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Adjunctive Ziprasidone in the Treatment of Bipolar I Depression

Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00483548
Collaborator
(none)
298
Enrollment
70
Locations
2
Arms
14
Duration (Months)
4.3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if a treatment regimen of ziprasidone plus a mood stabilizer is safe and effective in the short term treatment of Bipolar I Depression. Ziprasidone will be added to lithium, valproate or lamotrigine after the patient has been on a therapeutic dose of one of these mood stabilizers for at least 4 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
298 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Six-Week, Double-Blind, Multicenter, Placebo Controlled Study Evaluating The Efficacy And Safety Of Flexible Doses Of Oral Ziprasidone As Add-On, Adjunctive Therapy With Lithium, Valproate Or Lamotrigine In Bipolar I Depression
Study Start Date :
Oct 1, 2007
Actual Primary Completion Date :
Dec 1, 2008
Actual Study Completion Date :
Dec 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ziprasidone

Active treatment, double-blind, randomized treatment arm

Drug: Ziprasidone
Oral capsule formulation to be administered every day for duration of patient's participation in the trial - 40 mg on Day 1; 40 mg twice a day (BID) on Day 2; Flexible BID dosing of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg or 160 mg total daily dose from Day 3 through Week 6. Dose increases of up to 40 mg/day can occur after subject has received previous lower dose for at least 1 day.
Other Names:
  • Geodon, Zeldox

    		•
    Placebo Comparator: Placebo

    Inactive, placebo treatment, double-blind, randomized arm

    Drug: Placebo
    Matching placebo oral capsules to be administered as per the instructions for the ziprasidone arm

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [Baseline, Week 6]

      MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.

    Secondary Outcome Measures

    1. Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S) [Baseline, Week 6]

      CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scored from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

    2. MADRS Remission: Number of Subjects With Total MADRS Score ≤ 12 at Week 6 [Week 6]

      Number of subjects with MADRS total score ≤ 12 (indicates remission). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms).

    3. MADRS Response: Number of Subjects With Total MADRS Score Reduction ≥ 50 Percent From Baseline at Week 6 [Week 6]

      Number of subjects with reduction of ≥50 percent (%) in MADRS total score (indicates response). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Reduction calculated as ([A-B]/B*100): A=value at observation; B=baseline value.

    4. Clinical Global Impression - Improvement Scale (CGI-Improvement or CGI-I): Number of Subjects With Response (Much Improved or Very Much Improved) at Week 6 [Baseline, Week 6]

      Number of subjects with improvement defined as CGI-I response of 1 (very much improved) or 2 (much improved). CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected.

    5. Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 5]

      MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.

    6. Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 5]

      CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

    7. CGI-Improvement Score [Week 1, Week 2, Week 3, Week 4, Week 5, Week 6]

      CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected. Week 6 is the primary timepoint.

    8. Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score [Baseline, Week 2, Week 4, Week 6]

      HAM-A is a clinician rated 14-item scale that rates the intensity of psychic anxiety (items 1 to 6 and item 14) and somatic anxiety (items 7 to 13) on a 5-point severity scale; scores range from 0 (not present) to 4 (very severe); lower score indicates less affected. Change calculated as a difference between post-baseline observation and baseline HAM-A score values. Week 6 is the primary timepoint.

    9. Change From Baseline in Young Mania Rating Scale (YMRS) Total Score [Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6]

      YMRS is clinician rated 11-item scale (elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech [rate and amount], language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight) used to assess the severity of manic symptoms and effect of treatment on mania severity. Seven items ranked on scale from 0 to 4; 4 items ranked 0 to 8. Higher scores indicate greater severity. Change calculated as a difference between post-baseline observation and baseline YMRS score values. Week 6 is the primary timepoint.

    10. Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6 [Baseline, Week 6]

      GAF is a clinician rated scale to measure the severity of illness-related impairment in psychological, social, and occupational functioning using a 100-point scale (single score of 1 to 100) with 100 indicating a superior level of function. Change calculated as a difference between post-baseline observation and baseline GAF score values.

    11. Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3) [Baseline, Week 6]

      SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.

    12. Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5) [Baseline, Week 6]

      SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.

    13. Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6 [Baseline, Week 6]

      Q-LES-Q is a 16-item subject rated scale to measure satisfaction with areas of daily functioning (physical health, social relationships, medication, and overall life satisfaction); rated on a 5-point Likert scale: higher scores indicate greater enjoyment and satisfaction with general life activities. Scores for items 1 to 14 are summed for a total score and converted to 0 to 100 range. Items 15 and 16 measure satisfaction with medication and overall satisfaction and are analyzed separately. Change calculated as a difference between post-baseline observation and baseline Q-LES-Q score values.

    Other Outcome Measures

    1. Change From Baseline in Simpson Angus Scale (SAS) Score [Baseline, Week 2, Week 4, Week 6]

      SAS is a clinician rated 10-item scale to measure extrapyramidal side effects (Parkinsonism or Parkinsonian side effects induced with antipsychotics); rated on a 5-point scale with range 0 (absence of condition) to 4 (presence of condition in extreme form). Global score is sum of all scores divided by the total number of items. Change calculated as a difference between post-baseline observation and baseline SAS score values.

    2. Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS) [Baseline, Week 2, Week 4, Week 6]

      BARS is a clinician rated scale to evaluate akathisia associated with use of antipsychotic medications: objective motor restlessness, range 0 to 3; subjective complaints of restlessness and associated distress, range 0 to 3; global clinical assessment of akathisia, range 0 to 5. Higher scores indicate more affected. Change calculated as a difference between post-baseline observation and baseline BARS score values.

    3. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores [Baseline, Week 2, Week 4, Week 6]

      AIMS is a clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe); items 11 to 14 are No or Yes response to dental status and sleep movements and are assessed separately. AIMS total score is sum of first 7 items. Change calculated as a difference between post-baseline observation and baseline AIMS score values.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for Bipolar I disorder, most recent episode depressed, with or without rapid cycling and without psychotic features. Subjects receive therapeutic dose of lithium, valproate or lamotrigine for at least 4 weeks prior to randomization.
    Exclusion Criteria:

    • Patients with ultra-fast rapid cycling (8 or more mood episodes per year)

    • Significant heart disease including abnormalities in the heart's rhythm (QT prolongation)

    • Psychotic symptoms (hallucinations and/or delusions).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Chandler Arizona United States 85226
    2 Pfizer Investigational Site Litchfield Park Arizona United States 85340
    3 Pfizer Investigational Site Little Rock Arkansas United States 72211
    4 Pfizer Investigational Site Little Rock Arkansas United States 72223
    5 Pfizer Investigational Site Springdale Arkansas United States 72762
    6 Pfizer Investigational Site Costa Mesa California United States 92627
    7 Pfizer Investigational Site Oceanside California United States 92056
    8 Pfizer Investigational Site San Diego California United States 92108
    9 Pfizer Investigational Site Torrance California United States 90502
    10 Pfizer Investigational Site Boca Raton Florida United States 33486-1340
    11 Pfizer Investigational Site Boca Raton Florida United States 33486
    12 Pfizer Investigational Site Jacksonville Florida United States 32256-2006
    13 Pfizer Investigational Site Orlando Florida United States 32806
    14 Pfizer Investigational Site Saint Petersburg Florida United States 33702
    15 Pfizer Investigational Site Sanford Florida United States 32771
    16 Pfizer Investigational Site West Palm Beach Florida United States 33407
    17 Pfizer Investigational Site Chicago Illinois United States 60640
    18 Pfizer Investigational Site Skokie Illinois United States 60077
    19 Pfizer Investigational Site Greenwood Indiana United States 46143
    20 Pfizer Investigational Site Indianapolis Indiana United States 46260
    21 Pfizer Investigational Site Topeka Kansas United States 66606
    22 Pfizer Investigational Site Wichita Kansas United States 67207
    23 Pfizer Investigational Site Lake Charles Louisiana United States 70601
    24 Pfizer Investigational Site Rockville Maryland United States 20852
    25 Pfizer Investigational Site Boston Massachusetts United States 02135
    26 Pfizer Investigational Site Watertown Massachusetts United States 02472
    27 Pfizer Investigational Site Clinton Township Michigan United States 48038
    28 Pfizer Investigational Site Saint Charles Missouri United States 63301
    29 Pfizer Investigational Site Saint Louis Missouri United States 63044-2588
    30 Pfizer Investigational Site Lincoln Nebraska United States 68510
    31 Pfizer Investigational Site Nashua New Hampshire United States 03060
    32 Pfizer Investigational Site Cherry Hill New Jersey United States 08002
    33 Pfizer Investigational Site Clementon New Jersey United States 08021
    34 Pfizer Investigational Site Brooklyn New York United States 11201
    35 Pfizer Investigational Site Glen Oaks New York United States 11004
    36 Pfizer Investigational Site New York New York United States 10023
    37 Pfizer Investigational Site Olean New York United States 14760
    38 Pfizer Investigational Site Rochester New York United States 14618
    39 Pfizer Investigational Site Staten Island New York United States 10312
    40 Pfizer Investigational Site Chapel Hill North Carolina United States 27599
    41 Pfizer Investigational Site Cincinnati Ohio United States 45227
    42 Pfizer Investigational Site Cincinnati Ohio United States 45267-0516
    43 Pfizer Investigational Site Columbus Ohio United States 43210
    44 Pfizer Investigational Site Dayton Ohio United States 45408
    45 Pfizer Investigational Site Oklahoma City Oklahoma United States 73116
    46 Pfizer Investigational Site Oklahoma City Oklahoma United States 73119
    47 Pfizer Investigational Site Portland Oregon United States 97210
    48 Pfizer Investigational Site Philadelphia Pennsylvania United States 19104
    49 Pfizer Investigational Site Philadelphia Pennsylvania United States 19139
    50 Pfizer Investigational Site Memphis Tennessee United States 38117
    51 Pfizer Investigational Site Austin Texas United States 78754
    52 Pfizer Investigational Site Austin Texas United States 78756
    53 Pfizer Investigational Site Houston Texas United States 77040
    54 Pfizer Investigational Site Houston Texas United States 77074
    55 Pfizer Investigational Site Lake Jackson Texas United States 77566
    56 Pfizer Investigational Site Charlottesville Virginia United States 22903
    57 Pfizer Investigational Site Kirkland Washington United States 98033
    58 Pfizer Investigational Site Richland Washington United States 99352
    59 Pfizer Investigational Site Seattle Washington United States 98104
    60 Pfizer Investigational Site Brown Deer Wisconsin United States 53223
    61 Pfizer Investigational Site Westmead New South Wales Australia 2145
    62 Pfizer Investigational Site Everton Park Queensland Australia 4053
    63 Pfizer Investigational Site Spring Hill Queensland Australia 4000
    64 Pfizer Investigational Site Richmond Victoria Australia 3121
    65 Pfizer Investigational Site Ellisbridge Ahmedabad India 380 006
    66 Pfizer Investigational Site Ahmedabad Gujarat India 380 006
    67 Pfizer Investigational Site Aurangabad Maharashtra India 431005
    68 Pfizer Investigational Site Pune Maharashtra India 411 001
    69 Pfizer Investigational Site Pune Maharashtra India 411 004
    70 Pfizer Investigational Site Delhi New Delhi India 110027

    Sponsors and Collaborators

    • Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00483548
    Other Study ID Numbers:
    • A1281158
    First Posted:
    Jun 7, 2007
    Last Update Posted:
    Mar 10, 2021
    Last Verified:
    Feb 1, 2021
    Additional relevant MeSH terms:
    Depression
    Depressive Disorder
    Bipolar Disorder
    Ziprasidone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Period Title: Overall Study
    STARTED 148 150
    Received Study Treatment 147 147
    COMPLETED 88 104
    NOT COMPLETED 60 46

    Baseline Characteristics

    Arm/Group Title Ziprasidone Placebo Total
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Total of all reporting groups
    Overall Participants 147 147 294
    Age, Customized (participants) [Number]
    Between 18 and 65 years
    147
    100%
    146
    99.3%
    293
    99.7%
    >65 years
    0
    0%
    1
    0.7%
    1
    0.3%
    Sex: Female, Male (Count of Participants)
    Female
    89
    60.5%
    91
    61.9%
    180
    61.2%
    Male
    58
    39.5%
    56
    38.1%
    114
    38.8%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
    Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat analysis set (ITT): all randomized subjects who received at least 1 dose of double-blind treatment and had at least 1 post-baseline primary efficacy evaluation.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Mean (Standard Deviation) [scores on scale]
    -14.7
    (10.7)
    -13.2
    (10.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments N=141 per arm (282 total) needed for 85% power for 2-sided alpha=0.05 based on true mean difference=4.0 and standard deviation (SD)=11.0 for primary endpoint. Interim Analysis (IA) planned when 60% of subjects had completed study or discontinued prematurely to assess efficacy (nominal 2-sided p-value less than or equal to [≤] 0.0076) or futility (nominal 2-sided p-value greater than or equal to [≥] 0.5099).
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7921
    Comments Due to planned interim analysis of primary endpoint, to control type I error at 2-sided alpha=0.05, a nominal 2-sided p-value ≤0.0476 needed at final analysis to reject the null hypothesis of no treatment effect.
    Method ANCOVA Mixed-effects repeated-measures
    Comments No other adjustment made for multiple comparisons since all comparisons, except for single primary comparison, are considered secondary.
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.36
    Confidence Interval () 95%
    -3.07 to 2.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.37
    Estimation Comments Mixed-effects repeated-measures (MMRM) analysis of covariance model: fixed categorical effects of treatment, country, mood stabilizer type, visit, treatment-by-visit interaction, fixed continuous effect of baseline value and subject as random effect.
    2. Secondary Outcome
    Title Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S)
    Description CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scored from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Mean (Standard Deviation) [scores on scale]
    -1.5
    (1.3)
    -1.5
    (1.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; MMRM analysis of covariance model with fixed categorical effects of treatment, country, type of mood stabilizer, visit, treatment-by-visit interaction, fixed continuous effect of baseline value and subject as random effect.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7223
    Comments
    Method ANCOVA Mixed-effects repeated-measures
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.06
    Confidence Interval () 95%
    -0.25 to 0.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments
    3. Secondary Outcome
    Title MADRS Remission: Number of Subjects With Total MADRS Score ≤ 12 at Week 6
    Description Number of subjects with MADRS total score ≤ 12 (indicates remission). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms).
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; Last observation carried forward (LOCF)
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Number [participants]
    48
    32.7%
    54
    36.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5029
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.846
    Confidence Interval () 95%
    0.52 to 1.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio measures the odds of achieving remission (MADRS total score ≤ 12) from ziprasidone treated subjects versus placebo; a value > 1 favors ziprasidone.
    4. Secondary Outcome
    Title MADRS Response: Number of Subjects With Total MADRS Score Reduction ≥ 50 Percent From Baseline at Week 6
    Description Number of subjects with reduction of ≥50 percent (%) in MADRS total score (indicates response). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Reduction calculated as ([A-B]/B*100): A=value at observation; B=baseline value.
    Time Frame Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Number [participants]
    62
    42.2%
    65
    44.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8266
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.949
    Confidence Interval () 95%
    0.59 to 1.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio measures the odds of achieving response (≥ 50 % reduction in MADRS total score) from ziprasidone treated subjects versus placebo; a value > 1 favors ziprasidone.
    5. Secondary Outcome
    Title Clinical Global Impression - Improvement Scale (CGI-Improvement or CGI-I): Number of Subjects With Response (Much Improved or Very Much Improved) at Week 6
    Description Number of subjects with improvement defined as CGI-I response of 1 (very much improved) or 2 (much improved). CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Number [participants]
    66
    44.9%
    69
    46.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7924
    Comments Logistic regression model with treatment, country, and type of mood stabilizer.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.939
    Confidence Interval () 95%
    0.59 to 1.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
    Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.
    Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 1 (n=142, 141)
    -8.1
    (7.9)
    -6.1
    (7.3)
    Week 2 (n=121, 139)
    -11.7
    (8.9)
    -9.0
    (8.6)
    Week 3 (n=115, 130)
    -13.0
    (9.5)
    -11.0
    (9.2)
    Week 4 (n=106, 122)
    -14.1
    (9.6)
    -11.8
    (9.5)
    Week 5 (n=103, 112)
    -14.9
    (9.4)
    -13.3
    (10.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0594
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -1.68
    Confidence Interval () 95%
    -3.42 to 0.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.89
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2230
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -1.25
    Confidence Interval () 95%
    -3.27 to 0.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.03
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6971
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.43
    Confidence Interval () 95%
    -2.57 to 1.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.09
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5485
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.68
    Confidence Interval () 95%
    -2.89 to 1.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.12
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8322
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.25
    Confidence Interval () 95%
    -2.60 to 2.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.19
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
    Description CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.
    Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 1 (n=142, 141)
    -0.5
    (0.8)
    -0.4
    (0.8)
    Week 2 (n=120, 139)
    -0.9
    (1.1)
    -0.7
    (0.9)
    Week 3 (n=115, 130)
    -0.9
    (1.0)
    -0.9
    (1.0)
    Week 4 (n=106, 122)
    -1.1
    (1.1)
    -1.1
    (1.1)
    Week 5 (n=103, 112)
    -1.3
    (1.2)
    -1.3
    (1.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1771
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.12
    Confidence Interval () 95%
    -0.29 to 0.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.09
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1765
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.15
    Confidence Interval () 95%
    -0.37 to 0.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.11
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6765
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.05
    Confidence Interval () 95%
    -0.27 to 0.18
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.11
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9770
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.00
    Confidence Interval () 95%
    -0.24 to 0.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.12
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7907
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.04
    Confidence Interval () 95%
    -0.30 to 0.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    8. Secondary Outcome
    Title CGI-Improvement Score
    Description CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected. Week 6 is the primary timepoint.
    Time Frame Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 1 (n=142, 141)
    3.2
    (0.9)
    3.4
    (0.8)
    Week 2 (n=120, 138)
    2.9
    (1.1)
    3.1
    (1.0)
    Week 3 (n=115, 130)
    2.7
    (1.0)
    2.9
    (1.0)
    Week 4 (n=106, 122)
    2.6
    (1.2)
    2.8
    (1.2)
    Week 5 (n=103, 112)
    2.5
    (1.2)
    2.6
    (1.1)
    Week 6 (n=92, 108)
    2.4
    (1.2)
    2.4
    (1.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0392
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.22
    Confidence Interval () 95%
    -0.43 to -0.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.11
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2803
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.14
    Confidence Interval () 95%
    -0.38 to 0.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 3; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9835
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.00
    Confidence Interval () 95%
    -0.26 to 0.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7062
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.06
    Confidence Interval () 95%
    -0.34 to 0.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 5; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9518
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.01
    Confidence Interval () 95%
    -0.31 to 0.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4757
    Comments Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.11
    Confidence Interval () 95%
    -0.20 to 0.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score
    Description HAM-A is a clinician rated 14-item scale that rates the intensity of psychic anxiety (items 1 to 6 and item 14) and somatic anxiety (items 7 to 13) on a 5-point severity scale; scores range from 0 (not present) to 4 (very severe); lower score indicates less affected. Change calculated as a difference between post-baseline observation and baseline HAM-A score values. Week 6 is the primary timepoint.
    Time Frame Baseline, Week 2, Week 4, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 2 (n=136, 141)
    -5.6
    (6.8)
    -5.9
    (6.7)
    Week 4 (n=111, 127)
    -7.1
    (7.2)
    -7.4
    (7.6)
    Week 6 (n=100, 111)
    -8.5
    (7.9)
    -8.6
    (7.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6362
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.35
    Confidence Interval () 95%
    -1.12 to 1.82
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.75
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4565
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.59
    Confidence Interval () 95%
    -0.98 to 2.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.80
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4770
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.61
    Confidence Interval () 95%
    -1.08 to 2.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.86
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
    Description YMRS is clinician rated 11-item scale (elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech [rate and amount], language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight) used to assess the severity of manic symptoms and effect of treatment on mania severity. Seven items ranked on scale from 0 to 4; 4 items ranked 0 to 8. Higher scores indicate greater severity. Change calculated as a difference between post-baseline observation and baseline YMRS score values. Week 6 is the primary timepoint.
    Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 1 (n=142, 141)
    0.7
    (4.4)
    -0.2
    (3.5)
    Week 2 (n=121, 139)
    0.5
    (4.5)
    -0.2
    (4.3)
    Week 3 (n=115, 130)
    -0.0
    (4.5)
    -0.2
    (4.9)
    Week 4 (n=106, 122)
    -0.9
    (4.1)
    -1.1
    (4.2)
    Week 5 (n=103, 112)
    -0.9
    (3.9)
    -1.3
    (4.1)
    Week 6 (n=92, 108)
    -1.0
    (4.8)
    -0.9
    (4.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1277
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.70
    Confidence Interval () 95%
    -0.20 to 1.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2345
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.64
    Confidence Interval () 95%
    -0.41 to 1.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8337
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.13
    Confidence Interval () 95%
    -1.05 to 1.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.60
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4646
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.43
    Confidence Interval () 95%
    -0.73 to 1.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3993
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.50
    Confidence Interval () 95%
    -0.67 to 1.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7647
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.19
    Confidence Interval () 95%
    -1.08 to 1.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.65
    Estimation Comments
    11. Secondary Outcome
    Title Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6
    Description GAF is a clinician rated scale to measure the severity of illness-related impairment in psychological, social, and occupational functioning using a 100-point scale (single score of 1 to 100) with 100 indicating a superior level of function. Change calculated as a difference between post-baseline observation and baseline GAF score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; observed cases; Early Termination (ET) visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 6 (n=100, 110)
    14.7
    (13.8)
    11.2
    (12.3)
    ET (n=34, 27)
    0.0
    (7.1)
    2.8
    (9.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0108
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 4.24
    Confidence Interval () 95%
    0.99 to 7.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.65
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
    Description SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Total SDS: Week 6 (n=58, 63)
    -8.5
    (9.2)
    -3.7
    (8.2)
    Total SDS: ET (n=19, 14)
    0.2
    (6.8)
    -1.4
    (6.7)
    Work/School: Week 6 (n=58, 64)
    -2.1
    (3.5)
    -1.6
    (2.9)
    Work/School: ET (n=19, 14)
    0.4
    (3.0)
    -0.1
    (2.7)
    Social life: Week 6 (n=94, 102)
    -2.5
    (3.3)
    -1.7
    (3.2)
    Social life: ET (n=31, 23)
    -0.5
    (2.9)
    0.1
    (3.1)
    Family/Home: Week 6 (n=94, 102)
    -2.6
    (3.2)
    -1.7
    (3.3)
    Family/Home: ET (n=31, 23)
    0.2
    (2.3)
    -0.6
    (3.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Total SDS: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0010
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -4.56
    Confidence Interval () 95%
    -7.24 to -1.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.35
    Estimation Comments
    13. Secondary Outcome
    Title Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)
    Description SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Days lost: Week 6 (n=85, 93)
    -1.2
    (2.5)
    -0.7
    (2.3)
    Days lost: ET (n=29, 21)
    0.5
    (2.7)
    0.0
    (2.2)
    Days unproductive: Week 6 (n=87, 89)
    -1.6
    (2.8)
    -1.3
    (2.9)
    Days unproductive: ET (n=29, 21)
    -0.2
    (2.5)
    -0.1
    (3.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Days Lost: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1230
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.44
    Confidence Interval (2-Sided) 95%
    -1.00 to 0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Days Unproductive: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6232
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.17
    Confidence Interval (2-Sided) 95%
    -0.84 to 0.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    14. Other Pre-specified Outcome
    Title Change From Baseline in Simpson Angus Scale (SAS) Score
    Description SAS is a clinician rated 10-item scale to measure extrapyramidal side effects (Parkinsonism or Parkinsonian side effects induced with antipsychotics); rated on a 5-point scale with range 0 (absence of condition) to 4 (presence of condition in extreme form). Global score is sum of all scores divided by the total number of items. Change calculated as a difference between post-baseline observation and baseline SAS score values.
    Time Frame Baseline, Week 2, Week 4, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 2 (n=136, 141)
    0.1
    (0.8)
    -0.1
    (0.7)
    Week 4 (n=111, 126)
    0.0
    (0.8)
    0.0
    (0.6)
    Week 6 (n=100, 110)
    0.0
    (0.7)
    -0.1
    (0.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0096
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.17
    Confidence Interval () 95%
    0.04 to 0.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8134
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.02
    Confidence Interval () 95%
    -0.13 to 0.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0226
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.16
    Confidence Interval () 95%
    0.02 to 0.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments
    15. Other Pre-specified Outcome
    Title Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS)
    Description BARS is a clinician rated scale to evaluate akathisia associated with use of antipsychotic medications: objective motor restlessness, range 0 to 3; subjective complaints of restlessness and associated distress, range 0 to 3; global clinical assessment of akathisia, range 0 to 5. Higher scores indicate more affected. Change calculated as a difference between post-baseline observation and baseline BARS score values.
    Time Frame Baseline, Week 2, Week 4, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; Summarized as Global BARS; individual scores not summarized; (n)=number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Week 2 (n=135, 139)
    0.1
    (0.5)
    -0.0
    (0.4)
    Week 4 (n=111, 125)
    0.0
    (0.5)
    0.0
    (0.5)
    Week 6 (n=100, 110)
    0.0
    (0.6)
    -0.0
    (0.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0193
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.12
    Confidence Interval () 95%
    0.02 to 0.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.05
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4745
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.04
    Confidence Interval () 0.16%
    -0.07 to 0.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.06
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2613
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.07
    Confidence Interval () 95%
    -0.05 to 0.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.06
    Estimation Comments
    16. Other Pre-specified Outcome
    Title Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
    Description AIMS is a clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe); items 11 to 14 are No or Yes response to dental status and sleep movements and are assessed separately. AIMS total score is sum of first 7 items. Change calculated as a difference between post-baseline observation and baseline AIMS score values.
    Time Frame Baseline, Week 2, Week 4, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Total score: Week 2 (n=136, 142)
    0.1
    (0.7)
    -0.1
    (0.4)
    Total score: Week 4 (n=111, 127)
    -0.0
    (0.5)
    -0.0
    (0.5)
    Total score: Week 6 (n=100, 111)
    -0.0
    (0.6)
    -0.0
    (0.4)
    Global severity score: Week 2 (n=136, 142)
    0.0
    (0.4)
    -0.0
    (0.2)
    Global severity score: Week 4 (n=111, 127)
    0.0
    (0.3)
    0.0
    (0.2)
    Global severity score: Week 6 (n=100, 111)
    0.0
    (0.3)
    0.0
    (0.1)
    Incapacitation score: Week 2 (n=136, 142)
    0.0
    (0.2)
    -0.0
    (0.1)
    Incapacitation score: Week 4 (n=111, 127)
    0.0
    (0.1)
    -0.0
    (0.2)
    Incapacitation score: Week 6 (n=100, 111)
    0.0
    (0.1)
    0.0
    (0.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Total score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0271
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.11
    Confidence Interval () 95%
    0.01 to 0.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.05
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Total score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7462
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.01
    Confidence Interval () 95%
    -0.07 to 0.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.03
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Total score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9574
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.00
    Confidence Interval () 95%
    -0.08 to 0.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.04
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Global severity score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0844
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.05
    Confidence Interval () 95%
    -0.01 to 0.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.03
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Global severity score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5779
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.01
    Confidence Interval () 95%
    -0.04 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.02
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Global severity score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7455
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.01
    Confidence Interval () 95%
    -0.05 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.03
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Incapacitation score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3278
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.02
    Confidence Interval () 95%
    -0.02 to 0.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.02
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Incapacitation score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9097
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.00
    Confidence Interval () 95%
    -0.03 to 0.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.01
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Incapacitation score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9864
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.00
    Confidence Interval () 95%
    -0.04 to 0.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.02
    Estimation Comments
    17. Secondary Outcome
    Title Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
    Description Q-LES-Q is a 16-item subject rated scale to measure satisfaction with areas of daily functioning (physical health, social relationships, medication, and overall life satisfaction); rated on a 5-point Likert scale: higher scores indicate greater enjoyment and satisfaction with general life activities. Scores for items 1 to 14 are summed for a total score and converted to 0 to 100 range. Items 15 and 16 measure satisfaction with medication and overall satisfaction and are analyzed separately. Change calculated as a difference between post-baseline observation and baseline Q-LES-Q score values.
    Time Frame Baseline, Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    Measure Participants 145 145
    Total Q-LES-Q: Week 6 (n=82, 94)
    15.2
    (19.0)
    11.6
    (17.3)
    Total Q-LES-Q: ET (n=27, 17)
    -0.1
    (19.7)
    1.6
    (14.5)
    Medications: Week 6 (n=91, 93)
    0.4
    (1.2)
    0.3
    (1.1)
    Medications: ET (n=27, 20)
    -0.3
    (1.2)
    -0.4
    (0.8)
    Overall life satisfaction: Week 6 (n=94, 103)
    0.8
    (1.1)
    0.5
    (1.1)
    Overall life satisfaction: ET (n=31, 23)
    0.1
    (1.3)
    0.0
    (0.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Total Q-LES-Q: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5519
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 1.52
    Confidence Interval () 95%
    -3.50 to 6.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.54
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Medications: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5238
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value -0.09
    Confidence Interval () 95%
    -0.35 to 0.18
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Overall life satisfaction: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5360
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least squares mean
    Estimated Value 0.09
    Confidence Interval () 95%
    -0.19 to 0.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine). Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
    All Cause Mortality
    Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/147 (0.7%) 6/147 (4.1%)
    Cardiac disorders
    Palpitations 0/147 (0%) 1/147 (0.7%)
    Injury, poisoning and procedural complications
    Overdose 1/147 (0.7%) 0/147 (0%)
    Psychiatric disorders
    Bipolar I disorder 0/147 (0%) 1/147 (0.7%)
    Intentional self-injury 0/147 (0%) 1/147 (0.7%)
    Mania 0/147 (0%) 2/147 (1.4%)
    Suicidal ideation 0/147 (0%) 1/147 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/147 (0.7%) 0/147 (0%)
    Other (Not Including Serious) Adverse Events
    Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 96/147 (65.3%) 57/147 (38.8%)
    Gastrointestinal disorders
    Diarrhoea 7/147 (4.8%) 11/147 (7.5%)
    Nausea 16/147 (10.9%) 8/147 (5.4%)
    General disorders
    Fatigue 19/147 (12.9%) 6/147 (4.1%)
    Nervous system disorders
    Akathisia 8/147 (5.4%) 2/147 (1.4%)
    Dizziness 19/147 (12.9%) 9/147 (6.1%)
    Headache 17/147 (11.6%) 14/147 (9.5%)
    Sedation 21/147 (14.3%) 7/147 (4.8%)
    Somnolence 33/147 (22.4%) 7/147 (4.8%)
    Tremor 13/147 (8.8%) 10/147 (6.8%)
    Psychiatric disorders
    Anxiety 9/147 (6.1%) 1/147 (0.7%)
    Insomnia 17/147 (11.6%) 10/147 (6.8%)
    Restlessness 8/147 (5.4%) 2/147 (1.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.govCallCenter@pfizer.com
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00483548
    Other Study ID Numbers:
    • A1281158
    First Posted:
    Jun 7, 2007
    Last Update Posted:
    Mar 10, 2021
    Last Verified:
    Feb 1, 2021