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

Study Overview
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Brief Summary
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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.

Official Title
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A Six-Week, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Efficacy and Safety of Flexible Doses of Oral Ziprasidone in Outpatients With Bipolar I Depression

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Geodon (Ziprasidone)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Baseline to Week 6 | 
| 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. | Baseline to Week 3, Week 6 | 
| 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. | Week 1 to Week 6 | 
| 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. | Week 3, Week 6 | 
| 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 | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to Weeks 3, 6 | 
| 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. | Baseline to week 6 | 
| 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 | Baseline to week 6 | 
| 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 | Baseline to Week 6 | 
| 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. | Baseline to week 6 (Endpoint) | 
| 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. | Baseline to week 6 (endpoint) | 
| 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. | Baseline to week 6 (endpoint) | 
| 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) | Baseline to week 6 (endpoint) | 
| 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. | Baseline to week 6 (endpoint) | 
| 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. | Baseline to week 6 (endpoint) | 
| 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. | Baseline to Week 6 (endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar I Depression