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

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).

Time frame: Baseline, Week 3

Population: Intent to Treat population (ITT): all randomized subjects who received at least 1 dose of double-blind medication, who had 1 baseline and at least 1 post-baseline primary efficacy evaluation; excluding data from 2 sites that were closed due to Good Clinical Practices (GCP) deviations.

Anonymized pharmacogenomic blood draw to evaluate the pharmacogenomic basis for ziprasidone treatment responsivity.

Time frame: Baseline

Population: All subjects eligible (optional consent); samples were not to be analyzed as part of the current protocol and the analysis was not to be covered by the statistical analysis plan.

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).

Time frame: Baseline, Week 1, Week 2, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

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).

Time frame: Baseline, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations.

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).

Time frame: Baseline, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations.

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).

Time frame: Baseline, Week 1, Week 2, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

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).

Time frame: Baseline, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

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).

Time frame: Baseline, Week 1, Week 2

Population: ITT population excluding data from 2 sites that were closed to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.

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.

Time frame: Week 1, Week 2, Week 3

Population: ITT population excluding data from 2 sites that were closed due to GCP deviations; (n)=number of subjects for ziprasidone (higher dose), ziprasidone (lower dose), and placebo, respectively.