Bipolar Disorder
Conditions
Keywords
Bipolar I Depression
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.
Interventions
DRUGPlacebo
Subjects will start on placebo and remain on placebo for six weeks. All cards for the Placebo arm will be 0 mg bid.
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).
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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) |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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). | 185 |
| Placebo | 196 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 20 |
| Overall Study | dispensed wrong kit | 0 | 1 |
| Overall Study | dropped due to missed visits | 0 | 1 |
| Overall Study | family crisis | 0 | 1 |
| Overall Study | laboratory abnormality | 1 | 2 |
| Overall Study | Lack of Efficacy | 8 | 8 |
| Overall Study | Lost to Follow-up | 10 | 10 |
| Overall Study | patient incarcerated | 0 | 1 |
| Overall Study | Patient moved | 1 | 0 |
| Overall Study | patient non-compliant | 3 | 0 |
| Overall Study | patient no show | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 7 |
| Overall Study | Withdrawal by Subject | 24 | 10 |
Baseline characteristics
| Characteristic | Ziprasidone 20-80mg Bid | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 12.5 | 40.0 years STANDARD_DEVIATION 11.7 | 40.2 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 108 Participants | 111 Participants | 219 Participants |
| Sex: Female, Male Male | 77 Participants | 85 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / — | 73 / — |
| serious Total, serious adverse events | 3 / — | 4 / — |
Outcome results
Primary
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
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
Population: Weeks 1 - 6 are Intent to treat (ITT) population Observed Cases.~Overall is Average of Weeks 1 - 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 3 (n=149, 163) | -11.88 score on scale | Standard Error 0.83 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 5 (n=121, 146) | -14.53 score on scale | Standard Error 0.95 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=160, 176) | -9.99 score on scale | Standard Error 0.79 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=116, 141) | -14.88 score on scale | Standard Error 1.02 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=135, 153) | -13.29 score on scale | Standard Error 0.92 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Overall (n= 180, 190) | -11.97 score on scale | Standard Error 0.77 |
| Ziprasidone 20-80mg Bid | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 1 (n= 177, 189) | -7.23 score on scale | Standard Error 0.79 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Overall (n= 180, 190) | -10.09 score on scale | Standard Error 0.7 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 1 (n= 177, 189) | -5.02 score on scale | Standard Error 0.71 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=160, 176) | -8.13 score on scale | Standard Error 0.72 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 3 (n=149, 163) | -10.04 score on scale | Standard Error 0.83 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=135, 153) | -11.53 score on scale | Standard Error 0.85 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 5 (n=121, 146) | -12.55 score on scale | Standard Error 0.88 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=116, 141) | -13.24 score on scale | Standard Error 0.92 |
Comparison: Week 1p-value: 0.002Mixed Models Analysis
Comparison: Week 2p-value: 0.019Mixed Models Analysis
Comparison: Week 3p-value: 0.038Mixed Models Analysis
Comparison: Week 4p-value: 0.069Mixed Models Analysis
Comparison: Week 5p-value: 0.053Mixed Models Analysis
Comparison: 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.p-value: 0.154Mixed Models Analysis
Comparison: Overallp-value: 0.007Mixed Models Analysis
Secondary
Change in Anxiety/Somatizations Factor Total Score
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
Population: Weeks 3, 6 are Intent to treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Anxiety/Somatizations Factor Total Score | Week 3 (n =167, 177) | -2.84 score on scale | Standard Error 0.31 |
| Ziprasidone 20-80mg Bid | Change in Anxiety/Somatizations Factor Total Score | Week 6 (n =126, 150) | -4.09 score on scale | Standard Error 0.37 |
| Ziprasidone 20-80mg Bid | Change in Anxiety/Somatizations Factor Total Score | Endpoint (n =168, 181) | -2.18 score on scale | Standard Error 0.43 |
| Placebo | Change in Anxiety/Somatizations Factor Total Score | Week 3 (n =167, 177) | -2.61 score on scale | Standard Error 0.3 |
| Placebo | Change in Anxiety/Somatizations Factor Total Score | Week 6 (n =126, 150) | -3.96 score on scale | Standard Error 0.35 |
| Placebo | Change in Anxiety/Somatizations Factor Total Score | Endpoint (n =168, 181) | -2.57 score on scale | Standard Error 0.41 |
Comparison: Week 3p-value: 0.381ANCOVA
Comparison: Week 6p-value: 0.676ANCOVA
Comparison: Endpointp-value: 0.295ANCOVA
Secondary
Change in Bech Melancholia Score
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
Population: Weeks 3, 6 are Intent to Treat(ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Bech Melancholia Score | Week 3 (n =167, 177) | -5.22 score on scale | Standard Error 0.5 |
| Ziprasidone 20-80mg Bid | Change in Bech Melancholia Score | Week 6 (n =126, 150) | -6.82 score on scale | Standard Error 0.65 |
| Ziprasidone 20-80mg Bid | Change in Bech Melancholia Score | Endpoint (n =168, 181) | -3.73 score on scale | Standard Error 0.75 |
| Placebo | Change in Bech Melancholia Score | Week 3 (n =167, 177) | -4.28 score on scale | Standard Error 0.48 |
| Placebo | Change in Bech Melancholia Score | Week 6 (n =126, 150) | -6.20 score on scale | Standard Error 0.6 |
| Placebo | Change in Bech Melancholia Score | Endpoint (n =168, 181) | -3.61 score on scale | Standard Error 0.71 |
Comparison: Week 3p-value: 0.026ANCOVA
Comparison: Week 6p-value: 0.223ANCOVA
Comparison: Endpointp-value: 0.848ANCOVA
Secondary
Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer
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)
Population: Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 137, 158; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer | 4.72 score on scale | Standard Error 0.18 |
| Placebo | Change in Bipolar Cognition Rating Scale (BPCoRS) Global Rating by Interviewer | 4.63 score on scale | Standard Error 0.17 |
Comparison: Endpointp-value: 0.559ANOVA
Secondary
Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating
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)
Population: Baseline to Endpoint. Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 97, 104; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating | 4.66 score on scale | Standard Error 0.21 |
| Placebo | Change in Bipolar Cognition Rating Scale (BPCoRS) Informant Global Rating | 4.68 score on scale | Standard Error 0.21 |
Comparison: Endpointp-value: 0.898ANOVA
Secondary
Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject
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)
Population: Baseline to Endpoint. Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 141, 164; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject | -0.65 score on scale | Standard Error 0.24 |
| Placebo | Change in Bipolar Cognition Rating Scale (BPCoRS) Interviewer Global Rating of Subject | -0.73 score on scale | Standard Error 0.22 |
Comparison: Change from baseline to endpointp-value: 0.708ANOVA
Secondary
Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at 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.
Time frame: Baseline to Week 6 (endpoint)
Population: Endpoint is Intent to Treat (ITT) Last Observation Carried Forward (LOCF). n = 140, 162; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at Endpoint | 4.69 score on scale | Standard Error 0.19 |
| Placebo | Change in Bipolar Cognition Rating Scale (BPCoRS) Subject Rating at Endpoint | 4.81 score on scale | Standard Error 0.17 |
Comparison: Endpointp-value: 0.458ANOVA
Secondary
Change in Global Assessment of Functioning (GAF)
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)
Population: Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 154, 169; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Global Assessment of Functioning (GAF) | 9.59 score on scale | Standard Error 1.52 |
| Placebo | Change in Global Assessment of Functioning (GAF) | 9.53 score on scale | Standard Error 1.42 |
Comparison: Change from baseline to endpointp-value: 0.965ANCOVA
Secondary
Change in Global Clinical Improvement of Symptoms (CGI -I)
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
Population: Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases.~Overall is Average of Weeks 1 - 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 1 (n=177, 188) | 3.37 score on scale | Standard Error 0.1 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 5 (n=121, 146) | 2.61 score on scale | Standard Error 0.13 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 2 (n=160, 176) | 3.09 score on scale | Standard Error 0.11 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 6 (n=116, 140) | 2.52 score on scale | Standard Error 0.13 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 4 (n=135, 152) | 2.74 score on scale | Standard Error 0.12 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Overall (n=180, 190) | 2.87 score on scale | Standard Error 0.1 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 3 (n=149, 163) | 2.89 score on scale | Standard Error 0.12 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Overall (n=180, 190) | 3.06 score on scale | Standard Error 0.1 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 1 (n=177, 188) | 3.61 score on scale | Standard Error 0.1 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 2 (n=160, 176) | 3.29 score on scale | Standard Error 0.11 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 3 (n=149, 163) | 3.04 score on scale | Standard Error 0.11 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 4 (n=135, 152) | 2.94 score on scale | Standard Error 0.11 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 5 (n=121, 146) | 2.84 score on scale | Standard Error 0.12 |
| Placebo | Change in Global Clinical Improvement of Symptoms (CGI -I) | Week 6 (n=116, 140) | 2.64 score on scale | Standard Error 0.12 |
Comparison: Week 1p-value: 0.0099Mixed Models Analysis
Comparison: Week 2p-value: 0.0654Mixed Models Analysis
Comparison: Week 3p-value: 0.1807Mixed Models Analysis
Comparison: Week 4p-value: 0.0957Mixed Models Analysis
Comparison: Week 5p-value: 0.0752Mixed Models Analysis
Comparison: Week 6p-value: 0.3964Mixed Models Analysis
Comparison: Overallp-value: 0.0287Mixed Models Analysis
Secondary
Change in Global Clinical Severity of Symptoms (CGI-S)
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
Population: Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases.~Overall is Average of Weeks 1 - 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 4 (n=135, 152) | -1.03 score on scale | Standard Error 0.11 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 5 (n=121, 146) | -1.27 score on scale | Standard Error 0.11 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 1 (n=177, 188) | -0.39 score on scale | Standard Error 0.08 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 6 (n=116, 140) | -1.34 score on scale | Standard Error 0.11 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 3 (n=149, 163) | -0.88 score on scale | Standard Error 0.1 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Overall (n=180, 190) | -0.93 score on scale | Standard Error 0.08 |
| Ziprasidone 20-80mg Bid | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 2 (n=160, 176) | -0.66 score on scale | Standard Error 0.08 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Overall (n=180, 190) | -0.84 score on scale | Standard Error 0.08 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 1 (n=177, 188) | -0.25 score on scale | Standard Error 0.07 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 2 (n=160, 176) | -0.51 score on scale | Standard Error 0.08 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 3 (n=149, 163) | -0.84 score on scale | Standard Error 0.09 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 5 (n=121, 146) | -1.15 score on scale | Standard Error 0.1 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 6 (n=116, 140) | -1.28 score on scale | Standard Error 0.11 |
| Placebo | Change in Global Clinical Severity of Symptoms (CGI-S) | Week 4 (n=135, 152) | -0.98 score on scale | Standard Error 0.1 |
Comparison: Week 1p-value: 0.042Mixed Models Analysis
Comparison: Week 2p-value: 0.088Mixed Models Analysis
Comparison: Week 3p-value: 0.651Mixed Models Analysis
Comparison: Week 4p-value: 0.665Mixed Models Analysis
Comparison: Week 5p-value: 0.349Mixed Models Analysis
Comparison: Week 6p-value: 0.685Mixed Models Analysis
Comparison: Overallp-value: 0.257Mixed Models Analysis
Secondary
Change in Hamilton Anxiety Rating (HAM-A)
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
Population: Weeks 3, 6 are Intent to treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Hamilton Anxiety Rating (HAM-A) | Week 3 (n=167, 177) | -4.63 score on scale | Standard Error 0.69 |
| Ziprasidone 20-80mg Bid | Change in Hamilton Anxiety Rating (HAM-A) | Week 6 (n=126, 150) | -6.84 score on scale | Standard Error 0.91 |
| Ziprasidone 20-80mg Bid | Change in Hamilton Anxiety Rating (HAM-A) | Endpoint (n=168, 181) | -3.05 score on scale | Standard Error 1.06 |
| Placebo | Change in Hamilton Anxiety Rating (HAM-A) | Week 3 (n=167, 177) | -4.18 score on scale | Standard Error 0.66 |
| Placebo | Change in Hamilton Anxiety Rating (HAM-A) | Week 6 (n=126, 150) | -6.64 score on scale | Standard Error 0.84 |
| Placebo | Change in Hamilton Anxiety Rating (HAM-A) | Endpoint (n=168, 181) | -3.26 score on scale | Standard Error 1.01 |
Comparison: Week 3p-value: 0.434ANCOVA
Comparison: Week 6p-value: 0.777ANCOVA
Comparison: Endpointp-value: 0.82ANCOVA
Secondary
Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score
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
Population: Weeks 3, 6 are Intent to Treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Endpoint (n=168, 181) | -6.92 score on scale | Standard Error 1.36 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 3 (n=167, 177) | -8.73 score on scale | Standard Error 0.84 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 6 (n=126, 150) | -12.07 score on scale | Standard Error 1.06 |
| Placebo | Change in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Endpoint (n=168, 181) | -7.11 score on scale | Standard Error 1.3 |
Comparison: Week 3p-value: 0.112ANCOVA
Comparison: Week 6p-value: 0.352ANCOVA
Comparison: Endpointp-value: 0.873ANCOVA
Secondary
Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score
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)
Population: Change from baseline to Endpoint. Endpoint is Intent to Treat (ITT) population Last Observation Carried Forward (LOCF). n = 153, 168; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score | 0.06 score on scale | Standard Error 0.02 |
| Placebo | Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score | 0.06 score on scale | Standard Error 0.01 |
Comparison: Change from baseline to endpointp-value: 0.86ANCOVA
Secondary
Change in Retardation Factor Scores
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
Population: Weeks 3, 6 are Intent to treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Retardation Factor Scores | Week 3 (n =167, 177) | -3.22 score on scale | Standard Error 0.35 |
| Ziprasidone 20-80mg Bid | Change in Retardation Factor Scores | Week 6 (n =126, 150) | -4.38 score on scale | Standard Error 0.45 |
| Ziprasidone 20-80mg Bid | Change in Retardation Factor Scores | Endpoint (n =168, 181) | -2.24 score on scale | Standard Error 0.5 |
| Placebo | Change in Retardation Factor Scores | Week 3 (n =167, 177) | -2.68 score on scale | Standard Error 0.34 |
| Placebo | Change in Retardation Factor Scores | Week 6 (n =126, 150) | -3.66 score on scale | Standard Error 0.42 |
| Placebo | Change in Retardation Factor Scores | Endpoint (n =168, 181) | -1.88 score on scale | Standard Error 0.48 |
Comparison: Week 3p-value: 0.068ANCOVA
Comparison: Week 6p-value: 0.043ANCOVA
Comparison: Endpointp-value: 0.404ANCOVA
Secondary
Change in Sheehan Disability Scale (SDS) Total Score
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)
Population: Baseline to Endpoint. Endpoint is ITT population Last Observation Carried Forward (LOCF). n = 149, 162; N = 180, 190
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Sheehan Disability Scale (SDS) Total Score | -3.69 score on scale | Standard Error 0.93 |
| Placebo | Change in Sheehan Disability Scale (SDS) Total Score | -3.05 score on scale | Standard Error 0.91 |
Comparison: Baseline to endpointp-value: 0.428ANCOVA
Secondary
Change in Sleep Disturbance Factor Score
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
Population: Weeks 3, 6 are Intent to treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Sleep Disturbance Factor Score | Week 3 (n =167, 177) | -1.51 score on scale | Standard Error 0.24 |
| Ziprasidone 20-80mg Bid | Change in Sleep Disturbance Factor Score | Week 6 (n =126, 150) | -2.38 score on scale | Standard Error 0.28 |
| Ziprasidone 20-80mg Bid | Change in Sleep Disturbance Factor Score | Endpoint (n=168, 181) | -1.19 score on scale | Standard Error 0.3 |
| Placebo | Change in Sleep Disturbance Factor Score | Week 3 (n =167, 177) | -1.48 score on scale | Standard Error 0.23 |
| Placebo | Change in Sleep Disturbance Factor Score | Week 6 (n =126, 150) | -2.31 score on scale | Standard Error 0.26 |
| Placebo | Change in Sleep Disturbance Factor Score | Endpoint (n=168, 181) | -1.26 score on scale | Standard Error 0.29 |
Comparison: Week 3p-value: 0.899ANCOVA
Comparison: Week 6p-value: 0.739ANCOVA
Comparison: Endpointp-value: 0.797ANCOVA
Secondary
Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25)
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
Population: Weeks 3, 6 are Intent to Treat (ITT) population Observed Cases.~Endpoint is ITT population Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Placebo | Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25) | Week 3 (n=167, 177) | -10.76 score on scale | Standard Error 1.02 |
| Placebo | Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25) | Week 6 (n=126, 150) | -14.80 score on scale | Standard Error 1.22 |
| Placebo | Change in Total Score in Hamiliton Depression Rating Scale (HAM-D 25) | Endpoint (n=168, 181) | -8.58 score on scale | Standard Error 1.56 |
Comparison: Week 3p-value: 0.305ANCOVA
Comparison: Week 6p-value: 0.51ANCOVA
Comparison: Endpointp-value: 0.71ANCOVA
Secondary
Change in Total Score of Young Mania Rating Scale (YMRS)
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
Population: Week 1 - Week 6 is Intent to treat (ITT) population Observed Cases.~Overall is Average of Weeks 1 - 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 3 (n=149, 163) | -0.13 score on scale | Standard Error 0.41 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 5 (n=121, 146) | -0.94 score on scale | Standard Error 0.35 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 1 (n=177, 189) | 0.40 score on scale | Standard Error 0.36 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 6 (n=116, 141) | -0.45 score on scale | Standard Error 0.43 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 4 (n=135, 153) | -0.60 score on scale | Standard Error 0.36 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Overall (n=180, 190) | -0.20 score on scale | Standard Error 0.32 |
| Ziprasidone 20-80mg Bid | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 2 (n=160, 176) | 0.49 score on scale | Standard Error 0.39 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Overall (n=180, 190) | -0.27 score on scale | Standard Error 0.26 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 1 (n=177, 189) | 0.69 score on scale | Standard Error 0.33 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 2 (n=160, 176) | -0.13 score on scale | Standard Error 0.31 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 3 (n=149, 163) | 0.00 score on scale | Standard Error 0.34 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 4 (n=135, 153) | -0.77 score on scale | Standard Error 0.31 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 5 (n=121, 146) | -0.77 score on scale | Standard Error 0.31 |
| Placebo | Change in Total Score of Young Mania Rating Scale (YMRS) | Week 6 (n=116, 141) | -0.66 score on scale | Standard Error 0.37 |
Comparison: Week 1p-value: 0.468Mixed Models Analysis
Comparison: Week 2p-value: 0.11Mixed Models Analysis
Comparison: Week 3p-value: 0.738Mixed Models Analysis
Comparison: Week 4p-value: 0.617Mixed Models Analysis
Comparison: Week 5p-value: 0.642Mixed Models Analysis
Comparison: Week 6p-value: 0.644Mixed Models Analysis
Comparison: Overallp-value: 0.789Mixed Models Analysis
Secondary
Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7
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
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Endpoint: Yes | 59 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Endpoint: No | 109 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Endpoint: Yes | 55 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Week 3: Yes | 33 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Week 6: No | 99 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Week 3: No | 144 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Endpoint: No | 126 Participants |
| Placebo | Remission as Measured by Hamilton Asberg Depression Rating Scale (HAM-D 17) Total Score Less Than or Equal to 7 | Week 6: Yes | 51 Participants |
Comparison: Week 3p-value: 0.9863Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.1017Cochran-Mantel-Haenszel
Comparison: Endpointp-value: 0.4033Cochran-Mantel-Haenszel
Secondary
Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12
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
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 5: Yes | 70 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Endpoint: Yes | 87 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 3: No | 79 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Endpoint: No | 93 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 1: Yes | 41 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 5: No | 51 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 1: No | 136 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 4: No | 69 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 2: Yes | 54 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 6: Yes | 70 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 2: No | 106 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 4: Yes | 66 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 3: Yes | 70 Participants |
| Ziprasidone 20-80mg Bid | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 6: No | 46 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 3: Yes | 58 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 3: No | 105 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 4: Yes | 60 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 4: No | 93 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 5: Yes | 66 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 5: No | 80 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 6: Yes | 72 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 6: No | 69 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Endpoint: Yes | 81 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 1: Yes | 21 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 1: No | 168 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 2: Yes | 41 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Week 2: No | 135 Participants |
| Placebo | Remission as Measured by Montgomery Asberg Depression Scale (MADRS) Total Score Less Than or Equal to 12 | Endpoint: No | 109 Participants |
Comparison: Week 1p-value: 0.0005Cochran-Mantel-Haenszel
Comparison: Week 2p-value: 0.0099Cochran-Mantel-Haenszel
Comparison: Week 3p-value: 0.0423Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.0618Cochran-Mantel-Haenszel
Comparison: Week 5p-value: 0.0451Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.2633Cochran-Mantel-Haenszel
Comparison: Endpointp-value: 0.2206Cochran-Mantel-Haenszel
Secondary
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score
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
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Ziprasidone 20-80mg Bid | 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 |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Endpoint: Yes | 97 Participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 3: Yes | 65 Participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 6: No | 59 Participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 3: No | 112 Participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Endpoint: No | 84 Participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Hamilton Depression Rating Scale (HAM-D 17) Total Score | Week 6: Yes | 91 Participants |
Comparison: Week 3p-value: 0.2185Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.4124Cochran-Mantel-Haenszel
Comparison: Endpointp-value: 0.6098Cochran-Mantel-Haenszel
Secondary
Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score
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
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 1: Yes | 40 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 1: No | 137 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 2: Yes | 55 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 2: No | 105 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 3: Yes | 71 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 3: No | 78 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 4: Yes | 76 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 4: No | 59 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 5: Yes | 81 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 5: No | 40 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 6: Yes | 76 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 6: No | 40 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Endpoint: Yes | 95 participants |
| Ziprasidone 20-80mg Bid | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Endpoint: No | 85 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 6: Yes | 83 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 1: Yes | 24 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 4: No | 87 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 1: No | 168 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Endpoint: Yes | 97 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 2: Yes | 48 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 5: Yes | 77 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 2: No | 128 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 6: No | 58 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 3: Yes | 60 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 5: No | 69 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 3: No | 105 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Endpoint: No | 93 participants |
| Placebo | Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score | Week 4: Yes | 66 participants |
Comparison: Week 1p-value: 0.0056Cochran-Mantel-Haenszel
Comparison: Week 2p-value: 0.0866Cochran-Mantel-Haenszel
Comparison: Week 3p-value: 0.0568Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.013Cochran-Mantel-Haenszel
Comparison: Week 5p-value: 0.0188Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.6394Cochran-Mantel-Haenszel
Comparison: Endpointp-value: 0.7707Cochran-Mantel-Haenszel