Bipolar Disorder, Schizophrenia
Conditions
Keywords
Regulatory Post-Marketing Surveillance, Regulatory Pharmacovigilance, ziprasidone
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.
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.
Interventions
DRUGziprasidone
This is a non-interventional, pharmacovigilance study, therefore patients are on ziprasidone as prescribed by their doctor.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone HCl (Zeldox) Ziprasidone hydrochloride (HCl) dosed according to the approved indications for disease diagnosis per local product document | 3,391 |
| Total | 3,391 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 64 |
| Overall Study | Other | 309 |
Baseline characteristics
| Characteristic | Ziprasidone HCl (Zeldox) |
|---|---|
| Age, Customized <18 years | 105 participants |
| Age, Customized >=65 years | 186 participants |
| Age, Customized Between 18 and 44 years | 2377 participants |
| Age, Customized Between 45 and 64 years | 723 participants |
| CGI-S status - Per protocol population (PP) Among the most extremely ill | 39 participants |
| CGI-S status - Per protocol population (PP) Borderline mentally ill | 68 participants |
| CGI-S status - Per protocol population (PP) Markedly ill | 547 participants |
| CGI-S status - Per protocol population (PP) Mildly ill | 454 participants |
| CGI-S status - Per protocol population (PP) Moderately ill | 877 participants |
| CGI-S status - Per protocol population (PP) Normal, not ill at all | 3 participants |
| CGI-S status - Per protocol population (PP) Severely ill | 266 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Among the most extremely ill | 54 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Borderline mentally ill | 110 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Markedly ill | 808 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Mildly ill | 669 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Moderately ill | 1264 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Normal, not ill at all | 6 participants |
| Clinical Global Impression of Severity (CGI-S) status - Intent to treat population (ITT) Severely ill | 440 participants |
| Sex: Female, Male Female | 1926 Participants |
| Sex: Female, Male Male | 1465 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 392 / 3,391 |
| serious Total, serious adverse events | 2 / 3,391 |
Outcome results
Primary
Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Very much improved | 368 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Much improved | 1026 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Minimally improved | 1361 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | No change | 512 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Minimally worse | 71 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Much worse | 13 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - ITT | Very much worse | 0 participants |
Primary
Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Very much improved | 271 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Much improved | 751 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Minimally improved | 889 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | No change | 299 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Minimally worse | 36 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Much worse | 8 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Change From Baseline in Clinical Global Impression - Improvement (CGI-I) at Final Visit (up to Week 8) - PP | Very much worse | 0 participants |
Primary
Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Normal, not ill at all | 190 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Borderline mentally ill | 1125 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Mildly ill | 1325 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Moderately ill | 506 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Markedly ill | 156 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Severely ill | 46 particpants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Intent to Treat Population | Among the most extremely ill | 3 particpants |
Primary
Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Normal, not ill at all | 130 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Borderline mentally ill | 815 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Mildly ill | 889 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Moderately ill | 320 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Markedly ill | 77 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Severely ill | 21 participants |
| Ziprasidone HCl (Zeldox) | Number of Participants for Clinical Global Impression of Severity (CGI-S) Status at Final Visit (up to Week 8) - Per Protocol Population | Among the most extremely ill | 2 participants |
Other Pre-specified
Change From Baseline in Brief Psychiatric Rating Scale (BPRS ) - Improvement
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
Population: 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.
Other Pre-specified
Change From Baseline in Drug Attitude Inventory (DAI-10) - Improvement
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
Population: 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.