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Adjunctive Ziprasidone in the Treatment of Bipolar I Depression

Phase 3
Completed
Conditions
Bipolar Disorder
Depression, Bipolar
Interventions
Drug: Placebo
Registration Number
NCT00483548
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Brief Summary

The purpose of this study is to determine if a treatment regimen of ziprasidone plus a mood stabilizer is safe and effective in the short term treatment of Bipolar I Depression. Ziprasidone will be added to lithium, valproate or lamotrigine after the patient has been on a therapeutic dose of one of these mood stabilizers for at least 4 weeks.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
298
Inclusion Criteria
  • Adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for Bipolar I disorder, most recent episode depressed, with or without rapid cycling and without psychotic features. Subjects receive therapeutic dose of lithium, valproate or lamotrigine for at least 4 weeks prior to randomization.
Exclusion Criteria
  • Patients with ultra-fast rapid cycling (8 or more mood episodes per year)
  • Significant heart disease including abnormalities in the heart's rhythm (QT prolongation)
  • Psychotic symptoms (hallucinations and/or delusions).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboInactive, placebo treatment, double-blind, randomized arm
ZiprasidoneZiprasidoneActive treatment, double-blind, randomized treatment arm
Primary Outcome Measures
NameTimeMethod
Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total ScoreBaseline, Week 6

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); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.

Secondary Outcome Measures
NameTimeMethod
MADRS Remission: Number of Subjects With Total MADRS Score ≤ 12 at Week 6Week 6

Number of subjects with MADRS total score ≤ 12 (indicates remission). 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); total score 0 to 44 (higher score indicates greater severity of symptoms).

Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

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. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

MADRS Response: Number of Subjects With Total MADRS Score Reduction ≥ 50 Percent From Baseline at Week 6Week 6

Number of subjects with reduction of ≥50 percent (%) in MADRS total score (indicates response). 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); total score 0 to 44 (higher score indicates greater severity of symptoms). Reduction calculated as (\[A-B\]/B\*100): A=value at observation; B=baseline value.

Clinical Global Impression - Improvement Scale (CGI-Improvement or CGI-I): Number of Subjects With Response (Much Improved or Very Much Improved) at Week 6Baseline, Week 6

Number of subjects with improvement defined as CGI-I response of 1 (very much improved) or 2 (much improved). 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.

Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

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); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.

CGI-Improvement ScoreWeek 1, Week 2, Week 3, Week 4, Week 5, Week 6

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 6 is the primary timepoint.

Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total ScoreBaseline, Week 2, Week 4, Week 6

HAM-A is a clinician rated 14-item scale that rates the intensity of psychic anxiety (items 1 to 6 and item 14) and somatic anxiety (items 7 to 13) on a 5-point severity scale; scores range from 0 (not present) to 4 (very severe); lower score indicates less affected. Change calculated as a difference between post-baseline observation and baseline HAM-A score values. Week 6 is the primary timepoint.

Change From Baseline in Young Mania Rating Scale (YMRS) Total ScoreBaseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

YMRS is clinician rated 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. Higher scores indicate greater severity. Change calculated as a difference between post-baseline observation and baseline YMRS score values. Week 6 is the primary timepoint.

Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6Baseline, Week 6

GAF is a clinician rated scale to measure the severity of illness-related impairment in psychological, social, and occupational functioning using a 100-point scale (single score of 1 to 100) with 100 indicating a superior level of function. Change calculated as a difference between post-baseline observation and baseline GAF score values.

Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S)Baseline, Week 6

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. Scored from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)Baseline, Week 6

SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.

Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)Baseline, Week 6

SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.

Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6Baseline, Week 6

Q-LES-Q is a 16-item subject rated scale to measure satisfaction with areas of daily functioning (physical health, social relationships, medication, and overall life satisfaction); rated on a 5-point Likert scale: higher scores indicate greater enjoyment and satisfaction with general life activities. Scores for items 1 to 14 are summed for a total score and converted to 0 to 100 range. Items 15 and 16 measure satisfaction with medication and overall satisfaction and are analyzed separately. Change calculated as a difference between post-baseline observation and baseline Q-LES-Q score values.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇮🇳

Delhi, New Delhi, India

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