A Six-Week Study Evaluating The Efficacy And Safety Of Geodon In Patients With A Diagnosis Of 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, Randomized, Double-Blind, Multicenter, Fixed-Flexible Dose, Placebo-Controlled Study Evaluating the Efficacy and Safety of Oral Ziprasidone in Outpatients With Bipolar I Depression

Conditions
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Bipolar Disorder

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


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 Diagnostic and Statistical Manual (of Mental Disorders) - Fourth Edition - Text Revision (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 not otherwise specified (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: 20-40mg BID arm<br> | Drug: Geodon (Ziprasidone)<br>* Subjects will start at 20mg bid days 1-6, then flexible dosing starting on day 7 between 20-40mg bid (20mg bid or 40mg bid) for the remainder of the 6 week trial<br>|
| Active Comparator: 60-80mg bid arm<br> | Drug: Geodon (Ziprasidone)<br>* Subjects will start at 20mg bid days 1-2, then 40mg bid days 3-4, them 60mg bid for days 5-6 then flexible dosing starting on day 7 between 60-80mg bid (60 mg bid or 80mg bid) for the remainder of the 6 week trial<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects will start on placebo and remain on placebo for the remainder of the 6 week trial<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. Overall is average response of Weeks 1 - 6. MADRS is 10-item instrument measuring depression; scale 0(Normal) and 6(most abnormal). Total possible score is 0 - 60. | Baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Greater Than or Equal to 50 Percent Decrease From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)Total Score | Participants with MADRS Total Score greater or equal to 50 percent decrease from baseline responded yes; others responded no. Endpoint is last observation carried forward (LOCF) among Week 1 - Week 6; MADRS is 10-item instrument measuring depression; scale range 0(Normal) and 6 (most abnormal). Total possible score is 0 - 60 | Baseline to 6 weeks | 
| 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 HAMD-17 total score responded yes; others responded no. Endpoint is LOCF endpoint among Week 1 - 6; Total score is first 17 items of HAM-D 25: measures range of depressive symptoms; scale 0-2 or 0-4 with higher scores being more severe. Total possible score 0 - 52. | Baseline to 6 weeks | 
| Change in Global Assessment of Functioning (GAF)at Endpoint, Last Observation Carried Forward (LOCF) | Change is observed value at endpoint minus baseline value. Endpoint is Last Observation Carried Forward (LOCF) endpoint among Week 1 - 6; GAF is used to assess global psychological, social, & occupational functioning; 100=normal and 0=greatest abnormality | Baseline, 6 Weeks LOCF | 
| Remission as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Less Than or Equal to 12 | Response was Yes if MADRS Total Score was less than, equal to 12, if not, response was no. Endpoint is LOCF endpoint among Week 1 through 6; MADRS is 10-item instrument measuring depression; scale range 0(Normal) and 6(most abnormal) | Baseline to 6 weeks | 
| Remission as Measured by Hamilton Depression (HAM-D 17) Total Score Less Than or Equal to 7 | Response was yes when HAM-D 17 total score was less than or equal to 7 , if not, response was no. Endpoint is LOCF endpoint among Week 1 through Week 6. Total score is first 17 items of the HAM-D 25,which measures the range of depressive symptoms; scale 0-2 or 0-4 with higher scores being more severe. Total possible score 0 - 52. | Baseline to 6 weeks | 
| Change in Hamilton Depression (HAM-D 17) Total Score | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. Total score is first 17 items of the HAM-D 25, which measures the range of depressive symptoms patient currently experiencing; scale 0-2 or 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme. Total possible score 0 - 52. | Baseline to 6 weeks | 
| Change in Hamilton Anxiety Rating (HAM-A) | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. HAM-A is a 14-item scale: rates intensity of psychic anxiety and somatic anxiety on a 5-point severity scale (range: 0=not present to 4=very severe). Total possible score is 0 - 56. | Baseline to 6 weeks | 
| Change in Total Score of Young Mania Rating Scale (YMRS) | Change is observed value at each visit minus baseline value. Overall is average response of Weeks 1 - 6. YMRS: 11 item instrument with scale 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. | Baseline to 6 weeks | 
| Change in Assessment of Global Clinical Severity of Symptoms (CGI-S) | Change is observed value at each visit minus baseline value. Overall is average response of Weeks 1 - 6. CGI-S measures severity of patient's mental illness. Scale range: 0 = not assessed, 1 = normal, 7 = among most extremely ill | Baseline to 6 weeks | 
| Change in Global Clinical Improvement of Symptoms (CGI -I) | Change is observed value at each visit minus baseline value. Overall is average response of Weeks 1 - 6. 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 6 weeks | 
| Change in Total Score in Hamilton Depression (HAM-D 25) | Change: observed value at each visit minus baseline value. Endpoint is Last Observation Carried Forward (LOCF) endpoint among Week 1 through Week 6. HAM-D 25: measures the range of depressive symptoms experienced. 25 Items with Scale range:0-2 or 0-4; 0=absent or not depressed, 2 or 4=most severe or extreme.Total possible score is 0 - 72. | Baseline to 6 Weeks | 
| Response as Measured by CGI-I Score Less Than or Equal to 2 | Response each week was yes if CGI-I score less than or equal to 2 (much or very much improved), if not, response was no; Endpoint is LOCF endpoint among Week 1 through Week 6. CGI-I is a Global assessment of improvement in patient's condition. Scale range: 0=not assessed, 1=very much improved, 7=very much worse | Week 1 through Week 6 (endpoint) | 
| Change in Sheehan Disability Scale (SDS) Total Score at Endpoint | Observed value each visit minus baseline value. Endpoint is LOCF Week 1 through Week 6. SDS: patient rated measure of disability and impairment in 3 items: work/school, social life, family life/home responsibilities:0(no disruption)- 10(extreme disruption). Total possible is 30. | Baseline to Week 6 | 
| Change in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Total Score at Endpoint | Change is observed value at each visit minus baseline value. LOCF endpoint among Week 1 through Week 6. Q-LES-Q: 16-item instrument for patients assessment of his/her quality of life; overall level of satisfaction scale 1=very poor to 5=Very good (1 item re medication can be blank). Total possible score 15 - 80 | Baseline to 6 Weeks | 
| Change in Bech Melancholia Score | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. Bech Melancholia is the sum of Scores on 6 Items pertaining to melancholia within Hamilton Depression Rating Scale (HAM-D). Scale 0 to 4, higher scores reflecting greater severity;Total possible 0 - 24. | Baseline to 6 Weeks | 
| Change in Anxiety/Somatizations Factor Total Score | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This instrument = sum of Scores on 6 Items measuring anxiety/somatization within Hamilton Depression Rating Scale (HAM-D). Scale range is 0 to 4, higher scores reflecting greater severity. Total possible 0 - 24. | Baseline to 6 Weeks | 
| Change in Retardation Factor Scores | Change is observed value at each visit minus baseline value. This instrument = sum of Scores of 4 items on retardation within Hamilton Depression Rating Scale (HAM-D). Scale range is 0 to 4 with higher scores reflecting greater severity. Total possible is 0 - 16. | Baseline to 6 Weeks | 
| Change in Sleep Disturbance Factor Score | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This instrument = sum of Scores of 3 items on sleep disturbance within Hamilton Depression Rating Scale (HAM-D). Scale range 0 to 4 with higher scores reflecting greater severity. Total possible is 0 - 12. | Baseline to 6 weeks | 
| Change in Verbal Memory Trial Performance Total Score at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This test is part of Brief Assessment of Cognition and measures recall of 15 words repeated 5 times. Range 0-75 words, higher number reflects better recall. | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test Immediate Recall List 1 Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition measuring immediate recall of 15 emotional words; higher number of words is better recall. | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test Immediate Recall Non-Emotional Words List 1 at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This instrument measures immediate recall of 15 non-emotional words (List 1); higher number of words is better recall. | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Immediate Recall, List 2 Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This test is in Brief Assessment of Cognition and measures immediate recall of 15 emotional words (List 2); higher number of words is better recall | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Immediate Recall, List 2 Non-Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures immediate recall of 15 non-emotional words (List 2); higher number of words is better recall | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Immediate Recall, List 3 Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures immediate recall of 15 emotional words (List 3); higher number of words is better recall | Baseline to Week 6 LOCF | 
| Change in Affective Interference Test, Immediate Recall, List 3 Non-Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures immediate recall of 15 non-emotional words (List 3); higher number of words is better recall | Baseline to Week 6 LOCF | 
| Change in Affective Interference Test, Immediate Recall, Cued-Recall Non-Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures immediate recall (Cued) of 15 non-emotional words; higher number of words is better recall | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Immediate Recall, Cued-Recall Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures immediate recall (Cued) of 15 emotional words; higher number of words is better recall | Baseline to 6 Weeks LOCF | 
| Change in Digit Sequencing Task at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition in which patient sequences digits from lowest to highest. Range of number of correct responses (0-28); higher numbers show better digit sequencing and greater cognition. | Baseline to 6 Weeks LOCF | 
| Change in Token Motor Task at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition in which a patient places as many of 100 tokens (2 at a time) into a container as they can within 60 seconds. The higher number of tokens placed = patient is better at motor tasks | Baseline to 6 Weeks LOCF | 
| Change in Verbal Fluency in Naming Categories at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition.Patients are given 60 seconds to name as many words as possible within a given category. The more words named=better cognition. | Baseline to 6 Weeks LOCF | 
| Change in Verbal Fluency Controlled Word Association at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition. Patients given 60 seconds to generate as many words as possible that begin with a given letter; better verbal fluency = more words | Baseline to 6 Weeks LOCF | 
| Change in Symbol Coding at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition. For 90 seconds, Patient writes numerals 1-9 as matched to symbols. Range 0 to 110 with higher totals = better cognition. | Baseline to 6 Weeks LOCF | 
| Change in Tower of London Test at Endpoint | Change is observed value at each visit minus baseline value. Endpoint: LOCF endpoint among Week 1 through Week 6. Brief Assessment of Cognition: subjects asked to arrange balls in 2 pictures so they are identical and give the total number of ball movements to reach this arrangment. Range: 0-22; more correct = better cognition. | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Delayed Recognition, Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. Test in Brief Assessment of Cognition in which the number of correct emotional words in delayed recognition is measured. Range 0-75 with higher numbers showing better cognition. | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Delayed Recognition, Emotional Words False Alarms at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. Test in Brief Assessment of Cognition which measures number of correct emotional word's false alarms (during delayed recognition). Higher number = better cognition | Baseline to 6 Weeks LOCF | 
| Change in Affective Interference Test, Delayed Recognition, Non-Emotional Words at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures number of Non-Emotional Words (Delayed Recognition); higher number of words = better cognition | Baseline to Week 6 LOCF | 
| Change in Affective Interference Test, Delayed Recognition, Non-Emotional Words False Alarms at Endpoint | Change is observed value at each visit minus baseline value. Endpoint is LOCF endpoint among Week 1 through Week 6. This is a test in Brief Assessment of Cognition which measures number of correct non-eEmotional word's false alarms(at delayed recognition). Higher number of words = greater cognition | Baseline to Week 6 LOCF | 

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