Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39233   clinical trials with a EudraCT protocol, of which   6427   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    26-Week Open-Label Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder (Manic Or Mixed)

    Summary
    EudraCT number
    2015-000607-15
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    24 Jan 2008

    Results information
    Results version number
    v2(current)
    This version publication date
    26 Mar 2016
    First version publication date
    20 Jun 2015
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    identified a missing information regarding “mutually exclusive arms” in the subject disposition section

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    A1281133
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00265330
    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., 001 800-718-1021, ClinicalTrials.govCallCenter@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.govCallCenter@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
    10 Jul 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jan 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety and tolerability of oral ziprasidone (40-80 milligram [mg] twice a day [BID]) during long-term, open-label administration in children and adolescents with Bipolar I Disorder - Single Manic Episode; Bipolar I Disorder – Most Recent Episode Manic, or Bipolar I Disorder – Most Recent Episode Mixed.
    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
    17 Mar 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
    United States: 162
    Worldwide total number of subjects
    162
    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)
    41
    Adolescents (12-17 years)
    120
    Adults (18-64 years)
    1
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The number of subjects entering this trial was determined by the number of subjects electing to continue treatment after completing or withdrawing from the preceding double-blind study (A1281132: NCT00257166; 2015-000606-20).

    Pre-assignment
    Screening details
    A total of 169 subjects from the parent study were assigned to the extension study and 162 continued on and received study treatment in the extension study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Ziprasidone
    Arm description
    Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability.
    Arm type
    Experimental

    Investigational medicinal product name
    Ziprasidone
    Investigational medicinal product code
    Other name
    Geodon
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).

    Number of subjects in period 1
    Ziprasidone
    Started
    162
    Completed
    67
    Not completed
    95
         Discharged from Unit for Long Term Care
    1
         Principal Investigators Request
    1
         Began Taking Formulary Geodon
    1
         Lack of efficacy
    4
         Withdrew Consent
    1
         Family Scheduling Conflicts
    1
         Site Closed by Sponsor
    1
         Protocol Violation
    1
         Consent withdrawn by subject
    34
         Adverse Event
    41
         Lost to follow-up
    8
         Subject Wanted to Start Psychotherapy
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ziprasidone
    Reporting group description
    Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability.

    Reporting group values
    Ziprasidone Total
    Number of subjects
    162 162
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    13.3 ± 2.1 -
    Gender, Male/Female
    Units: subjects
        Female
    72 72
        Male
    90 90

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Ziprasidone
    Reporting group description
    Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability.

    Primary: Young Mania Rating Scale (YMRS) Total Score Change from Baseline

    Close Top of page
    End point title
    Young Mania Rating Scale (YMRS) Total Score Change from Baseline [1]
    End point description
    YMRS: 11-item instrument with scales 0 (normal) to 4 (highest abnormal)for 7 items and 0 (normal) to 8 (highest abnormal) for 4 items. Total possible 0 - 60. Baseline is from parent study A1281132. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation).
    End point type
    Primary
    End point timeframe
    Baseline and 26 Weeks; 26 Weeks Last Observation Carried Forward (LOCF)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: score on scale
    arithmetic mean (standard deviation)
        Week 2 (n=153)
    -3.8 ± 9
        Week 6 (n=122)
    -4 ± 9.1
        Week 18 (n=76)
    -6.3 ± 12.7
        Week 26 (n=69)
    -6.1 ± 11.6
        Early Termination (n=59)
    1.5 ± 11.3
        Week 26-LOCF (n=153)
    -3.3 ± 10.7
    No statistical analyses for this end point

    Primary: Clinical Global Impression of Severity (CGI-S) Change from Baseline

    Close Top of page
    End point title
    Clinical Global Impression of Severity (CGI-S) Change from Baseline [2]
    End point description
    CGI-S Scale:standardized assessment tool to rate severity of subject’s illness; assesses investigator’s impression of subject’s current illness state. Change: score at observation minus score at baseline. Score: 1 (not ill at all) to 7 (among most extremely ill). Baseline = last available observation from parent double-blind study(A1281132). The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation).
    End point type
    Primary
    End point timeframe
    Baseline and 26 Weeks; 26 Weeks LOCF
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: score on scale
    arithmetic mean (standard deviation)
        Week 1 (n=159)
    -0.2 ± 0.9
        Week 2 (n=150)
    -0.5 ± 1.2
        Week 6 (n=122)
    -0.4 ± 1.1
        Week 10 (n=99)
    -0.7 ± 1.3
        Week 14 (n=85)
    -0.7 ± 1.2
        Week 18 (n=76)
    -0.7 ± 1.5
        Week 22 (n=70)
    -0.8 ± 1.3
        Week 26 (n=69)
    -1.1 ± 1.4
        Early Termination (n=48)
    0.4 ± 1.1
        Week 26-LOCF (n=160)
    -0.4 ± 1.3
    No statistical analyses for this end point

    Primary: Incidence of Lab Abnormalities

    Close Top of page
    End point title
    Incidence of Lab Abnormalities [3]
    End point description
    Number of subjects with an abnormal lab value for those parameters with 5 percent (%) or greater incidence of abnormality. Total number of subjects with given laboratory test at given visit. Range: N=136-134, with the exception of Insulin (N=115).
    End point type
    Primary
    End point timeframe
    Week 26
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    136
    Units: subjects
    number (not applicable)
        Bicarbonate (N=136)
    44
        Urine blood/Hemoglobin (N=136)
    34
        Urine ketones (N=136)
    32
        Testosterone (N=134)
    22
        Urine specific gravity (N=136)
    13
        Urine red blood cells (N=136)
    13
        Monocytes (N=134)
    9
        Triglycerides (N=136)
    10
        Urine white blood cells (N=136)
    10
        Insulin (N=115)
    8
    No statistical analyses for this end point

    Primary: Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol

    Close Top of page
    End point title
    Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol [4]
    End point description
    Mean Change: lab value at observation minus lab value at baseline. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test).
    End point type
    Primary
    End point timeframe
    Week 6, Week 26
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    134
    Units: milligram /deciliter (mg/dL)
    arithmetic mean (standard deviation)
        LDL cholesterol Week 6 (n=113)
    -7.5 ± 19.7
        LDL cholesterol Week 26 (n=59)
    -8.9 ± 19.5
        LDL cholesterol Early Termination (n=44)
    -7.6 ± 20.1
        Fasting cholesterol Week 6 (n=113)
    -7.7 ± 21.8
        Fasting cholesterol Week 26 (n=59)
    -10.3 ± 22.7
        Fasting cholesterol Early Termination (n=44)
    -8.6 ± 24.9
    No statistical analyses for this end point

    Primary: Change in Hormones

    Close Top of page
    End point title
    Change in Hormones [5]
    End point description
    Mean Change: lab value at observation minus lab value at baseline. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test).
    End point type
    Primary
    End point timeframe
    Week 6, Week 26
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    131
    Units: nanogram/deciliter (ng/dL)
    arithmetic mean (standard deviation)
        Testosterone Week 6 (n=80)
    0.9 ± 84.3
        Testosterone Week 26 (n=38)
    -23.4 ± 112.9
        Testosterone Early Termination (n=32)
    -0.4 ± 61.8
        Prolactin Week 6 (n=110)
    2.7 ± 13.2
        Prolactin Week 26 (n=59)
    1.9 ± 8.5
        Prolactin Early Termination (n=40)
    1 ± 11.6
        Insulin-like growth factor Week 6 (n=95)
    -19.9 ± 63.4
        Insulin-like growth factor Week 26 (n=47)
    -9.2 ± 68.1
        Insulin-like growth factor Early Term (n=34)
    -8.4 ± 66.5
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Supine Systolic Blood Pressure

    Close Top of page
    End point title
    Mean Change from Baseline in Supine Systolic Blood Pressure [6]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: millimeters of mercury (mm Hg)
    arithmetic mean (standard deviation)
        Week 1 (n=155)
    0.4 ± 11.4
        Week 2 (n=142)
    1.1 ± 10.4
        Week 6/pre-dose (n=115)
    1.2 ± 9.5
        Week 6/5-7 hours post dose (n=108)
    1.2 ± 9.9
        Week 10 (n=93)
    1.4 ± 10.1
        Week 14 (n=82)
    -0.7 ± 10.1
        Week 18 (n=74)
    0.4 ± 11.7
        Week 22 (n=69)
    1.7 ± 10.5
        Week 26 (n=68)
    2.9 ± 11.4
        Early Termination (n=75)
    1.3 ± 11.8
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Supine Diastolic Blood Pressure

    Close Top of page
    End point title
    Mean Change from Baseline in Supine Diastolic Blood Pressure [7]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: millimeters mercury (mm Hg)
    arithmetic mean (standard deviation)
        Week 1 (n=155)
    -0.5 ± 8.8
        Week 2 (n=142)
    0.5 ± 8.7
        Week 6/pre-dose (n=115)
    0.6 ± 9.7
        Week 6/5-7 hours post dose (n=108)
    0.5 ± 8.8
        Week 10 (n=93)
    -0.4 ± 10.1
        Week 14 (n=82)
    -2.4 ± 8.3
        Week 18 (n=74)
    -0.6 ± 9.8
        Week 22 (n=69)
    -0.7 ± 9.4
        Week 26 (n=68)
    1.5 ± 10.4
        Early Termination (n=75)
    1.3 ± 8.1
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Supine Pulse Rates

    Close Top of page
    End point title
    Mean Change from Baseline in Supine Pulse Rates [8]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: beats per minute
    arithmetic mean (standard deviation)
        Week 1 (n=155)
    1.4 ± 12.4
        Week 2 (n=142)
    2 ± 11.7
        Week 6/pre-dose (n=115)
    -1.8 ± 11.6
        Week 6/5-7 hours post dose (n=108)
    1 ± 12.3
        Week 10 (n=93)
    1.4 ± 11.8
        Week 14 (n=82)
    -3 ± 12.4
        Week 18 (n=74)
    -3.5 ± 12.2
        Week 22 (n=69)
    -2.1 ± 11.7
        Week 26 (n=68)
    -3 ± 11.2
        Early Termination (n=75)
    3.9 ± 13.9
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Standing Systolic Blood Pressure

    Close Top of page
    End point title
    Mean Change from Baseline in Standing Systolic Blood Pressure [9]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    161
    Units: mm Hg
    arithmetic mean (standard deviation)
        Week 1 (n=154)
    1.4 ± 10.5
        Week 2 (n=141)
    3.7 ± 11.7
        Week 6/pre-dose (n=115)
    1.6 ± 9.6
        Week 6/5-7 hours post dose (n=108)
    2 ± 9.5
        Week 10 (n=93)
    2.4 ± 11
        Week 14 (n=82)
    0.5 ± 11.3
        Week 18 (n=74)
    3.1 ± 10.5
        Week 22 (n=70)
    3.2 ± 10
        Week 26 (n=68)
    3.6 ± 10.9
        Early Termination (n=75)
    3 ± 11.4
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Standing Diastolic Blood Pressure

    Close Top of page
    End point title
    Mean Change from Baseline in Standing Diastolic Blood Pressure [10]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    161
    Units: mm Hg
    arithmetic mean (standard deviation)
        Week 1 (n=154)
    0.7 ± 9.1
        Week 2 (n=141)
    2 ± 9.8
        Week 6/pre-dose (n=115)
    1.4 ± 9.8
        Week 6/5-7 hours post dose (n=108)
    1.2 ± 9.9
        Week 10 (n=93)
    1.6 ± 10.8
        Week 14 (n=82)
    -0.1 ± 9.8
        Week 18 (n=74)
    1.1 ± 8.8
        Week 22 (n=70)
    0.5 ± 8.5
        Week 26 (n=68)
    2.8 ± 8.3
        Early Termination (n=75)
    3.4 ± 10.8
    No statistical analyses for this end point

    Primary: Mean Change from Baseline in Standing Pulse Rates

    Close Top of page
    End point title
    Mean Change from Baseline in Standing Pulse Rates [11]
    End point description
    Mean Change: vital sign value at observation minus vital sign value at baseline.
    End point type
    Primary
    End point timeframe
    Week 1 through Week 26
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    161
    Units: beats per minute
    arithmetic mean (standard deviation)
        Week 1 (n=154)
    3.5 ± 14
        Week 2 (n=140)
    2.9 ± 13.4
        Week 6/pre-dose (n=115)
    0.3 ± 13.1
        Week 6/5-7 hours post dose (n=108)
    3.8 ± 13.9
        Week 10 (n=93)
    2.6 ± 14.5
        Week 14 (n=82)
    0.5 ± 14.7
        Week 18 (n=74)
    -0.3 ± 12.5
        Week 22 (n=70)
    1.2 ± 14.7
        Week 26 (n=68)
    -0.9 ± 12.9
        Early Termination (n=75)
    4.8 ± 13.8
    No statistical analyses for this end point

    Primary: Mean Change from Baseline for Body Weight

    Close Top of page
    End point title
    Mean Change from Baseline for Body Weight [12]
    End point description
    Mean change; body weight value at observation minus body weight value at baseline.
    End point type
    Primary
    End point timeframe
    Week 6, Week 26
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: kilogram
    arithmetic mean (standard deviation)
        Week 6 (n=119)
    1.3 ± 3
        Week 26 (n=68)
    3.9 ± 5.4
        Early Termination (n=74)
    1.4 ± 2.8
    No statistical analyses for this end point

    Primary: Mean Change from Baseline for Body Mass Index (BMI) Z-Score

    Close Top of page
    End point title
    Mean Change from Baseline for Body Mass Index (BMI) Z-Score [13]
    End point description
    Mean change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
    End point type
    Primary
    End point timeframe
    Week 6, 26, early termination
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: score on scale
    arithmetic mean (standard deviation)
        Week 6 (n=119)
    0 ± 0.3
        Week 26 (n=68)
    0.1 ± 0.5
        Early Termination (n=74)
    0 ± 0.3
    No statistical analyses for this end point

    Primary: Body Mass Index (BMI) Z-score frequency

    Close Top of page
    End point title
    Body Mass Index (BMI) Z-score frequency [14]
    End point description
    Change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
    End point type
    Primary
    End point timeframe
    Week 6
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: subjects
        Less than (<)-4
    0
        Greater than or equal to (≥)-4 to <-3
    0
        ≥-3 to <-2
    0
        ≥-2 to <-1
    0
        ≥-1 to <0
    53
        ≥0 to <1
    61
        ≥1 to <2
    1
        ≥2 to <3
    0
        ≥3 to <4
    0
        ≥4
    0
    No statistical analyses for this end point

    Primary: Body Mass Index (BMI) Z-score frequency

    Close Top of page
    End point title
    Body Mass Index (BMI) Z-score frequency [15]
    End point description
    Change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
    End point type
    Primary
    End point timeframe
    Week 26
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: subjects
        <-4
    0
        ≥-4 to <-3
    0
        ≥-3 to <-2
    0
        ≥-2 to <-1
    1
        ≥-1 to <0
    27
        ≥0 to <1
    39
        ≥1 to <2
    0
        ≥2 to <3
    0
        ≥3 to <4
    0
        ≥4
    0
    No statistical analyses for this end point

    Primary: Mean Change from Baseline for QTcF intervals

    Close Top of page
    End point title
    Mean Change from Baseline for QTcF intervals [16]
    End point description
    QT intervals (observed in an electrocardiogram) corrected using Fridericia’s formula (QTcF). Mean change: mean change of observation minus baseline. Baseline: last available observation in the parent double-blind study.
    End point type
    Primary
    End point timeframe
    Baseline to Week 26 (end of study)
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    162
    Units: millisecond
    arithmetic mean (standard deviation)
        Week 1 (n=152)
    4.8 ± 18.5
        Week 2 (n=137)
    3.5 ± 17.7
        Week 6/pre-dose (n=111)
    7.6 ± 17.7
        Week 6/5-7 hours post dose (n=107)
    7 ± 18.4
        Week 10 (n=91)
    4.3 ± 18.8
        Week 14 (n=81)
    6.2 ± 17.4
        Week 18 (n=73)
    7.4 ± 15.4
        Week 22 (n=68)
    8.1 ± 16.1
        Week 26 (n=64)
    7.1 ± 15.2
        Early Termination (n=45)
    2.7 ± 17
    No statistical analyses for this end point

    Primary: Frequency of largest categorical increases in QTcF for males

    Close Top of page
    End point title
    Frequency of largest categorical increases in QTcF for males [17]
    End point description
    QT intervals (observed in an electrocardiogram) corrected with Fridericia's Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
    End point type
    Primary
    End point timeframe
    Week 26 (end of study)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    89
    Units: subjects
        ≥450 msec (millisecond)
    0
        ≥460 msec
    0
        ≥480 msec
    0
        ≥30 msec increase
    28
        ≥60 msec increase
    0
    No statistical analyses for this end point

    Primary: Frequency of largest categorical increases in QTcF for females

    Close Top of page
    End point title
    Frequency of largest categorical increases in QTcF for females [18]
    End point description
    QT interval (observed in an electrocardiogram) corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
    End point type
    Primary
    End point timeframe
    Week 26 (end of study)
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    71
    Units: subjects
        ≥450 msec
    3
        ≥460 msec
    0
        ≥480 msec
    0
        ≥30 msec increase
    10
        ≥60 msec increase
    2
    No statistical analyses for this end point

    Primary: Frequency of largest categorical increases in QTcF - all subjects

    Close Top of page
    End point title
    Frequency of largest categorical increases in QTcF - all subjects [19]
    End point description
    QT intervals (observed in an electrocardiogram)corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
    End point type
    Primary
    End point timeframe
    Week 26 (end of study)
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be reported for this endpoint. 
    End point values
    Ziprasidone
    Number of subjects analysed
    160
    Units: subjects
        ≥450 msec
    3
        ≥460 msec
    0
        ≥480 msec
    0
        ≥30 msec increase
    38
        ≥60 msec increase
    2
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    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
    Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kg or greater, the target dosage range was 40-80 mg BID (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).

    Serious adverse events
    Ziprasidone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 162 (10.49%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    3 / 162 (1.85%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Conversion disorder
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucinations, mixed
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Delusion
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Negative thoughts
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Homicidal ideation
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Self-injurious behavior
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    4 / 162 (2.47%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Oppositional defiant disorder
         subjects affected / exposed
    2 / 162 (1.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Mania
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 162 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Ziprasidone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    123 / 162 (75.93%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 162 (5.56%)
         occurrences all number
    10
    Nasal congestion
         subjects affected / exposed
    12 / 162 (7.41%)
         occurrences all number
    13
    Nervous system disorders
    Headache
         subjects affected / exposed
    36 / 162 (22.22%)
         occurrences all number
    53
    Dizziness
         subjects affected / exposed
    12 / 162 (7.41%)
         occurrences all number
    14
    Sedation
         subjects affected / exposed
    43 / 162 (26.54%)
         occurrences all number
    48
    Somnolence
         subjects affected / exposed
    38 / 162 (23.46%)
         occurrences all number
    50
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    11 / 162 (6.79%)
         occurrences all number
    11
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    22 / 162 (13.58%)
         occurrences all number
    26
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    15 / 162 (9.26%)
         occurrences all number
    16
    Vomiting
         subjects affected / exposed
    12 / 162 (7.41%)
         occurrences all number
    16
    Nausea
         subjects affected / exposed
    13 / 162 (8.02%)
         occurrences all number
    15
    Abdominal discomfort
         subjects affected / exposed
    11 / 162 (6.79%)
         occurrences all number
    11

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Dec 2006
    1- In assessments, fasting glucose and glycosylated hemoglobin (HbA1c) were added to clinical laboratory testing. 2- Daily dose of study medication for subjects with a body weight of ≥ 45 kg changed to 40-80 mg/day from 60-80 mg/day. 3- In trial design, minimum dose of the preceding double-blind study was decided for the dose reduction in subjects ≥45 kg, who cannot tolerate a dose of 80 mg/day. 4- In Trial Treatment, inhaled steroids were also added along with the topical steroids in the category of medicines for which use is allowed only if taken during preceding double-blind study with stable dose and clinical condition; and benzhexol and other anticholinergics were added in the category of medicines which are allowed without condition. 5- An additional category (≥460 msec) was used in QTcF reporting. 6- A change was made in the reporting priorities of AEs. A decision was made to report the treatment-emergent AEs as the main safety output, and “All AEs” were reported as additional tables. Combined data are the main analyses and consist of all subjects, regardless of the treatment assignment in the preceding double-blind study (A1281132).

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    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.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA