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Safety and Maintenance of Effect of Ziprasidone Plus a Mood Stabilizer in Bipolar I Disorder (Manic or Mixed)

Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00280566
Collaborator
(none)
584
Enrollment
108
Locations
2
Arms
29
Duration (Months)
5.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if ziprasidone plus a mood stabilizer will continue to be a safe and effective treatment regimen for adults with Bipolar I Disorder (manic or mixed symptoms) after they have achieved 8 consecutive weeks of symptom improvement on the regimen.

Condition or Disease Intervention/Treatment Phase
  • Drug: Placebo
  • Drug: Ziprasidone Oral Capsule
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
584 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, 6-Month, Double-Blind Trial in Subjects With Bipolar I Disorder to Evaluate the Continued Safety and Maintenance of Effect of Ziprasidone Plus a Mood Stabilizer (vs Placebo Plus a Mood Stabilizer) Following a Minimum of 2 Months of Response to Open-Label Treatment With Both Agents
Study Start Date :
Dec 1, 2005
Actual Primary Completion Date :
May 1, 2008
Actual Study Completion Date :
May 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ziprasidone

Active treatment, double-blind, randomized arm

Drug: Ziprasidone Oral Capsule
Oral capsule formulation: Patients will be treated initially with open-label ziprasidone in the range of 40-80 mg BID for at least 10 weeks and up to 16 weeks. Patients who achieve a stable treatment regimen and whose symptoms stabilize for 8 consecutive weeks by Week 16 (Week 10 at the earliest) will be randomized. Patients randomized to ziprasidone will continue to receive the same stable treatment regimen achieved during the open-label treatment, ie, either 40 mg BID, 60 mg BID or 80 mg BID for up to 24 weeks of double-blind treatment.
Other Names:
  • Geodon, Zeldox

    		•
    Placebo Comparator: Placebo

    Placebo treatment, double-blind, randomized arm

    Drug: Placebo
    Oral capsule formulation: Patients will be treated initially with open-label ziprasidone in the range of 40-80 mg BID (twice a day) for at least 10 weeks and up to 16 weeks. Patients who achieve a stable treatment regimen and whose symptoms stabilize for 8 consecutive weeks by Week 16 (Week 10 at the earliest) will be randomized. Patients randomized to placebo will be tapered off the open-label ziprasidone by 20 mg BID every 2 days (in a double-blinded manner) until they are completely off ziprasidone and are on matching placebo capsules for up to 24 weeks of double-blind treatment.

    Outcome Measures

    Primary Outcome Measures

    1. Time to Intervention for a Mood Episode During Double Blind Period [Period 2: 24 weeks or time of early termination]

      Time to Intervention for Mood Episode (TIME) while on randomized drug after at least 8 weeks of symptom reduction on open-label ziprasidone plus mood stabilizer. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.

    Secondary Outcome Measures

    1. Time to Discontinuation for Any Reason During Double Blind Period 2 [Period 2: 24 weeks or time of early termination]

      Key Secondary endpoint is time to discontinuation for any reason. Profile of patients remaining in the trial over time.

    2. Modified Time to Intervention for a Mood Episode (TIME) [Period 2: Week 24 or time of early termination]

      Time to intervention for a mood episode or time to discontinuation for treatment related adverse events, or death due to drug, or death due to disease. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.

    3. Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period [Period 2: Weeks 1 - 24 or time of early termination]

      Period 2 Baseline = last observation in Period 1 to the start of Period 2. MRS is 11-item scale to measure mania; derived from Schedule for Affective Disorders and Schizophrenia-Change Behavior (SADS-CB). Subscales: Manic Syndrome (elevated mood, less need for sleep, excessive energy and activity, grandiosity), Behavior and Ideation (irritability, motor hyperactivity, accelerated speech, racing thoughts, poor judgment), and Impaired Insight. Racing thoughts range=0 to 2 (highest level of abnormal=2); all other items 0 to 5 (highest level of abnormal=5). Higher score = greater abnormality.

    4. Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period [Period 2: Weeks 1 - 24 or time of early termination]

      Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Clinical Global Impression Severity Score is 7-item scale rates severity of illness from 0=not assessed, 1= normal to 7=most extremely ill.

    5. Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period [Period 2: Weeks 1 - 24 or time of early termination]

      Clinical Global Impression measures 7 items in Global assessment of improvement in patient's condition; 0=not assessed, 1= very much improved to 7= very much worse.

    6. Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period [Period 2: Weeks 1 - 24 or time of early termination]

      Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. MADRS is 10-item instrument measuring depression: scales from 0=Normal to 6 = most abnormal.

    7. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period [Period 2: Weeks 4 - 24 or time of early termination]

      Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive and Negative Syndrome Scale Total Score is 30-item scale measuring severity of psychopathology (16 items), positive symptoms (7 items) and negative symptoms (7 items); scale from 1 (absent) to 7 (extreme)

    8. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period [Period 2: Weeks 4 - 24 or time of early termination]

      Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive Scale is 7-items derived from PANSS; 1 (absent), 2 (minimal) to 7 (extreme).

    9. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period [Period 2: Weeks 4 - 24 or time of early termination]

      Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Negative Scale is 7 items derived from PANSS; scale is 1 (absent) to 7 (extreme).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Adults meeting DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for Bipolar I Disorder (currently with manic or mixed symptoms)

    Exclusion Criteria:

    Ultra rapid cyclers and subjects with significant cardiovascular disease including history of QT prolongation and/or congenital long QT syndrome

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Birmingham Alabama United States 35226
    2 Pfizer Investigational Site Birmingham Alabama United States 35294
    3 Pfizer Investigational Site Birmingham Alabama United States 35924
    4 Pfizer Investigational Site Scottsdale Arizona United States 85251
    5 Pfizer Investigational Site Little Rock Arkansas United States 72223
    6 Pfizer Investigational Site Costa Mesa California United States 92626
    7 Pfizer Investigational Site Los Angeles California United States 90026
    8 Pfizer Investigational Site National City California United States 91950
    9 Pfizer Investigational Site Sacramento California United States 95823
    10 Pfizer Investigational Site San Diego California United States 92108
    11 Pfizer Investigational Site Temecula California United States 92590
    12 Pfizer Investigational Site Temecula California United States 92591
    13 Pfizer Investigational Site Altamonte Springs Florida United States 32701
    14 Pfizer Investigational Site Fort Lauderdale Florida United States 33319
    15 Pfizer Investigational Site Fort Myers Florida United States 33912
    16 Pfizer Investigational Site Jacksonville Florida United States 32216
    17 Pfizer Investigational Site Maitland Florida United States 32751
    18 Pfizer Investigational Site Miami Florida United States 33016
    19 Pfizer Investigational Site Miami Florida United States 33126
    20 Pfizer Investigational Site North Miami Florida United States 33161
    21 Pfizer Investigational Site Orlando Florida United States 32806
    22 Pfizer Investigational Site Tavares Florida United States 32778
    23 Pfizer Investigational Site Decatur Georgia United States 30033
    24 Pfizer Investigational Site Smyrna Georgia United States 30080
    25 Pfizer Investigational Site Honolulu Hawaii United States 96826
    26 Pfizer Investigational Site Des Plaines Illinois United States 60016
    27 Pfizer Investigational Site Libertyville Illinois United States 60048
    28 Pfizer Investigational Site Naperville Illinois United States 60540
    29 Pfizer Investigational Site Naperville Illinois United States 60563
    30 Pfizer Investigational Site Oak Brook Illinois United States 60523
    31 Pfizer Investigational Site Schaumburg Illinois United States 60194
    32 Pfizer Investigational Site Terre Haute Indiana United States 47802
    33 Pfizer Investigational Site Topeka Kansas United States 66606
    34 Pfizer Investigational Site Wichita Kansas United States 67207
    35 Pfizer Investigational Site Lexington Kentucky United States 40509
    36 Pfizer Investigational Site Owensboro Kentucky United States 42301
    37 Pfizer Investigational Site Baltimore Maryland United States 21285
    38 Pfizer Investigational Site Rockville Maryland United States 20852
    39 Pfizer Investigational Site Pittsfield Massachusetts United States 01201
    40 Pfizer Investigational Site Taunton Massachusetts United States 02780
    41 Pfizer Investigational Site Olive Branch Mississippi United States 38654
    42 Pfizer Investigational Site Ridgeland Mississippi United States 39157
    43 Pfizer Investigational Site Saint Charles Missouri United States 63301
    44 Pfizer Investigational Site Lincoln Nebraska United States 68506
    45 Pfizer Investigational Site Lincoln Nebraska United States 68510
    46 Pfizer Investigational Site Omaha Nebraska United States 68131
    47 Pfizer Investigational Site Las Vegas Nevada United States 89106
    48 Pfizer Investigational Site Nashua New Hampshire United States 03060
    49 Pfizer Investigational Site Paramus New Jersey United States 07652
    50 Pfizer Investigational Site Teaneck New Jersey United States 07666
    51 Pfizer Investigational Site Buffalo New York United States 14215
    52 Pfizer Investigational Site Olean New York United States 14760
    53 Pfizer Investigational Site Rochester New York United States 14618
    54 Pfizer Investigational Site Raleigh North Carolina United States 27609
    55 Pfizer Investigational Site Cincinnati Ohio United States 45267-0559
    56 Pfizer Investigational Site Columbus Ohio United States 43210
    57 Pfizer Investigational Site Toledo Ohio United States 43609
    58 Pfizer Investigational Site Bethany Oklahoma United States 73008
    59 Pfizer Investigational Site Oklahoma City Oklahoma United States 73103
    60 Pfizer Investigational Site Oklahoma City Oklahoma United States 73116
    61 Pfizer Investigational Site Media Pennsylvania United States 19063
    62 Pfizer Investigational Site Pittsburgh Pennsylvania United States 15206
    63 Pfizer Investigational Site Pittsburgh Pennsylvania United States 15213
    64 Pfizer Investigational Site Memphis Tennessee United States 38117
    65 Pfizer Investigational Site Arlington Texas United States 76012
    66 Pfizer Investigational Site Austin Texas United States 78756
    67 Pfizer Investigational Site Bellaire Texas United States 77401
    68 Pfizer Investigational Site Dallas Texas United States 75231
    69 Pfizer Investigational Site Dallas Texas United States 75390-9121
    70 Pfizer Investigational Site DeSoto Texas United States 75115
    71 Pfizer Investigational Site Houston Texas United States 77008
    72 Pfizer Investigational Site Houston Texas United States 77054
    73 Pfizer Investigational Site Houston Texas United States 77057
    74 Pfizer Investigational Site Santiago RM Chile
    75 Pfizer Investigational Site Santiago Chile
    76 Pfizer Investigational Site Angouleme France 16000
    77 Pfizer Investigational Site Brest Naval France 29240
    78 Pfizer Investigational Site Douai France 59500
    79 Pfizer Investigational Site Mulhouse France 68100
    80 Pfizer Investigational Site Berlin Germany 13509
    81 Pfizer Investigational Site Berlin Germany 14050
    82 Pfizer Investigational Site Cham Germany 93413
    83 Pfizer Investigational Site Essen Germany 45136
    84 Pfizer Investigational Site Ciudad de Guatemala Guatemala
    85 Pfizer Investigational Site Guatemala Guatemala
    86 Pfizer Investigational Site New Territories Hong Kong
    87 Pfizer Investigational Site Ellisbridge Ahmedabad India 380 006
    88 Pfizer Investigational Site Tirupati Andhra Pradesh India 517 507
    89 Pfizer Investigational Site Bangalore Karnataka India 560 010
    90 Pfizer Investigational Site Mysore Karnataka India 570004
    91 Pfizer Investigational Site Chennai Tamil Nadu India 600 003
    92 Pfizer Investigational Site Ludhiana India 141001
    93 Pfizer Investigational Site Pune India 411 030
    94 Pfizer Investigational Site Catania Italy 95123
    95 Pfizer Investigational Site Firenze Italy 50134
    96 Pfizer Investigational Site Parma Italy 43100
    97 Pfizer Investigational Site Pisa Italy 56126
    98 Pfizer Investigational Site Mexico DF Mexico 03740
    99 Pfizer Investigational Site Zapopan Jalisco Mexico 45200
    100 Pfizer Investigational Site Arkhangelskaya Obl, Primorsky Raion Russian Federation 163530
    101 Pfizer Investigational Site Khotkovo Russian Federation 141371
    102 Pfizer Investigational Site Barcelona Spain 08019
    103 Pfizer Investigational Site Barcelona Spain 08036
    104 Pfizer Investigational Site Madrid Spain 28007
    105 Pfizer Investigational Site Taipei Taiwan 110
    106 Pfizer Investigational Site Taipei Taiwan 112
    107 Pfizer Investigational Site Caracas Distrito Capital Venezuela 1010
    108 Pfizer Investigational Site Caracas Distrito Capital Venezuela 1050

    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:
    NCT00280566
    Other Study ID Numbers:
    • A1281137
    First Posted:
    Jan 23, 2006
    Last Update Posted:
    Mar 25, 2021
    Last Verified:
    Mar 1, 2021
    Additional relevant MeSH terms:
    Bipolar Disorder
    Ziprasidone

    Study Results

    Participant Flow

    Recruitment Details Trial intended to be outpatient trial. Patients hospitalized at the screening visit due to disease under study were to be stable enough for outpatient status within approximately 5 days.
    Pre-assignment Detail Period 1:open label stabilization (ziprasidone plus lithium or valproic acid mood stabilizer). Period 2:subjects stabilized for 8 weeks randomized to blinded treatment (ziprasidone plus mood stabilizer or placebo plus mood stabilizer). 241 completed Period 1, 238 summarized in Period 2: 1 subject not randomized to Period 2, 2 excluded as per note.
    Arm/Group Title Period 1 Open Label Ziprasidone Ziprasidone Placebo
    Arm/Group Description 40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy. Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period. Double-blind,randomized to placebo plus mood stabilizer. Subjects were tapered off ziprasidone onto placebo by decreasing 20 mg BID every 2 days during the first week of Period 2
    Period Title: Period 1 Open Label Ziprasidone
    STARTED 584 0 0
    COMPLETED 241 0 0
    NOT COMPLETED 343 0 0
    Period Title: Period 1 Open Label Ziprasidone
    STARTED 0 127 111
    COMPLETED 0 84 54
    NOT COMPLETED 0 43 57

    Baseline Characteristics

    Arm/Group Title Ziprasidone Placebo Total
    Arm/Group Description Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period. Double-blind,randomized to placebo plus mood stabilizer. Subjects were tapered off ziprasidone onto placebo by decreasing 20 mg BID every 2 days during the first week of Period 2 Total of all reporting groups
    Overall Participants 127 111 238
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    39.6
    (12.3)
    38.0
    (11.6)
    38.4
    (11.8)
    Sex: Female, Male (Count of Participants)
    Female
    51
    40.2%
    58
    52.3%
    109
    45.8%
    Male
    76
    59.8%
    53
    47.7%
    129
    54.2%

    Outcome Measures

    1. Primary Outcome
    Title Time to Intervention for a Mood Episode During Double Blind Period
    Description Time to Intervention for Mood Episode (TIME) while on randomized drug after at least 8 weeks of symptom reduction on open-label ziprasidone plus mood stabilizer. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.
    Time Frame Period 2: 24 weeks or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat (ITT):Subjects took at least 1 dose double blind medication and had at least 1 post randomization observation. Double Blind Period followed at least 8 weeks open-label ziprasidone plus mood stabilizer; 25 out of 127 and 36 out of 111 subjects had an intervention for a mood episode.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Mean (Standard Error) [Days]
    172.159
    (5.646)
    143.133
    (7.532)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Equality of Survival Curves across the treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0104
    Comments
    Method Log Rank
    Comments alpha = 0.05 level of significance
    2. Secondary Outcome
    Title Time to Discontinuation for Any Reason During Double Blind Period 2
    Description Key Secondary endpoint is time to discontinuation for any reason. Profile of patients remaining in the trial over time.
    Time Frame Period 2: 24 weeks or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat (ITT). Number of participants who discontinued was 43 and 57 for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 43 57
    Mean (Standard Error) [days]
    153.526
    (6.454)
    123.313
    (7.524)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments alpha = 0.05 level of significance
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0047
    Comments
    Method Log Rank
    Comments No adjustment made for multiple comparisons
    3. Secondary Outcome
    Title Modified Time to Intervention for a Mood Episode (TIME)
    Description Time to intervention for a mood episode or time to discontinuation for treatment related adverse events, or death due to drug, or death due to disease. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.
    Time Frame Period 2: Week 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat (ITT). 29 out of 127 ziprasidone subjects and 38 out of 111 placebo subjects met the modified criteria for an intervention for a mood episode
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Mean (Standard Error) [Days]
    168.145
    (5.857)
    140.325
    (7.627)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments alpha = 0.05 level of significance
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0205
    Comments No adjustment made for multiple comparisons
    Method Log Rank
    Comments
    4. Secondary Outcome
    Title Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period
    Description Period 2 Baseline = last observation in Period 1 to the start of Period 2. MRS is 11-item scale to measure mania; derived from Schedule for Affective Disorders and Schizophrenia-Change Behavior (SADS-CB). Subscales: Manic Syndrome (elevated mood, less need for sleep, excessive energy and activity, grandiosity), Behavior and Ideation (irritability, motor hyperactivity, accelerated speech, racing thoughts, poor judgment), and Impaired Insight. Racing thoughts range=0 to 2 (highest level of abnormal=2); all other items 0 to 5 (highest level of abnormal=5). Higher score = greater abnormality.
    Time Frame Period 2: Weeks 1 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 1 (n=121, 106)
    -0.2
    (3.0)
    0.8
    (5.1)
    Week 2 (n=116, 95)
    -0.4
    (4.2)
    -0.1
    (4.7)
    Week 4 (n=117,95)
    -0.6
    (3.7)
    0.2
    (5.4)
    Week 8 (n=107, 79)
    -0.3
    (5.7)
    0.8
    (5.4)
    Week 12 (n=98, 70)
    -1.0
    (4.3)
    1.2
    (8.2)
    Week 16 (n=94,65)
    -1.4
    (4.3)
    1.2
    (6.3)
    Week 20 (n=84, 58)
    -1.1
    (6.5)
    0.2
    (5.1)
    Week 24 (n=85,53)
    -1.1
    (5.5)
    0.3
    (4.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1: Difference in Change during Period 2 MMRM ANCOVA: center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1247
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.85
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7515
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.20
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.62
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3074
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.63
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.62
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0758
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.25
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.71
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0162
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.98
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.01
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.83
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0242
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.21
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0161
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.71
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.71
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    5. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period
    Description Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Clinical Global Impression Severity Score is 7-item scale rates severity of illness from 0=not assessed, 1= normal to 7=most extremely ill.
    Time Frame Period 2: Weeks 1 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 1 (n=122, 106)
    0.1
    (0.7)
    0.3
    (1.0)
    Week 2 (n=117, 95)
    0.2
    (0.9)
    0.2
    (1.0)
    Week 4 (n=117, 95)
    -0.0
    (0.7)
    0.1
    (0.9)
    Week 8 (n=107, 79)
    -0.0
    (0.8)
    -0.1
    (0.8)
    Week 12 (n=98, 70)
    -0.1
    (0.9)
    0.0
    (1.1)
    Week 16 (n=94, 65)
    -0.1
    (0.9)
    0.0
    (1.1)
    Week 20 (n=83, 58)
    -0.1
    (0.9)
    -0.2
    (1.0)
    Week 24 (n=85, 53)
    -0.2
    (1.0)
    -0.2
    (1.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0088
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.24
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.09
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3677
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.11
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0734
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.18
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.10
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9166
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.01
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.11
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2791
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.14
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1460
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.23
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7301
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.05
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8162
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.03
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    6. Secondary Outcome
    Title Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period
    Description Clinical Global Impression measures 7 items in Global assessment of improvement in patient's condition; 0=not assessed, 1= very much improved to 7= very much worse.
    Time Frame Period 2: Weeks 1 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 1 (n=122, 106)
    2.3
    (1.2)
    2.8
    (1.6)
    Week 2 (n=117, 95)
    2.4
    (1.4)
    2.6
    (1.6)
    Week 4 (n=117, 95
    2.3
    (1.2)
    2.5
    (1.5)
    Week 8 (n=107, 79)
    2.3
    (1.4)
    2.2
    (1.2)
    Week 12 (n=98, 70)
    2.2
    (1.3)
    2.2
    (1.4)
    Week 16 (n=94, 65)
    2.3
    (1.4)
    2.5
    (1.5)
    Week 20 (n=83, 58)
    2.1
    (1.4)
    2.1
    (1.4)
    Week 24 (n=85, 53)
    2.2
    (1.3)
    2.2
    (1.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0013
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.48
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1167
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.27
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.17
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0188
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.40
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.17
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3413
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.15
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2760
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.18
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.51
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.19
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1317
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.27
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1666
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.25
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    7. Secondary Outcome
    Title Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period
    Description Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. MADRS is 10-item instrument measuring depression: scales from 0=Normal to 6 = most abnormal.
    Time Frame Period 2: Weeks 1 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 1 (n=121, 106)
    -0.2
    (4.9)
    2.7
    (7.3)
    Week 2 (n=117, 95)
    1.1
    (7.4)
    2.7
    (7.1)
    Week 4 (n=117, 95)
    -0.3
    (5.3)
    1.6
    (6.0)
    Week 8 (n=107, 79)
    0.4
    (5.9)
    0.4
    (5.3)
    Week 12 (n=98, 70)
    1.1
    (5.9)
    0.6
    (5.4)
    Week 16 (n=94,65)
    1.2
    (6.3)
    0.4
    (3.9)
    Week 20 (n=84, 58)
    0.5
    (5.6)
    -0.2
    (4.9)
    Week 24 (n=85, 53)
    0.4
    (6.4)
    1.0
    (6.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0023
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.29
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.75
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1412
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.34
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.91
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0861
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.49
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.87
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5992
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.43
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5873
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.41
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.76
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2116
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.97
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.78
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1847
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.90
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.68
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9972
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.00
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    8. Secondary Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period
    Description Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive and Negative Syndrome Scale Total Score is 30-item scale measuring severity of psychopathology (16 items), positive symptoms (7 items) and negative symptoms (7 items); scale from 1 (absent) to 7 (extreme)
    Time Frame Period 2: Weeks 4 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 4 (n=123, 98)
    0.4
    (8.7)
    1.5
    (6.9)
    Week 8 (n=107, 79)
    -0.1
    (8.3)
    -0.8
    (6.0)
    Week 12 (n=98, 70)
    -0.1
    (6.5)
    0.3
    (9.4)
    Week 16 (n=94, 65)
    -0.0
    (7.1)
    0.7
    (8.7)
    Week 20 (n=84, 58)
    -0.2
    (7.4)
    -1.0
    (6.1)
    Week 24 (n=85, 53)
    -0.6
    (8.0)
    -0.9
    (7.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5954
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.49
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.93
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3414
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.89
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.93
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9745
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.23
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5627
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.85
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.47
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7410
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.36
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.10
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9632
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.04
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.88
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    9. Secondary Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period
    Description Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive Scale is 7-items derived from PANSS; 1 (absent), 2 (minimal) to 7 (extreme).
    Time Frame Period 2: Weeks 4 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 4 (n=123, 98)
    0.0
    (1.6)
    0.1
    (1.4)
    Week 8 (n=107, 79)
    -0.2
    (2.0)
    -0.2
    (1.9)
    Week 12 (n=98, 70)
    -0.3
    (1.7)
    0.3
    (3.3)
    Week 16 (n=94, 65)
    -0.4
    (1.8)
    0.0
    (2.1)
    Week 20 (n=84, 58)
    -0.2
    (2.2)
    -0.1
    (2.1)
    Week 24 (n=85, 53)
    -0.2
    (2.2)
    -0.1
    (2.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9538
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.01
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.22
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8541
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.05
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.25
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1084
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.52
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0380
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.56
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.27
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2649
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.39
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.35
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2394
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.32
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.27
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    10. Secondary Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period
    Description Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Negative Scale is 7 items derived from PANSS; scale is 1 (absent) to 7 (extreme).
    Time Frame Period 2: Weeks 4 - 24 or time of early termination

    Outcome Measure Data

    Analysis Population Description
    intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
    Arm/Group Title Ziprasidone Placebo
    Arm/Group Description Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer Randomized to Double Blind Therapy with Placebo plus mood stabilizer
    Measure Participants 127 111
    Week 4 (n=123, 98)
    0.2
    (3.1)
    0.4
    (2.2)
    Week 8 (n=107, 79)
    0.2
    (3.2)
    -0.1
    (1.8)
    Week 12 (n=98, 70)
    0.1
    (2.5)
    0.1
    (2.1)
    Week 16 (n=94, 65)
    0.3
    (3.1)
    0.4
    (2.6)
    Week 20 (n=84, 58)
    -0.0
    (2.3)
    -0.4
    (1.8)
    Week 24 (n=85, 53)
    -0.1
    (2.6)
    -0.1
    (2.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8117
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.07
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0443
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.51
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.26
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3039
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.29
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9953
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.00
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Deviation
    Value: 0.46
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1653
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.44
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ziprasidone, Placebo
    Comments Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5771
    Comments
    Method MMRM ANCOVA
    Comments MMRM ANCOVA = mixed effects repeated measures analysis of covariance.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.18
    Confidence Interval () %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Mean Difference (Final Values) = Least Squares Mean

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Period 1 Open Label Ziprasidone Ziprasidone Placebo
    Arm/Group Description 40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy. Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period. Double-blind,randomized to placebo plus mood stabilizer. Subjects were tapered off ziprasidone onto placebo by decreasing 20 mg BID every 2 days during the first week of Period 2
    All Cause Mortality
    Period 1 Open Label Ziprasidone Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Period 1 Open Label Ziprasidone Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/ (NaN) 3/ (NaN) 2/ (NaN)
    Cardiac disorders
    Arrhythmia 0/584 (0%) 1/127 (0.8%) 0/112 (0%)
    Infections and infestations
    Influenza 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Nervous system disorders
    Dystonia 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Psychiatric disorders
    Affect lability 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Anxiety 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Bipolar I disorder 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Bipolar disorder 2/584 (0.3%) 0/127 (0%) 0/112 (0%)
    Depression 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Depression suicidal 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Mania 2/584 (0.3%) 0/127 (0%) 2/112 (1.8%)
    Psychiatric decompensation 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Psychotic disorder 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Suicidal ideation 2/584 (0.3%) 2/127 (1.6%) 0/112 (0%)
    Suicide attempt 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Vascular disorders
    Thrombophlebitis 1/584 (0.2%) 0/127 (0%) 0/112 (0%)
    Other (Not Including Serious) Adverse Events
    Period 1 Open Label Ziprasidone Ziprasidone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 362/ (NaN) 22/ (NaN) 24/ (NaN)
    Gastrointestinal disorders
    Nausea 42/584 (7.2%) 0/127 (0%) 0/112 (0%)
    General disorders
    Fatigue 44/584 (7.5%) 0/127 (0%) 0/112 (0%)
    Infections and infestations
    Upper respiratory tract infection 0/584 (0%) 5/127 (3.9%) 6/112 (5.4%)
    Nervous system disorders
    Akathisia 47/584 (8%) 0/127 (0%) 0/112 (0%)
    Dizziness 49/584 (8.4%) 0/127 (0%) 0/112 (0%)
    Headache 32/584 (5.5%) 0/127 (0%) 0/112 (0%)
    Sedation 134/584 (22.9%) 0/127 (0%) 0/112 (0%)
    Somnolence 99/584 (17%) 0/127 (0%) 0/112 (0%)
    Tremor 73/584 (12.5%) 8/127 (6.3%) 4/112 (3.6%)
    Psychiatric disorders
    Insomnia 59/584 (10.1%) 7/127 (5.5%) 12/112 (10.7%)
    Mania 0/584 (0%) 3/127 (2.4%) 6/112 (5.4%)

    Limitations/Caveats

    This is a maintenance of effect design using a survival analysis methodology. In such a design it may be difficult to interpret timepoint by timepoint treatment group comparisons in MRS, CGI-S, CGI-I, MADRS, and PANSS.

    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 info 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:
    NCT00280566
    Other Study ID Numbers:
    • A1281137
    First Posted:
    Jan 23, 2006
    Last Update Posted:
    Mar 25, 2021
    Last Verified:
    Mar 1, 2021