Bipolar Disorder, Bipolar Mania
Conditions
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.
Interventions
DRUGPlacebo
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.
DRUGZiprasidone Oral Capsule
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.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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) 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). |
| 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). |
| 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. |
Countries
Chile, France, Germany, Guatemala, Hong Kong, India, Italy, Mexico, Russia, Spain, Taiwan, United States, Venezuela
Participant flow
Recruitment details
Trial intended to be outpatient trial. Patients hospitalized at the screening visit due to disease under study were to be stable enough for outpatient status within approximately 5 days.
Pre-assignment details
Period 1:open label stabilization (ziprasidone plus lithium or valproic acid mood stabilizer). Period 2:subjects stabilized for 8 weeks randomized to blinded treatment (ziprasidone plus mood stabilizer or placebo plus mood stabilizer). 241 completed Period 1, 238 summarized in Period 2: 1 subject not randomized to Period 2, 2 excluded as per note.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period. | 127 |
| Placebo Double-blind,randomized to placebo plus mood stabilizer. Subjects were tapered off ziprasidone onto placebo by decreasing 20 mg BID every 2 days during the first week of Period 2 | 111 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 Open Label Ziprasidone | Adverse Event | 148 | 0 | 0 |
| Period 1 Open Label Ziprasidone | Laboratory Abnormality | 3 | 0 | 0 |
| Period 1 Open Label Ziprasidone | Lack of Efficacy | 31 | 0 | 0 |
| Period 1 Open Label Ziprasidone | Lost to Follow-up | 35 | 0 | 0 |
| Period 1 Open Label Ziprasidone | Miscellaneous | 50 | 0 | 0 |
| Period 1 Open Label Ziprasidone | Withdrawal by Subject | 76 | 0 | 0 |
| Period 2 Double Blind | Adverse Event | 0 | 11 | 15 |
| Period 2 Double Blind | Laboratory Abnormality | 0 | 1 | 0 |
| Period 2 Double Blind | Lack of Efficacy | 0 | 9 | 22 |
| Period 2 Double Blind | Lost to Follow-up | 0 | 3 | 6 |
| Period 2 Double Blind | miscellaneous | 0 | 10 | 5 |
| Period 2 Double Blind | Withdrawal by Subject | 0 | 9 | 9 |
Baseline characteristics
| Characteristic | Ziprasidone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 12.3 | 38.0 years STANDARD_DEVIATION 11.6 | 38.4 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 51 Participants | 58 Participants | 109 Participants |
| Sex: Female, Male Male | 76 Participants | 53 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 362 / — | 22 / — | 24 / — |
| serious Total, serious adverse events | 15 / — | 3 / — | 2 / — |
Outcome results
Primary
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
Population: Intent to Treat (ITT):Subjects took at least 1 dose double blind medication and had at least 1 post randomization observation. Double Blind Period followed at least 8 weeks open-label ziprasidone plus mood stabilizer; 25 out of 127 and 36 out of 111 subjects had an intervention for a mood episode.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Time to Intervention for a Mood Episode During Double Blind Period | 172.159 Days | Standard Error 5.646 |
| Placebo | Time to Intervention for a Mood Episode During Double Blind Period | 143.133 Days | Standard Error 7.532 |
Comparison: Equality of Survival Curves across the treatment groups.p-value: 0.0104Log Rank
Secondary
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
Population: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 1 (n=122, 106) | 0.1 scores on scale | Standard Deviation 0.7 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 0.2 scores on scale | Standard Deviation 0.9 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 4 (n=117, 95) | -0.0 scores on scale | Standard Deviation 0.7 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.0 scores on scale | Standard Deviation 0.8 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | -0.1 scores on scale | Standard Deviation 0.9 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 16 (n=94, 65) | -0.1 scores on scale | Standard Deviation 0.9 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 20 (n=83, 58) | -0.1 scores on scale | Standard Deviation 0.9 |
| Ziprasidone | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.2 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.2 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 1 (n=122, 106) | 0.3 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.0 scores on scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 0.2 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 20 (n=83, 58) | -0.2 scores on scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 4 (n=117, 95) | 0.1 scores on scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 16 (n=94, 65) | 0.0 scores on scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Clinical Global Impression Severity (CGI-S) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.1 scores on scale | Standard Deviation 0.8 |
Comparison: Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0088MMRM ANCOVA
Comparison: Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.3677MMRM ANCOVA
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0734MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.9166MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.2791MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.146MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.7301MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.8162MMRM ANCOVA
Secondary
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.
Time frame: Period 2: Weeks 1 - 24 or time of early termination
Population: Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 1 (n=121, 106) | -0.2 scores on scale | Standard Deviation 3 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 2 (n=116, 95) | -0.4 scores on scale | Standard Deviation 4.2 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 4 (n=117,95) | -0.6 scores on scale | Standard Deviation 3.7 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.3 scores on scale | Standard Deviation 5.7 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 12 (n=98, 70) | -1.0 scores on scale | Standard Deviation 4.3 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 16 (n=94,65) | -1.4 scores on scale | Standard Deviation 4.3 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 20 (n=84, 58) | -1.1 scores on scale | Standard Deviation 6.5 |
| Ziprasidone | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 24 (n=85,53) | -1.1 scores on scale | Standard Deviation 5.5 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 24 (n=85,53) | 0.3 scores on scale | Standard Deviation 4.2 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 1 (n=121, 106) | 0.8 scores on scale | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 12 (n=98, 70) | 1.2 scores on scale | Standard Deviation 8.2 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 2 (n=116, 95) | -0.1 scores on scale | Standard Deviation 4.7 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 20 (n=84, 58) | 0.2 scores on scale | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 4 (n=117,95) | 0.2 scores on scale | Standard Deviation 5.4 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 16 (n=94,65) | 1.2 scores on scale | Standard Deviation 6.3 |
| Placebo | Change From Baseline in Mania Rating Scale (MRS) by Visit During Double Blind Period | Week 8 (n=107, 79) | 0.8 scores on scale | Standard Deviation 5.4 |
Comparison: Week 1: Difference in Change during Period 2 MMRM ANCOVA: center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1247MMRM ANCOVA
Comparison: Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.7515MMRM ANCOVA
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.3074MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0758MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0162MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0003MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0242MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0161MMRM ANCOVA
Secondary
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
Population: Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 1 (n=121, 106) | -0.2 scores on scale | Standard Deviation 4.9 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 1.1 scores on scale | Standard Deviation 7.4 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 4 (n=117, 95) | -0.3 scores on scale | Standard Deviation 5.3 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | 0.4 scores on scale | Standard Deviation 5.9 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 1.1 scores on scale | Standard Deviation 5.9 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 16 (n=94,65) | 1.2 scores on scale | Standard Deviation 6.3 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 20 (n=84, 58) | 0.5 scores on scale | Standard Deviation 5.6 |
| Ziprasidone | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | 0.4 scores on scale | Standard Deviation 6.4 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | 1.0 scores on scale | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 1 (n=121, 106) | 2.7 scores on scale | Standard Deviation 7.3 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.6 scores on scale | Standard Deviation 5.4 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 2.7 scores on scale | Standard Deviation 7.1 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.2 scores on scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 4 (n=117, 95) | 1.6 scores on scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 16 (n=94,65) | 0.4 scores on scale | Standard Deviation 3.9 |
| Placebo | Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | 0.4 scores on scale | Standard Deviation 5.3 |
Comparison: Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0023MMRM ANCOVA
Comparison: Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariatep-value: 0.1412MMRM ANCOVA
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0861MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.5992MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.5873MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.2116MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1847MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.9972MMRM ANCOVA
Secondary
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
Population: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 4 (n=123, 98) | 0.2 scores on scale | Standard Deviation 3.1 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 8 (n=107, 79) | 0.2 scores on scale | Standard Deviation 3.2 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.1 scores on scale | Standard Deviation 2.5 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 16 (n=94, 65) | 0.3 scores on scale | Standard Deviation 3.1 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.0 scores on scale | Standard Deviation 2.3 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.1 scores on scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.4 scores on scale | Standard Deviation 1.8 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 4 (n=123, 98) | 0.4 scores on scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 16 (n=94, 65) | 0.4 scores on scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.1 scores on scale | Standard Deviation 1.8 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.1 scores on scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.1 scores on scale | Standard Deviation 2.1 |
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.8117MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0443MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.3039MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.9953MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1653MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.5771MMRM ANCOVA
Secondary
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
Population: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 4 (n=123, 98) | 0.0 scores on scale | Standard Deviation 1.6 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.2 scores on scale | Standard Deviation 2 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 12 (n=98, 70) | -0.3 scores on scale | Standard Deviation 1.7 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 16 (n=94, 65) | -0.4 scores on scale | Standard Deviation 1.8 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.2 scores on scale | Standard Deviation 2.2 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.2 scores on scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.1 scores on scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 4 (n=123, 98) | 0.1 scores on scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 16 (n=94, 65) | 0.0 scores on scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.2 scores on scale | Standard Deviation 1.9 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.1 scores on scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Postive Scale by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.3 scores on scale | Standard Deviation 3.3 |
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.9538MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.8541MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1084MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.038MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.2649MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.2394MMRM ANCOVA
Secondary
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
Population: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.1 scores on scale | Standard Deviation 8.3 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 16 (n=94, 65) | -0.0 scores on scale | Standard Deviation 7.1 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 4 (n=123, 98) | 0.4 scores on scale | Standard Deviation 8.7 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 20 (n=84, 58) | -0.2 scores on scale | Standard Deviation 7.4 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 12 (n=98, 70) | -0.1 scores on scale | Standard Deviation 6.5 |
| Ziprasidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.6 scores on scale | Standard Deviation 8 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 24 (n=85, 53) | -0.9 scores on scale | Standard Deviation 7.4 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 4 (n=123, 98) | 1.5 scores on scale | Standard Deviation 6.9 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 8 (n=107, 79) | -0.8 scores on scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 0.3 scores on scale | Standard Deviation 9.4 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 16 (n=94, 65) | 0.7 scores on scale | Standard Deviation 8.7 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Visit During Double Blind Period | Week 20 (n=84, 58) | -1.0 scores on scale | Standard Deviation 6.1 |
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.5954MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.3414MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariatep-value: 0.9745MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.5627MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.741MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.9632MMRM ANCOVA
Secondary
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
Population: Intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 1 (n=122, 106) | 2.3 scores on scale | Standard Deviation 1.2 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 2.4 scores on scale | Standard Deviation 1.4 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 4 (n=117, 95 | 2.3 scores on scale | Standard Deviation 1.2 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | 2.3 scores on scale | Standard Deviation 1.4 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 2.2 scores on scale | Standard Deviation 1.3 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 16 (n=94, 65) | 2.3 scores on scale | Standard Deviation 1.4 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 20 (n=83, 58) | 2.1 scores on scale | Standard Deviation 1.4 |
| Ziprasidone | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | 2.2 scores on scale | Standard Deviation 1.3 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 24 (n=85, 53) | 2.2 scores on scale | Standard Deviation 1.4 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 1 (n=122, 106) | 2.8 scores on scale | Standard Deviation 1.6 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 12 (n=98, 70) | 2.2 scores on scale | Standard Deviation 1.4 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 2 (n=117, 95) | 2.6 scores on scale | Standard Deviation 1.6 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 20 (n=83, 58) | 2.1 scores on scale | Standard Deviation 1.4 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 4 (n=117, 95 | 2.5 scores on scale | Standard Deviation 1.5 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 16 (n=94, 65) | 2.5 scores on scale | Standard Deviation 1.5 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score by Visit During Double Blind Period | Week 8 (n=107, 79) | 2.2 scores on scale | Standard Deviation 1.2 |
Comparison: Week 1 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0013MMRM ANCOVA
Comparison: Week 2 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1167MMRM ANCOVA
Comparison: Week 4 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0188MMRM ANCOVA
Comparison: Week 8 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.3413MMRM ANCOVA
Comparison: Week 12 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.276MMRM ANCOVA
Comparison: Week 16 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.0085MMRM ANCOVA
Comparison: Week 20 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1317MMRM ANCOVA
Comparison: Week 24 mixed effects repeated measures analysis of covariance (MMRM ANCOVA): center, subject within center as random effects; treatment, visit, visit by treatment interaction as fixed effects and baseline score as covariate.p-value: 0.1666MMRM ANCOVA
Secondary
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
Population: Intent to Treat (ITT). 29 out of 127 ziprasidone subjects and 38 out of 111 placebo subjects met the modified criteria for an intervention for a mood episode
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Modified Time to Intervention for a Mood Episode (TIME) | 168.145 Days | Standard Error 5.857 |
| Placebo | Modified Time to Intervention for a Mood Episode (TIME) | 140.325 Days | Standard Error 7.627 |
Comparison: alpha = 0.05 level of significancep-value: 0.0205Log Rank
Secondary
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
Population: Intent to Treat (ITT). Number of participants who discontinued was 43 and 57 for ziprasidone and placebo, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Time to Discontinuation for Any Reason During Double Blind Period 2 | 153.526 days | Standard Error 6.454 |
| Placebo | Time to Discontinuation for Any Reason During Double Blind Period 2 | 123.313 days | Standard Error 7.524 |
Comparison: alpha = 0.05 level of significancep-value: 0.0047Log Rank