Efficacy and Tolerability of Switching to Ziprasidone From Other Antipsychotics

• Sponsor: Bronx Psychiatric Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00458211
• Collaborator: Pfizer (Industry), Buffalo Psychiatric Center (Other), Rochester Psychiatric Center (Other)
• Enrollment: 40
• Locations: 2
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 20
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Because ziprasidone has not been extensively studied and is not widely accepted in the severely mentally ill in State hospitals this study aims to demonstrate its effectiveness and relative lack of side effects. 75 patients with schizophrenia or schizoaffective disorder who need a change of medication because of ineffectiveness or side effects will be changed to ziprasidone and followed with detailed assessments for eight weeks.

The hypothesis is that they will improve and have fewer side effects.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: ziprasidone	Phase 4

Detailed Description

Ziprasidone has been found in studies and practice to be efficacious and tolerated well but has not been well studied or well accepted in the very severely ill in State Hospitals. This study aims to fill that gap by examining 75 patients with schizophrenia or schizoaffective disorder who require a change of medication because of poor response or unacceptable side effects.

After signing consent and having a baseline assessment they will, if necessary, be reduced to one antipsychotic then started on ziprasidone, increasing to 160mg the second day. The one antipsychotic they had been on will be reduced over a week and stopped. The ziprasidone can be increased to 240mg after three weeks if necessary.

The study will last eight weeks with efficacy assessed by Clinical Global Impressions (CGI), Positive and Negative Syndrome Scale (PANSS) every two weeks and Brief Assessment of Cognition, Calgary Depression Scale for Schizophrenia, Personal Evaluation of Transitions in Treatment and Medical Outcomes Study Cognitive Questions at the beginning and end. Side effects will be measured by movement disorder scales (Simpson-Angus scale for Parkinsonism (SANRS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Scale (BAS)), ECG and weight and blood metabolic measures.

The hypothesis is that ziprasidone will be generally effective and that side effects especially metabolic indices will be reduced.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Efficacy and Tolerability of Switching to Ziprasidone From Other Antipsychotic Medications
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Open label change to ziprasidone	Drug: ziprasidone; Ziprasidone by mouth 40mg twice a day (bid) for one day, then 80mg bid; may be increased to 120mg bid after three weeks

Outcome Measures

Primary Outcome Measures

1. Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia [Baseline to 8 weeks]

   Minimum score 32 (best) maximum 210 (worst)

Secondary Outcome Measures

1. Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. [8 weeks]

   CGI-S scores from 1 = normal to 7 = most extremely ill

2. Weight [8 weeks]

3. Fasting Glucose [8 weeks]

   Amount of glucose in the blood in mg/dl

4. Cholesterol [8 weeks]

5. Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia [8 weeks]

   Scores 0 (none) to 4 (severe) choreo-athetoid and dystonic movements of seven parts of the body with a maximum score 28

6. Simpson-Angus Scale Measures Drug Induced Parkinsonism [8 weeks]

   Measures 10 signs, (not all of which are now considered Parkinsonism), minimum score 0 (no Parkinsonism) maximum 40.

7. Corrected QT Interval (QTc) [8 weeks]

   Time interval between Q and T waves on EKG corrected for pulse rate. Over 500 msec may be dangerous

8. Brief Assessment of Cognition in Schizophrenia (BACS) [8 weeks]

   Scores on the BACS scale, which measures cognition, were changed to Z-scores based on normal controls from Keefe (2008) A Z-score of zero would indicate cognition the same as the normal controls. Negative scores indicate cognition worse than the normal. Theoretically there are no maximum or minimum scores.

9. Calgary Depression Scale for Schizophrenia [8 weeks]

   Score on scale, from 0 to 27, above 6 considered indicative of depression, higher scores mean worse outcome,

10. Personal Evaluation of Transitions in Treatment Scale (PETiTP [8 weeks]

    PETiT is a 30 item self administered scale measuring response to and tolerability and adherence to antipsychotic medication in people with schizophrenia. The range is 30 to 100. Higher scores are better. Although different features are assessed there is a single total score - no subscales.

11. Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) [8 weeks]

    MOS-COG measures day to day problems in six aspects of cognitive functioning. The scores are converted to 0-100 and so can range from 0 to 100 with 100 being the best. Population means are 70 to 80.

12. Barnes Akathisia Scale [8 weeks]

    Barnes Akathisia Scale measures akathisia: a score of zero is none (good) maximum score is 12

13. HbA1c [8 weeks]

    Lab measure of glycated hemoglobin indicative of blood glucose over the last three months. At that time in the US measured as a percentage (of glucose attached to hemoglobin). No maximum or minimum but over 6.5% is generally considered indicative of diabetes.

14. Insulin Level [8 weeks]

    Measure of the amount of insulin in the blood, in uIU/ml. No minimum or maximum but fasting levels are usually below 25 uIU/ml. After a dose of glucose they may be 30 to 230 uIU/ml.

15. Antipsychotic Medication Costs [8 weeks]

    No data were collected because it turned out we had no way of measuring the costs. No subjects were analysed by costs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Schizophrenia or schizoaffective

• Capacity to give consent

• Stable, on the same medication for a month but only partial response or with unacceptable side effects 18-65 years of age

Exclusion Criteria:

• Repeated non-compliance

• Current depot medication

• Active medical conditions

• QTc >500msec

• Previous non-response

• Previous treatment with ziprasidone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bronx Psychiatric Center	Bronx	New York	United States	10461
2	Buffalo Psychiatric Center	Buffalo	New York	United States	14213

Sponsors and Collaborators

• Bronx Psychiatric Center
• Pfizer
• Buffalo Psychiatric Center
• Rochester Psychiatric Center

Investigators

• Principal Investigator: Nigel Bark, MD, Bronx Psychiatric Center
• Principal Investigator: Jeffrey Grace, MD, Buffalo Psychiatric Center
• Principal Investigator: Steven Schwarzkopf, MD, Rochester Psychiatric Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nigel Bark MD, Director of Scizophrenia Research, Bronx Psychiatric Center
• ClinicalTrials.gov Identifier: NCT00458211
• Other Study ID Numbers: BPCIRB 03-02
• First Posted: Apr 10, 2007
• Last Update Posted: May 1, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Nigel Bark MD, Director of Scizophrenia Research, Bronx Psychiatric Center: Schizophrenia; Ziprasidone
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Ziprasidone

Study Results

Participant Flow

Recruitment Details	40 subjects from three State Hospitals were recruited and participated between 2005 and 2008: four in-patients from Rochester Psychiatric Center, 17 out-patients from Buffalo Psychiatric Center and 19 in-patients from Bronx Psychiatric Center

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals
Period Title: Overall Study
STARTED	40
COMPLETED	24
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Overall Participants	40
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	39 97.5%
>=65 years	1 2.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (15)
Sex: Female, Male (Count of Participants)
Female	22 55%
Male	18 45%
Region of Enrollment (participants) [Number]
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia
Description	Minimum score 32 (best) maximum 210 (worst)
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

The four Rochester subjects were dropped as Rochester could not continue the study.19 Bronx and 17 Buffalo subjects were analyzed separately because they were so different(see baseline characteristics)

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	95 (16)
Bronx end	99 (25)
Buffalo baseline	72 (22)
Buffalo end	62 (19)

2. Secondary Outcome

Title	Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness.
Description	CGI-S scores from 1 = normal to 7 = most extremely ill
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

17 Buffalo subjects and 19 Bronx subjects

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	4.6 (0.6)
Bronx end	4.9 (0.8)
Buffalo baseline	3.5 (0.9)
Buffalo end	2.8 (0.8)

3. Secondary Outcome

Title	Weight
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Same as PANNS above

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	195 (43)
Bronx end	193 (41)
Buffalo baseline	213 (57)
Buffalo end	204 (52)

4. Secondary Outcome

Title	Fasting Glucose
Description	Amount of glucose in the blood in mg/dl
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

See PANSS above

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	91 (28)
Bronx end	82 (24)
Buffalo baseline	94 (18)
Buffalo end	93 (19)

5. Secondary Outcome

Title	Cholesterol
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

See PANSS above

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	185 (44)
Bronx end	160 (28)
Buffalo baseline	186 (42)
Buffalo end	179 (36)

6. Secondary Outcome

Title	Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia
Description	Scores 0 (none) to 4 (severe) choreo-athetoid and dystonic movements of seven parts of the body with a maximum score 28
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

17 Buffalo subjects and 19 Bronx subjects

Arm/Group Title	Experimental
Arm/Group Description	All subjects, 17 at Buffalo and 19 at Bronx were given Ziprasidone.
Measure Participants	36
Bronx baseline	0.3 (0.8)
Bronx end	0.3 (0.7)
Buffalo baseline	2.9 (3.1)
Buffalo end	1.6 (1.4)

7. Secondary Outcome

Title	Simpson-Angus Scale Measures Drug Induced Parkinsonism
Description	Measures 10 signs, (not all of which are now considered Parkinsonism), minimum score 0 (no Parkinsonism) maximum 40.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

see PANNS above

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	0.2 (0.5)
Bronx end	0.1 (0.2)
Buffalo baseline	3.6 (3.6)
Buffalo end	2.5 (2.6)

8. Secondary Outcome

Title	Corrected QT Interval (QTc)
Description	Time interval between Q and T waves on EKG corrected for pulse rate. Over 500 msec may be dangerous
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
Measure Participants	36
Bronx baseline	396 (18)
Bronx end	411 (15)
Buffalo baeline	412 (21)
Buffalo end	427 (17)

9. Secondary Outcome

Title	Brief Assessment of Cognition in Schizophrenia (BACS)
Description	Scores on the BACS scale, which measures cognition, were changed to Z-scores based on normal controls from Keefe (2008) A Z-score of zero would indicate cognition the same as the normal controls. Negative scores indicate cognition worse than the normal. Theoretically there are no maximum or minimum scores.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The overall number of participants is made up of 17 at Buffalo and 19 in the Bronx

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals, 17 at Buffalo, 19 at Bronx
Measure Participants	36
Bronx baseline	-14 (6.0)
Bronx end	-13 (5.3)
Buffalo baseline	-12 (5.9)
Buffalo end	-11 (6.5)

10. Secondary Outcome

Title	Calgary Depression Scale for Schizophrenia
Description	Score on scale, from 0 to 27, above 6 considered indicative of depression, higher scores mean worse outcome,
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

19 at Bronx, 17 at Buffalo

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals
Measure Participants	36
Bronx baseline	5.4 (4.4)
Bronx end	5.3 (3.8)
Buffalo baseline	3.4 (3.7)
Buffalo end	1.3 (2.0)

11. Secondary Outcome

Title	Personal Evaluation of Transitions in Treatment Scale (PETiTP
Description	PETiT is a 30 item self administered scale measuring response to and tolerability and adherence to antipsychotic medication in people with schizophrenia. The range is 30 to 100. Higher scores are better. Although different features are assessed there is a single total score - no subscales.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

36 subjects entered, 17 at Buffalo and 19 in the Bronx

Arm/Group Title	Experimental
Arm/Group Description	All subjects, 17 at Buffalo and 19 at Bronx were given Ziprasidone.
Measure Participants	36
Bronx baseline	43 (9.7)
Bronx end	45 (11)
Buffalo baseline	46 (11)
Buffalo end	48 (13)

12. Secondary Outcome

Title	Medical Outcomes Study Cognitive Functioning Scale (MOS-COG)
Description	MOS-COG measures day to day problems in six aspects of cognitive functioning. The scores are converted to 0-100 and so can range from 0 to 100 with 100 being the best. Population means are 70 to 80.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All subjects, 17 at Buffalo, 19 in the Bronx

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals, 17 at Buffalo, 19 at Bronx
Measure Participants	36
Bronx baseline	17 (5.8)
Bronx end	16 (6.3)
Buffalo baseline	18 (5.4)
Buffalo end	19 (3.9)

13. Secondary Outcome

Title	Barnes Akathisia Scale
Description	Barnes Akathisia Scale measures akathisia: a score of zero is none (good) maximum score is 12
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All subjects entered, 17 at Buffalo, 19 at Bronx

Arm/Group Title	Experimental
Arm/Group Description	All subjects, 17 at Buffalo and 19 at Bronx were given Ziprasidone.
Measure Participants	36
Bronx baseline	0.6 (1.7)
Bronx end	0.8 (1.7)
Buffalo baseline	1.4 (1.5)
Buffalo end	1.1 (1.7)

14. Secondary Outcome

Title	HbA1c
Description	Lab measure of glycated hemoglobin indicative of blood glucose over the last three months. At that time in the US measured as a percentage (of glucose attached to hemoglobin). No maximum or minimum but over 6.5% is generally considered indicative of diabetes.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All subjects entered, 19 in the Bronx, 17 at Buffalo

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals
Measure Participants	36
Bronx baseline	5.3 (0.6)
Bronx end	5.4 (0.7)
Buffalo baseline	6.0 (0.9)
Buffalo end	5.7 (0.8)

15. Secondary Outcome

Title	Insulin Level
Description	Measure of the amount of insulin in the blood, in uIU/ml. No minimum or maximum but fasting levels are usually below 25 uIU/ml. After a dose of glucose they may be 30 to 230 uIU/ml.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All subjects entered, 17 at Buffalo, 19 at Bronx

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone up to 120mg twice a day with meals, 17 at Buffalo, 19 at Bronx
Measure Participants	36
Bronx baseline	10 (7.2)
Bronx end	13 (14)
Buffalo baseline	12 (9.2)
Buffalo end	17 (14)

16. Secondary Outcome

Title	Antipsychotic Medication Costs
Description	No data were collected because it turned out we had no way of measuring the costs. No subjects were analysed by costs
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

We had no measure of costs, no data were collected

Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone ziprasidone: Ziprasidone by mouth 40mg twice a day (bid) for one day, then 80mg bid; may be increased to 120mg bid after three weeks
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected during the time subjects were in the study - screening till 8 weeks on ziprasidone.
Arm/Group Title	Experimental
Arm/Group Description	Open label change to ziprasidone
All Cause Mortality
	Experimental
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)
Psychiatric disorders
Hospitalization	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.