3-week Study to Evaluate Efficacy and Safety of Ziprasidone With Either Lithium or Divalproex in Acutely Manic Subjects

Study Overview
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Brief Summary
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3-week study to evaluate efficacy and safety of ziprasidone with either lithium or divalproex in acutely manic subjects

Official Title
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A Three-Week, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Efficacy and Safety of Add-On Oral Ziprasidone in Subjects With Acute Mania Treated With Lithium or Divalproex

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Ziprasidone
* Drug: 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 manic (296.4x), or mixed (296.6x) as defined in Diagnostic and Statistical Manual of Mental Disorders - Text Revision (DSM-IV TR) and determined by the Mini International Neuropsychiatric Interview (MINI). At screening and at baseline (within 12 hours prior to the first dose of double-blind medication) subjects must have a Young Mania Rating Scale score of 18 or higher. Subjects must be actively receiving lithium or divalproex for their bipolar disorder in order to be considered for this study. Exclusion Criteria: Subjects with a Diagnostic and Statistical Manual of Mental Disorders IV- Text Revision (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 (NOS) (298.9). Subjects with other DSM-IV-TR Axis I or Axis II disorders (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
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo with mood stabilizer (either lithium or divalproex)<br>|
| Experimental: Ziprasidone 20-40mg twice a day (BID)<br> | Drug: Ziprasidone<br>* Flexible dosing, 20-40mg BID, with a mood stabilizer (either lithium or divalproex)<br>* Other names: Geodon, Zeldox;|
| Experimental: Ziprasidone 60-80mg BID<br> | Drug: Ziprasidone<br>* Flexible dosing, 60-80mg BID, with a mood stabilizer (either lithium or divalproex)<br>* Other names: Geodon, Zeldox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 3 in Young Mania Rating Scale (YMRS) | YMRS is an 11-item scale (elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech [rate and amount], language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight) used to assess the severity of manic symptoms and effect of treatment on mania severity. Seven items ranked on scale from 0 to 4; 4 items ranked 0 to 8. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value). | Baseline, Week 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 1 and Week 2 in YMRS | YMRS is an 11-item scale (elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech [rate and amount], language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight) used to assess the severity of manic symptoms and effect of treatment on mania severity. Seven items ranked on scale from 0 to 4; 4 items ranked 0 to 8. Total possible score 0 to 60: higher scores indicate greater severity. Change calculated as mean of (value of YMRS score at observation minus baseline value). | Baseline, Week 1, Week 2 | 
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Scores | MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal) with anchors at 2-point intervals; total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as mean of (value of MADRS score at observation minus baseline value). | Baseline, Week 1, Week 2, Week 3 | 
| Change From Baseline in Clinical Global Impression Scale - Severity (CGI-S) Score | CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Rating ranges from 1 (normal, not at all ill) to 7 (among the most severely ill subjects); higher score = more affected. Change calculated as mean of (value of CGI-S score at observation minus baseline value). | Baseline, Week 1, Week 2, Week 3 | 
| Clinical Global Impression - Improvement (CGI-I) Scale Scores | CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score = more affected. | Week 1, Week 2, Week 3 | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Score | PANSS is a 30-item scale to measure severity of psychopathology (16 items); positive scale (7 items); negative scale (7 items); summarized as positive score, negative score, and total score. Scores rated 1 (absent symptoms) to 7 (extreme); total score range 30 to 210: higher score indicates greater severity. Change calculated as mean of (value of PANSS score at observation minus baseline value). | Baseline, Week 3 | 
| Change From Baseline in Global Assessment of Functioning (GAF) Score | GAF measures the severity of illness-related impairment in psychological, social, and occupational functioning; rated on a 100-point scale (single score of 1 to 100) with 100 indicating superior functioning. Change calculated as mean of (value of GAF score at observation minus baseline value). | Baseline, Week 3 | 
| Change From Baseline in Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning (LIFE-RIFT) Score | LIFE-RIFT measures severity of illness-related impairment in 4 domains: work, interpersonal relations, recreation, and global satisfaction; has a total score and individual domain scores. Domain scores range from 1 to 5 (scores ≥ 2 reflect impaired functioning). Total score is sum of the 4 domains with range of 4 (very good) to 20 (very poor): higher scores indicate greater impairment. Change calculated as mean of (value of LIFE-RIFT score at observation minus baseline value). | Baseline, Week 3 | 
| Anonymized Pharmacogenomic Blood Draw | Anonymized pharmacogenomic blood draw to evaluate the pharmacogenomic basis for ziprasidone treatment responsivity. | Baseline |