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

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

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

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Ziprasidone; Drug: Ziprasidone

• Study Type: Interventional
• Enrollment (Actual): 680
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Pfizer Investigational Site
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Pfizer Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Pfizer Investigational Site
  • California
    • Cerritos, California, United States, 90703
      • Pfizer Investigational Site
    • Costa Mesa, California, United States, 92626
      • Pfizer Investigational Site
    • Escondido, California, United States, 92025
      • Pfizer Investigational Site
    • Glendale, California, United States, 91204
      • Pfizer Investigational Site
    • Huntington Beach, California, United States, 92647
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90057
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90061
      • Pfizer Investigational Site
    • National City, California, United States, 91950
      • Pfizer Investigational Site
    • Oceanside, California, United States, 92056
      • Pfizer Investigational Site
    • San Diego, California, United States, 92120
      • Pfizer Investigational Site
    • San Diego, California, United States, 92126
      • Pfizer Investigational Site
    • San Diego, California, United States, 92114
      • Pfizer Investigational Site
    • Torrance, California, United States, 90505
      • Pfizer Investigational Site
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Pfizer Investigational Site
    • New Britain, Connecticut, United States, 06050
      • Pfizer Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
    • Fort Lauderdale, Florida, United States, 33308
      • Pfizer Investigational Site
    • Fort Lauderdale, Florida, United States, 33301
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32607
      • Pfizer Investigational Site
    • Hollywood, Florida, United States, 33021
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32256-2006
      • Pfizer Investigational Site
    • Lauderhill, Florida, United States, 33119
      • Pfizer Investigational Site
    • North Miami, Florida, United States, 33161
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pfizer Investigational Site
  • Illinois
    • Des Plaines, Illinois, United States, 60016
      • Pfizer Investigational Site
    • Hoffman Estates, Illinois, United States, 60169
      • Pfizer Investigational Site
    • Hoffman Estates, Illinois, United States, 60194
      • Pfizer Investigational Site
    • Schaumburg, Illinois, United States, 60194
      • Pfizer Investigational Site
  • Indiana
    • Greenwood, Indiana, United States, 46143
      • Pfizer Investigational Site
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Pfizer Investigational Site
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Pfizer Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Pfizer Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64133
      • Pfizer Investigational Site
    • Saint Charles, Missouri, United States, 63304
      • Pfizer Investigational Site
    • Saint Louis, Missouri, United States, 63128
      • Pfizer Investigational Site
    • Saint Louis, Missouri, United States, 63118
      • Pfizer Investigational Site
    • Saint Louis, Missouri, United States, 63044-2588
      • Pfizer Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89102
      • Pfizer Investigational Site
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • Pfizer Investigational Site
    • Princeton, New Jersey, United States, 08540
      • Pfizer Investigational Site
  • New York
    • Amityville, New York, United States, 11701
      • Pfizer Investigational Site
    • Buffalo, New York, United States, 14215
      • Pfizer Investigational Site
    • Cedarhurst, New York, United States, 11516
      • Pfizer Investigational Site
    • Elmsford, New York, United States, 10523
      • Pfizer Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0559
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45219
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45220
      • Pfizer Investigational Site
    • Cleveland, Ohio, United States, 44113
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19149
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29405
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75228
      • Pfizer Investigational Site
    • Irving, Texas, United States, 75062
      • Pfizer Investigational Site
    • Plano, Texas, United States, 75024
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229-3900
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78259-3509
      • Pfizer Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23230
      • Pfizer Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • Pfizer Investigational Site
    • Kirkland, Washington, United States, 98033
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Sachs GS, Vanderburg DG, Edman S, Karayal ON, Kolluri S, Bachinsky M, Cavus I. Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 2: influence of protocol-specific eligibility criteria on signal detection. J Clin Psychiatry. 2012 Nov;73(11):1420-5. doi: 10.4088/JCP.11m07389.
• Sachs GS, Vanderburg DG, Karayal ON, Kolluri S, Bachinsky M, Cavus I. Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 1: results of a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2012 Nov;73(11):1412-9. doi: 10.4088/JCP.11m07388.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: April 6, 2006
• First Submitted That Met QC Criteria: April 6, 2006
• First Posted (Estimate): April 10, 2006

Study Record Updates

• Last Update Posted (Actual): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Ziprasidone
• Other Study ID Numbers: A1281143