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    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 (Most Recent Episode Manic)

    Summary
    EudraCT number
    		 2020-004088-26
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    31 Jul 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Feb 2021
    First version publication date
    10 Feb 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A1281201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03768726
    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 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2020
    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 (20-80 mg BID) during long term, open label administration in children and adolescents with Bipolar I Disorder who participated in Study A1281198.
    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 Council for 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
    21 Dec 2018
    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: 23
    Worldwide total number of subjects
    23
    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)
    3
    Adolescents (12-17 years)
    20
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects who participated in study A1281198 (NCT02075047) and consented for treatment with open label ziprasidone were enrolled in the current study.

    Pre-assignment
    Screening details
    		 Study was conducted in the United States from 21-Dec-2018 to 31-July-2020.

    Period 1
    Period 1 title
    Open Label Treatment Phase (26 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Double Blind Ziprasidone to Open Label Ziprasidone
    Arm description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ziprasidone
    Investigational medicinal product code
    CP-88,059-1
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ziprasidone capsules orally once daily for 4 weeks. Subjects with body weight less than 45 kg received 60 to 80 mg/day and subjects with body weight >=45 kg received 120-160 mg/day.

    Arm title
    		 Double Blind Placebo to Open Label Ziprasidone
    Arm description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ziprasidone
    Investigational medicinal product code
    CP-88,059-1
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ziprasidone capsules orally once daily for 4 weeks. Subjects with body weight less than 45 kg received 60 to 80 mg/day and subjects with body weight >=45 kg received 120-160 mg/day.

    Number of subjects in period 1
    		Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Started
    10
    13
    Completed
    2
    10
    Not completed
    8
    3
         Consent withdrawn by subject
    3
    1
         Adverse event, non-fatal
    2
    2
         Withdrawal By Parent/Guardian
    2
    -
         Lost to follow-up
    1
    -
    Period 2
    Period 2 title
    Follow-Up Phase (1 Week)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Double Blind Ziprasidone to Open Label Ziprasidone
    Arm description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Double Blind Placebo to Open Label Ziprasidone
    Arm description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Started
    2
    10
    Completed
    2
    9
    Not completed
    6
    3
         Consent withdrawn by subject
    2
    -
         Adverse event, non-fatal
    2
    2
         Withdrawal By Parent/Guardian
    1
    1
         Unspecified
    1
    -
    Joined
    6
    2
         Continued to follow up
    6
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double Blind Ziprasidone to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.

    Reporting group title
    Double Blind Placebo to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.

    Reporting group values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone Total
    Number of subjects
    		 10 13 23
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 1 2 3
        Adolescents (12-17 years)
    		 9 11 20
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 14.0 ± 2.3 14.2 ± 2.0 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 5 7 12
        Male
    		 5 6 11
    Race Characteristics
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 1 2
        White
    		 8 10 18
        More than one race
    		 1 1 2
        Unknown or Not Reported
    		 0 0 0
    Ethnicity Characteristics
    Units: Subjects
        Hispanic or Latino
    		 0 0 0
        Not Hispanic or Latino
    		 9 13 22
        Unknown or Not Reported
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Double Blind Ziprasidone to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.

    Reporting group title
    Double Blind Placebo to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.
    Reporting group title
    Double Blind Ziprasidone to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.

    Reporting group title
    Double Blind Placebo to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.

    Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [1]
    End point description
    An AE was any untoward medical occurrence in a subject who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study.
    End point type
    Primary
    End point timeframe
    Day 1 up to 1 week after last dose of study medication (maximum up to 27 weeks)
    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 analyzed for this end point.
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: subjects
        AEs
    7
    12
        SAEs
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities

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    End point title
    		 Number of Subjects With Laboratory Abnormalities
    End point description
    Hemoglobin(Hg),hematocrit,erythrocytes:<0.8*lower limits of normal(LLN); platelets:<0.5*LLN>1.75*upper limits of normal(ULN);leukocytes(leu),glucose-fasting:<0.6*LLN>1.5*ULN; lymphocytes(lym), lym/leu, neutrophils(neu), neu/leu, protein, albumin, phosphate, free thyroxine, thyroid stimulating hormone:<0.8*LLN>1.2*ULN;basophils (bas), bas/leu, eosinophils(eos), eos/leu, monocytes(mon), mon/leu:>1.2*ULN; bilirubin (total,direct,indirect):>1.5*ULN;aspartate aminotransferase(AT), alanine AT, lactate dehydrogenase, alkaline phosphatase:>3.0*ULN;blood urea nitrogen, creatinine, cholesterol (total,LDL,HDL), triglycerides, Hg A1C:>1.3*ULN;sodium:<0.95*LLN>1.05*ULN;potassium, chloride, calcium, magnesium, bicarbonate:<0.9*LLLN>1.1*ULN;prolactin:>1.1*ULN;creatine kinase:>2.0*ULN;urobilinogen:>=1;Urine-specific gravity:<1.003>1.030, pH:<4.5 >8, glucose,protein,bilirubin,nitrite,leukocyte esterase,ketones:>=1. Safety analysis set. 'Number of Subjects Analysed’: subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 up to 1 week after last dose of study medication (maximum up to 27 weeks)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    8
    13
    Units: subjects
    5
    11
    No statistical analyses for this end point

    Secondary: Number of Subjects With Physical Examination Abnormalities at Baseline and Week 26

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    End point title
    		 Number of Subjects With Physical Examination Abnormalities at Baseline and Week 26
    End point description
    Parameters assessed for physical examination included: oral/tympanic temperature, general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts (if medically indicated), abdomen, external genitalia (if medically indicated), extremities, back/spinal system, lymph nodes or worsening of medical history conditions. Abnormality in physical examination was at the investigator's discretion. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: subjects
        Baseline
    0
    0
        Week 26
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Blood Pressure (BP) at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (ET) and Follow-up Visit

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    End point title
    		 Change From Baseline in Blood Pressure (BP) at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (ET) and Follow-up Visit
    End point description
    Change from baseline in sitting and standing systolic BP (SBP) and diastolic BP (DBP) in millimeter of mercury (mmHg) was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: mmHg
    arithmetic mean (standard deviation)
        Sitting SBP, Baseline (n =10, 13)
    111.70 ± 13.712
    111.38 ± 11.384
        Sitting SBP, Change at Week 1 (n =9,12)
    2.44 ± 10.944
    -1.00 ± 11.505
        Sitting SBP, Change at Week 2 (n =7,12)
    0.43 ± 6.024
    0.08 ± 10.431
        Sitting SBP, Change at Week 4 (n =7,12)
    3.29 ± 8.036
    -1.83 ± 8.321
        Sitting SBP, Change at Week 6 (n =6,11)
    3.17 ± 6.969
    -3.45 ± 11.903
        Sitting SBP, Change at Week 10 (n =5,11)
    -0.80 ± 9.203
    -3.09 ± 11.674
        Sitting SBP, Change at Week 14 (n =5,11)
    -2.80 ± 9.011
    -7.09 ± 8.949
        Sitting SBP, Change at Week 18 (n =3,11)
    -2.67 ± 8.327
    -0.82 ± 10.852
        Sitting SBP, Change at Week 22 (n =2,10)
    -5.00 ± 1.414
    1.40 ± 11.568
        Sitting SBP, Change at Week 26/ET (n =8,13)
    -0.63 ± 9.620
    -2.23 ± 14.219
        Sitting SBP, Change at Follow up (n =4,3)
    0.75 ± 7.365
    7.67 ± 4.041
        Standing SBP, Baseline (n =10,13)
    113.40 ± 10.690
    111.38 ± 12.738
        Standing SBP, Change at Week 1 (n =9,11)
    -0.67 ± 11.916
    -1.00 ± 8.161
        Standing SBP, Change at Week 2 (n =7,12)
    2.86 ± 13.753
    1.33 ± 12.759
        Standing SBP, Change at Week 4 (n =7,12)
    -1.57 ± 7.138
    2.17 ± 11.707
        Standing SBP, Change at Week 6 (n =6,11)
    1.67 ± 7.230
    -2.00 ± 14.457
        Standing SBP, Change at Week 10 (n =5,11)
    -0.60 ± 9.423
    -2.18 ± 11.391
        Standing SBP, Change at Week 14 (n =5,11)
    -0.80 ± 9.039
    -4.55 ± 6.933
        Standing SBP, Change at Week 18 (n =3,11)
    -2.67 ± 8.327
    -1.73 ± 13.342
        Standing SBP, Change at Week 22 (n =2,10)
    -7.00 ± 7.071
    5.40 ± 13.006
        Standing SBP, Change at Week 26/ET(n =8,12)
    -3.38 ± 7.230
    -5.33 ± 12.010
        Standing SBP, Change at Follow up (n =4, 2)
    -5.50 ± 8.544
    2.50 ± 4.950
        Sitting DBP, Baseline (n =10,13)
    71.00 ± 7.688
    72.00 ± 9.256
        Sitting DBP, Change at Week 1 (n =9,12)
    0.67 ± 10.794
    -1.67 ± 9.633
        Sitting DBP, Change at Week 2 (n =7, 12)
    -4.14 ± 3.185
    0.17 ± 8.376
        Sitting DBP, Change at Week 4 (n =7, 12)
    0.14 ± 6.768
    -2.17 ± 10.744
        Sitting DBP, Change at Week 6 (n =6, 11)
    -0.83 ± 8.183
    1.00 ± 13.176
        Sitting DBP, Change at Week 10 (n =5,11)
    -3.40 ± 4.393
    -7.09 ± 10.387
        Sitting DBP, Change at Week 14 (n =5, 11)
    -6.20 ± 6.058
    -3.91 ± 10.094
        Sitting DBP, Change at Week 18 (n =3,11)
    -2.67 ± 3.786
    0.27 ± 15.186
        Sitting DBP, Change at Week 22 (n =2,10)
    -5.50 ± 2.121
    -1.30 ± 9.019
        Sitting DBP, Change at Week 26/ET (n =8,13)
    -2.50 ± 6.302
    -2.46 ± 10.548
        Sitting DBP, Change at Follow up (n =4,3)
    -1.75 ± 13.175
    -1.67 ± 8.145
        Standing DBP, Baseline (n =10, 13)
    73.90 ± 6.402
    74.85 ± 4.930
        Standing DBP, Change at Week 1 (n =9, 11)
    -1.00 ± 7.483
    -4.45 ± 6.654
        Standing DBP, Change at Week 2 (n =7, 12)
    -4.14 ± 3.132
    -0.33 ± 4.924
        Standing DBP, Change at Week 4 (n =7,12)
    -3.14 ± 7.625
    -2.67 ± 10.465
        Standing DBP, Change at Week 6 (n =6, 11)
    -1.17 ± 5.776
    -2.82 ± 7.910
        Standing DBP, Change at Week 10 (n =5, 11)
    0.40 ± 5.941
    -4.36 ± 7.215
        Standing DBP, Change at Week 14 (n =5, 11)
    -3.00 ± 3.317
    -4.09 ± 7.516
        Standing DBP, Change at Week 18 (n =3,11)
    -5.33 ± 3.055
    -0.91 ± 12.136
        Standing DBP, Change at Week 22 (n =2,10)
    0.00 ± 5.657
    -4.30 ± 10.646
        Standing DBP, Change at Week 26/ET (n =8, 12)
    -0.50 ± 4.408
    -4.33 ± 8.700
        Standing DBP, Change at Follow-up (n =4, 2)
    -7.75 ± 10.905
    -3.00 ± 2.828
    No statistical analyses for this end point

    Secondary: Change From Baseline in Pulse Rate at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (ET) and Follow-up Visit

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    End point title
    		 Change From Baseline in Pulse Rate at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (ET) and Follow-up Visit
    End point description
    Change from baseline pulse rate in beats per minute was reported in sitting and standing positions. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: beats per minute
    arithmetic mean (standard deviation)
        Sitting, Baseline (n =10, 13)
    77.90 ± 9.678
    73.38 ± 11.701
        Sitting, Change at Week 1 (n =9, 12)
    0.78 ± 8.969
    2.00 ± 9.254
        Sitting, Change at Week 2 (n =7, 12)
    0.00 ± 6.758
    8.08 ± 11.782
        Sitting, Change at Week 4 (n =7, 12)
    -3.29 ± 7.365
    2.00 ± 9.789
        Sitting, Change at Week 6 (n =6, 11)
    -1.17 ± 7.139
    2.00 ± 10.954
        Sitting, Change at Week 10 (n =5, 11)
    3.40 ± 11.261
    0.18 ± 14.098
        Sitting, Change at Week 14 (n =5, 11)
    -3.00 ± 14.799
    -0.91 ± 13.308
        Sitting, Change at Week 18 (n =3, 11)
    -0.33 ± 8.622
    1.09 ± 10.606
        Sitting, Change at Week 22 (n =2, 10)
    -12.00 ± 8.485
    4.30 ± 12.056
        Sitting, Change at Week 26/ET (n =8, 13)
    -2.50 ± 11.452
    -2.69 ± 8.5787
        Sitting, Change at Follow-up (n =4, 3)
    -2.50 ± 9.469
    2.67 ± 12.858
        Standing, Baseline (n =9, 12)
    80.00 ± 11.303
    83.08 ± 13.554
        Standing, Change at Week 1 (n =8, 11)
    2.75 ± 9.270
    1.09 ± 11.709
        Standing, Change at Week 2 (n =6, 11)
    5.33 ± 7.528
    7.18 ± 12.131
        Standing, Change at Week 4 (n =6, 11)
    2.67 ± 10.270
    1.27 ± 17.641
        Standing, Change at Week 6 (n =5, 10)
    -3.00 ± 6.000
    0.70 ± 13.857
        Standing, Change at Week 10 (n =4, 10)
    6.00 ± 10.066
    -0.20 ± 12.017
        Standing, Change at Week 14 (n =5, 10)
    -2.20 ± 13.236
    -6.00 ± 10.914
        Standing, Change at Week 18 (n =3, 10)
    -2.00 ± 6.928
    2.30 ± 13.639
        Standing, Change at Week 22 (n =2, 10)
    -10.00 ± 2.828
    2.50 ± 12.095
        Standing, Change at Week 26/ET (n =7, 12)
    2.86 ± 14.381
    -0.33 ± 10.680
        Standing, Change at Follow-up (n =3, 2)
    -3.33 ± 4.619
    -1.00 ± 21.213
    No statistical analyses for this end point

    Secondary: Change From Baseline in Height and Waist Circumference at Week 6, 26/ Early Termination Visit (ET) and Follow-up Visit

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    End point title
    		 Change From Baseline in Height and Waist Circumference at Week 6, 26/ Early Termination Visit (ET) and Follow-up Visit
    End point description
    Change from baseline in height and waist circumference in centimeter (cm) was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 6, 26/Early Termination (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: cm
    arithmetic mean (standard deviation)
        Height, Baseline (n =10, 13)
    159.82 ± 10.182
    161.69 ± 11.996
        Height, Change at Week 6 (n =6, 11)
    0.27 ± 0.455
    0.77 ± 0.984
        Height, Change at Week 26/ET (n =7, 13)
    2.04 ± 1.938
    0.55 ± 1.535
        Height, Change at Follow-up (n =3, 3)
    0.90 ± 1.562
    2.42 ± 1.413
        Waist Circumference, Baseline (n 10, 13)
    78.89 ± 11.278
    80.23 ± 13.981
        Waist Circumference, Change at Week 6 (n =6, 11)
    -0.94 ± 2.483
    2.23 ± 7.527
        Waist Circumference,Change at Week 26/ET(n =7,13)
    -1.02 ± 2.278
    1.29 ± 4.210
        Waist Circumference, Change at Follow-up (n =3, 3)
    -6.40 ± 13.777
    2.01 ± 3.778
    No statistical analyses for this end point

    Secondary: Change From Baseline in Body Weight at Week 6, 26/ Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Body Weight at Week 6, 26/ Early Termination Visit and Follow-up Visit
    End point description
    Change from baseline in body weight in kilogram (kg) was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 6, 26/Early Termination (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: kg
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    57.76 ± 17.634
    62.40 ± 19.375
        Change at Week 6 (n =6, 11)
    0.82 ± 1.343
    0.78 ± 2.530
        Change at Week 26/Early Termination (n =7, 13)
    1.62 ± 2.528
    2.33 ± 4.431
        Change at Follow-up (n =3, 3)
    1.47 ± 1.629
    4.68 ± 2.639
    No statistical analyses for this end point

    Secondary: Change From Baseline in Body Mass Index (BMI) at Week 6, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Body Mass Index (BMI) at Week 6, 26/Early Termination Visit and Follow-up Visit
    End point description
    Change from baseline in BMI in kilogram per meter square (kg/m^2) was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 6, 26/Early Termination (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: kg/m^2
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    22.31 ± 5.081
    23.37 ± 4.709
        Change at Week 6 (n =6, 11)
    0.38 ± 0.519
    0.91 ± 2.234
        Change at Week 26/Early Termination (n =7, 13)
    0.19 ± 0.954
    0.78 ± 1.800
        Change at Follow-up (n =3, 3)
    0.35 ± 0.589
    1.54 ± 1.447
    No statistical analyses for this end point

    Secondary: Change From Baseline in Body Mass Index (BMI) Z-score at Week 6, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Body Mass Index (BMI) Z-score at Week 6, 26/Early Termination Visit and Follow-up Visit
    End point description
    BMI z-score was reported using the Children’s Hospital of Philadelphia z-score calculator. Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 6, 26/Early Termination (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    0.58 ± 1.187
    1.06 ± 0.852
        Change at Week 6 (n =6, 11)
    0.12 ± 0.122
    -0.02 ± 0.511
        Change at Week 26/Early Termination (n =7, 13)
    0.21 ± 0.747
    0.11 ± 0.506
        Change at Follow-up (n =3, 3)
    0.01 ± 0.207
    0.26 ± 0.330
    No statistical analyses for this end point

    Secondary: Change From Baseline in Heart Rate at Day 1, Week 1, 2, 4, 6, 14, 22, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Heart Rate at Day 1, Week 1, 2, 4, 6, 14, 22, 26/Early Termination Visit and Follow-up Visit
    End point description
    Change from baseline in heart rate in beats per minute was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows. “99999” signifies that standard deviation was not estimable as only 1 subject was evaluable at specified instances.
    End point type
    Secondary
    End point timeframe
    Baseline (Baseline visit in the double-blind study A1281198), Day 1 (last measurement from A1281198), Week 1, 2, 4, 6, 14, 22, 26/ET (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: beats per minute
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    77.8 ± 9.19
    71.5 ± 14.12
        Change at Day 1 (n =8, 12)
    -4.0 ± 9.40
    -1.2 ± 9.09
        Change at Week 1 (n =9, 12)
    -2.0 ± 19.24
    0.4 ± 16.12
        Change at Week 2 (n =7, 12)
    7.4 ± 16.69
    5.0 ± 16.28
        Change at Week 4 (n =7, 12)
    -7.3 ± 8.08
    0.4 ± 13.20
        Change at Week 6 (n =6, 11)
    -5.0 ± 13.04
    -3.9 ± 14.49
        Change at Week 14 (n =5, 11)
    -0.6 ± 15.22
    -2.6 ± 15.23
        Change at Week 22 (n =2, 10)
    -5.0 ± 0.00
    0.3 ± 16.99
        Change at Week 26/Early Termination (n =8, 13)
    -7.8 ± 12.33
    -3.0 ± 8.69
        Change at Follow-up (n =1, 1)
    -15.0 ± 99999
    -13.0 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Electrocardiogram (ECG) Parameters at Day 1, Week 1, 2, 4, 6, 14, 22, 26/Early Termination Visit (ET) and Follow-up Visit

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    End point title
    		 Change From Baseline in Electrocardiogram (ECG) Parameters at Day 1, Week 1, 2, 4, 6, 14, 22, 26/Early Termination Visit (ET) and Follow-up Visit
    End point description
    Change from baseline in PR interval, QT interval corrected using the Bazett’s correction (QTcB), QT interval corrected using the Fridericia's formula (QTcF), QT interval, RR interval, QRS duration in millisecond (msec) was reported. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows. “99999” signifies that standard deviation was not estimable as only 1 subject was evaluable at specified instances.
    End point type
    Secondary
    End point timeframe
    Baseline (Baseline visit in the double-blind study A1281198), Day 1 (last measurement from A1281198), Week 1, 2, 4, 6, 14, 22, 26/ET (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: msec
    arithmetic mean (standard deviation)
        PR interval, Baseline (n =10, 13)
    145.3 ± 14.77
    148.5 ± 14.47
        PR interval, Change at Day 1 (n =8, 12)
    1.0 ± 9.07
    0.4 ± 10.25
        PR interval, Change at Week 1 (n =9, 12)
    3.6 ± 14.17
    -2.6 ± 9.17
        PR interval, Change at Week 2 (n =7, 12)
    -4.6 ± 9.22
    2.3 ± 11.69
        PR interval, Change at Week 4 (n =7, 12)
    3.0 ± 5.16
    1.1 ± 10.17
        PR interval, Change at Week 6 (n =6, 11)
    0.0 ± 12.60
    4.0 ± 10.89
        PR interval, Change at Week 14 (n =5, 11)
    -6.8 ± 4.87
    -2.0 ± 9.42
        PR interval, Change at Week 22 (n =2, 10)
    12.5 ± 17.68
    1.7 ± 9.25
        PR interval, Change at Week 26/ET (n =8, 13)
    -0.3 ± 7.76
    -0.9 ± 12.70
        PR interval, Change at Follow-up (n =1, 1)
    -3.0 ± 99999
    17.0 ± 99999
        QTcB interval, Baseline (n =10, 13)
    415.8 ± 16.13
    412.4 ± 18.87
        QTcB interval, Change at Day 1 (n =8, 12)
    1.0 ± 13.31
    2.2 ± 15.72
        QTcB interval, Change at Week 1 (n =9, 12)
    1.2 ± 18.34
    15.6 ± 21.74
        QTcB interval, Change at Week 2 (n =7, 12)
    6.4 ± 17.58
    11.4 ± 24.01
        QTcB interval, Change at Week 4 (n =7, 12)
    -7.4 ± 9.36
    2.9 ± 18.81
        QTcB interval, Change at Week 6 (n =6, 11)
    9.0 ± 23.04
    0.2 ± 27.75
        QTcB interval, Change at Week 14 (n =5, 11)
    -5.0 ± 21.30
    3.9 ± 24.20
        QTcB interval, Change at Week 22 (n =2, 10)
    19.0 ± 8.49
    8.9 ± 30.94
        QTcB interval, Change at Week 26/ET (n =8, 13)
    3.0 ± 26.88
    2.5 ± 21.43
        QTcB interval, Change at Follow-up (n =1, 1)
    -14.0 ± 99999
    -5.0 ± 99999
        QTcF interval, Baseline (n =10, 13)
    398.5 ± 14.80
    401.8 ± 18.57
        QTcF interval, Change at Day 1 (n =8, 12)
    3.8 ± 13.36
    2.3 ± 11.40
        QTcF interval, Change at Week 1 (n =9, 12)
    3.0 ± 12.65
    14.0 ± 13.74
        QTcF interval, Change at Week 2 (n =7, 12)
    -0.3 ± 15.30
    5.8 ± 13.98
        QTcF interval, Change at Week 4 (n =7, 12)
    -1.3 ± 13.90
    1.3 ± 12.87
        QTcF interval, Change at Week 6 (n =6, 11)
    12.5 ± 17.21
    3.2 ± 18.94
        QTcF interval, Change at Week 14 (n =5, 11)
    -4.6 ± 10.01
    6.2 ± 12.62
        QTcF interval, Change at Week 22 (n =2, 10)
    23.5 ± 7.78
    7.0 ± 21.21
        QTcF interval, Change at Week 26/ET (n =8, 13)
    10.6 ± 16.77
    4.3 ± 17.51
        QTcF interval, Change at Follow-up (n =1, 1)
    0.0 ± 99999
    6.0 ± 99999
        QT interval, Baseline (n =10, 13)
    366.3 ± 21.79
    382.8 ± 35.86
        QT interval, Change at Day 1 (n =8, 12)
    9.6 ± 22.88
    2.2 ± 17.17
        QT interval, Change at Week 1 (n =9, 12)
    7.8 ± 37.06
    10.8 ± 29.55
        QT interval, Change at Week 2 (n =7, 12)
    -11.4 ± 32.93
    -4.1 ± 26.25
        QT interval, Change at Week 4 (n =7, 12)
    10.4 ± 25.34
    -2.1 ± 25.98
        QT interval, Change at Week 6 (n =6, 11)
    20.5 ± 26.71
    9.0 ± 25.65
        QT interval, Change at Week 14 (n =5, 11)
    -3.4 ± 20.70
    10.6 ± 21.47
        QT interval, Change at Week 22 (n =2, 10)
    34.0 ± 5.66
    4.1 ± 31.27
        QT interval, Change at Week 26/ET (n =8, 13)
    24.5 ± 18.90
    7.2 ± 20.99
        QT interval, Change at Follow-up (n =1,1)
    23.0 ± 99999
    26.0 ± 99999
        RR interval, Baseline (n =10, 13)
    781.0 ± 95.07
    873.6 ± 171.26
        RR interval, Change at Day 1 (n =8, 12)
    33.6 ± 100.49
    -5.7 ± 102.47
        RR interval, Change at Week 1 (n =9, 12)
    30.7 ± 203.15
    -17.7 ± 187.46
        RR interval, Change at Week 2 (n =7, 12)
    -73.3 ± 161.14
    -61.2 ± 179.08
        RR interval , Change at Week 4 (n =7, 12)
    70.1 ± 86.24
    -26.9 ± 159.35
        RR interval, Change at Week 6 (n =6, 11)
    56.5 ± 152.31
    40.6 ± 173.34
        RR interval, Change at Week 14 (n =5, 11)
    3.6 ± 157.07
    33.2 ± 169.68
        RR interval, Change at Week 22 (n =2, 10)
    69.0 ± 12.73
    -13.7 ± 208.06
        RR interval, Change at Week 26/ET (n =8, 13)
    99.1 ± 165.02
    20.4 ± 111.79
        RR interval, Change at Follow-up (n =1, 1)
    134.0 ± 99999
    134.0 ± 99999
        QRS duration, Baseline (n =10, 13)
    84.4 ± 7.23
    85.8 ± 5.90
        QRS duration, Change at Day 1 (n =8, 12)
    2.1 ± 3.76
    2.8 ± 3.41
        QRS duration, Change at Week 1 (n =9, 12)
    1.0 ± 3.54
    3.8 ± 5.64
        QRS duration, Change at Week 2 (n =7, 12)
    0.1 ± 3.24
    1.7 ± 6.31
        QRS duration, Change at Week 4 (n =7, 12)
    2.0 ± 4.16
    1.5 ± 5.25
        QRS duration, Change at Week 6 (n =6, 11)
    -0.8 ± 3.06
    2.5 ± 5.05
        QRS duration, Change at Week 14 (n =5, 11)
    -1.2 ± 4.15
    2.9 ± 7.30
        QRS duration, Change at Week 22 (n =2, 10)
    1.0 ± 2.83
    -0.3 ± 6.60
        QRS duration, Change at Week 26/ET (n =8, 13)
    3.5 ± 4.54
    3.5 ± 4.93
        QRS duration, Change at Follow-up (n =1, 1)
    -4.0 ± 99999
    11.0 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Simpson-Angus Rating Scale (SARS) Total Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit
    End point description
    SARS: 10-item clinician rated instrument to assess parkinsonian symptoms and related extrapyramidal side effects. All 10 items were anchored on a 5-point scale: range 0 (absence of condition, normal) to 4 (the most extreme form of condition). Total score is sum of individual item scores, ranged from 0 (normal) to 40 (most extreme symptoms and effects); higher score indicates more affected. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n' signifies number of subjects evaluable for each specified rows. Data for this endpoint is reported only for those time points’ categories where at least 1 reporting arm had non-zero values.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    0.4 ± 1.26
    0.0 ± 0.00
        Change at Week 1 (n =9, 12)
    -0.2 ± 0.67
    0.0 ± 0.00
        Change at Week 2 (n =7, 12)
    0.0 ± 0.00
    0.2 ± 0.39
        Change at Week 4 (n =7, 12)
    0.0 ± 0.00
    0.2 ± 0.58
        Change at Week 6 (n =6, 11)
    0.0 ± 0.00
    0.2 ± 0.40
        Change at Week 26/ Early Termination (n =8, 13)
    -0.5 ± 1.41
    0.0 ± 0.00
    No statistical analyses for this end point

    Secondary: Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Barnes Akathisia Rating Scale (BAS): Global Clinical Assessment of Akathisia Subscale Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit
    End point description
    BAS: clinician rated scale to assess akathisia by determining the degree of subjective restlessness and distress associated with restlessness. First 3 items (objective, subjective, and distress related to restlessness) were rated on a 4-point scale with range 0 (no symptoms) to 3 (maximum severity of symptoms). Item 4, global clinical assessment of akathisia, was rated on a 6-point scale range 0 (no symptoms) to 5 (maximum severity of symptoms); higher score indicates increased severity. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    0.0 ± 0.00
    0.2 ± 0.38
        Change at Week 1 (n =9, 12)
    0.0 ± 0.00
    -0.1 ± 0.29
        Change at Week 2 (n =7, 12)
    0.0 ± 0.00
    0.3 ± 1.07
        Change at Week 4 (n =7, 12)
    0.0 ± 0.00
    0.1 ± 0.29
        Change at Week 6 (n =6, 11)
    0.0 ± 0.00
    -0.2 ± 0.40
        Change at Week 10 (n =5, 11)
    0.0 ± 0.00
    -0.2 ± 0.40
        Change at Week 14 (n =5, 11)
    0.0 ± 0.00
    -0.2 ± 0.40
        Change at Week 18 (n =3, 11)
    0.0 ± 0.00
    -0.2 ± 0.40
        Change at Week 22 (n =2, 10)
    0.0 ± 0.00
    -0.2 ± 0.42
        Change at Week 26/ Early Termination (n =8, 13)
    0.0 ± 0.00
    -0.2 ± 0.38
        Change at Follow-up (n =2, 3)
    0.0 ± 0.00
    -0.3 ± 0.58
    No statistical analyses for this end point

    Secondary: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit

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    End point title
    		 Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) - Movement Cluster Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit and Follow-up Visit
    End point description
    AIMS: clinician rated 12-item scale to document occurrences of dyskinesia in subjects, specifically tardive dyskinesia. Items 1 to 10, scored as 0 (none) to 4 (severe); higher score indicates greater severity. Items 11 to 12 are questions with No or Yes response. Only the sum of the first 7 items were calculated to evaluate AIMS movement cluster score, giving it a possible score range of 0 (none) to 28 (maximum severity), higher scores indicate greater severity. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows. Data for this endpoint is reported only for those time points’ categories where at least 1 reporting arm had non-zero values.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Change at Week 2 (n =7,12)
    0.0 ± 0.00
    0.3 ± 0.87
        Change at Week 6 (n =6, 11)
    0.0 ± 0.00
    0.1 ± 0.30
    No statistical analyses for this end point

    Secondary: Number of Subjects With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS)

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    End point title
    		 Number of Subjects With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS)
    End point description
    C-SSRS:a measure used to identify and assess subjects at risk for suicide. It is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. C-SSRS items were mapped to the following C-CASA categories:completed suicide, attempted suicide (actual attempt; aborted attempt; interrupted attempt), non-suicidal self-injurious behavior, preparatory acts, suicidal ideation (wish to be dead; non-specific active suicidal thoughts [AST]; active suicidal ideation with any methods [not plan],without intent to act; active suicidal ideation with some intent to act, without specific plan; active suicidal ideation with specific plan and intent; self-injurious behavior,no suicidal intent). Safety analysis set. Here ‘n’ signifies number of subjects evaluable for each specified rows. Data for this endpoint is reported only for those time points’ categories where at least 1 reporting arm had non-zero values.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (ET, anytime till Week 26), Follow-up Visit (1 week from last dose of study medication, anytime maximum up to Week 27)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: subjects
        Week 6: Wish to be dead (n =6, 11)
    0
    1
        Week 10: Wish to be dead (n =5, 11)
    0
    1
        Week 26/ET: Wish to be dead (n =8, 13)
    0
    1
        Week 26/ET: Non-specific AST (n =8, 13)
    0
    1
        Week 26/ET: AST With No Plan, Intent (n =8, 13)
    0
    1
    No statistical analyses for this end point

    Secondary: Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Week 26/Early Termination Visit

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    End point title
    		 Change From Baseline in Children's Depression Rating Scale (CDRS-R) Total Score at Week 26/Early Termination Visit
    End point description
    CDRS-R: clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (maximum impairment). Higher scores indicated greater impairment. Total score calculated as sum of the 17 items ranged from 1 (no impairment) to 119 (maximum impairment); higher score indicated greater impairment. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Early Termination Visit (anytime till Week 26)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    68.2 ± 16.40
    67.7 ± 13.28
        Change at Week 26/Early Termination (n =8, 11)
    1.6 ± 11.60
    7.2 ± 10.13
    No statistical analyses for this end point

    Secondary: Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 1, 2, 6, 14, 22, 26/Early Termination Visit

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    End point title
    		 Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 1, 2, 6, 14, 22, 26/Early Termination Visit
    End point description
    YMRS: an 11-item scale that measured the severity of manic episodes. Four items (irritability, speech, thought content, and disruptive/ aggressive behavior) were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score was sum of score of all 11 items and ranged from 0 (no symptoms) to 60 (extreme severity of symptoms), higher score indicated higher severity of mania. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here 'n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 6, 14, 22, 26/Early Termination Visit (anytime till Week 26)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    12.7 ± 8.31
    12.0 ± 5.46
        Change at Week 1 (n =9, 12)
    0.6 ± 10.71
    -5.5 ± 6.87
        Change at Week 2 (n =7, 12)
    -3.1 ± 5.90
    -3.4 ± 7.42
        Change at Week 6 (n =6, 11)
    1.3 ± 10.01
    -3.7 ± 7.71
        Change at Week 14 (n =5, 11)
    0.8 ± 8.84
    -5.8 ± 3.95
        Change at Week 22 (n =2, 10)
    0.5 ± 9.19
    -4.0 ± 7.29
        Change at Week 26/Early Termination (n =8, 13)
    -1.9 ± 4.85
    -6.4 ± 5.50
    No statistical analyses for this end point

    Secondary: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit

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    End point title
    		 Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit
    End point description
    CGI-S: 7-point clinician rated scale to assess severity of subject's current illness state; range: 1 (normal or not ill at all) to 7 (among the most extremely ill), higher scores indicated more severity of illness. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 1, 2, 4, 6, 10, 14, 18, 22, 26/Early Termination Visit (anytime till Week 26)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    2.7 ± 1.25
    2.5 ± 0.97
        Change at Week 1 (n =9, 12)
    0.3 ± 1.12
    -0.3 ± 1.07
        Chang at Week 2 (n =7, 12)
    0.1 ± 1.21
    -0.3 ± 0.98
        Change at Week 4 (n =7, 12)
    0.0 ± 1.00
    -0.2 ± 1.40
        Change at Week 6 (n =6, 11)
    0.5 ± 1.38
    0.0 ± 1.26
        Change at Week 10 (n =5, 11)
    -0.2 ± 0.84
    -0.1 ± 0.83
        Change at Week 14 (n =5, 11)
    0.0 ± 1.00
    -0.5 ± 1.04
        Change at Week 18 (n =3, 11)
    -0.7 ± 1.15
    -0.4 ± 1.12
        Change at Week 22 (n =2, 10)
    -1.0 ± 1.41
    -0.2 ± 1.14
        Change at Week 26/Early Termination (n =8, 13)
    -0.1 ± 1.25
    -0.5 ± 1.05
    No statistical analyses for this end point

    Secondary: Change From Baseline in Children's Global Assessment Scale (CGAS) Total Score at Week 26/Early Termination Visit

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    End point title
    		 Change From Baseline in Children's Global Assessment Scale (CGAS) Total Score at Week 26/Early Termination Visit
    End point description
    CGAS: a clinician-rated global assessment item for children based on symptoms and social functioning in home, school, and community settings. Scores on this single item ranged from 1-100 (higher levels indicate greater health), with descriptive anchors for every 10-point interval. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study. Here ‘n’ signifies number of subjects evaluable for each specified rows.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, last measurement from A1281198), Week 26/Early Termination Visit (anytime till Week 26)
    End point values
    		 Double Blind Ziprasidone to Open Label Ziprasidone Double Blind Placebo to Open Label Ziprasidone
    Number of subjects analysed
    10
    13
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =10, 13)
    68.2 ± 16.40
    67.7 ± 13.28
        Change at Week 26/Early Termination (n =8, 11)
    1.6 ± 11.60
    7.2 ± 10.13
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 up to 1 week after last dose of study medication (maximum up to 27 weeks)
    Adverse event reporting additional description
    Same event may appear as both AE and SAE. An event may be categorized as serious in 1 subject and non-serious in other, or subject may experience both SAE and non-SAE. The safety analysis set included all subjects who took at least 1 dose of study medication in this open-label extension study.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Double Blind Placebo to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on placebo in study A1281198,received ziprasidone,under double-blind conditions for maximum up to Week 2,where dose was titrated up to appropriate weight-adjusted target dose per discretion of investigator to maintain optimal efficacy and tolerability.Subjects with weight >=45 kg:target dose range was total daily dose of 120-160 mg/day given in 2 divided doses with food.Subjects with weight <45 kg:target dose range was total daily dose of 60-80 mg/day given in 2 divided doses with food.Subjects who did not tolerate dose of 80 mg/day were allowed to have dose reduction and to continue study treatment at lower dose that was tolerable to them.Minimum permitted dose was 40 mg/day (20 mg BID) for all subjects.Any subject unable to tolerate ziprasidone during Week 1 was discontinued from study.After Week 2 to Week 26,for >=45 kg subjects and after Week 1 to Week 26 for <45 kg subjects,dosing was open label and flexible.Subjects were followed up for 1 Week after last dose.

    Reporting group title
    Double Blind Ziprasidone to Open Label Ziprasidone
    Reporting group description
    		 Subjects who were on ziprasidone in study A1281198, continued to receive ziprasidone, under double-blind conditions for maximum up to Week 2. Any subject if unable to tolerate the ziprasidone during Week 1 was discontinued from the study. After Week 2 to Week 26, dosing was open label and flexible. Subjects were followed up for 1 Week after last dose.

    Serious adverse events
    		 Double Blind Placebo to Open Label Ziprasidone Double Blind Ziprasidone to Open Label Ziprasidone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Double Blind Placebo to Open Label Ziprasidone Double Blind Ziprasidone to Open Label Ziprasidone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 13 (92.31%)
    7 / 10 (70.00%)
    Investigations
    Blood insulin increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Streptococcus test positive
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Ligament injury
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ligament sprain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Dystonia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Lethargy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Memory impairment
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Sedation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    Somnolence
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 10 (30.00%)
         occurrences all number
    1
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    7 / 13 (53.85%)
    0 / 10 (0.00%)
         occurrences all number
    8
    0
    Feeling abnormal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    3 / 13 (23.08%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    Vomiting
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Respiratory disorder
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Hallucination, auditory
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Helicobacter infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Feb 2019
    Protocol summary included trial design and trial treatments were amended.

    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.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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