3-week Study to Evaluate Efficacy and Safety of Ziprasidone With Either Lithium or Divalproex in Acutely Manic Subjects

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00312494
• Collaborator: (none)
• Enrollment: 680
• Locations: 66
• Arms: 3
• Duration (Months): 32
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

3-week study to evaluate efficacy and safety of ziprasidone with either lithium or divalproex in acutely manic subjects

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Placebo; Drug: Ziprasidone; Drug: Ziprasidone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 680 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Three-Week, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Efficacy and Safety of Add-On Oral Ziprasidone in Subjects With Acute Mania Treated With Lithium or Divalproex
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo with mood stabilizer (either lithium or divalproex)
Experimental: Ziprasidone 20-40mg twice a day (BID)	Drug: Ziprasidone; Flexible dosing, 20-40mg BID, with a mood stabilizer (either lithium or divalproex); Other Names: Geodon, Zeldox
Experimental: Ziprasidone 60-80mg BID	Drug: Ziprasidone; Flexible dosing, 60-80mg BID, with a mood stabilizer (either lithium or divalproex); Other Names: Geodon, Zeldox

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 3 in Young Mania Rating Scale (YMRS) [Baseline, Week 3]

   YMRS is an 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. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value).

Secondary Outcome Measures

1. Change From Baseline to Week 1 and Week 2 in YMRS [Baseline, Week 1, Week 2]

   YMRS is an 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. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value).

2. Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Scores [Baseline, Week 1, Week 2, Week 3]

   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) with anchors at 2-point intervals; total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as mean of (value of MADRS score at observation minus baseline value).

3. Change From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Score [Baseline, Week 1, Week 2, Week 3]

   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. Rating ranges from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score = more affected. Change calculated as mean of (value of CGI-S score at observation minus baseline value).

4. Clinical Global Impression - Improvement (CGI-I) Scale Scores [Week 1, Week 2, Week 3]

   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 Positive and Negative Syndrome Scale (PANSS) Score [Baseline, Week 3]

   PANSS is a 30-item scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Scores rated 1 (absent symptoms) to 7 (extreme); total score range 30 to 210: higher score indicates greater severity. Change calculated as mean of (value of PANSS score at observation minus baseline value).

6. Change From Baseline in Global Assessment of Functioning (GAF) Score [Baseline, Week 3]

   GAF measures the severity of illness-related impairment in psychological, social, and occupational functioning; rated on a 100-point scale (single score of 1 to 100) with 100 indicating superior functioning. Change calculated as mean of (value of GAF score at observation minus baseline value).

7. Change From Baseline in Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning (LIFE-RIFT) Score [Baseline, Week 3]

   LIFE-RIFT measures severity of illness-related impairment in 4 domains: work, interpersonal relations, recreation, and global satisfaction; has a total score and individual domain scores. Domain scores range from 1 to 5 (scores ≥ 2 reflect impaired functioning). Total score is sum of the 4 domains with range of 4 (very good) to 20 (very poor): higher scores indicate greater impairment. Change calculated as mean of (value of LIFE-RIFT score at observation minus baseline value).

8. Anonymized Pharmacogenomic Blood Draw [Baseline]

   Anonymized pharmacogenomic blood draw to evaluate the pharmacogenomic basis for ziprasidone treatment responsivity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have a primary diagnosis of Bipolar I Disorder, most recent episode manic (296.4x), or mixed (296.6x) as defined in Diagnostic and Statistical Manual of Mental Disorders - Text Revision (DSM-IV TR) and determined by the Mini International Neuropsychiatric Interview (MINI).

• At screening and at baseline (within 12 hours prior to the first dose of double-blind medication) subjects must have a Young Mania Rating Scale score of 18 or higher.

• Subjects must be actively receiving lithium or divalproex for their bipolar disorder in order to be considered for this study.

Exclusion Criteria:

• Subjects with a Diagnostic and Statistical Manual of Mental Disorders IV- Text Revision (DSM-IV TR) diagnosis of schizophrenia (295.XX), schizoaffective disorder (295.70), schizophreniform disorder (295.40), delusional disorder (297.1), or psychotic disorder not otherwise specified (NOS) (298.9).

• Subjects with other DSM-IV-TR Axis I or Axis II disorders (in addition to Bipolar I disorder) are ineligible if the comorbid condition is clinically unstable, requires treatment, or has been a primary focus of treatment within the 6-month period prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Dothan	Alabama	United States	36303
2	Pfizer Investigational Site	Scottsdale	Arizona	United States	85251
3	Pfizer Investigational Site	Little Rock	Arkansas	United States	72211
4	Pfizer Investigational Site	Cerritos	California	United States	90703
5	Pfizer Investigational Site	Costa Mesa	California	United States	92626
6	Pfizer Investigational Site	Escondido	California	United States	92025
7	Pfizer Investigational Site	Glendale	California	United States	91204
8	Pfizer Investigational Site	Huntington Beach	California	United States	92647
9	Pfizer Investigational Site	Los Angeles	California	United States	90057
10	Pfizer Investigational Site	Los Angeles	California	United States	90061
11	Pfizer Investigational Site	National City	California	United States	91950
12	Pfizer Investigational Site	Oceanside	California	United States	92056
13	Pfizer Investigational Site	San Diego	California	United States	92114
14	Pfizer Investigational Site	San Diego	California	United States	92120
15	Pfizer Investigational Site	San Diego	California	United States	92126
16	Pfizer Investigational Site	Torrance	California	United States	90505
17	Pfizer Investigational Site	Hartford	Connecticut	United States	06106
18	Pfizer Investigational Site	New Britain	Connecticut	United States	06050
19	Pfizer Investigational Site	DeLand	Florida	United States	32720
20	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33301
21	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33308
22	Pfizer Investigational Site	Gainesville	Florida	United States	32607
23	Pfizer Investigational Site	Hollywood	Florida	United States	33021
24	Pfizer Investigational Site	Jacksonville	Florida	United States	32256-2006
25	Pfizer Investigational Site	Lauderhill	Florida	United States	33119
26	Pfizer Investigational Site	North Miami	Florida	United States	33161
27	Pfizer Investigational Site	Atlanta	Georgia	United States	30308
28	Pfizer Investigational Site	Honolulu	Hawaii	United States	96813
29	Pfizer Investigational Site	Des Plaines	Illinois	United States	60016
30	Pfizer Investigational Site	Hoffman Estates	Illinois	United States	60169
31	Pfizer Investigational Site	Hoffman Estates	Illinois	United States	60194
32	Pfizer Investigational Site	Schaumburg	Illinois	United States	60194
33	Pfizer Investigational Site	Greenwood	Indiana	United States	46143
34	Pfizer Investigational Site	Prairie Village	Kansas	United States	66206
35	Pfizer Investigational Site	Glen Burnie	Maryland	United States	21061
36	Pfizer Investigational Site	Flowood	Mississippi	United States	39232
37	Pfizer Investigational Site	Kansas City	Missouri	United States	64133
38	Pfizer Investigational Site	Saint Charles	Missouri	United States	63304
39	Pfizer Investigational Site	Saint Louis	Missouri	United States	63044-2588
40	Pfizer Investigational Site	Saint Louis	Missouri	United States	63118
41	Pfizer Investigational Site	Saint Louis	Missouri	United States	63128
42	Pfizer Investigational Site	Las Vegas	Nevada	United States	89102
43	Pfizer Investigational Site	Las Vegas	Nevada	United States	89103
44	Pfizer Investigational Site	Clementon	New Jersey	United States	08021
45	Pfizer Investigational Site	Princeton	New Jersey	United States	08540
46	Pfizer Investigational Site	Amityville	New York	United States	11701
47	Pfizer Investigational Site	Buffalo	New York	United States	14215
48	Pfizer Investigational Site	Cedarhurst	New York	United States	11516
49	Pfizer Investigational Site	Elmsford	New York	United States	10523
50	Pfizer Investigational Site	Raleigh	North Carolina	United States	27609
51	Pfizer Investigational Site	Cincinnati	Ohio	United States	45219
52	Pfizer Investigational Site	Cincinnati	Ohio	United States	45220
53	Pfizer Investigational Site	Cincinnati	Ohio	United States	45267-0559
54	Pfizer Investigational Site	Cleveland	Ohio	United States	44113
55	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73112
56	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19149
57	Pfizer Investigational Site	Charleston	South Carolina	United States	29405
58	Pfizer Investigational Site	Dallas	Texas	United States	75228
59	Pfizer Investigational Site	Irving	Texas	United States	75062
60	Pfizer Investigational Site	Plano	Texas	United States	75024
61	Pfizer Investigational Site	San Antonio	Texas	United States	78229-3900
62	Pfizer Investigational Site	San Antonio	Texas	United States	78259-3509
63	Pfizer Investigational Site	Richmond	Virginia	United States	23229
64	Pfizer Investigational Site	Richmond	Virginia	United States	23230
65	Pfizer Investigational Site	Bellevue	Washington	United States	98004
66	Pfizer Investigational Site	Kirkland	Washington	United States	98033

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:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00312494
• Other Study ID Numbers: A1281143
• First Posted: Apr 10, 2006
• Last Update Posted: Mar 29, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Bipolar Disorder; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Period Title: Overall Study
STARTED	232	226	222
Received Study Treatment	223	216	217
COMPLETED	161	168	179
NOT COMPLETED	71	58	43

Baseline Characteristics

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo	Total
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer	Total of all reporting groups
Overall Participants	223	216	217	656
Age, Customized (participants) [Number]
<18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 44 years	125 56.1%	124 57.4%	126 58.1%	375 57.2%
Between 45 and 64 years	96 43%	92 42.6%	90 41.5%	278 42.4%
>=65 years	2 0.9%	0 0%	1 0.5%	3 0.5%
Sex: Female, Male (Count of Participants)
Female	100 44.8%	108 50%	110 50.7%	318 48.5%
Male	123 55.2%	108 50%	107 49.3%	338 51.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 3 in Young Mania Rating Scale (YMRS)
Description	YMRS is an 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. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value).
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

Intent to Treat population (ITT): all randomized subjects who received at least 1 dose of double-blind medication, who had 1 baseline and at least 1 post-baseline primary efficacy evaluation; excluding data from 2 sites that were closed due to Good Clinical Practices (GCP) deviations.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Least Squares Mean (Standard Error) [scores on scale]	-10.19 (0.78)	-10.95 (0.80)	-9.47 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	N=135/arm (405 total) for 85% power for 2-sample t-test (2-sided alpha=0.05) based on true mean difference=3.5 and SD=10. Interim Analysis (IA) to validate sample-size assumptions and adjust sample-size if needed. Based on IA results total sample-size increased to N=223/arm (669 total) to maintain desired power. Null Hypothesis=No statistically significant difference between add-on ziprasidone (higher, lower dose) and add-on placebo groups with respect to the population mean for primary endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1077
	Comments	The p-values reported are unadjusted for multiple comparisons. Dunnet's procedure for multiple dose comparisons to placebo was used for primary efficacy measure at Week 3.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 Mixed Model Repeated Measures (MMRM) with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline YMRS total score. Tests were 2-sided and performed at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4274
	Comments	The p-values reported are unadjusted for multiple comparisons. Dunnet's procedure for multiple dose comparisons to placebo was used for primary efficacy measure at Week 3.
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline to Week 1 and Week 2 in YMRS
Description	YMRS is an 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. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value).
Time Frame	Baseline, Week 1, Week 2

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Week 1 (n=202, 205, 200)	-4.38 (0.65)	-4.56 (0.65)	-5.10 (0.70)
Week 2 (n=178, 188, 186)	-7.10 (0.72)	-7.56 (0.73)	-8.24 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline YMRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4025
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline YMRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2830
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline YMRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4125
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline YMRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1527
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Scores
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) with anchors at 2-point intervals; total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as mean of (value of MADRS score at observation minus baseline value).
Time Frame	Baseline, Week 1, Week 2, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Week 1 (n=202, 205, 200)	-2.16 (0.52)	-2.47 (0.49)	-1.11 (0.63)
Week 2 (n=178, 188, 186)	-3.27 (0.57)	-3.24 (0.55)	-1.71 (0.66)
Week 3 (n=163, 172, 170)	-4.20 (0.63)	-3.79 (0.64)	-2.90 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0101
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0694
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0183
	Comments	The p-values reported are unadjusted for multiple comparisons
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0176
	Comments	The p-values reported are unadjusted for multiple comparisons
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2302
	Comments	The p-values reported are unadjusted for multiple comparisons
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline MADRS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0796
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Score
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. Rating ranges from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score = more affected. Change calculated as mean of (value of CGI-S score at observation minus baseline value).
Time Frame	Baseline, Week 1, Week 2, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Week 1 (n=202, 206, 200)	-0.35 (0.06)	-0.43 (0.06)	-0.39 (0.07)
Week 2 (n=178, 188, 186)	-0.70 (0.08)	-0.74 (0.07)	-0.73 (0.09)
Week 3 (n=163, 172, 171)	-0.94 (0.08)	-1.13 (0.09)	-1.00 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6191
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5629
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9049
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7153
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2420
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline as covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6121
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I) Scale Scores
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.
Time Frame	Week 1, Week 2, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Week 1 (n=202, 206, 200)	3.34 (0.09)	3.34 (0.09)	3.38 (0.08)
Week 2 (n=178, 188, 186)	3.02 (0.10)	2.91 (0.09)	2.98 (0.10)
Week 3 (n=163, 172, 171)	2.65 (0.11)	2.57 (0.11)	2.72 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6138
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 1 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6536
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4758
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 2 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7581
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2221
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, and treatment by visit interaction.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5665
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Score
Description	PANSS is a 30-item scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Scores rated 1 (absent symptoms) to 7 (extreme); total score range 30 to 210: higher score indicates greater severity. Change calculated as mean of (value of PANSS score at observation minus baseline value).
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Week 3 total score (n=198, 199, 189)	-4.87 (1.86)	-5.34 (1.68)	-3.44 (1.84)
Week 3 positive score (n=198, 199, 189)	-1.94 (0.52)	-2.26 (0.52)	-1.56 (0.56)
Week 3 negative score (n=198, 199, 189)	-0.58 (0.51)	-0.43 (0.51)	-0.20 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 total score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1063
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 total score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2499
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 positive score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS positive score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0876
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 positive score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS positive score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3623
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 negative score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS negative score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4686
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 negative score MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline PANSS negative score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2202
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Change From Baseline in Global Assessment of Functioning (GAF) Score
Description	GAF measures the severity of illness-related impairment in psychological, social, and occupational functioning; rated on a 100-point scale (single score of 1 to 100) with 100 indicating superior functioning. Change calculated as mean of (value of GAF score at observation minus baseline value).
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Least Squares Mean (Standard Error) [scores on scale]	8.79 (1.23)	9.62 (1.25)	7.79 (1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline GAF score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0728
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline GAF score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3174
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

8. Secondary Outcome

Title	Change From Baseline in Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning (LIFE-RIFT) Score
Description	LIFE-RIFT measures severity of illness-related impairment in 4 domains: work, interpersonal relations, recreation, and global satisfaction; has a total score and individual domain scores. Domain scores range from 1 to 5 (scores ≥ 2 reflect impaired functioning). Total score is sum of the 4 domains with range of 4 (very good) to 20 (very poor): higher scores indicate greater impairment. Change calculated as mean of (value of LIFE-RIFT score at observation minus baseline value).
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

ITT population excluding data from 2 sites that were closed due to GCP deviations.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	211	210	201
Least Squares Mean (Standard Error) [scores on scale]	-1.68 (0.45)	-1.58 (0.50)	-1.27 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Lower Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline LIFE-RIFT total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4460
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone (Higher Dose), Placebo
	Comments	Week 3 MMRM with model terms: treatment, length of prior lithium/divalproex usage, type of mood stabilizer therapy, rapid cycling, hospitalization status, visit, treatment by visit interaction, and baseline LIFE-RIFT total score.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3253
	Comments	The p-values reported are unadjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments

9. Secondary Outcome

Title	Anonymized Pharmacogenomic Blood Draw
Description	Anonymized pharmacogenomic blood draw to evaluate the pharmacogenomic basis for ziprasidone treatment responsivity.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All subjects eligible (optional consent); samples were not to be analyzed as part of the current protocol and the analysis was not to be covered by the statistical analysis plan.

Arm/Group Title	Ziprasidone (Higher Dose)	Ziprasidone (Lower Dose)	Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer	Ziprasidone 40 to 80 mg daily + Mood Stabilizer	Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
Measure Participants	0	0	0

Adverse Events

Adverse Event Reporting Description	Safety population: all randomized subjects who were administered at least 1 dose of double-blind medication; includes data from the 2 sites that were closed due to GCP deviations.
Arm/Group Title	Ziprasidone (Higher Dose)		Ziprasidone (Lower Dose)		Placebo
Arm/Group Description	Ziprasidone 120 to 160 mg daily + Mood Stabilizer		Ziprasidone 40 to 80 mg daily + Mood Stabilizer		Placebo (matching ziprasidone higher dose or ziprasidone lower dose) + Mood Stabilizer
All Cause Mortality
	Ziprasidone (Higher Dose)		Ziprasidone (Lower Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone (Higher Dose)		Ziprasidone (Lower Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/223 (2.2%)		4/216 (1.9%)		4/217 (1.8%)
General disorders
Chest pain	0/223 (0%)		0/216 (0%)		1/217 (0.5%)
Infections and infestations
Cellulitis	1/223 (0.4%)		0/216 (0%)		0/217 (0%)
Injury, poisoning and procedural complications
Intentional overdose	0/223 (0%)		1/216 (0.5%)		0/217 (0%)
Overdose	0/223 (0%)		1/216 (0.5%)		1/217 (0.5%)
Thermal burn	1/223 (0.4%)		0/216 (0%)		0/217 (0%)
Investigations
Blood pressure increased	0/223 (0%)		1/216 (0.5%)		0/217 (0%)
Nervous system disorders
Anterograde amnesia	0/223 (0%)		1/216 (0.5%)		0/217 (0%)
Psychiatric disorders
Acute psychosis	1/223 (0.4%)		0/216 (0%)		0/217 (0%)
Agitation	1/223 (0.4%)		0/216 (0%)		0/217 (0%)
Alcohol abuse	0/223 (0%)		1/216 (0.5%)		0/217 (0%)
Bipolar I disorder	1/223 (0.4%)		1/216 (0.5%)		1/217 (0.5%)
Drug abuse	0/223 (0%)		1/216 (0.5%)		0/217 (0%)
Emotional disorder	0/223 (0%)		0/216 (0%)		1/217 (0.5%)
Suicide attempt	0/223 (0%)		1/216 (0.5%)		1/217 (0.5%)
Other (Not Including Serious) Adverse Events
	Ziprasidone (Higher Dose)		Ziprasidone (Lower Dose)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/223 (60.1%)		99/216 (45.8%)		82/217 (37.8%)
Gastrointestinal disorders
Abdominal discomfort	6/223 (2.7%)		2/216 (0.9%)		2/217 (0.9%)
Diarrhoea	12/223 (5.4%)		10/216 (4.6%)		7/217 (3.2%)
Dry mouth	6/223 (2.7%)		1/216 (0.5%)		3/217 (1.4%)
Nausea	11/223 (4.9%)		11/216 (5.1%)		13/217 (6%)
Salivary hypersecretion	5/223 (2.2%)		4/216 (1.9%)		0/217 (0%)
Vomiting	13/223 (5.8%)		6/216 (2.8%)		4/217 (1.8%)
General disorders
Fatigue	11/223 (4.9%)		3/216 (1.4%)		5/217 (2.3%)
Infections and infestations
Nasopharyngitis	7/223 (3.1%)		1/216 (0.5%)		4/217 (1.8%)
Upper respiratory tract infection	5/223 (2.2%)		7/216 (3.2%)		5/217 (2.3%)
Metabolism and nutrition disorders
Increased appetite	1/223 (0.4%)		5/216 (2.3%)		0/217 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/223 (1.3%)		5/216 (2.3%)		1/217 (0.5%)
Musculoskeletal stiffness	4/223 (1.8%)		6/216 (2.8%)		1/217 (0.5%)
Pain in extremity	5/223 (2.2%)		7/216 (3.2%)		2/217 (0.9%)
Nervous system disorders
Akathisia	15/223 (6.7%)		8/216 (3.7%)		5/217 (2.3%)
Dizziness	16/223 (7.2%)		5/216 (2.3%)		6/217 (2.8%)
Extrapyramidal disorder	11/223 (4.9%)		4/216 (1.9%)		1/217 (0.5%)
Headache	10/223 (4.5%)		19/216 (8.8%)		16/217 (7.4%)
Sedation	33/223 (14.8%)		17/216 (7.9%)		18/217 (8.3%)
Somnolence	26/223 (11.7%)		19/216 (8.8%)		5/217 (2.3%)
Tremor	12/223 (5.4%)		6/216 (2.8%)		7/217 (3.2%)
Restlessness	6/223 (2.7%)		3/216 (1.4%)		0/217 (0%)
Psychiatric disorders
Agitation	6/223 (2.7%)		4/216 (1.9%)		1/217 (0.5%)
Anxiety	5/223 (2.2%)		2/216 (0.9%)		2/217 (0.9%)
Insomnia	8/223 (3.6%)		3/216 (1.4%)		5/217 (2.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/223 (2.2%)		1/216 (0.5%)		2/217 (0.9%)

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.