Safety and Maintenance of Effect of Ziprasidone Plus a Mood Stabilizer in Bipolar I Disorder (Manic or Mixed)

Phase 3

Completed

Conditions: Bipolar Mania
Bipolar Disorder

Interventions: Drug: Placebo
Drug: Ziprasidone Oral Capsule

Registration Number: NCT00280566

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

Brief Summary: The purpose of this study is to determine if ziprasidone plus a mood stabilizer will continue to be a safe and effective treatment regimen for adults with Bipolar I Disorder (manic or mixed symptoms) after they have achieved 8 consecutive weeks of symptom improvement on the regimen.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 584

Inclusion Criteria

Adults meeting DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for Bipolar I Disorder (currently with manic or mixed symptoms)

Exclusion Criteria

Ultra rapid cyclers and subjects with significant cardiovascular disease including history of QT prolongation and/or congenital long QT syndrome

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo treatment, double-blind, randomized arm
Ziprasidone	Ziprasidone Oral Capsule	Active treatment, double-blind, randomized arm

Primary Outcome Measures

Name	Time	Method
Time to Intervention for a Mood Episode During Double Blind Period	Period 2: 24 weeks or time of early termination	Time to Intervention for Mood Episode (TIME) while on randomized drug after at least 8 weeks of symptom reduction on open-label ziprasidone plus mood stabilizer. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.

Secondary Outcome Measures

Name	Time	Method
Modified Time to Intervention for a Mood Episode (TIME)	Period 2: Week 24 or time of early termination	Time to intervention for a mood episode or time to discontinuation for treatment related adverse events, or death due to drug, or death due to disease. Mood episode considered to have occurred and subject discontinued if one or more of the following: Investigator (INV) decides discontinuation is in best interest of subject; loss of effect and/or change to treatment regimen (INV judgment); subject hospitalized for disease under study; Mania Rating Scale (MRS) and/or Montgomery-Asberg Rating Scale (MADRS) rating is ≥18 for 2 consecutive visits scheduled no more than 10 days apart.
Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period	Period 2: Weeks 1 - 24 or time of early termination	Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. MADRS is 10-item instrument measuring depression: scales from 0=Normal to 6 = most abnormal.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period	Period 2: Weeks 4 - 24 or time of early termination	Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive Scale is 7-items derived from PANSS; 1 (absent), 2 (minimal) to 7 (extreme).
Time to Discontinuation for Any Reason During Double Blind Period 2	Period 2: 24 weeks or time of early termination	Key Secondary endpoint is time to discontinuation for any reason. Profile of patients remaining in the trial over time.
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period	Period 2: Weeks 1 - 24 or time of early termination	Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Clinical Global Impression Severity Score is 7-item scale rates severity of illness from 0=not assessed, 1= normal to 7=most extremely ill.
Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period	Period 2: Weeks 1 - 24 or time of early termination	Clinical Global Impression measures 7 items in Global assessment of improvement in patient's condition; 0=not assessed, 1= very much improved to 7= very much worse.
Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period	Period 2: Weeks 1 - 24 or time of early termination	Period 2 Baseline = last observation in Period 1 to the start of Period 2. MRS is 11-item scale to measure mania; derived from Schedule for Affective Disorders and Schizophrenia-Change Behavior (SADS-CB). Subscales: Manic Syndrome (elevated mood, less need for sleep, excessive energy and activity, grandiosity), Behavior and Ideation (irritability, motor hyperactivity, accelerated speech, racing thoughts, poor judgment), and Impaired Insight. Racing thoughts range=0 to 2 (highest level of abnormal=2); all other items 0 to 5 (highest level of abnormal=5). Higher score = greater abnormality.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period	Period 2: Weeks 4 - 24 or time of early termination	Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Positive and Negative Syndrome Scale Total Score is 30-item scale measuring severity of psychopathology (16 items), positive symptoms (7 items) and negative symptoms (7 items); scale from 1 (absent) to 7 (extreme)
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period	Period 2: Weeks 4 - 24 or time of early termination	Baseline for Period 2 is the last observation in Period 1 to the start of Period 2. Negative Scale is 7 items derived from PANSS; scale is 1 (absent) to 7 (extreme).