Trial Outcomes & Findings for Safety and Maintenance of Effect of Ziprasidone Plus a Mood Stabilizer in Bipolar I Disorder (Manic or Mixed) (NCT NCT00280566)
NCT ID: NCT00280566
Last Updated: 2021-03-25
Results Overview
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.
COMPLETED
PHASE3
584 participants
Period 2: 24 weeks or time of early termination
2021-03-25
Participant Flow
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.
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.
Participant milestones
| Measure |
Period 1 Open Label Ziprasidone
40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy.
|
Ziprasidone
Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period.
|
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
|
|---|---|---|---|
|
Period 1 Open Label Ziprasidone
STARTED
|
584
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
COMPLETED
|
241
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
NOT COMPLETED
|
343
|
0
|
0
|
|
Period 2 Double Blind
STARTED
|
0
|
127
|
111
|
|
Period 2 Double Blind
COMPLETED
|
0
|
84
|
54
|
|
Period 2 Double Blind
NOT COMPLETED
|
0
|
43
|
57
|
Reasons for withdrawal
| Measure |
Period 1 Open Label Ziprasidone
40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy.
|
Ziprasidone
Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period.
|
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
|
|---|---|---|---|
|
Period 1 Open Label Ziprasidone
Lack of Efficacy
|
31
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
Laboratory Abnormality
|
3
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
Adverse Event
|
148
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
Lost to Follow-up
|
35
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
Withdrawal by Subject
|
76
|
0
|
0
|
|
Period 1 Open Label Ziprasidone
Miscellaneous
|
50
|
0
|
0
|
|
Period 2 Double Blind
Lack of Efficacy
|
0
|
9
|
22
|
|
Period 2 Double Blind
Laboratory Abnormality
|
0
|
1
|
0
|
|
Period 2 Double Blind
Adverse Event
|
0
|
11
|
15
|
|
Period 2 Double Blind
Lost to Follow-up
|
0
|
3
|
6
|
|
Period 2 Double Blind
Withdrawal by Subject
|
0
|
9
|
9
|
|
Period 2 Double Blind
miscellaneous
|
0
|
10
|
5
|
Baseline Characteristics
Safety and Maintenance of Effect of Ziprasidone Plus a Mood Stabilizer in Bipolar I Disorder (Manic or Mixed)
Baseline characteristics by cohort
| Measure |
Ziprasidone
n=127 Participants
Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period.
|
Placebo
n=111 Participants
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
|
Total
n=238 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.6 years
STANDARD_DEVIATION 12.3 • n=5 Participants
|
38.0 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
38.4 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period 2: 24 weeks or time of early terminationPopulation: 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.
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
Time to Intervention for a Mood Episode During Double Blind Period
|
172.159 Days
Standard Error 5.646 • Interval 7.0 to 201.0
|
143.133 Days
Standard Error 7.532
|
SECONDARY outcome
Timeframe: Period 2: 24 weeks or time of early terminationPopulation: Intent to Treat (ITT). Number of participants who discontinued was 43 and 57 for ziprasidone and placebo, respectively.
Key Secondary endpoint is time to discontinuation for any reason. Profile of patients remaining in the trial over time.
Outcome measures
| Measure |
Ziprasidone
n=43 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=57 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
Time to Discontinuation for Any Reason During Double Blind Period 2
|
153.526 days
Standard Error 6.454
|
123.313 days
Standard Error 7.524
|
SECONDARY outcome
Timeframe: Period 2: Week 24 or time of early terminationPopulation: 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
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
Modified Time to Intervention for a Mood Episode (TIME)
|
168.145 Days
Standard Error 5.857
|
140.325 Days
Standard Error 7.627
|
SECONDARY outcome
Timeframe: Period 2: Weeks 1 - 24 or time of early terminationPopulation: Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
1.2 scores on scale
Standard Deviation 6.3
|
|
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
|
0.2 scores on scale
Standard Deviation 5.1
|
|
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
|
0.3 scores on scale
Standard Deviation 4.2
|
|
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 3.0
|
0.8 scores on scale
Standard Deviation 5.1
|
|
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
|
-0.1 scores on scale
Standard Deviation 4.7
|
|
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
|
0.2 scores on scale
Standard Deviation 5.4
|
|
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
|
0.8 scores on scale
Standard Deviation 5.4
|
|
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
|
1.2 scores on scale
Standard Deviation 8.2
|
SECONDARY outcome
Timeframe: Period 2: Weeks 1 - 24 or time of early terminationPopulation: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
0.3 scores on scale
Standard Deviation 1.0
|
|
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
|
0.2 scores on scale
Standard Deviation 1.0
|
|
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
|
0.1 scores on scale
Standard Deviation 0.9
|
|
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
|
-0.1 scores on scale
Standard Deviation 0.8
|
|
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
|
0.0 scores on scale
Standard Deviation 1.1
|
|
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
|
0.0 scores on scale
Standard Deviation 1.1
|
|
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
|
-0.2 scores on scale
Standard Deviation 1.0
|
|
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 1.0
|
-0.2 scores on scale
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: Period 2: Weeks 1 - 24 or time of early terminationPopulation: Intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
2.8 scores on scale
Standard Deviation 1.6
|
|
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
|
2.6 scores on scale
Standard Deviation 1.6
|
|
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
|
2.5 scores on scale
Standard Deviation 1.5
|
|
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
|
2.2 scores on scale
Standard Deviation 1.2
|
|
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
|
2.2 scores on scale
Standard Deviation 1.4
|
|
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
|
2.5 scores on scale
Standard Deviation 1.5
|
|
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
|
2.1 scores on scale
Standard Deviation 1.4
|
|
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
|
2.2 scores on scale
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: Period 2: Weeks 1 - 24 or time of early terminationPopulation: Intent to Treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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.
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
2.7 scores on scale
Standard Deviation 7.3
|
|
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
|
2.7 scores on scale
Standard Deviation 7.1
|
|
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
|
1.6 scores on scale
Standard Deviation 6.0
|
|
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
|
0.4 scores on scale
Standard Deviation 5.3
|
|
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
|
0.6 scores on scale
Standard Deviation 5.4
|
|
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
|
0.4 scores on scale
Standard Deviation 3.9
|
|
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
|
-0.2 scores on scale
Standard Deviation 4.9
|
|
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
|
1.0 scores on scale
Standard Deviation 6.5
|
SECONDARY outcome
Timeframe: Period 2: Weeks 4 - 24 or time of early terminationPopulation: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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)
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
1.5 scores on scale
Standard Deviation 6.9
|
|
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
|
-0.8 scores on scale
Standard Deviation 6.0
|
|
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
|
0.3 scores on scale
Standard Deviation 9.4
|
|
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
|
0.7 scores on scale
Standard Deviation 8.7
|
|
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
|
-1.0 scores on scale
Standard Deviation 6.1
|
|
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 8.0
|
-0.9 scores on scale
Standard Deviation 7.4
|
SECONDARY outcome
Timeframe: Period 2: Weeks 4 - 24 or time of early terminationPopulation: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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).
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
0.1 scores on scale
Standard Deviation 1.4
|
|
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 2.0
|
-0.2 scores on scale
Standard Deviation 1.9
|
|
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
|
0.3 scores on scale
Standard Deviation 3.3
|
|
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
|
0.0 scores on scale
Standard Deviation 2.1
|
|
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
|
-0.1 scores on scale
Standard Deviation 2.1
|
|
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
|
-0.1 scores on scale
Standard Deviation 2.1
|
SECONDARY outcome
Timeframe: Period 2: Weeks 4 - 24 or time of early terminationPopulation: intent to treat (ITT); (n) = number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.
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).
Outcome measures
| Measure |
Ziprasidone
n=127 Participants
Randomized to Double Blind Therapy with Ziprasidone plus mood stabilizer
|
Placebo
n=111 Participants
Randomized to Double Blind Therapy with Placebo plus mood stabilizer
|
|---|---|---|
|
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
|
0.4 scores on scale
Standard Deviation 2.2
|
|
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
|
-0.1 scores on scale
Standard Deviation 1.8
|
|
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
|
0.1 scores on scale
Standard Deviation 2.1
|
|
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
|
0.4 scores on scale
Standard Deviation 2.6
|
|
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
|
-0.4 scores on scale
Standard Deviation 1.8
|
|
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
|
-0.1 scores on scale
Standard Deviation 2.1
|
Adverse Events
Period 1 Open Label Ziprasidone
Ziprasidone
Placebo
Serious adverse events
| Measure |
Period 1 Open Label Ziprasidone
40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy.
|
Ziprasidone
Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period.
|
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
|
|---|---|---|---|
|
Infections and infestations
Influenza
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/584
|
0.79%
1/127
|
0.00%
0/112
|
|
Nervous system disorders
Dystonia
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Affect lability
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Anxiety
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Bipolar I disorder
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Bipolar disorder
|
0.34%
2/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Depression
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Depression suicidal
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Mania
|
0.34%
2/584
|
0.00%
0/127
|
1.8%
2/112
|
|
Psychiatric disorders
Psychiatric decompensation
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Psychotic disorder
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Psychiatric disorders
Suicidal ideation
|
0.34%
2/584
|
1.6%
2/127
|
0.00%
0/112
|
|
Psychiatric disorders
Suicide attempt
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Vascular disorders
Thrombophlebitis
|
0.17%
1/584
|
0.00%
0/127
|
0.00%
0/112
|
Other adverse events
| Measure |
Period 1 Open Label Ziprasidone
40 - 80 milligram (mg) ziprasidone twice/day (BID) plus mood stabilizer. Dose adjusted on basis of toleration and efficacy.
|
Ziprasidone
Double-blind, randomized ziprasidone at the dose level received during the last 4 weeks of Open Label Period.
|
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
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
7.2%
42/584
|
0.00%
0/127
|
0.00%
0/112
|
|
General disorders
Fatigue
|
7.5%
44/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/584
|
3.9%
5/127
|
5.4%
6/112
|
|
Nervous system disorders
Akathisia
|
8.0%
47/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Nervous system disorders
Dizziness
|
8.4%
49/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Nervous system disorders
Headache
|
5.5%
32/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Nervous system disorders
Sedation
|
22.9%
134/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Nervous system disorders
Somnolence
|
17.0%
99/584
|
0.00%
0/127
|
0.00%
0/112
|
|
Nervous system disorders
Tremor
|
12.5%
73/584
|
6.3%
8/127
|
3.6%
4/112
|
|
Psychiatric disorders
Insomnia
|
10.1%
59/584
|
5.5%
7/127
|
10.7%
12/112
|
|
Psychiatric disorders
Mania
|
0.00%
0/584
|
2.4%
3/127
|
5.4%
6/112
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
- Publication restrictions are in place
Restriction type: OTHER