A Non-Interventional Post-Marketing Surveillance Study to Evaluate the Safety and Efficacy of Zeldox Capsule

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01053429
• Collaborator: (none)
• Enrollment: 3,391
• Duration (Months): 56

Study Details

Study Description

Brief Summary

This is a regulatory-required non-interventional pharmacovigilance study exploring the safety profile of ziprasidone HCL monohydrate 20mg, 40mg, 60mg, 80mg in the real world patient population, thus, safety (and/or efficacy) signals will be checked at every visit during the contracted study period until the maximum study end date, per the protocol, of April 2010.

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

Detailed Description

All patients diagnosed with schizophrenia or acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features will be included in the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 3391 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Post-Marketing Surveillance (PMS) Study to Evaluate Safety and Efficacy of Zeldox Capsule
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
observational cohort	Drug: ziprasidone; This is a non-interventional, pharmacovigilance study, therefore patients are on ziprasidone as prescribed by their doctor.; Other Names: Geodon, Zeldox

Outcome Measures

Primary Outcome Measures

1. Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population [Baseline up to Week 8]

   CGI-S is a single-item clinician rated scale to rate the severity of a participant's illness over time. Scores range from 1 (normal, not ill at all) to 7 (among the most extremely ill); higher score indicates more affected.

2. Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population [Baseline up to Week 8]

   CGI-S is a single-item clinician rated scale to rate the severity of a participant's illness over time. Scores range from 1 (normal, not ill at all) to 7 (among the most extremely ill); higher score indicates more affected.

3. Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT [Baseline up to Week 8]

   CGI-I is a single-item clinician rated scale used to assess the participant's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.

4. Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP [Baseline up to Week 8]

   CGI-I is a single-item clinician rated scale used to assess the participant's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.

Other Outcome Measures

1. Change From Baseline in Brief Psychiatric Rating Scale (BPRS ) - Improvement [Baseline up to Week 8]

   BPRS-A: 18-item clinician rated scale to assess somatic concern, anxiety, emotional withdrawal, disorganization, hallucinatory behavior, guilt feelings, suspiciousness, disorientation, tension, mannerisms, posturing, grandiosity, depressive mood, hostility, motor retardation, uncooperativeness, unusual thought content, blunted affect, and excitement. Ratings anchored to improve consistency for a single rater over time or between raters. Items rated on 7-point scale 0 (not present) to 6 (extremely severe). Total score=sum of items (range 0 to 108); higher scores indicate increased pathology.

2. Change From Baseline in Drug Attitude Inventory (DAI-10) - Improvement [Baseline up to Week 8]

   DAI-10: a 10-item scale to assess how the attitude of participants with schizophrenia toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranges from -10 to 10, where a positive score indicates a positive subjective response (compliant); a negative score indicates non-compliance.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients diagnosed with schizophrenia

Exclusion Criteria:

• Patients who have known hypersensitivity to any ingredient of the product

• Patients who have had a recent acute myocardial infarction

• Patients who have uncompensated heart failure

• Patients who have conditions with a potential to increase QT interval (QT-interval prolongation or history of QT prolongation; congenital long QT syndrome; use with other drugs known to increase the QT interval; arrhythmias treated with class I and III antiarrhythmic drugs)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01053429
• Other Study ID Numbers: A1281140
• First Posted: Jan 21, 2010
• Last Update Posted: Mar 3, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Regulatory Post-Marketing Surveillance; Regulatory Pharmacovigilance; ziprasidone
• Additional relevant MeSH terms: Schizophrenia; Bipolar Disorder; Ziprasidone

Study Results

Participant Flow

Pre-assignment Detail	Pediatric patients <18 years of age (N=105) were enrolled in error by some sites and were subsequently reported as protocol violations. Given that the objective of this Non-interventional study was to observe the safety and efficacy of Zeldox in real life, the data collected from these participants was included in the safety and efficacy analyses.

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Period Title: Overall Study
STARTED	3391
COMPLETED	3018
NOT COMPLETED	373

Baseline Characteristics

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Overall Participants	3391
Age, Customized (participants) [Number]
<18 years	105 3.1%
Between 18 and 44 years	2377 70.1%
Between 45 and 64 years	723 21.3%
>=65 years	186 5.5%
Sex: Female, Male (Count of Participants)
Female	1926 56.8%
Male	1465 43.2%
Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) (participants) [Number]
Normal, not ill at all	6 0.2%
Borderline mentally ill	110 3.2%
Mildly ill	669 19.7%
Moderately ill	1264 37.3%
Markedly ill	808 23.8%
Severely ill	440 13%
Among the most extremely ill	54 1.6%
CGI-S status - Per protocol population (PP) (participants) [Number]
Normal, not ill at all	3 0.1%
Borderline mentally ill	68 2%
Mildly ill	454 13.4%
Moderately ill	877 25.9%
Markedly ill	547 16.1%
Severely ill	266 7.8%
Among the most extremely ill	39 1.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population
Description	CGI-S is a single-item clinician rated scale to rate the severity of a participant's illness over time. Scores range from 1 (normal, not ill at all) to 7 (among the most extremely ill); higher score indicates more affected.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population (ITT): administered at least 1 dose of study treatment at least once a week and observed for at least 1 efficacy assessment. N=number of participants with evaluable data at observation. Efficacy analysis planned for CGI-S at each visit but completed at last visit (no set schedule for study visits).

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	3351
Normal, not ill at all	190
Borderline mentally ill	1125
Mildly ill	1325
Moderately ill	506
Markedly ill	156
Severely ill	46
Among the most extremely ill	3

2. Primary Outcome

Title	Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population
Description	CGI-S is a single-item clinician rated scale to rate the severity of a participant's illness over time. Scores range from 1 (normal, not ill at all) to 7 (among the most extremely ill); higher score indicates more affected.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP): participants in ITT group with study treatment for at least 8 (± 1 week) since enrollment and observed for final efficacy (inpatient visit or phone call). N=participants with evaluable data at observation. Efficacy analysis planned for CGI-S at each visit but completed at last visit (no set schedule for study visits).

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	2254
Normal, not ill at all	130 3.8%
Borderline mentally ill	815 24%
Mildly ill	889 26.2%
Moderately ill	320 9.4%
Markedly ill	77 2.3%
Severely ill	21 0.6%
Among the most extremely ill	2 0.1%

3. Primary Outcome

Title	Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT
Description	CGI-I is a single-item clinician rated scale used to assess the participant's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

ITT; N=number of participants with evaluable data at observation. Efficacy analysis planned for CGI-I at each visit but completed at last visit (no set schedule for study visits).

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	3351
Very much improved	368 10.9%
Much improved	1026 30.3%
Minimally improved	1361 40.1%
No change	512 15.1%
Minimally worse	71 2.1%
Much worse	13 0.4%
Very much worse	0 0%

4. Primary Outcome

Title	Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP
Description	CGI-I is a single-item clinician rated scale used to assess the participant's improvement or worsening from baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse); higher score indicates more affected.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

PP; N=number of participants with evaluable data at observation. Efficacy analysis planned for CGI-I at each visit but completed at last visit (no set schedule for study visits).

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	2254
Very much improved	271 8%
Much improved	751 22.1%
Minimally improved	889 26.2%
No change	299 8.8%
Minimally worse	36 1.1%
Much worse	8 0.2%
Very much worse	0 0%

5. Other Pre-specified Outcome

Title	Change From Baseline in Brief Psychiatric Rating Scale (BPRS ) - Improvement
Description	BPRS-A: 18-item clinician rated scale to assess somatic concern, anxiety, emotional withdrawal, disorganization, hallucinatory behavior, guilt feelings, suspiciousness, disorientation, tension, mannerisms, posturing, grandiosity, depressive mood, hostility, motor retardation, uncooperativeness, unusual thought content, blunted affect, and excitement. Ratings anchored to improve consistency for a single rater over time or between raters. Items rated on 7-point scale 0 (not present) to 6 (extremely severe). Total score=sum of items (range 0 to 108); higher scores indicate increased pathology.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Safety analysis set: all participants who received at least 1 dose of study treatment. It was recommended to use the optional BPRS tool to gather additional information for the improvement score under usual practice. The optional BPRS tool was not used during the study.

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	0

6. Other Pre-specified Outcome

Title	Change From Baseline in Drug Attitude Inventory (DAI-10) - Improvement
Description	DAI-10: a 10-item scale to assess how the attitude of participants with schizophrenia toward their medications may affect compliance. Respondents indicate 'true' or 'false' for each item. An overall calculated score ranges from -10 to 10, where a positive score indicates a positive subjective response (compliant); a negative score indicates non-compliance.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Safety analysis set. It was recommended to use the optional DAI-10 tool to gather additional information for the improvement score under usual practice. The optional DAI-10 tool was not used during the study.

Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Arm/Group Title	Ziprasidone HCl (Zeldox)
Arm/Group Description	Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document
All Cause Mortality
	Ziprasidone HCl (Zeldox)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ziprasidone HCl (Zeldox)
	Affected / at Risk (%)	# Events
Total	2/3391 (0.1%)
General disorders
Asthenia	1/3391 (0%)
Injury, poisoning and procedural complications
Open wound	1/3391 (0%)
Investigations
Electrocardiogram QT prolonged	1/3391 (0%)
Nervous system disorders
Dizziness	1/3391 (0%)
Psychiatric disorders
Psychotic disorder	1/3391 (0%)
Suicide attempt	1/3391 (0%)
Other (Not Including Serious) Adverse Events
	Ziprasidone HCl (Zeldox)
	Affected / at Risk (%)	# Events
Total	392/3391 (11.6%)
Blood and lymphatic system disorders
Leukopenia	1/3391 (0%)
Cardiac disorders
Palpitations	2/3391 (0.1%)
Tachycardia	1/3391 (0%)
Eye disorders
Oculogyric crisis	1/3391 (0%)
Vision blurred	6/3391 (0.2%)
Gastrointestinal disorders
Abdominal pain	2/3391 (0.1%)
Constipation	13/3391 (0.4%)
Dyspepsia	4/3391 (0.1%)
Gastrointestinal disorder	1/3391 (0%)
Nausea	24/3391 (0.7%)
Salivary hypersecretion	1/3391 (0%)
Vomiting	4/3391 (0.1%)
General disorders
Asthenia	33/3391 (1%)
Drug ineffective	2/3391 (0.1%)
Gait disturbance	3/3391 (0.1%)
Pyrexia	1/3391 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/3391 (0%)
Investigations
Weight decreased	1/3391 (0%)
Weight increased	1/3391 (0%)
Metabolism and nutrition disorders
Polydipsia	3/3391 (0.1%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/3391 (0%)
Muscular weakness	1/3391 (0%)
Myalgia	1/3391 (0%)
Nervous system disorders
Akathisia	80/3391 (2.4%)
Dizziness	26/3391 (0.8%)
Dysarthria	3/3391 (0.1%)
Dystonia	14/3391 (0.4%)
Extrapyramidal disorder	68/3391 (2%)
Headache	20/3391 (0.6%)
Hypertonia	2/3391 (0.1%)
Hypokinesia	3/3391 (0.1%)
Memory impairment	2/3391 (0.1%)
Motor dysfunction	1/3391 (0%)
Paraesthesia	1/3391 (0%)
Paralysis	1/3391 (0%)
Sedation	1/3391 (0%)
Somnolence	72/3391 (2.1%)
Tremor	12/3391 (0.4%)
Visual field defect	1/3391 (0%)
Psychiatric disorders
Aggression	1/3391 (0%)
Agitation	8/3391 (0.2%)
Anxiety	39/3391 (1.2%)
Blunted affect	1/3391 (0%)
Drug dependence	1/3391 (0%)
Hallucination	4/3391 (0.1%)
Insomnia	58/3391 (1.7%)
Schizophrenia	1/3391 (0%)
Sleep disorder	2/3391 (0.1%)
Thinking abnormal	2/3391 (0.1%)
Nocturia	1/3391 (0%)
Renal and urinary disorders
Dysuria	2/3391 (0.1%)
Reproductive system and breast disorders
Mammary duct ectasia	1/3391 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/3391 (0.1%)
Skin and subcutaneous tissue disorders
Pruritus	1/3391 (0%)
Rash	4/3391 (0.1%)
Rash generalised	1/3391 (0%)
Skin disorder	2/3391 (0.1%)
Vascular disorders
Hypotension	2/3391 (0.1%)

Limitations/Caveats

Per the Statistical Analysis Plan Amendment CGI-S and CGI-I endpoints analyzed as frequency counts (categorical) rather than the planned CGI-S mean change from baseline and CGI-I mean scores (continuous); any additional analyses would be exploratory.

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.