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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
584
Oral capsule formulation: Patients will be treated initially with open-label ziprasidone in the range of 40-80 mg BID (twice a day) for at least 10 weeks and up to 16 weeks. Patients who achieve a stable treatment regimen and whose symptoms stabilize for 8 consecutive weeks by Week 16 (Week 10 at the earliest) will be randomized. Patients randomized to placebo will be tapered off the open-label ziprasidone by 20 mg BID every 2 days (in a double-blinded manner) until they are completely off ziprasidone and are on matching placebo capsules for up to 24 weeks of double-blind treatment.
Oral capsule formulation: Patients will be treated initially with open-label ziprasidone in the range of 40-80 mg BID for at least 10 weeks and up to 16 weeks. Patients who achieve a stable treatment regimen and whose symptoms stabilize for 8 consecutive weeks by Week 16 (Week 10 at the earliest) will be randomized. Patients randomized to ziprasidone will continue to receive the same stable treatment regimen achieved during the open-label treatment, ie, either 40 mg BID, 60 mg BID or 80 mg BID for up to 24 weeks of double-blind treatment.
Time to Intervention for a Mood Episode During Double Blind Period
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.
Time frame: Period 2: 24 weeks or time of early termination
Time to Discontinuation for Any Reason During Double Blind Period 2
Key Secondary endpoint is time to discontinuation for any reason. Profile of patients remaining in the trial over time.
Time frame: Period 2: 24 weeks or time of early termination
Modified Time to Intervention for a Mood Episode (TIME)
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.
Time frame: Period 2: Week 24 or time of early termination
Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period
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.
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Time frame: Period 2: Weeks 1 - 24 or time of early termination
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period
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.
Time frame: Period 2: Weeks 1 - 24 or time of early termination
Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period
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.
Time frame: Period 2: Weeks 1 - 24 or time of early termination
Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period
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.
Time frame: Period 2: Weeks 1 - 24 or time of early termination
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period
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)
Time frame: Period 2: Weeks 4 - 24 or time of early termination
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period
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 frame: Period 2: Weeks 4 - 24 or time of early termination
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period
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).
Time frame: Period 2: Weeks 4 - 24 or time of early termination