Trial Outcomes & Findings for A Six-week Flexible Dose Study Evaluating the Efficacy and Safety of Geodon in Patients With Bipolar I Depression. (NCT NCT00282464)

NCT ID: NCT00282464

Last Updated: 2021-03-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

392 participants

Primary outcome timeframe

Baseline to Week 6

Results posted on

2021-03-29

Participant Flow

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

Participant milestones

Participant milestones
Measure
Ziprasidone 20-80mg Bid
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).
Placebo
Overall Study
STARTED
185
196
Overall Study
COMPLETED
112
134
Overall Study
NOT COMPLETED
73
62

Reasons for withdrawal

Reasons for withdrawal
Measure
Ziprasidone 20-80mg Bid
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).
Placebo
Overall Study
Adverse Event
26
20
Overall Study
Lack of Efficacy
8
8
Overall Study
Lost to Follow-up
10
10
Overall Study
Withdrawal by Subject
24
10
Overall Study
laboratory abnormality
1
2
Overall Study
Protocol Violation
0
7
Overall Study
Patient moved
1
0
Overall Study
patient non-compliant
3
0
Overall Study
patient no show
0
1
Overall Study
patient incarcerated
0
1
Overall Study
family crisis
0
1
Overall Study
dispensed wrong kit
0
1
Overall Study
dropped due to missed visits
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ziprasidone 20-80mg Bid
n=185 Participants
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).
Placebo
n=196 Participants
Total
n=381 Participants
Total of all reporting groups
Age, Continuous
40.4 years
STANDARD_DEVIATION 12.5 • n=5 Participants
40.0 years
STANDARD_DEVIATION 11.7 • n=7 Participants
40.2 years
STANDARD_DEVIATION 12.1 • n=5 Participants
Sex: Female, Male
Female
108 Participants
n=5 Participants
111 Participants
n=7 Participants
219 Participants
n=5 Participants
Sex: Female, Male
Male
77 Participants
n=5 Participants
85 Participants
n=7 Participants
162 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

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

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 1 (n= 177, 189)
-7.23 score on scale
Standard Error 0.79
-5.02 score on scale
Standard Error 0.71
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 2 (n=160, 176)
-9.99 score on scale
Standard Error 0.79
-8.13 score on scale
Standard Error 0.72
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 3 (n=149, 163)
-11.88 score on scale
Standard Error 0.83
-10.04 score on scale
Standard Error 0.83
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Overall (n= 180, 190)
-11.97 score on scale
Standard Error 0.77
-10.09 score on scale
Standard Error 0.70
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 4 (n=135, 153)
-13.29 score on scale
Standard Error 0.92
-11.53 score on scale
Standard Error 0.85
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 5 (n=121, 146)
-14.53 score on scale
Standard Error 0.95
-12.55 score on scale
Standard Error 0.88
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Week 6 (n=116, 141)
-14.88 score on scale
Standard Error 1.02
-13.24 score on scale
Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: 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)

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)

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 1: Yes
40 participants
24 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 1: No
137 participants
168 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 2: Yes
55 participants
48 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 2: No
105 participants
128 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 3: Yes
71 participants
60 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 3: No
78 participants
105 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 4: Yes
76 participants
66 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 4: No
59 participants
87 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 5: Yes
81 participants
77 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 5: No
40 participants
69 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 6: Yes
76 participants
83 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Week 6: No
40 participants
58 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Endpoint: Yes
95 participants
97 participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
Endpoint: No
85 participants
93 participants

SECONDARY outcome

Timeframe: Baseline to Week 3, Week 6

Population: 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)

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 6: No
41 Participants
59 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Endpoint: Yes
95 Participants
97 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Endpoint: No
73 Participants
84 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 3: Yes
72 Participants
65 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 3: No
95 Participants
112 Participants
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 6: Yes
85 Participants
91 Participants

SECONDARY outcome

Timeframe: Week 1 to Week 6

Population: 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)

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 1: Yes
41 Participants
21 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 1: No
136 Participants
168 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 2: Yes
54 Participants
41 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 2: No
106 Participants
135 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 3: Yes
70 Participants
58 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 3: No
79 Participants
105 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 4: Yes
66 Participants
60 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 4: No
69 Participants
93 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 5: Yes
70 Participants
66 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 5: No
51 Participants
80 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 6: Yes
70 Participants
72 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Week 6: No
46 Participants
69 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Endpoint: Yes
87 Participants
81 Participants
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
Endpoint: No
93 Participants
109 Participants

SECONDARY outcome

Timeframe: Week 3, Week 6

Population: 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)

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Endpoint: Yes
59 Participants
55 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Endpoint: No
109 Participants
126 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Week 3: Yes
32 Participants
33 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Week 3: No
135 Participants
144 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Week 6: Yes
56 Participants
51 Participants
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
Week 6: No
70 Participants
99 Participants

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 3 (n=167, 177)
-9.91 score on scale
Standard Error 0.88
-8.73 score on scale
Standard Error 0.84
Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Week 6 (n=126, 150)
-12.91 score on scale
Standard Error 1.15
-12.07 score on scale
Standard Error 1.06
Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score
Endpoint (n=168, 181)
-6.92 score on scale
Standard Error 1.36
-7.11 score on scale
Standard Error 1.30

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25)
Week 3 (n=167, 177)
-11.68 score on scale
Standard Error 1.07
-10.76 score on scale
Standard Error 1.02
Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25)
Week 6 (n=126, 150)
-15.48 score on scale
Standard Error 1.32
-14.80 score on scale
Standard Error 1.22
Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25)
Endpoint (n=168, 181)
-8.06 score on scale
Standard Error 1.64
-8.58 score on scale
Standard Error 1.56

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Bech Melancholia Score
Week 3 (n =167, 177)
-5.22 score on scale
Standard Error 0.50
-4.28 score on scale
Standard Error 0.48
Change in Bech Melancholia Score
Week 6 (n =126, 150)
-6.82 score on scale
Standard Error 0.65
-6.20 score on scale
Standard Error 0.6
Change in Bech Melancholia Score
Endpoint (n =168, 181)
-3.73 score on scale
Standard Error 0.75
-3.61 score on scale
Standard Error 0.71

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Anxiety/Somatizations Factor Total Score
Week 3 (n =167, 177)
-2.84 score on scale
Standard Error 0.31
-2.61 score on scale
Standard Error 0.30
Change in Anxiety/Somatizations Factor Total Score
Week 6 (n =126, 150)
-4.09 score on scale
Standard Error 0.37
-3.96 score on scale
Standard Error 0.35
Change in Anxiety/Somatizations Factor Total Score
Endpoint (n =168, 181)
-2.18 score on scale
Standard Error 0.43
-2.57 score on scale
Standard Error 0.41

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Retardation Factor Scores
Week 3 (n =167, 177)
-3.22 score on scale
Standard Error 0.35
-2.68 score on scale
Standard Error 0.34
Change in Retardation Factor Scores
Week 6 (n =126, 150)
-4.38 score on scale
Standard Error 0.45
-3.66 score on scale
Standard Error 0.42
Change in Retardation Factor Scores
Endpoint (n =168, 181)
-2.24 score on scale
Standard Error 0.50
-1.88 score on scale
Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Sleep Disturbance Factor Score
Week 3 (n =167, 177)
-1.51 score on scale
Standard Error 0.24
-1.48 score on scale
Standard Error 0.23
Change in Sleep Disturbance Factor Score
Week 6 (n =126, 150)
-2.38 score on scale
Standard Error 0.28
-2.31 score on scale
Standard Error 0.26
Change in Sleep Disturbance Factor Score
Endpoint (n=168, 181)
-1.19 score on scale
Standard Error 0.30
-1.26 score on scale
Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline to Weeks 3, 6

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Hamilton Anxiety Rating (HAM-A)
Week 3 (n=167, 177)
-4.63 score on scale
Standard Error 0.69
-4.18 score on scale
Standard Error 0.66
Change in Hamilton Anxiety Rating (HAM-A)
Week 6 (n=126, 150)
-6.84 score on scale
Standard Error 0.91
-6.64 score on scale
Standard Error 0.84
Change in Hamilton Anxiety Rating (HAM-A)
Endpoint (n=168, 181)
-3.05 score on scale
Standard Error 1.06
-3.26 score on scale
Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline to week 6

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

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 1 (n=177, 189)
0.40 score on scale
Standard Error 0.36
0.69 score on scale
Standard Error 0.33
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 2 (n=160, 176)
0.49 score on scale
Standard Error 0.39
-0.13 score on scale
Standard Error 0.31
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 3 (n=149, 163)
-0.13 score on scale
Standard Error 0.41
0.00 score on scale
Standard Error 0.34
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 4 (n=135, 153)
-0.60 score on scale
Standard Error 0.36
-0.77 score on scale
Standard Error 0.31
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 5 (n=121, 146)
-0.94 score on scale
Standard Error 0.35
-0.77 score on scale
Standard Error 0.31
Change in Total Score of Young Mania Rating Scale (YMRS)
Week 6 (n=116, 141)
-0.45 score on scale
Standard Error 0.43
-0.66 score on scale
Standard Error 0.37
Change in Total Score of Young Mania Rating Scale (YMRS)
Overall (n=180, 190)
-0.20 score on scale
Standard Error 0.32
-0.27 score on scale
Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline to week 6

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

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 1 (n=177, 188)
-0.39 score on scale
Standard Error 0.08
-0.25 score on scale
Standard Error 0.07
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 2 (n=160, 176)
-0.66 score on scale
Standard Error 0.08
-0.51 score on scale
Standard Error 0.08
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 3 (n=149, 163)
-0.88 score on scale
Standard Error 0.10
-0.84 score on scale
Standard Error 0.09
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 4 (n=135, 152)
-1.03 score on scale
Standard Error 0.11
-0.98 score on scale
Standard Error 0.10
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 5 (n=121, 146)
-1.27 score on scale
Standard Error 0.11
-1.15 score on scale
Standard Error 0.10
Change in Global Clinical Severity of Symptoms (CGI-S)
Week 6 (n=116, 140)
-1.34 score on scale
Standard Error 0.11
-1.28 score on scale
Standard Error 0.11
Change in Global Clinical Severity of Symptoms (CGI-S)
Overall (n=180, 190)
-0.93 score on scale
Standard Error 0.08
-0.84 score on scale
Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline to Week 6

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

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=180 Participants
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).
Placebo
n=190 Participants
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 1 (n=177, 188)
3.37 score on scale
Standard Error 0.10
3.61 score on scale
Standard Error 0.10
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 2 (n=160, 176)
3.09 score on scale
Standard Error 0.11
3.29 score on scale
Standard Error 0.11
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 3 (n=149, 163)
2.89 score on scale
Standard Error 0.12
3.04 score on scale
Standard Error 0.11
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 4 (n=135, 152)
2.74 score on scale
Standard Error 0.12
2.94 score on scale
Standard Error 0.11
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 5 (n=121, 146)
2.61 score on scale
Standard Error 0.13
2.84 score on scale
Standard Error 0.12
Change in Global Clinical Improvement of Symptoms (CGI -I)
Week 6 (n=116, 140)
2.52 score on scale
Standard Error 0.13
2.64 score on scale
Standard Error 0.12
Change in Global Clinical Improvement of Symptoms (CGI -I)
Overall (n=180, 190)
2.87 score on scale
Standard Error 0.10
3.06 score on scale
Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline to week 6 (Endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=154 Participants
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).
Placebo
n=169 Participants
Change in Global Assessment of Functioning (GAF)
9.59 score on scale
Standard Error 1.52
9.53 score on scale
Standard Error 1.42

SECONDARY outcome

Timeframe: Baseline to week 6 (endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=153 Participants
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).
Placebo
n=168 Participants
Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score
0.06 score on scale
Standard Error 0.02
0.06 score on scale
Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline to week 6 (endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=149 Participants
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).
Placebo
n=162 Participants
Change in Sheehan Disability Scale (SDS) Total Score
-3.69 score on scale
Standard Error 0.93
-3.05 score on scale
Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline to week 6 (endpoint)

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

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)

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=141 Participants
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).
Placebo
n=164 Participants
Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject
-0.65 score on scale
Standard Error 0.24
-0.73 score on scale
Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline to week 6 (endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=97 Participants
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).
Placebo
n=104 Participants
Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating
4.66 score on scale
Standard Error 0.21
4.68 score on scale
Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline to week 6 (endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=137 Participants
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).
Placebo
n=158 Participants
Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer
4.72 score on scale
Standard Error 0.18
4.63 score on scale
Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline to Week 6 (endpoint)

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

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.

Outcome measures

Outcome measures
Measure
Ziprasidone 20-80mg Bid
n=140 Participants
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).
Placebo
n=162 Participants
Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at Endpoint
4.69 score on scale
Standard Error 0.19
4.81 score on scale
Standard Error 0.17

Adverse Events

Ziprasidone 20-80mg Bid

Serious events: 3 serious events
Other events: 93 other events
Deaths: 0 deaths

Placebo

Serious events: 4 serious events
Other events: 73 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ziprasidone 20-80mg Bid
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).
Placebo
Injury, poisoning and procedural complications
Skin laceration
0.00%
0/185
0.51%
1/196
Psychiatric disorders
Bipolar disorder
0.00%
0/185
0.51%
1/196
Psychiatric disorders
Psychotic disorder
0.00%
0/185
0.51%
1/196
Psychiatric disorders
Suicidal ideation
1.1%
2/185
0.51%
1/196
Psychiatric disorders
Suicide attempt
0.54%
1/185
0.00%
0/196

Other adverse events

Other adverse events
Measure
Ziprasidone 20-80mg Bid
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).
Placebo
Gastrointestinal disorders
Diarrhoea
4.3%
8/185
7.7%
15/196
Gastrointestinal disorders
Nausea
5.9%
11/185
10.7%
21/196
General disorders
Fatigue
7.0%
13/185
4.1%
8/196
Nervous system disorders
Dizziness
6.5%
12/185
5.1%
10/196
Nervous system disorders
Headache
11.4%
21/185
10.7%
21/196
Nervous system disorders
Sedation
11.9%
22/185
3.1%
6/196
Nervous system disorders
Somnolence
13.5%
25/185
2.6%
5/196
Psychiatric disorders
Depression
3.2%
6/185
6.6%
13/196
Psychiatric disorders
Insomnia
4.9%
9/185
5.1%
10/196

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER