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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
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
  Hide Participant Flow

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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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 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
  Show All Outcome Measures

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

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

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

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

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

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

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

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

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

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 ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13
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. Suicide Ideation (Item 13) detects changes in suicidality over time. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment).
Time Frame Baseline, Week 1 through Week 6  
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.
ITT; N=number of subjects with analyzable data at baseline; (n)=number of subjects with analyzable data at post-baseline observation for ziprasidone and placebo, respectively. LOCF imputation used for Week 6 LOCF timepoint.

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]
  192     90  
Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13  
[units: scores on a scale]
Mean ± Standard Deviation
   
Week 1 (n=188, 86)     -0.1  ± 0.4     -0.0  ± 0.5  
Week 2 (n=182, 86)     -0.0  ± 0.5     -0.1  ± 0.5  
Week 3 (n=165, 74)     -0.1  ± 0.5     -0.1  ± 0.3  
Week 4 (n=154, 63)     0.0  ± 0.5     -0.1  ± 0.5  
Week 5 (n=141, 54)     0.0  ± 0.4     -0.1  ± 0.5  
Week 6 (n=134, 52)     -0.0  ± 0.3     -0.1  ± 0.4  
Week 6 [LOCF] (n=189, 87)     0.0  ± 0.6     -0.0  ± 0.5  

No statistical analysis provided for Change From Baseline in Child Depression Rating Scale - Revised (CDRS-R): Suicide Ideation Item 13



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

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

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

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

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 ]

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 ]

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

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

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


  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.


  More Information