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High-Dose Oral Ziprasidone Versus Conventional Dosing in Participants With Residual Schizophrenia Symptoms (HDZ)

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ClinicalTrials.gov Identifier: NCT00403546
Recruitment Status : Completed
First Posted : November 23, 2006
Results First Posted : June 6, 2017
Last Update Posted : June 6, 2017
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: Ziprasidone 80-160 mg/d
Drug: Placebo
Drug: Ziprasidone 160 mg/d
Enrollment 131
Recruitment Details  
Pre-assignment Details Upon signing informed consent participants not already taking ziprasidone were instructed to start open-label ziprasidone for 3 weeks. Of 131 participants who signed informed consent 75 started ziprasidone and 56 were already on ziprasidone. Those completing open-label and those on ziprasidone were then screened.
Arm/Group Title Standard Treatment Ziprasidone High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description Upon signing informed consent participants with schizophrenia or schizoaffective disorder, who were not yet taking ziprasidone could initiate open-label standard treatment ziprasidone (160 milligrams per day [160 mg/d]: 80 mg twice daily) for a minimum of 3 weeks to be eligible for screening to enter the randomized trial. Participants who were already taking standard treatment ziprasidone for 3 weeks or longer at time of enrollment were eligible for screening, as well. Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks. Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Period Title: Signed Informed Consent/Open-Label
Started 131 0 0
Completed 103 0 0
Not Completed 28 0 0
Reason Not Completed
Withdrew Consent             6             0             0
Early Termination             8             0             0
Terminated by Investigator             9             0             0
Adverse Event             5             0             0
Period Title: Screening Phase
Started 103 0 0
Completed 75 [1] 0 0
Not Completed 28 0 0
Reason Not Completed
Screening Failure             22             0             0
Adverse Event             1             0             0
Terminated Prior to Randomization             5             0             0
[1]
All participants who completed Screening were randomized to the High-Dose and Placebo arms.
Period Title: Randomized Trial
Started 0 [1] 38 37
Completed 0 21 21
Not Completed 0 17 16
Reason Not Completed
Early Terminations             0             17             16
[1]
All participants who completed Screening were randomized to the High-Dose and Placebo arms.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone Total
Hide Arm/Group Description Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks. Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks. Total of all reporting groups
Overall Number of Baseline Participants 38 37 75
Hide Baseline Analysis Population Description
All participants who entered the Randomized Trial.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 37 participants 75 participants
39.2  (12.0) 41.0  (11.9) 40.0  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 37 participants 75 participants
Female
11
  28.9%
12
  32.4%
23
  30.7%
Male
27
  71.1%
25
  67.6%
52
  69.3%
1.Primary Outcome
Title Number of Events Recorded Based on Ziprasidone Side Effects Checklist During Randomized Trial
Hide Description Side effects were tracked using the Side Effect Checklist for ziprasidone, which is a well-validated 17 item scale that records the presence or absence of side effects. Total number of side effect events is reported here.
Time Frame From Baseline up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the randomized trial.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 37
Measure Type: Number
Unit of Measure: side effect events
633 588
2.Primary Outcome
Title Change From Baseline in Simpson Angus Scale for Extrapyramidal Symptoms (SAS)
Hide Description The SAS is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity. A positive change from baseline indicates a worse outcome.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All study participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 37 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 37 participants 36 participants
1.5  (2.0) 1.5  (2.7)
Change from Baseline at Week 2 Number Analyzed 32 participants 31 participants
0.44  (1.93) -0.65  (2.21)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
0.46  (2.08) -0.35  (2.12)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
0.59  (3.06) -0.09  (2.41)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-0.10  (2.49) -0.10  (2.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.980
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-1.09 to 1.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.08 to 1.95
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
-0.32 to 1.77
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.62 to 1.62
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.840
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-1.32 to 1.08
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in the Barnes Akathisia Scale (BAS)
Hide Description BAS is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0 – 3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0 – 5. Total score ranges from 0 to 14 with a higher score indicating increased severity. A positive change from baseline indicates a worse outcome.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
1.2  (2.2) 1.4  (2.4)
Change from Baseline at Week 2 Number Analyzed 33 participants 31 participants
0.00  (2.61) 0.13  (1.69)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
-0.27  (2.88) -0.48  (2.17)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
-0.95  (2.46) -0.45  (2.11)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-0.62  (2.09) -0.29  (2.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.737
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-1.23 to 0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.764
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-1.09 to 0.80
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.642
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.82 to 1.32
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.570
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-1.50 to 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.894
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-1.34 to 1.17
Estimation Comments [Not Specified]
4.Primary Outcome
Title Number of Participants With High and Low Levels in Serum Prolactin Concentration
Hide Description Blood samples were taken at baseline and Week 8 to measure serum prolactin concentrations. Normal range for females (non-pregnant) is 2-29 nanograms per deciliter (ng/dL) and for males 2-18 ng/dL. Values above the normal range were reported as High and values below the normal range were reported as Low. Reported here is the number of participants with high prolactin concentration and the number of participants with low prolactin concentration.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 37
Measure Type: Number
Unit of Measure: participants
High Prolactin at Baseline Number Analyzed 38 participants 37 participants
9 10
High Prolactin up to Week 8 Number Analyzed 21 participants 21 participants
7 6
Low Prolactin at Baseline Number Analyzed 38 participants 37 participants
1 1
Low Prolactin up to Week 8 Number Analyzed 21 participants 21 participants
1 0
5.Primary Outcome
Title Vital Signs: Systolic and Diastolic Blood Pressure Levels
Hide Description Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at regular times during the study. Normal SBP is defined as 120 millimeters of mercury (mmHg) or below and normal DBP is defined as 80 mmHg or below. Change from baseline is indicated for each time point. A positive change from baseline indicates and increase in blood pressure and a negative change from baseline indicates a decrease.
Time Frame Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 37
Mean (Standard Deviation)
Unit of Measure: mmHg
SBP Baseline Number Analyzed 38 participants 37 participants
123.2  (14.5) 125.0  (15.3)
SBP Week 1 Number Analyzed 38 participants 36 participants
123.9  (13.58) 122.3  (15.14)
SBP Week 2 Number Analyzed 33 participants 31 participants
124.5  (14.23) 124.9  (16.09)
SBP Week 4 Number Analyzed 26 participants 24 participants
124.8  (16.47) 124.3  (16.92)
SBP Week 6 Number Analyzed 22 participants 22 participants
122.5  (18.63) 127.3  (13.64)
SBP Week 8 Number Analyzed 21 participants 21 participants
125.1  (16.76) 121.3  (11.73)
DBP Baseline Number Analyzed 38 participants 37 participants
77.63  (11.49) 78.43  (9.30)
DBP Week 1 Number Analyzed 38 participants 36 participants
77.18  (9.10) 76.56  (8.59)
DBP Week 2 Number Analyzed 33 participants 31 participants
79.24  (10.12) 77.81  (12.16)
DBP Week 4 Number Analyzed 26 participants 23 participants
78.08  (11.36) 79.17  (10.47)
DBP Week 6 Number Analyzed 22 participants 22 participants
77.73  (14.61) 82.18  (12.98)
DBP Week 8 Number Analyzed 21 participants 21 participants
79.24  (12.84) 75.67  (9.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.599
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.82
Confidence Interval (2-Sided) 95%
-8.68 to 5.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.235
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.53
Confidence Interval (2-Sided) 95%
-2.31 to 9.37
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.449
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.83
Confidence Interval (2-Sided) 95%
-3.80 to 8.57
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.301
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.64
Confidence Interval (2-Sided) 95%
-3.28 to 10.56
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.842
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.75
Confidence Interval (2-Sided) 95%
-8.13 to 6.63
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments SBP at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.33
Confidence Interval (2-Sided) 95%
-1.43 to 14.09
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.741
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.80
Confidence Interval (2-Sided) 95%
-5.62 to 4.02
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Week 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.552
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
-3.32 to 6.19
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.268
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.83
Confidence Interval (2-Sided) 95%
-2.18 to 7.84
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.719
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
-4.53 to 6.56
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.334
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.86
Confidence Interval (2-Sided) 95%
-8.68 to 2.96
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments DBP at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.38
Confidence Interval (2-Sided) 95%
-1.61 to 10.37
Estimation Comments [Not Specified]
6.Primary Outcome
Title Electrocardiogram (EKG): Number of Participants With an Increase From Baseline to Corrected QT (QTc) Interval >/= 500 Milliseconds (Msec)
Hide Description QT interval is a measure of the time between the start of the Q wave and the end of the T wave as determined by electrocardiogram (EKG). The corrected QT Interval (QTc) adjusts the QT interval for heart rate. The number of participants with an increase to QTc interval >/= 500 msec was reported.
Time Frame 6 hours after dosing of Weeks 1, 2 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 34
Measure Type: Number
Unit of Measure: participants
Week 1 Number Analyzed 38 participants 34 participants
0 1
Week 2 Number Analyzed 31 participants 29 participants
0 0
Week 8 Number Analyzed 21 participants 21 participants
0 0
7.Primary Outcome
Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score
Hide Description The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Total PANSS score consists of 7 items in the Negative subscale, 7 items in the Positive subscale and 16 items in the General Psychopathology scale. Total PANSS score ranges from 30 to 210. A higher score indicates a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
74.7  (16.1) 71.9  (12.6)
Change from Baseline at Week 2 Number Analyzed 33 participants 31 participants
-4.03  (7.65) -4.16  (9.92)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
-5.08  (6.91) -6.87  (9.51)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
-8.73  (9.48) -4.32  (11.36)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-8.62  (7.79) -5.48  (10.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.416
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed models analysis with random slopes
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.77
Confidence Interval (2-Sided) 95%
-3.97 to 9.50
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.854
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
-3.59 to 4.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.406
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
-2.68 to 6.58
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.256
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.01
Confidence Interval (2-Sided) 95%
-8.23 to 2.21
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.642
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.37
Confidence Interval (2-Sided) 95%
-7.20 to 4.45
Estimation Comments [Not Specified]
8.Primary Outcome
Title Percentage of Participants With Response
Hide Description Response was defined as a reduction in the PANSS total score from baseline by 20% or greater, calculated by first subtracting 30 (the PANSS minimum possible total score). Response rate is the percentage of participants with a response.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 33 31
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 Number Analyzed 33 participants 31 participants
24.2 38.7
Week 4 Number Analyzed 26 participants 23 participants
23.1 60.9
Week 6 Number Analyzed 22 participants 22 participants
36.4 31.8
Week 8 Number Analyzed 21 participants 21 participants
33.3 42.9
9.Primary Outcome
Title Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
Hide Description AIMS is a rating scale measuring involuntary movements known as tardive dyskinesia, that sometimes develop as a side effect of long-term treatment with antipsychotic medications. The AIMS score was calculated as the sum of questions 1 through 7 of the AIMS instrument, which includes assessments of involuntary movements in the face, lips, jaw, tongue, upper and lower extremities, and neck/shoulders/hips. Each item is rated on a five-point scale of severity from 0–4 with 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Total scores range from 0 to 28. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
0.6  (1.2) 1.3  (2.4)
Change from Baseline at Week 2 Number Analyzed 33 participants 30 participants
0.00  (1.09) -0.53  (1.50)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
0.46  (1.63) -0.43  (2.11)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
0.55  (1.18) 0.18  (1.44)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
0.90  (1.95) 0.10  (2.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-1.55 to 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.262
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.33 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.209
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
-0.33 to 1.49
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.950
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-1.01 to 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection High-Dose Ziprasidone, Placebo, Standard Treatment Ziprasidone
Comments At Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.340
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
-0.61 to 1.76
Estimation Comments [Not Specified]
10.Primary Outcome
Title Number of Treatment-emergent Adverse Events During Randomized Trial
Hide Description Adverse event: any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Serious adverse event (SAE): significant hazard, contraindication, side effect, or precaution, which fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Time Frame From Baseline up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population includes all participants who received at least one dose of study medication.
Arm/Group Title High Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 37
Measure Type: Number
Unit of Measure: adverse events
Serious Adverse Events 4 3
Non-serious Adverse Events 85 95
11.Secondary Outcome
Title Change From Baseline in Positive Subscale Score of PANSS
Hide Description The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Positive symptoms as defined by the American Psychiatric Association refer to an excess or distortion of normal functions and include the following 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution and hostility. Score ranges from 7 to 49 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
19.6  (5.5) 18.2  (5.1)
Change from Baseline at Week 2 Number Analyzed 33 participants 31 participants
-1.30  (3.25) -0.90  (3.25)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
-2.08  (3.19) -1.57  (3.36)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
-3.09  (3.75) -0.91  (3.15)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-3.24  (3.35) -1.52  (3.01)
12.Secondary Outcome
Title Change From Baseline in PANSS Negative Subscale Score
Hide Description The PANSS is a medical scale and was used for measuring symptom severity of participants with schizophrenia in this study. Negative symptoms as defined by the American Psychiatric Association represent a diminution or loss of normal functions and include the following 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. Score ranges from 7 to 49 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
18.1  (5.8) 17.9  (5.3)
Change from Baseline at Week 2 Number Analyzed 33 participants 31 participants
-0.30  (2.70) -1.16  (4.66)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
-1.04  (2.14) -2.04  (5.80)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
-1.59  (4.02) -1.68  (5.45)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-1.90  (2.98) -1.52  (5.72)
13.Secondary Outcome
Title Change From Baseline in the Calgary Depression Rating Scale (CDRS) Total Score
Hide Description The CDRS was used to assess the level of depression in participants with schizophrenia. The questionnaire consists of 9 questions rated on a 4-point scale from 0 to 3. Total range is 0 to 27 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 2, Week 4, Week 6, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 37 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 37 participants 36 participants
3.8  (3.9) 4.9  (4.2)
Change from Baseline at Week 2 Number Analyzed 32 participants 31 participants
-0.72  (3.32) -1.61  (3.78)
Change from Baseline at Week 4 Number Analyzed 26 participants 23 participants
0.19  (3.72) -1.83  (3.90)
Change from Baseline at Week 6 Number Analyzed 22 participants 22 participants
-0.32  (3.64) -2.45  (4.01)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
-0.62  (4.57) -2.14  (3.84)
14.Secondary Outcome
Title Change From Baseline in Clinical Global Impression- Severity (CGI-S) Score
Hide Description CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis. Score ranges from 1 to 7 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
4.1  (0.7) 4.3  (0.6)
Change from Baseline at Week 8 Number Analyzed 20 participants 19 participants
-0.25  (0.72) -0.05  (0.40)
15.Secondary Outcome
Title Change From Baseline in Clinical Global Impression - Improvement (CGI-I) Score
Hide Description CGI-I is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to baseline. Score ranges from 1 to 7 with a higher score indicating a worse outcome. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 29 22
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 29 participants 22 participants
3.8  (0.5) 3.9  (0.9)
Change from Baseline at Week 8 Number Analyzed 14 participants 14 participants
-0.57  (0.94) -0.43  (0.65)
16.Secondary Outcome
Title Change From Baseline in Global Assessment of Functioning (GAF) Score
Hide Description GAF is a numeric scale used to rate social, occupational, and psychological functioning of participants. Scores range from 100 (extremely high functioning) to 1 (severely impaired). A positive change from baseline indicates an improvement.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 38 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 38 participants 36 participants
44.4  (12.3) 49.0  (14.7)
Change from Baseline at Week 8 Number Analyzed 21 participants 21 participants
3.24  (7.76) 4.86  (11.28)
17.Secondary Outcome
Title Change in Schizophrenia Cognition Rating Scale (SCoRS) Score
Hide Description SCoRS is a 20 item interview-based clinical assessment that evaluates cognitive deficits and the degree to which these deficits impair participants’ day-to-day functioning. The following cognitive domains are assessed: attention, memory, working memory, language production, reasoning, problem solving, motor skills, and social cognition. Score ranges from 1 to 10 with a higher score indicating a greater degree of impairment. A negative change from baseline indicates an improvement.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with available data at each time point.
Arm/Group Title High-Dose Ziprasidone Placebo, Standard Treatment Ziprasidone
Hide Arm/Group Description:
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks.
Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
Overall Number of Participants Analyzed 37 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 37 participants 35 participants
4.9  (1.5) 4.3  (1.6)
Change from Baseline at Week 8 Number Analyzed 20 participants 20 participants
-0.75  (0.85) 0.25  (1.77)
Time Frame During open-label phase, screening phase and randomized trial from signing of informed consent up to approximately 12 weeks for participants who initiated ziprasidone as part of the open label phase and 9 weeks for participants who entered directly into the screening phase and randomized trial.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Standard Treatment Ziprasidone Open-label Phase Standard Treatment Ziprasidone Screening Phase High-Dose Ziprasidone Randomized Trial Placebo, Standard Treatment Ziprasidone Randomized Trial
Hide Arm/Group Description Upon signing informed consent participants with schizophrenia or schizoaffective disorder, who were not yet taking ziprasidone could initiate open-label standard treatment ziprasidone (160 milligrams per day [160 mg/d]: 80 mg twice daily) for a minimum of 3 weeks to be eligible for screening to enter the randomized trial. Participants who had taken standard treatment ziprasidone for 3 weeks or longer were eligible for screening to enter the randomized trial. Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take ziprasidone oral capsule twice daily added to their regular open-label ziprasidone dose (total of 240 mg/d). After the first week, the study drug was increased to a total ziprasidone dose of 320 mg/d for 7 weeks. Participants with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks were instructed to take matching placebo oral capsule twice daily added to their regular open-label ziprasidone dose of 160 mg/d. After the first week, the matching placebo was increased to two capsules twice daily and their regular open-label ziprasidone remained the same (160 mg/d) for 7 weeks.
All-Cause Mortality
Standard Treatment Ziprasidone Open-label Phase Standard Treatment Ziprasidone Screening Phase High-Dose Ziprasidone Randomized Trial Placebo, Standard Treatment Ziprasidone Randomized Trial
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Standard Treatment Ziprasidone Open-label Phase Standard Treatment Ziprasidone Screening Phase High-Dose Ziprasidone Randomized Trial Placebo, Standard Treatment Ziprasidone Randomized Trial
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/131 (3.05%)   2/103 (1.94%)   4/38 (10.53%)   3/37 (8.11%) 
Immune system disorders         
Asthma   0/131 (0.00%)  0/103 (0.00%)  1/38 (2.63%)  0/37 (0.00%) 
Nervous system disorders         
Facial paresis   0/131 (0.00%)  0/103 (0.00%)  1/38 (2.63%)  0/37 (0.00%) 
Psychiatric disorders         
Hostility   1/131 (0.76%)  1/103 (0.97%)  0/38 (0.00%)  0/37 (0.00%) 
Psychosis   1/131 (0.76%)  0/103 (0.00%)  0/38 (0.00%)  1/37 (2.70%) 
Suicidal ideation   1/131 (0.76%)  0/103 (0.00%)  1/38 (2.63%)  1/37 (2.70%) 
Drug abuse   1/131 (0.76%)  0/103 (0.00%)  0/38 (0.00%)  0/37 (0.00%) 
Paranoia   0/131 (0.00%)  0/103 (0.00%)  0/38 (0.00%)  1/37 (2.70%) 
Hallucination   0/131 (0.00%)  0/103 (0.00%)  1/38 (2.63%)  0/37 (0.00%) 
Surgical and medical procedures         
Psychosocial support   0/131 (0.00%)  1/103 (0.97%)  0/38 (0.00%)  0/37 (0.00%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Standard Treatment Ziprasidone Open-label Phase Standard Treatment Ziprasidone Screening Phase High-Dose Ziprasidone Randomized Trial Placebo, Standard Treatment Ziprasidone Randomized Trial
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/131 (28.24%)   28/103 (27.18%)   23/38 (60.53%)   19/37 (51.35%) 
Cardiac disorders         
Tachycardia   3/131 (2.29%)  3/103 (2.91%)  3/38 (7.89%)  3/37 (8.11%) 
Gastrointestinal disorders         
Constipation   4/131 (3.05%)  1/103 (0.97%)  1/38 (2.63%)  4/37 (10.81%) 
Diarrhoea   1/131 (0.76%)  2/103 (1.94%)  2/38 (5.26%)  1/37 (2.70%) 
Dry mouth   4/131 (3.05%)  3/103 (2.91%)  2/38 (5.26%)  2/37 (5.41%) 
Nausea   1/131 (0.76%)  0/103 (0.00%)  0/38 (0.00%)  2/37 (5.41%) 
Salivary hypersecretion   1/131 (0.76%)  0/103 (0.00%)  0/38 (0.00%)  2/37 (5.41%) 
Vomiting   0/131 (0.00%)  1/103 (0.97%)  0/38 (0.00%)  2/37 (5.41%) 
General disorders         
Malaise   0/131 (0.00%)  0/103 (0.00%)  2/38 (5.26%)  1/37 (2.70%) 
Pain   0/131 (0.00%)  1/103 (0.97%)  1/38 (2.63%)  2/37 (5.41%) 
Nervous system disorders         
Headache   3/131 (2.29%)  1/103 (0.97%)  4/38 (10.53%)  2/37 (5.41%) 
Psychiatric disorders         
Anxiety   0/131 (0.00%)  0/103 (0.00%)  0/38 (0.00%)  2/37 (5.41%) 
Depression   1/131 (0.76%)  0/103 (0.00%)  0/38 (0.00%)  2/37 (5.41%) 
Insomnia   6/131 (4.58%)  4/103 (3.88%)  2/38 (5.26%)  3/37 (8.11%) 
Nervousness   3/131 (2.29%)  1/103 (0.97%)  2/38 (5.26%)  3/37 (8.11%) 
Paranoia   0/131 (0.00%)  1/103 (0.97%)  3/38 (7.89%)  2/37 (5.41%) 
Somnolence   6/131 (4.58%)  4/103 (3.88%)  6/38 (15.79%)  4/37 (10.81%) 
Renal and urinary disorders         
Urinary incontinence   0/131 (0.00%)  0/103 (0.00%)  2/38 (5.26%)  1/37 (2.70%) 
Respiratory, thoracic and mediastinal disorders         
Pharyngitis   1/131 (0.76%)  1/103 (0.97%)  0/38 (0.00%)  2/37 (5.41%) 
Skin and subcutaneous tissue disorders         
Rash   1/131 (0.76%)  0/103 (0.00%)  3/38 (7.89%)  0/37 (0.00%) 
Vascular disorders         
Hypertension   12/131 (9.16%)  5/103 (4.85%)  7/38 (18.42%)  5/37 (13.51%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Donald C. Goff, MD
Organization: Massachusetts General Hospital
EMail: Donald.Goff@nyumc.org
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Responsible Party: Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00403546     History of Changes
Other Study ID Numbers: 2005-P-001372
First Submitted: November 21, 2006
First Posted: November 23, 2006
Results First Submitted: April 17, 2017
Results First Posted: June 6, 2017
Last Update Posted: June 6, 2017