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Safety And Efficacy 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:
NCT00257192
First received: November 21, 2005
Last updated: December 2, 2011
Last verified: December 2011
History of Changes
Results First Received: March 23, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Schizophrenia
Interventions: Drug: placebo
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
A planned interim analysis resulted in recommendation from Data Safety Monitoring Board (DSMB) to terminate study due to futility per the interim analysis charter (p-value = 0.9840). Only one active subject in the study was affected by this decision.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening visit followed by a 1 to 10 day period to allow for wash-out of exclusionary medications.

Reporting Groups
  Description
Ziprasidone Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Placebo Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.

Participant Flow:   Overall Study
    Ziprasidone     Placebo  
STARTED     193     91 [1]
Received Study Treatment     193     90  
COMPLETED     135     52  
NOT COMPLETED     58     39  
Adverse Event                 21                 10  
Laboratory abnormality                 1                 1  
Lost to Follow-up                 3                 3  
Insufficient clinical response                 18                 18  
Withdrawal by Subject                 14                 2  
Randomized but not treated                 0                 1  
Study terminated by sponsor                 1                 0  
Miscellaneous                 0                 4  
[1] Includes 1 subject randomized but not treated



  Baseline Characteristics
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Reporting Groups
  Description
Ziprasidone Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Placebo Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Total Total of all reporting groups

Baseline Measures
    Ziprasidone     Placebo     Total  
Number of Participants  
[units: participants]
 		  193     90     283  
Age, Customized  
[units: participants]
 		     
>12 years and <13 years at start of treatment     4     0     4  
Between 13 and 17 years     189     90     279  
Age  
[units: years]
Mean ± Standard Deviation 		  15.3  ± 1.4     15.4  ± 1.4     15.3  ± 1.4  
Gender  
[units: participants]
 		     
Female     84     28     112  
Male     109     62     171  
Ethnicity  
[units: participants]
 		     
Hispanic / Latino     21     9     30  
Not Hispanic / Latino     172     81     253  
Race  
[units: particpants]
 		     
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) [1]
[units: particpants]
 		     
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) [1]
[units: participants]
 		     
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) [1]
[units: participants]
 		     
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)]
Mean ± Standard Deviation 		  164.9  ± 10.1     167.8  ± 10.0     165.8  ± 10.1  
Weight  
[units: kilograms (kg)]
Mean ± Standard Deviation 		  61.2  ± 15.5     64.3  ± 15.7     62.2  ± 15.6  
[1] 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).



  Outcome Measures
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1.  Primary:   Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total Score at Week 6   [ Time Frame: Baseline, Week 6 ]
  Show Outcome Measure 1

2.  Secondary:   Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 6   [ Time Frame: Baseline, Week 6 ]
  Show Outcome Measure 2

3.  Secondary:   Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 6   [ Time Frame: Baseline, Week 6 ]
  Show Outcome Measure 3

4.  Secondary:   Change From Baseline in PANSS: Positive and Negative Subscales at Week 6   [ Time Frame: Baseline, Week 6 ]
  Show Outcome Measure 4

5.  Secondary:   Clinical Global Impression of Improvement (CGI-I) Score at Week 6   [ Time Frame: Baseline, Week 6 ]
  Show Outcome Measure 5

6.  Secondary:   Change From Baseline in Children's Global Assessment Scale (CGAS)   [ Time Frame: Baseline, Week 2, Week 4, Week 6, Early termination (ET) ]
  Show Outcome Measure 6

7.  Secondary:   Change From Baseline in Child Health Questionnaire (CHQ)   [ Time Frame: Baseline, Week 6, ET ]
  Show Outcome Measure 7

8.  Secondary:   Change From Baseline in Children's Problem Behavior and Aggression Questionnaire (CPBAQ) Total Score   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Total Score   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 9

10.  Secondary:   Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 10

11.  Secondary:   Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Impaired Schoolwork Item 1   [ Time Frame: Baseline, Week 2, Week 6 ]
  Show Outcome Measure 11

12.  Secondary:   Change From Baseline in CNS Vital Signs Cognitive Test Battery (Includes Sedation Item): Subscales   [ Time Frame: Baseline, Week 6, ET ]
  Show Outcome Measure 12

13.  Secondary:   Change From Baseline in CNS Vital Signs Cognitive Test Battery: Neurocognitive Index   [ Time Frame: Baseline, Week 6, ET ]
  Show Outcome Measure 13

14.  Secondary:   Change From Baseline in Movement Disorder Scales: Simpson-Angus Rating Scale (SARS)   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 14

15.  Secondary:   Change From Baseline in Movement Disorder Scales: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment Item   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 15

16.  Secondary:   Change From Baseline in Movement Disorder Scales: Abnormal Involuntary Movement Scale (AIMS) Movement Cluster Score   [ Time Frame: Baseline, Week 1 through Week 6 ]
  Show Outcome Measure 16

17.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: School Situation   [ Time Frame: Baseline, Week 2, Week 6, ET ]
  Show Outcome Measure 17

18.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: School Attendance   [ Time Frame: Baseline, Week 2, Week 6, ET ]
  Hide Outcome Measure 18

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, Week 2, Week 6, 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.
ITT; N=number of subjects analyzable for School Placement Questionnaire; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively. ET includes observations from visits not within windowing criteria. LOCF imputation used for Week 6 LOCF timepoint.

Reporting Groups
  Description
Ziprasidone Oral (PO) capsules administered twice daily (BID) with meals; titrated from a starting dose of 20 milligrams per day (mg/day) over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kilograms (kg); target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.
Placebo Placebo matching ziprasidone administration: PO capsules administered BID) with meals; titrated from a starting dose of 20 mg/day over 2 weeks with dose increases of 20 mg/day every second day up to a target dose range of 120 to 160 mg/day for subjects with body weight ≥ 45 kg; target dose for subjects with body weight < 45 kg is 60 to 80 mg/day. After titration dose is attained, flexible dosing range of 80 to 160 (if body weight ≥ 45 kg) or 40 to 80 mg/day (if body weight < 45 kg) for duration of the study.

Measured Values
    Ziprasidone     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  189     87  
Number of Subjects Per Response on the School Placement Questionnaire: School Attendance  
[units: participants]
 		   
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  

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



19.  Secondary:   Number of Subjects Per Response on the School Placement Questionnaire: Overall School Performance   [ Time Frame: Baseline, Week 2, Week 6, ET ]
  Show Outcome Measure 19


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00257192     History of Changes
Other Study ID Numbers: A1281134
Study First Received: November 21, 2005
Results First Received: March 23, 2010
Last Updated: December 2, 2011
Health Authority: United States: Food and Drug Administration