A Six-week Flexible Dose Study Evaluating the Efficacy and Safety of Geodon in Patients With Bipolar I Depression.

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00282464
• Collaborator: (none)
• Enrollment: 392
• Locations: 43
• Arms: 2
• Duration (Months): 24.9
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a 6-week trial that evaluates the efficacy and safety of Geodon (ziprasidone) in outpatient subjects ages 18 and older with Bipolar Disorder type I, depressed. Subjects are required to undergo a washout period of at least 7 days of any prior med.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 392 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Six-Week, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Efficacy and Safety of Flexible Doses of Oral Ziprasidone in Outpatients With Bipolar I Depression
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ziprasidone 20 and 60mg For the Ziprasidone arm, the Baseline card will contain 20 mg bid (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).	Drug: Geodon (Ziprasidone); Ziprasidone flexible dosing treatment arm (20-80 mg bid). For the Ziprasidone arm, the Baseline card will contain 20 mg bid (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Placebo Comparator: Placebo	Drug: Placebo; Subjects will start on placebo and remain on placebo for six weeks. All cards for the Placebo arm will be 0 mg bid.

Outcome Measures

Primary Outcome Measures

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

   Change is observed value at each visit minus baseline value. MADRS:10-item instrument measuring depression; scale range between 0(Normal) - 6(most abnormal)for each item. Total possible score is 0 - 60. Overall is average response Week 1 - Week 6.

Secondary Outcome Measures

1. Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score [Baseline to Week 6]

   Participants with MADRS Total Score greater than or equal to 50 percent decrease from baseline responded yes; others responded no. MADRS: 10-item instrument measuring depression; scale 0(Normal) & 6 (most abnormal)for each item. Total possible score is 0 - 60. Endpoint is last observation carried forward (LOCF)

2. Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score [Baseline to Week 3, Week 6]

   Participants with greater than or equal to 50 percent decrease from baseline in HAM-D 17 total score responded yes; others responded no. Total score is first 17 items of the HAM-D 25: measures range of depressive symptoms. Scale: 8 items 0-2 & 9 items 0-4, higher scores being more severe. Total possible score is 0 - 52. Endpoint is LOCF.

3. Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 [Week 1 to Week 6]

   Remission response is yes if MADRS total score less than or equal to 12; if not, response is no. MADRS: 10-item instrument measuring depression; scale 0(Normal) & 6(most abnormal).Total possible score is 0 - 60. Endpoint is LOCF.

4. Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 [Week 3, Week 6]

   Remission response is yes when HAM-D 17 total score is less than or equal to 7; if not, response is no. Total score is first 17 items of HAM-D 25, measures range of depressive symptoms. Scale: 8 items 0-2 and 9 items 0-4, higher scores more severe. Total possible score is 0 - 52. Endpoint is LOCF.

5. Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score [Baseline to Weeks 3, 6]

   Change is observed value at each visit minus baseline value. HAM-D 17 Total score is first 17 items of HAM-D 25; measures range of depressive symptoms patient currently experiencing. Scale: 8 items 0-2 & 9 items 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme. Total possible score is 0 - 52.Endpoint is LOCF

6. Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25) [Baseline to Weeks 3, 6]

   Change is observed value at each visit minus baseline value. HAM-D: 25-item instrument measuring the range of depressive symptoms patient currently experiencing. Scale: 14 items 0-2 & 11 items 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme. Total possible score is 0 - 72. Endpoint is LOCF.

7. Change in Bech Melancholia Score [Baseline to Weeks 3, 6]

   Change is observed value at each visit minus baseline value. Bech Melancholia is sum of scores on 6 Items pertaining to melancholia within HAM-D. Scale range 0 to 4; higher scores, greater severity. Total possible score is 0 - 24. Endpoint is LOCF.

8. Change in Anxiety/Somatizations Factor Total Score [Baseline to Weeks 3, 6]

   Change is observed value at each visit minus baseline value. This test is sum of Scores on 6 Items pertaining to anxiety/somatization within HAM-D. Scale range 0 to 4 with higher scores reflecting greater severity. Total possible score is 0 - 24. Endpoint is LOCF.

9. Change in Retardation Factor Scores [Baseline to Weeks 3, 6]

   Change is observed value at each visit minus baseline value. Retardation Factor is the sum of scores of 4 items which pertain to retardation within HAM-D. Scores 0 to 4, higher scores reflecting greater severity.Total possible score is 0 - 16. Endpoint is LOCF.

10. Change in Sleep Disturbance Factor Score [Baseline to Weeks 3, 6]

    Change is observed value at each visit minus baseline value. Sleep Disturbance is the sum of scores of 3 items which pertain to sleep disturbance within Hamilton Depression Rating Scale (HAM-D). Scale range 0 to 4 with higher scores reflecting greater severity. Total possible score is 0 - 12.

11. Change in Hamilton Anxiety Rating (HAM-A) [Baseline to Weeks 3, 6]

    Change is observed value at each visit minus baseline value. HAM-A:14-item scale to rate the intensity of psychic anxiety (items 1- 6, 14) and somatic anxiety (items 7-13) on a 5-point severity scale (0=not present to 4=very severe). Total possible score is 0 - 56.

12. Change in Total Score of Young Mania Rating Scale (YMRS) [Baseline to week 6]

    Change is observed value at each visit minus baseline value. YMRS: 11 item instrument with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60. Overall is average response Week 1 - 6.

13. Change in Global Clinical Severity of Symptoms (CGI-S) [Baseline to week 6]

    Change is observed value at each visit minus baseline value. CGI-S is an instrument to measure severity of mental illness. Scale range: 0 = not assessed, 1 = normal, 7 = among most extremely ill

14. Change in Global Clinical Improvement of Symptoms (CGI -I) [Baseline to Week 6]

    Change is observed value at each visit minus baseline value. CGI-I is an instrument for Global assessment of improvement in patient's condition. Scale range:0=not assessed, 1=very much improved, 7=very much worse

15. Change in Global Assessment of Functioning (GAF) [Baseline to week 6 (Endpoint)]

    Change is observed value at each visit minus baseline value. GAF is an instrument used to assess global psychological, social, & occupational functioning. Scale range: 100 = normal and 0 = greatest abnormality.

16. Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score [Baseline to week 6 (endpoint)]

    Change is observed value at each visit minus baseline value. Q-LES-Q: 16- item instrument for a patient's assessment of his/her quality of life. Scale range: overall level of satisfaction 1=very poor to 5=Very good. 1 item (medication)can be left blank. Total possible score 15 - 80.

17. Change in Sheehan Disability Scale (SDS) Total Score [Baseline to week 6 (endpoint)]

    Change is observed value at each visit minus baseline value. SDS is a patient rated measure of disability and impairment in work/school, social life, family life/home responsibilities. Scale range: 0-10 with 0=no disruption,10=extreme disruption. Total possible score is 0 - 30.

18. Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject [Baseline to week 6 (endpoint)]

    Change is observed value at each visit minus baseline value. BPCoRs: Subject interview with 20-items measuring cognitive deficits & degree of affect on functioning. Scale range:0 to 4, higher numbers, greater impairment. Total possible score is 0 - 80. Endpoint=last observation carried forward (LOCF)

19. Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating [Baseline to week 6 (endpoint)]

    Change is observed value at each visit minus baseline value. Informant Global Rating is interview with informant of subject using BPCoRS, a 20-item instrument measuring cognitive deficits & degree of affect on functioning. Scale: 0 to 4, higher numbers = greater impairment. Total possible score is 0 - 80. Endpoint is LOCF.

20. Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer [Baseline to week 6 (endpoint)]

    Change in Rating by interviewer, using BPCoRS, 20-item instrument measuring cognitive deficits and the degree of affect on functioning; 4 point scale with higher numbers reflecting greater impairment.Total possible score is 0 - 80.

21. Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at Endpoint [Baseline to Week 6 (endpoint)]

    Change is observed value at each visit minus baseline value. Subject Rating: Subject's perceived change in status using a 20-item instrument measuring cognitive deficits and degree of affect on funtioning. Scale 0 to 4, higher numbers reflecting greater impairment. Total possible score is 0 - 80. Endpoint is last observation carried forward.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects must have a primary diagnosis of Bipolar I Disorder, most recent episode depressed, with or without rapid cycling, without psychotic features, as defined in DSM-IV-TR (296.5X) and confirmed by a structured Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria:

• Subjects with a DSM-IV TR diagnosis of schizophrenia (295.XX), schizoaffective disorder (295.70), schizophreniform disorder (295.40), delusional disorder (297.1), or psychotic disorder NOS (298.9).

• Subjects with other DSM-IV TR Axis I or Axis II disorder (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	Little Rock	Arkansas	United States	77205
3	Pfizer Investigational Site	Anaheim	California	United States	92804
4	Pfizer Investigational Site	Cerritos	California	United States	90703
5	Pfizer Investigational Site	Chula Vista	California	United States	91910
6	Pfizer Investigational Site	Escondido	California	United States	92025
7	Pfizer Investigational Site	Los Angeles	California	United States	90027-5302
8	Pfizer Investigational Site	Riverside	California	United States	92506
9	Pfizer Investigational Site	San Diego	California	United States	92126
10	Pfizer Investigational Site	Santa Ana	California	United States	92705
11	Pfizer Investigational Site	Denver	Colorado	United States	80220
12	Pfizer Investigational Site	Darien	Connecticut	United States	06820
13	Pfizer Investigational Site	Boca Raton	Florida	United States	33432
14	Pfizer Investigational Site	Bradenton	Florida	United States	34208
15	Pfizer Investigational Site	Jacksonville	Florida	United States	32256-2006
16	Pfizer Investigational Site	Melbourne	Florida	United States	32901
17	Pfizer Investigational Site	Orange City	Florida	United States	32763
18	Pfizer Investigational Site	Tampa	Florida	United States	33613
19	Pfizer Investigational Site	Atlanta	Georgia	United States	30328
20	Pfizer Investigational Site	Marietta	Georgia	United States	30060
21	Pfizer Investigational Site	Eagle	Idaho	United States	83616
22	Pfizer Investigational Site	Granite City	Illinois	United States	62040-4749
23	Pfizer Investigational Site	Terre Haute	Indiana	United States	47802
24	Pfizer Investigational Site	Glen Burnie	Maryland	United States	21061
25	Pfizer Investigational Site	Towson	Maryland	United States	21204
26	Pfizer Investigational Site	Rochester	Minnesota	United States	55905
27	Pfizer Investigational Site	Saint Louis	Missouri	United States	63118
28	Pfizer Investigational Site	Princeton	New Jersey	United States	08540
29	Pfizer Investigational Site	Brooklyn	New York	United States	11223
30	Pfizer Investigational Site	Brooklyn	New York	United States	11235
31	Pfizer Investigational Site	New York	New York	United States	10003
32	Pfizer Investigational Site	Olean	New York	United States	14760
33	Pfizer Investigational Site	Durham	North Carolina	United States	27704
34	Pfizer Investigational Site	Raleigh	North Carolina	United States	27609
35	Pfizer Investigational Site	Toledo	Ohio	United States	43623
36	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74135
37	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19149
38	Pfizer Investigational Site	Scranton	Pennsylvania	United States	18503
39	Pfizer Investigational Site	Lincoln	Rhode Island	United States	02865
40	Pfizer Investigational Site	Dallas	Texas	United States	75231
41	Pfizer Investigational Site	Houston	Texas	United States	77007
42	Pfizer Investigational Site	San Antonio	Texas	United States	78229
43	Pfizer Investigational Site	Charlottesville	Virginia	United States	22903-4895

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: NCT00282464
• Other Study ID Numbers: A1281139
• First Posted: Jan 26, 2006
• Last Update Posted: Mar 29, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Bipolar I Depression
• Additional relevant MeSH terms: Depression; Bipolar Disorder; Ziprasidone

Study Results

Participant Flow

Pre-assignment Detail	7 day washout: psychotropic drugs and lithium. 4 week washout: monoamine oxidase inhibitors. Depot neuroleptic DC'd 6 months before study entry.11 subjects assigned to but not treated with drug: 9 lost to follow up, 1 no longer willing to participate, 1 DC'd due to protocol violation

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Period Title: Overall Study
STARTED	185	196
COMPLETED	112	134
NOT COMPLETED	73	62

Baseline Characteristics

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo	Total
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).	Total of all reporting groups
Overall Participants	185	196	381
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.4 (12.5)	40.0 (11.7)	40.2 (12.1)
Sex: Female, Male (Count of Participants)
Female	108 58.4%	111 56.6%	219 57.5%
Male	77 41.6%	85 43.4%	162 42.5%

Outcome Measures

1. Secondary Outcome

Title	Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Description	Participants with MADRS Total Score greater than or equal to 50 percent decrease from baseline responded yes; others responded no. MADRS: 10-item instrument measuring depression; scale 0(Normal) & 6 (most abnormal)for each item. Total possible score is 0 - 60. Endpoint is last observation carried forward (LOCF)
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Weeks 1 - 6 are Intent to treat (ITT) population Observed Cases Not all subjects responded at each week. Endpoint is ITT population Last Observation Carried Forward (LOCF)

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1: Yes	40 21.6%	24 12.2%
Week 1: No	137 74.1%	168 85.7%
Week 2: Yes	55 29.7%	48 24.5%
Week 2: No	105 56.8%	128 65.3%
Week 3: Yes	71 38.4%	60 30.6%
Week 3: No	78 42.2%	105 53.6%
Week 4: Yes	76 41.1%	66 33.7%
Week 4: No	59 31.9%	87 44.4%
Week 5: Yes	81 43.8%	77 39.3%
Week 5: No	40 21.6%	69 35.2%
Week 6: Yes	76 41.1%	83 42.3%
Week 6: No	40 21.6%	58 29.6%
Endpoint: Yes	95 51.4%	97 49.5%
Endpoint: No	85 45.9%	93 47.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0056
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0866
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0568
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0130
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0188
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6394
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7707
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

2. Secondary Outcome

Title	Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Description	Participants with greater than or equal to 50 percent decrease from baseline in HAM-D 17 total score responded yes; others responded no. Total score is first 17 items of the HAM-D 25: measures range of depressive symptoms. Scale: 8 items 0-2 & 9 items 0-4, higher scores being more severe. Total possible score is 0 - 52. Endpoint is LOCF.
Time Frame	Baseline to Week 3, Week 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Not all subjects responded at each week. Endpoint is ITT population Last Observation Carried Forward (LOCF)

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3: Yes	72 38.9%	65 33.2%
Week 3: No	95 51.4%	112 57.1%
Week 6: Yes	85 45.9%	91 46.4%
Week 6: No	41 22.2%	59 30.1%
Endpoint: Yes	95 51.4%	97 49.5%
Endpoint: No	73 39.5%	84 42.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2185
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4124
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6098
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

3. Secondary Outcome

Title	Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Description	Remission response is yes if MADRS total score less than or equal to 12; if not, response is no. MADRS: 10-item instrument measuring depression; scale 0(Normal) & 6(most abnormal).Total possible score is 0 - 60. Endpoint is LOCF.
Time Frame	Week 1 to Week 6

Outcome Measure Data

Analysis Population Description

Weeks 1 - 6 are Intent to treat (ITT) population Observed Cases. Not all subjects responded at each week. Endpoint is ITT population Last Observation Carried Forward (LOCF)

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1: Yes	41 22.2%	21 10.7%
Week 1: No	136 73.5%	168 85.7%
Week 2: Yes	54 29.2%	41 20.9%
Week 2: No	106 57.3%	135 68.9%
Week 3: Yes	70 37.8%	58 29.6%
Week 3: No	79 42.7%	105 53.6%
Week 4: Yes	66 35.7%	60 30.6%
Week 4: No	69 37.3%	93 47.4%
Week 5: Yes	70 37.8%	66 33.7%
Week 5: No	51 27.6%	80 40.8%
Week 6: Yes	70 37.8%	72 36.7%
Week 6: No	46 24.9%	69 35.2%
Endpoint: Yes	87 47%	81 41.3%
Endpoint: No	93 50.3%	109 55.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0423
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0618
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0451
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2633
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2206
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

4. Secondary Outcome

Title	Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Description	Remission response is yes when HAM-D 17 total score is less than or equal to 7; if not, response is no. Total score is first 17 items of HAM-D 25, measures range of depressive symptoms. Scale: 8 items 0-2 and 9 items 0-4, higher scores more severe. Total possible score is 0 - 52. Endpoint is LOCF.
Time Frame	Week 3, Week 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Not all subjects responded at each week. Endpoint is ITT population Last Observation Carried Forward (LOCF)

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3: Yes	32 17.3%	33 16.8%
Week 3: No	135 73%	144 73.5%
Week 6: Yes	56 30.3%	51 26%
Week 6: No	70 37.8%	99 50.5%
Endpoint: Yes	59 31.9%	55 28.1%
Endpoint: No	109 58.9%	126 64.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9863
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1017
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4033
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test stratified by study center and rapid cycling strata was used to compare remission and response rates between ziprasidone and placebo groups

5. Primary Outcome

Title	Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description	Change is observed value at each visit minus baseline value. MADRS:10-item instrument measuring depression; scale range between 0(Normal) - 6(most abnormal)for each item. Total possible score is 0 - 60. Overall is average response Week 1 - Week 6.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Weeks 1 - 6 are Intent to treat (ITT) population Observed Cases. Overall is Average of Weeks 1 - 6.

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1 (n= 177, 189)	-7.23 (0.79)	-5.02 (0.71)
Week 2 (n=160, 176)	-9.99 (0.79)	-8.13 (0.72)
Week 3 (n=149, 163)	-11.88 (0.83)	-10.04 (0.83)
Week 4 (n=135, 153)	-13.29 (0.92)	-11.53 (0.85)
Week 5 (n=121, 146)	-14.53 (0.95)	-12.55 (0.88)
Week 6 (n=116, 141)	-14.88 (1.02)	-13.24 (0.92)
Overall (n= 180, 190)	-11.97 (0.77)	-10.09 (0.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	No multiple comparison adjustment is applicable. Statistical significance level was 0.05
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6 An estimated sample size of 180 was needed per treatment arm in order to achieve 85% power to detect a treatment difference of 3.5 in the mean change from baseline to Week 6 in MADRS total score with a two-sided t-test at the 0.05 significance level. The common standard deviation was estimated as 11.0. The null hypotheses is equality of mean change from baseline to Week 6 in MADRS total score between ziprasidone and placebo groups.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.154
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Overall
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

6. Secondary Outcome

Title	Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Description	Change is observed value at each visit minus baseline value. HAM-D 17 Total score is first 17 items of HAM-D 25; measures range of depressive symptoms patient currently experiencing. Scale: 8 items 0-2 & 9 items 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme. Total possible score is 0 - 52.Endpoint is LOCF
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to Treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n=167, 177)	-9.91 (0.88)	-8.73 (0.84)
Week 6 (n=126, 150)	-12.91 (1.15)	-12.07 (1.06)
Endpoint (n=168, 181)	-6.92 (1.36)	-7.11 (1.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.352
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.873
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

7. Secondary Outcome

Title	Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25)
Description	Change is observed value at each visit minus baseline value. HAM-D: 25-item instrument measuring the range of depressive symptoms patient currently experiencing. Scale: 14 items 0-2 & 11 items 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme. Total possible score is 0 - 72. Endpoint is LOCF.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to Treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n=167, 177)	-11.68 (1.07)	-10.76 (1.02)
Week 6 (n=126, 150)	-15.48 (1.32)	-14.80 (1.22)
Endpoint (n=168, 181)	-8.06 (1.64)	-8.58 (1.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.305
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.510
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made.
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.710
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

8. Secondary Outcome

Title	Change in Bech Melancholia Score
Description	Change is observed value at each visit minus baseline value. Bech Melancholia is sum of scores on 6 Items pertaining to melancholia within HAM-D. Scale range 0 to 4; higher scores, greater severity. Total possible score is 0 - 24. Endpoint is LOCF.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to Treat(ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n =167, 177)	-5.22 (0.50)	-4.28 (0.48)
Week 6 (n =126, 150)	-6.82 (0.65)	-6.20 (0.6)
Endpoint (n =168, 181)	-3.73 (0.75)	-3.61 (0.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.223
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.848
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

9. Secondary Outcome

Title	Change in Anxiety/Somatizations Factor Total Score
Description	Change is observed value at each visit minus baseline value. This test is sum of Scores on 6 Items pertaining to anxiety/somatization within HAM-D. Scale range 0 to 4 with higher scores reflecting greater severity. Total possible score is 0 - 24. Endpoint is LOCF.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n =167, 177)	-2.84 (0.31)	-2.61 (0.30)
Week 6 (n =126, 150)	-4.09 (0.37)	-3.96 (0.35)
Endpoint (n =168, 181)	-2.18 (0.43)	-2.57 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.381
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.676
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.295
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

10. Secondary Outcome

Title	Change in Retardation Factor Scores
Description	Change is observed value at each visit minus baseline value. Retardation Factor is the sum of scores of 4 items which pertain to retardation within HAM-D. Scores 0 to 4, higher scores reflecting greater severity.Total possible score is 0 - 16. Endpoint is LOCF.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n =167, 177)	-3.22 (0.35)	-2.68 (0.34)
Week 6 (n =126, 150)	-4.38 (0.45)	-3.66 (0.42)
Endpoint (n =168, 181)	-2.24 (0.50)	-1.88 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.404
	Comments	For all efficacy analyses, no multiple comparisons adjustments were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

11. Secondary Outcome

Title	Change in Sleep Disturbance Factor Score
Description	Change is observed value at each visit minus baseline value. Sleep Disturbance is the sum of scores of 3 items which pertain to sleep disturbance within Hamilton Depression Rating Scale (HAM-D). Scale range 0 to 4 with higher scores reflecting greater severity. Total possible score is 0 - 12.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF)

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n =167, 177)	-1.51 (0.24)	-1.48 (0.23)
Week 6 (n =126, 150)	-2.38 (0.28)	-2.31 (0.26)
Endpoint (n=168, 181)	-1.19 (0.30)	-1.26 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.899
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.739
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.797
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

12. Secondary Outcome

Title	Change in Hamilton Anxiety Rating (HAM-A)
Description	Change is observed value at each visit minus baseline value. HAM-A:14-item scale to rate the intensity of psychic anxiety (items 1- 6, 14) and somatic anxiety (items 7-13) on a 5-point severity scale (0=not present to 4=very severe). Total possible score is 0 - 56.
Time Frame	Baseline to Weeks 3, 6

Outcome Measure Data

Analysis Population Description

Weeks 3, 6 are Intent to treat (ITT) population Observed Cases. Endpoint is ITT population Last Observation Carried Forward (LOCF).

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 3 (n=167, 177)	-4.63 (0.69)	-4.18 (0.66)
Week 6 (n=126, 150)	-6.84 (0.91)	-6.64 (0.84)
Endpoint (n=168, 181)	-3.05 (1.06)	-3.26 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.777
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.820
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

13. Secondary Outcome

Title	Change in Total Score of Young Mania Rating Scale (YMRS)
Description	Change is observed value at each visit minus baseline value. YMRS: 11 item instrument with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal; 4 or 8=most abnormal. Total possible score is 0 - 60. Overall is average response Week 1 - 6.
Time Frame	Baseline to week 6

Outcome Measure Data

Analysis Population Description

Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases. Overall is Average of Weeks 1 - 6.

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1 (n=177, 189)	0.40 (0.36)	0.69 (0.33)
Week 2 (n=160, 176)	0.49 (0.39)	-0.13 (0.31)
Week 3 (n=149, 163)	-0.13 (0.41)	0.00 (0.34)
Week 4 (n=135, 153)	-0.60 (0.36)	-0.77 (0.31)
Week 5 (n=121, 146)	-0.94 (0.35)	-0.77 (0.31)
Week 6 (n=116, 141)	-0.45 (0.43)	-0.66 (0.37)
Overall (n=180, 190)	-0.20 (0.32)	-0.27 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.468
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.738
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.617
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.644
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Overall
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.789
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

14. Secondary Outcome

Title	Change in Global Clinical Severity of Symptoms (CGI-S)
Description	Change is observed value at each visit minus baseline value. CGI-S is an instrument to measure severity of mental illness. Scale range: 0 = not assessed, 1 = normal, 7 = among most extremely ill
Time Frame	Baseline to week 6

Outcome Measure Data

Analysis Population Description

Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases. Overall is Average of Weeks 1 - 6.

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1 (n=177, 188)	-0.39 (0.08)	-0.25 (0.07)
Week 2 (n=160, 176)	-0.66 (0.08)	-0.51 (0.08)
Week 3 (n=149, 163)	-0.88 (0.10)	-0.84 (0.09)
Week 4 (n=135, 152)	-1.03 (0.11)	-0.98 (0.10)
Week 5 (n=121, 146)	-1.27 (0.11)	-1.15 (0.10)
Week 6 (n=116, 140)	-1.34 (0.11)	-1.28 (0.11)
Overall (n=180, 190)	-0.93 (0.08)	-0.84 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.042
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.651
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.665
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.349
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Overall
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.257
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction & fixed continuous effect of baseline value

15. Secondary Outcome

Title	Change in Global Clinical Improvement of Symptoms (CGI -I)
Description	Change is observed value at each visit minus baseline value. CGI-I is an instrument for Global assessment of improvement in patient's condition. Scale range:0=not assessed, 1=very much improved, 7=very much worse
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases. Overall is Average of Weeks 1 - 6.

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	180	190
Week 1 (n=177, 188)	3.37 (0.10)	3.61 (0.10)
Week 2 (n=160, 176)	3.09 (0.11)	3.29 (0.11)
Week 3 (n=149, 163)	2.89 (0.12)	3.04 (0.11)
Week 4 (n=135, 152)	2.74 (0.12)	2.94 (0.11)
Week 5 (n=121, 146)	2.61 (0.13)	2.84 (0.12)
Week 6 (n=116, 140)	2.52 (0.13)	2.64 (0.12)
Overall (n=180, 190)	2.87 (0.10)	3.06 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0654
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1807
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0957
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0752
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3964
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Overall
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0287
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	Mixed Models Analysis
	Comments	Fixed categorical effect: treatment, rapid cycling, center, visit, prior hosp & treatment-by-visit interaction.

16. Secondary Outcome

Title	Change in Global Assessment of Functioning (GAF)
Description	Change is observed value at each visit minus baseline value. GAF is an instrument used to assess global psychological, social, & occupational functioning. Scale range: 100 = normal and 0 = greatest abnormality.
Time Frame	Baseline to week 6 (Endpoint)

Outcome Measure Data

Analysis Population Description

Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 154, 169; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	154	169
Least Squares Mean (Standard Error) [score on scale]	9.59 (1.52)	9.53 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Change from baseline to endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.965
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

17. Secondary Outcome

Title	Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score
Description	Change is observed value at each visit minus baseline value. Q-LES-Q: 16- item instrument for a patient's assessment of his/her quality of life. Scale range: overall level of satisfaction 1=very poor to 5=Very good. 1 item (medication)can be left blank. Total possible score 15 - 80.
Time Frame	Baseline to week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Change from baseline to Endpoint. Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 153, 168; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	153	168
Least Squares Mean (Standard Error) [score on scale]	0.06 (0.02)	0.06 (0.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Change from baseline to endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

18. Secondary Outcome

Title	Change in Sheehan Disability Scale (SDS) Total Score
Description	Change is observed value at each visit minus baseline value. SDS is a patient rated measure of disability and impairment in work/school, social life, family life/home responsibilities. Scale range: 0-10 with 0=no disruption,10=extreme disruption. Total possible score is 0 - 30.
Time Frame	Baseline to week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Baseline to Endpoint. Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 149, 162; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	149	162
Least Squares Mean (Standard Error) [score on scale]	-3.69 (0.93)	-3.05 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Baseline to endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.428
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANCOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

19. Secondary Outcome

Title	Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject
Description	Change is observed value at each visit minus baseline value. BPCoRs: Subject interview with 20-items measuring cognitive deficits & degree of affect on functioning. Scale range:0 to 4, higher numbers, greater impairment. Total possible score is 0 - 80. Endpoint=last observation carried forward (LOCF)
Time Frame	Baseline to week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Baseline to Endpoint. Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 141, 164; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	141	164
Least Squares Mean (Standard Error) [score on scale]	-0.65 (0.24)	-0.73 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Change from baseline to endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.708
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANOVA
	Comments	ANOVA model included effects of treatment, rapid cycling, center and prior hospitalization status

20. Secondary Outcome

Title	Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating
Description	Change is observed value at each visit minus baseline value. Informant Global Rating is interview with informant of subject using BPCoRS, a 20-item instrument measuring cognitive deficits & degree of affect on functioning. Scale: 0 to 4, higher numbers = greater impairment. Total possible score is 0 - 80. Endpoint is LOCF.
Time Frame	Baseline to week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Baseline to Endpoint. Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 97, 104; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	97	104
Least Squares Mean (Standard Error) [score on scale]	4.66 (0.21)	4.68 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.898
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANOVA
	Comments	ANCOVA model included effects of treatment, rapid cycling, center, prior hospitalization status, as well as baseline value as a covariate.

21. Secondary Outcome

Title	Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer
Description	Change in Rating by interviewer, using BPCoRS, 20-item instrument measuring cognitive deficits and the degree of affect on functioning; 4 point scale with higher numbers reflecting greater impairment.Total possible score is 0 - 80.
Time Frame	Baseline to week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 137, 158; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	137	158
Least Squares Mean (Standard Error) [score on scale]	4.72 (0.18)	4.63 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.559
	Comments	For all secondary efficacy analyses, no multiple comparison adjustment were made
	Method	ANOVA
	Comments	ANOVA model included effects of treatment, rapid cycling, center and prior hospitalization status.

22. Secondary Outcome

Title	Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at Endpoint
Description	Change is observed value at each visit minus baseline value. Subject Rating: Subject's perceived change in status using a 20-item instrument measuring cognitive deficits and degree of affect on funtioning. Scale 0 to 4, higher numbers reflecting greater impairment. Total possible score is 0 - 80. Endpoint is last observation carried forward.
Time Frame	Baseline to Week 6 (endpoint)

Outcome Measure Data

Analysis Population Description

Endpoint is Intent to Treat (ITT) Last Observation Carried Forward (LOCF). n = 140, 162; N = 180, 190

Arm/Group Title	Ziprasidone 20-80mg Bid	Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
Measure Participants	140	162
Least Squares Mean (Standard Error) [score on scale]	4.69 (0.19)	4.81 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ziprasidone 20-80mg Bid, Placebo
	Comments	Endpoint
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.458
	Comments	For all secondary efficacy analyses, no multiple adjustments were made
	Method	ANOVA
	Comments	ANVOVA model included effects of treatment, rapid cycling, center and prior hospitalization status.

Adverse Events

Arm/Group Title	Ziprasidone 20-80mg Bid		Placebo
Arm/Group Description	For the Ziprasidone arm, the Baseline card will contain 20 milligrams (mg) twice daily (bid) (one 20 mg capsule) for days 1-2 and 40 mg bid (two 20 mg capsules) for days 3-6. Cards A, B, C, and D will contain either 20 mg bid (one 20 mg capsule), 40 mg bid (two 20 mg capsules), 60 mg bid (one 60 mg capsule), or 80 mg bid (one 60 mg capsule and one 20 mg capsule).
All Cause Mortality
	Ziprasidone 20-80mg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone 20-80mg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/ (NaN)		4/ (NaN)
Injury, poisoning and procedural complications
Skin laceration	0/185 (0%)		1/196 (0.5%)
Psychiatric disorders
Bipolar disorder	0/185 (0%)		1/196 (0.5%)
Psychotic disorder	0/185 (0%)		1/196 (0.5%)
Suicidal ideation	2/185 (1.1%)		1/196 (0.5%)
Suicide attempt	1/185 (0.5%)		0/196 (0%)
Other (Not Including Serious) Adverse Events
	Ziprasidone 20-80mg Bid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/ (NaN)		73/ (NaN)
Gastrointestinal disorders
Diarrhoea	8/185 (4.3%)		15/196 (7.7%)
Nausea	11/185 (5.9%)		21/196 (10.7%)
General disorders
Fatigue	13/185 (7%)		8/196 (4.1%)
Nervous system disorders
Dizziness	12/185 (6.5%)		10/196 (5.1%)
Headache	21/185 (11.4%)		21/196 (10.7%)
Sedation	22/185 (11.9%)		6/196 (3.1%)
Somnolence	25/185 (13.5%)		5/196 (2.6%)
Psychiatric disorders
Depression	6/185 (3.2%)		13/196 (6.6%)
Insomnia	9/185 (4.9%)		10/196 (5.1%)

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 mo from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.