Trial Outcomes & Findings for Adjunctive Ziprasidone in the Treatment of Bipolar I Depression (NCT NCT00483548)

NCT ID: NCT00483548

Last Updated: 2021-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

298 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2021-03-10

Participant Flow

Participant milestones

Participant milestones
Measure
Ziprasidone
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Overall Study
STARTED
148
150
Overall Study
Received Study Treatment
147
147
Overall Study
COMPLETED
88
104
Overall Study
NOT COMPLETED
60
46

Reasons for withdrawal

Reasons for withdrawal
Measure
Ziprasidone
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Overall Study
Randomized; not treated with study drug
1
3
Overall Study
Adverse Event
25
14
Overall Study
Laboratory abnormality
1
2
Overall Study
Lack of Efficacy
4
8
Overall Study
Protocol Violation
11
7
Overall Study
Pregnancy
1
0
Overall Study
Protocol required discontinuation
6
6
Overall Study
Unable to comply with protocol schedule
1
0
Overall Study
Non-compliance with medication
2
0
Overall Study
Lost to Follow-up
3
4
Overall Study
Withdrawal by Subject
5
2

Baseline Characteristics

Adjunctive Ziprasidone in the Treatment of Bipolar I Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ziprasidone
n=147 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=147 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Total
n=294 Participants
Total of all reporting groups
Age, Customized
Between 18 and 65 years
147 participants
n=5 Participants
146 participants
n=7 Participants
293 participants
n=5 Participants
Age, Customized
>65 years
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Sex: Female, Male
Female
89 Participants
n=5 Participants
91 Participants
n=7 Participants
180 Participants
n=5 Participants
Sex: Female, Male
Male
58 Participants
n=5 Participants
56 Participants
n=7 Participants
114 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Intent to Treat analysis set (ITT): all randomized subjects who received at least 1 dose of double-blind treatment and had at least 1 post-baseline primary efficacy evaluation.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
-14.7 scores on scale
Standard Deviation 10.7
-13.2 scores on scale
Standard Deviation 10.4

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S)
-1.5 scores on scale
Standard Deviation 1.3
-1.5 scores on scale
Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 6

Population: ITT; Last observation carried forward (LOCF)

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).

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
MADRS Remission: Number of Subjects With Total MADRS Score ≤ 12 at Week 6
48 participants
54 participants

SECONDARY outcome

Timeframe: Week 6

Population: ITT; LOCF

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
MADRS Response: Number of Subjects With Total MADRS Score Reduction ≥ 50 Percent From Baseline at Week 6
62 participants
65 participants

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT; LOCF

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Clinical Global Impression - Improvement Scale (CGI-Improvement or CGI-I): Number of Subjects With Response (Much Improved or Very Much Improved) at Week 6
66 participants
69 participants

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

Population: ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
Week 1 (n=142, 141)
-8.1 scores on scale
Standard Deviation 7.9
-6.1 scores on scale
Standard Deviation 7.3
Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
Week 2 (n=121, 139)
-11.7 scores on scale
Standard Deviation 8.9
-9.0 scores on scale
Standard Deviation 8.6
Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
Week 3 (n=115, 130)
-13.0 scores on scale
Standard Deviation 9.5
-11.0 scores on scale
Standard Deviation 9.2
Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
Week 4 (n=106, 122)
-14.1 scores on scale
Standard Deviation 9.6
-11.8 scores on scale
Standard Deviation 9.5
Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)
Week 5 (n=103, 112)
-14.9 scores on scale
Standard Deviation 9.4
-13.3 scores on scale
Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

Population: ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
Week 1 (n=142, 141)
-0.5 scores on scale
Standard Deviation 0.8
-0.4 scores on scale
Standard Deviation 0.8
Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
Week 2 (n=120, 139)
-0.9 scores on scale
Standard Deviation 1.1
-0.7 scores on scale
Standard Deviation 0.9
Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
Week 3 (n=115, 130)
-0.9 scores on scale
Standard Deviation 1.0
-0.9 scores on scale
Standard Deviation 1.0
Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
Week 4 (n=106, 122)
-1.1 scores on scale
Standard Deviation 1.1
-1.1 scores on scale
Standard Deviation 1.1
Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)
Week 5 (n=103, 112)
-1.3 scores on scale
Standard Deviation 1.2
-1.3 scores on scale
Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

Population: ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
CGI-Improvement Score
Week 1 (n=142, 141)
3.2 scores on scale
Standard Deviation 0.9
3.4 scores on scale
Standard Deviation 0.8
CGI-Improvement Score
Week 2 (n=120, 138)
2.9 scores on scale
Standard Deviation 1.1
3.1 scores on scale
Standard Deviation 1.0
CGI-Improvement Score
Week 3 (n=115, 130)
2.7 scores on scale
Standard Deviation 1.0
2.9 scores on scale
Standard Deviation 1.0
CGI-Improvement Score
Week 4 (n=106, 122)
2.6 scores on scale
Standard Deviation 1.2
2.8 scores on scale
Standard Deviation 1.2
CGI-Improvement Score
Week 5 (n=103, 112)
2.5 scores on scale
Standard Deviation 1.2
2.6 scores on scale
Standard Deviation 1.1
CGI-Improvement Score
Week 6 (n=92, 108)
2.4 scores on scale
Standard Deviation 1.2
2.4 scores on scale
Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6

Population: ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score
Week 2 (n=136, 141)
-5.6 scores on scale
Standard Deviation 6.8
-5.9 scores on scale
Standard Deviation 6.7
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score
Week 4 (n=111, 127)
-7.1 scores on scale
Standard Deviation 7.2
-7.4 scores on scale
Standard Deviation 7.6
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score
Week 6 (n=100, 111)
-8.5 scores on scale
Standard Deviation 7.9
-8.6 scores on scale
Standard Deviation 7.5

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

Population: ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 4 (n=106, 122)
-0.9 scores on scale
Standard Deviation 4.1
-1.1 scores on scale
Standard Deviation 4.2
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 1 (n=142, 141)
0.7 scores on scale
Standard Deviation 4.4
-0.2 scores on scale
Standard Deviation 3.5
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 2 (n=121, 139)
0.5 scores on scale
Standard Deviation 4.5
-0.2 scores on scale
Standard Deviation 4.3
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 3 (n=115, 130)
-0.0 scores on scale
Standard Deviation 4.5
-0.2 scores on scale
Standard Deviation 4.9
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 5 (n=103, 112)
-0.9 scores on scale
Standard Deviation 3.9
-1.3 scores on scale
Standard Deviation 4.1
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Week 6 (n=92, 108)
-1.0 scores on scale
Standard Deviation 4.8
-0.9 scores on scale
Standard Deviation 4.6

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT; observed cases; Early Termination (ET) visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6
Week 6 (n=100, 110)
14.7 scores on scale
Standard Deviation 13.8
11.2 scores on scale
Standard Deviation 12.3
Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6
ET (n=34, 27)
0.0 scores on scale
Standard Deviation 7.1
2.8 scores on scale
Standard Deviation 9.1

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Total SDS: Week 6 (n=58, 63)
-8.5 scores on scale
Standard Deviation 9.2
-3.7 scores on scale
Standard Deviation 8.2
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Total SDS: ET (n=19, 14)
0.2 scores on scale
Standard Deviation 6.8
-1.4 scores on scale
Standard Deviation 6.7
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Work/School: Week 6 (n=58, 64)
-2.1 scores on scale
Standard Deviation 3.5
-1.6 scores on scale
Standard Deviation 2.9
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Work/School: ET (n=19, 14)
0.4 scores on scale
Standard Deviation 3.0
-0.1 scores on scale
Standard Deviation 2.7
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Social life: Week 6 (n=94, 102)
-2.5 scores on scale
Standard Deviation 3.3
-1.7 scores on scale
Standard Deviation 3.2
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Social life: ET (n=31, 23)
-0.5 scores on scale
Standard Deviation 2.9
0.1 scores on scale
Standard Deviation 3.1
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Family/Home: Week 6 (n=94, 102)
-2.6 scores on scale
Standard Deviation 3.2
-1.7 scores on scale
Standard Deviation 3.3
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)
Family/Home: ET (n=31, 23)
0.2 scores on scale
Standard Deviation 2.3
-0.6 scores on scale
Standard Deviation 3.2

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)
Days lost: Week 6 (n=85, 93)
-1.2 days
Standard Deviation 2.5
-0.7 days
Standard Deviation 2.3
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)
Days lost: ET (n=29, 21)
0.5 days
Standard Deviation 2.7
0.0 days
Standard Deviation 2.2
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)
Days unproductive: Week 6 (n=87, 89)
-1.6 days
Standard Deviation 2.8
-1.3 days
Standard Deviation 2.9
Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)
Days unproductive: ET (n=29, 21)
-0.2 days
Standard Deviation 2.5
-0.1 days
Standard Deviation 3.7

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

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.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Total Q-LES-Q: Week 6 (n=82, 94)
15.2 scores on scale
Standard Deviation 19.0
11.6 scores on scale
Standard Deviation 17.3
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Total Q-LES-Q: ET (n=27, 17)
-0.1 scores on scale
Standard Deviation 19.7
1.6 scores on scale
Standard Deviation 14.5
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Medications: Week 6 (n=91, 93)
0.4 scores on scale
Standard Deviation 1.2
0.3 scores on scale
Standard Deviation 1.1
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Medications: ET (n=27, 20)
-0.3 scores on scale
Standard Deviation 1.2
-0.4 scores on scale
Standard Deviation 0.8
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Overall life satisfaction: Week 6 (n=94, 103)
0.8 scores on scale
Standard Deviation 1.1
0.5 scores on scale
Standard Deviation 1.1
Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6
Overall life satisfaction: ET (n=31, 23)
0.1 scores on scale
Standard Deviation 1.3
0.0 scores on scale
Standard Deviation 0.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 2, Week 4, Week 6

Population: ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

SAS is a clinician rated 10-item scale to measure extrapyramidal side effects (Parkinsonism or Parkinsonian side effects induced with antipsychotics); rated on a 5-point scale with range 0 (absence of condition) to 4 (presence of condition in extreme form). Global score is sum of all scores divided by the total number of items. Change calculated as a difference between post-baseline observation and baseline SAS score values.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Simpson Angus Scale (SAS) Score
Week 2 (n=136, 141)
0.1 scores on scale
Standard Deviation 0.8
-0.1 scores on scale
Standard Deviation 0.7
Change From Baseline in Simpson Angus Scale (SAS) Score
Week 4 (n=111, 126)
0.0 scores on scale
Standard Deviation 0.8
0.0 scores on scale
Standard Deviation 0.6
Change From Baseline in Simpson Angus Scale (SAS) Score
Week 6 (n=100, 110)
0.0 scores on scale
Standard Deviation 0.7
-0.1 scores on scale
Standard Deviation 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 2, Week 4, Week 6

Population: ITT; Summarized as Global BARS; individual scores not summarized; (n)=number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.

BARS is a clinician rated scale to evaluate akathisia associated with use of antipsychotic medications: objective motor restlessness, range 0 to 3; subjective complaints of restlessness and associated distress, range 0 to 3; global clinical assessment of akathisia, range 0 to 5. Higher scores indicate more affected. Change calculated as a difference between post-baseline observation and baseline BARS score values.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS)
Week 2 (n=135, 139)
0.1 scores on scale
Standard Deviation 0.5
-0.0 scores on scale
Standard Deviation 0.4
Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS)
Week 4 (n=111, 125)
0.0 scores on scale
Standard Deviation 0.5
0.0 scores on scale
Standard Deviation 0.5
Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS)
Week 6 (n=100, 110)
0.0 scores on scale
Standard Deviation 0.6
-0.0 scores on scale
Standard Deviation 0.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 2, Week 4, Week 6

Population: ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

AIMS is a clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe); items 11 to 14 are No or Yes response to dental status and sleep movements and are assessed separately. AIMS total score is sum of first 7 items. Change calculated as a difference between post-baseline observation and baseline AIMS score values.

Outcome measures

Outcome measures
Measure
Ziprasidone
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=145 Participants
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Total score: Week 2 (n=136, 142)
0.1 scores on scale
Standard Deviation 0.7
-0.1 scores on scale
Standard Deviation 0.4
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Total score: Week 4 (n=111, 127)
-0.0 scores on scale
Standard Deviation 0.5
-0.0 scores on scale
Standard Deviation 0.5
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Total score: Week 6 (n=100, 111)
-0.0 scores on scale
Standard Deviation 0.6
-0.0 scores on scale
Standard Deviation 0.4
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Global severity score: Week 2 (n=136, 142)
0.0 scores on scale
Standard Deviation 0.4
-0.0 scores on scale
Standard Deviation 0.2
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Global severity score: Week 4 (n=111, 127)
0.0 scores on scale
Standard Deviation 0.3
0.0 scores on scale
Standard Deviation 0.2
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Global severity score: Week 6 (n=100, 111)
0.0 scores on scale
Standard Deviation 0.3
0.0 scores on scale
Standard Deviation 0.1
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Incapacitation score: Week 2 (n=136, 142)
0.0 scores on scale
Standard Deviation 0.2
-0.0 scores on scale
Standard Deviation 0.1
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Incapacitation score: Week 4 (n=111, 127)
0.0 scores on scale
Standard Deviation 0.1
-0.0 scores on scale
Standard Deviation 0.2
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores
Incapacitation score: Week 6 (n=100, 111)
0.0 scores on scale
Standard Deviation 0.1
0.0 scores on scale
Standard Deviation 0.2

Adverse Events

Ziprasidone

Serious events: 1 serious events
Other events: 96 other events
Deaths: 0 deaths

Placebo

Serious events: 6 serious events
Other events: 57 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ziprasidone
n=147 participants at risk
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=147 participants at risk
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Cardiac disorders
Palpitations
0.00%
0/147
0.68%
1/147
Injury, poisoning and procedural complications
Overdose
0.68%
1/147
0.00%
0/147
Psychiatric disorders
Bipolar I disorder
0.00%
0/147
0.68%
1/147
Psychiatric disorders
Intentional self-injury
0.00%
0/147
0.68%
1/147
Psychiatric disorders
Mania
0.00%
0/147
1.4%
2/147
Psychiatric disorders
Suicidal ideation
0.00%
0/147
0.68%
1/147
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.68%
1/147
0.00%
0/147

Other adverse events

Other adverse events
Measure
Ziprasidone
n=147 participants at risk
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Placebo
n=147 participants at risk
Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
Gastrointestinal disorders
Diarrhoea
4.8%
7/147
7.5%
11/147
Gastrointestinal disorders
Nausea
10.9%
16/147
5.4%
8/147
General disorders
Fatigue
12.9%
19/147
4.1%
6/147
Nervous system disorders
Akathisia
5.4%
8/147
1.4%
2/147
Nervous system disorders
Dizziness
12.9%
19/147
6.1%
9/147
Nervous system disorders
Headache
11.6%
17/147
9.5%
14/147
Nervous system disorders
Sedation
14.3%
21/147
4.8%
7/147
Nervous system disorders
Somnolence
22.4%
33/147
4.8%
7/147
Nervous system disorders
Tremor
8.8%
13/147
6.8%
10/147
Psychiatric disorders
Anxiety
6.1%
9/147
0.68%
1/147
Psychiatric disorders
Insomnia
11.6%
17/147
6.8%
10/147
Psychiatric disorders
Restlessness
5.4%
8/147
1.4%
2/147

Additional Information

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Phone: 1-800-718-1021

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 information other than study results.
  • Publication restrictions are in place

Restriction type: OTHER