5  ± 32.8  
Physical Health: Week 26 LOCF (n=163)     77.8  ± 31.2  
Bodily Pain: Week 6 (n=163)     80.8  ± 21.6  
Bodily Pain: Week 26 (n=75)     84.4  ± 21.5  
Bodily Pain: ET (n=124)     81.0  ± 22.7  
Bodily Pain: Week 26 LOCF (n=164)     82.5  ± 21.3  
Emotion, Behavior: Week 6 (n=163)     53.3  ± 32.6  
Emotion, Behavior: Week 26 (n=74)     60.1  ± 31.2  
Emotion, Behavior: ET (n=123)     49.5  ± 34.5  
Emotion, Behavior: Week 26 LOCF (n=163)     54.8  ± 32.2  
Time Impact on Parent: Week 6 (n=163)     62.0  ± 26.6  
Time Impact on Parent: Week 26 (n=75)     69.9  ± 23.5  
Time Impact on Parent: ET (n=124)     59.9  ± 28.6  
Time Impact on Parent: Week 26 LOCF (n=164)     65.1  ± 26.3  
Emotional Impact on Parent: Week 6 (n=163)     49.5  ± 24.6  
Emotional Impact on Parent: Week 26 (n=75)     57.2  ± 24.7  
Emotional Impact on Parent: ET (n=124)     43.4  ± 25.9  
Emotional Impact on Parent: Week 26 LOCF (n=164)     52.2  ± 26.0  
Mental Health: Week 6 (n=163)     63.6  ± 16.1  
Mental Health: Week 26 (n=75)     66.7  ± 16.5  
Mental Health: ET (n=124)     60.8  ± 18.3  
Mental Health: Week 26 LOCF (n=164)     65.1  ± 16.1  
Physical Function: Week 6 (n=163)     80.4  ± 22.3  
Physical Function: Week 26 (n=75)     84.9  ± 19.0  
Physical Function: ET (n=124)     79.5  ± 23.4  
Physical Function: Week 26 LOCF (n=164)     81.4  ± 21.9  
Behavior Scale: Week 6 (n=163)     62.7  ± 16.8  
Behavior Scale: Week 26 (n=75)     64.5  ± 20.0  
Behavior Scale: ET (n=124)     60.2  ± 18.7  
Behavior Scale: Week 26 LOCF (n=164)     63.0  ± 18.4  
Self-Esteem: Week 6 (n=163)     52.7  ± 20.3  
Self-Esteem: Week 26 (n=74)     55.3  ± 21.0  
Self-Esteem: ET (n=124)     52.6  ± 21.7  
Self-Esteem: Week 26 LOCF (n=163)     54.5  ± 20.6  
General Health Perception: Week 6 (n=163)     50.3  ± 15.3  
General Health Perception: Week 26 (n=75)     51.8  ± 16.4  
General Health Perception: ET (n=124)     49.7  ± 15.1  
General Health Perception: Week 26 LOCF (n=164)     50.3  ± 15.4  
Family Activities: Week 6 (n=163)     60.1  ± 24.9  
Family Activities: Week 26 (n=75)     63.9  ± 24.1  
Family Activities: ET (n=124)     56.3  ± 27.6  
Family Activities: Week 26 LOCF (n=164)     61.6  ± 26.1  
Physical Health Global Subscale: Week 6 (n=163)     44.1  ± 11.7  
Physical Health Global Subscale: Week 26 (n=74)     46.6  ± 10.9  
Physical Health Global: ET (n=123)     43.8  ± 12.9  
Physical Health Global: Week 26 LOCF (n=163)     44.8  ± 12.2  
Psychosocial Health Global: Week 6 (n=163)     35.7  ± 10.4  
Psychosocial Health Global: Week 26 (n=74)     38.5  ± 10.9  
Psychosocial Health Global: ET (n=123)     33.7  ± 11.9  
Psychosocial Health Global: Week 26 LOCF (n=163)     36.8  ± 10.7  

No statistical analysis provided for Change From Baseline in Child Health Questionnaire (CHQ)



13.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: School Situation   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Number of Subjects Per Response on the School Placement Questionnaire: School Situation
Measure 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, Weeks 6 and 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects analyzable for School Placement Questionnaire; n=number of subjects with analyzable data at baseline and post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  221  
Number of Subjects Per Response on the School Placement Questionnaire: School Situation  
[units: participants]
 
Baseline: Enrolled or Attend (n=221)     63  
Baseline: Not Attend or Mental Illness (n=221)     59  
Baseline: Not Attend or Other (n=221)     4  
Baseline: Enrolled or Vacation (n=221)     26  
Baseline: Not Enrolled or Mental Illness (n=221)     42  
Baseline: Not Enrolled or Other (n=221)     27  
Week 6: Enrolled or Attend (n=166)     68  
Week 6: Not Attend or Mental Illness (n=166)     32  
Week 6: Not Attend or Other (n=166)     1  
Week 6: Enrolled or Vacation (n=166)     14  
Week 6: Not Enrolled or Mental Illness (n=166)     29  
Week 6: Not Enrolled or Other (n=166)     22  
Week 26: Enrolled or Attend (n=75)     35  
Week 26: Not Attend or Mental Illness (n=75)     9  
Week 26: Not Attend or Other (n=75)     0  
Week 26: Enrolled or Vacation (n=75)     5  
Week 26: Not Enrolled or Mental Illness (n=75)     13  
Week 26: Not Enrolled or Other (n=75)     13  
ET: Enrolled or Attend (n=125)     42  
ET: Not Attend or Mental Illness (n=125)     35  
ET: Not Attend or Other (n=125)     1  
ET: Enrolled or Vacation (n=125)     9  
ET: Not Enrolled or Mental Illness (n=125)     21  
ET: Not Enrolled or Other (n=125)     17  
Week 26 LOCF: Enrolled or Attend (n=166)     75  
Week 26 LOCF: Not Attend or Mental Illness (n=166)     30  
Week 26 LOCF: Not Attend or Other (n=166)     1  
Week 26 LOCF: Enrolled or Vacation (n=166)     8  
Wk 26 LOCF: Not Enrolled or Mental Illness (n=166)     28  
Week 26 LOCF: Not Enrolled or Other (n=166)     24  

No statistical analysis provided for Number of Subjects Per Response on the School Placement Questionnaire: School Situation



14.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: School Attendance   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Number of Subjects Per Response on the School Placement Questionnaire: School Attendance
Measure 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, Weeks 6 and 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects analyzable for School Placement Questionnaire; n=number of subjects with analyzable data at baseline and post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  133  
Number of Subjects Per Response on the School Placement Questionnaire: School Attendance  
[units: participants]
 
Baseline: No Absences (n=133)     25  
Baseline: Only a Few Absences (n=133)     37  
Baseline: Frequent Absences (n=133)     12  
Baseline: Did Not Attend (n=133)     36  
Baseline: Not Applicable or Vacation (n=133)     23  
Week 6: No Absences (n=95)     31  
Week 6: Only a Few Absences (n=95)     29  
Week 6: Frequent Absences (n=95)     11  
Week 6: Did Not Attend (n=95)     10  
Week 6: Not Applicable or Vacation (n=95)     14  
Week 26: No Absences (n=42)     14  
Week 26: Only a Few Absences (n=42)     16  
Week 26: Frequent Absences (n=42)     7  
Week 26: Did Not Attend (n=42)     0  
Week 26: Not Applicable or Vacation (n=42)     5  
ET: No Absences (n=62)     16  
ET: Only a Few Absences (n=62)     23  
ET: Frequent Absences (n=62)     5  
ET: Did Not Attend (n=62)     11  
ET: Not Applicable or Vacation (n=62)     7  
Week 26 LOCF: No Absences (n=93)     32  
Week 26 LOCF: Only a Few Absences (n=93)     32  
Week 26 LOCF: Frequent Absences (n=93)     14  
Week 26 LOCF: Did Not Attend (n=93)     7  
Week 26 LOCF: Not Applicable or Vacation (n=93)     8  

No statistical analysis provided for Number of Subjects Per Response on the School Placement Questionnaire: School Attendance



15.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance   [ Time Frame: Baseline, Weeks 6 and 26, ET ]

Measure Type Secondary
Measure Title Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance
Measure 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, Weeks 6 and 26, ET  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set. N=number of subjects analyzable for School Placement Questionnaire; n=number of subjects with analyzable data at baseline and post-baseline observation. Baseline was the last available observation from Study A1281134 (NCT00257192). LOCF imputation used for Week 26 LOCF time point.

Reporting Groups
  Description
Ziprasidone Titrated over a 2-week period, starting with an evening dose of 20 mg/day, and subsequent dose increases of 20 mg/day every second day up to a target dose of 80 to 160 mg/day for subjects weighing > = 45 kg. For subjects with a body weight < 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). Doses could have been reduced to a minimum of 40 mg/day (20 mg BID).

Measured Values
    Ziprasidone  
Number of Participants Analyzed  
[units: participants]
  103  
Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance  
[units: participants]
 
Baseline: Excellent (n=103)     5  
Baseline: Good (n=103)     25  
Baseline: Fair (n=103)     40  
Baseline: Poor (n=103)     23  
Baseline: Very Poor (n=103)     10  
Week 6: Excellent (n=73)     2  
Week 6: Good (n=73)     23  
Week 6: Fair (n=73)     34  
Week 6: Poor (n=73)     14  
Week 6: Very Poor (n=73)     0  
Week 26: Excellent (n=37)     1  
Week 26: Good (n=37)     10  
Week 26: Fair (n=37)     18  
Week 26: Poor (n=37)     5  
Week 26: Very Poor (n=37)     3  
ET: Excellent (n=48)     0  
ET: Good (n=48)     15  
ET: Fair (n=48)     23  
ET: Poor (n=48)     6  
ET: Very Poor (n=48)     4  
Week 26 LOCF: Excellent (n=80)     1  
Week 26 LOCF: Good (n=80)     22  
Week 26 LOCF: Fair (n=80)     39  
Week 26 LOCF: Poor (n=80)     15  
Week 26 LOCF: Very Poor (n=80)     3  

No statistical analysis provided for Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The AE tables were amended to incorporate previously unreported AEs that were found during an independent audit and verified by the investigators.


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