Schizophrenia
Conditions
Keywords
Intramuscular ziprasidone, agitation, efficacy and safety
Brief summary
This local registration study is to confirm the hypothesis of the efficacy, tolerability and safety of ziprasidone IM (intramuscular) in the Chinese population with agitation in schizophrenia
Interventions
DRUGIntramuscular ziprasidone mesylate
The recommended dose is 10 to 20 mg administered as required up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every two hours; doses of 20 mg may be administered every four hours up to a maximum of 40 mg/day for 3 days.
The haloperidol group will receive an initial intramuscular injection of haloperidol 5mg, following on which 5mg haloperidol may be repeated every 4-8 hours to a maximum of 20 mg /day for 3 days.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female Chinese subjects aged 18-65 years (including 65) at screening. * Subjects meeting the ICD-10 (Classification of Mental and Behavioral Disorders) criteria for schizophrenia (F20.X). * Subjects who are in acute phase of schizophrenia and are appropriate to receive intramuscular medication for at least 3 days
Exclusion criteria
* History of clinically significant physical illness especially myocardial infarction, non compensatory heart failure etc. * Subjects receiving an investigational agent in the previous 3 months prior to screening. * Use of antipsychotic agents within 12 hours or parenteral benzodiazepines within 4 hours prior to randomization and during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours | Baseline, 72 hours | BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. Change: score at final visit minus score at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BPRS Agitation Subscale Response at 72 Hours | 72 hours | The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. A response was defined as a \> 30 percent reduction from baseline in BPRS agitation subscale score. |
| Change From Baseline in BPRS Agitation Subscale Score at 72 Hours | Baseline, 72 hours | The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. Change: score at final visit minus score at baseline. |
| Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours | 72 hours | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours | Baseline, 72 hours | CGI-S: 7-point clinician rated scale to assess severity of subject's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline. |
| Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours | Baseline, 72 hours | BARS measures the degree of agitated behavior using a 7-point scale describing increasing levels of activity (1 =difficult or unable to rouse; 2 = asleep but responds normally to verbal or physical contact; 3 = drowsy, appears sedated; 4 = quiet and awake \[normal level of activity\]; 5 = signs of overt \[physical or verbal\] activity, calms down with instructions; 6 = extremely or continuously active, not requiring restraint; 7 = violent, requires restraint. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone An initial IM injection of ziprasidone 10 or 20 mg. Additional doses could have been administered according to clinical need (the total daily parenteral dose could not have exceeded 40 mg IM) for a total of 72 hours of possible treatment. | 189 |
| Haloperidol An initial IM injection of haloperidol 5 mg. Following, 5 mg haloperidol could have been repeated every 4 to 8 hours to a maximum of 20 mg of haloperidol in 24 hours, depending on clinical need. The total IM treatment was continued for 72 hours. | 187 |
| Total | 376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Ziprasidone | Haloperidol | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 161 participants | 157 participants | 318 participants |
| Age, Customized < 18 years | 0 participants | 2 participants | 2 participants |
| Age, Customized 45 to 64 years | 28 participants | 28 participants | 56 participants |
| Age, Customized > = 65 years | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 99 Participants | 98 Participants | 197 Participants |
| Sex: Female, Male Male | 90 Participants | 89 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 189 | 107 / 187 |
| serious Total, serious adverse events | 0 / 189 | 0 / 187 |
Outcome results
Primary
Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours
BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. Change: score at final visit minus score at baseline.
Time frame: Baseline, 72 hours
Population: Per protocol (PP) population = Full Analysis Set (FAS) subjects (ie, randomized subjects who took at least one dose of study medication) who provided a baseline and 72 hour BPRS total score and did not deviate from the protocol in a significant manner.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours | -17.32 scores on a scale | Standard Error 0.692 |
| Haloperidol | Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours | -18.44 scores on a scale | Standard Error 0.72 |
Secondary
BPRS Agitation Subscale Response at 72 Hours
The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. A response was defined as a \> 30 percent reduction from baseline in BPRS agitation subscale score.
Time frame: 72 hours
Population: FAS. Missing data were replaced by last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ziprasidone | BPRS Agitation Subscale Response at 72 Hours | Response | 149 participants |
| Ziprasidone | BPRS Agitation Subscale Response at 72 Hours | No Response | 39 participants |
| Haloperidol | BPRS Agitation Subscale Response at 72 Hours | Response | 155 participants |
| Haloperidol | BPRS Agitation Subscale Response at 72 Hours | No Response | 29 participants |
Secondary
Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours
BARS measures the degree of agitated behavior using a 7-point scale describing increasing levels of activity (1 =difficult or unable to rouse; 2 = asleep but responds normally to verbal or physical contact; 3 = drowsy, appears sedated; 4 = quiet and awake \[normal level of activity\]; 5 = signs of overt \[physical or verbal\] activity, calms down with instructions; 6 = extremely or continuously active, not requiring restraint; 7 = violent, requires restraint.
Time frame: Baseline, 72 hours
Population: FAS. Missing data were replaced by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours | -0.93 scores on a scale | Standard Error 0.044 |
| Haloperidol | Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours | -1.06 scores on a scale | Standard Error 0.044 |
Secondary
Change From Baseline in BPRS Agitation Subscale Score at 72 Hours
The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. Change: score at final visit minus score at baseline.
Time frame: Baseline, 72 hours
Population: FAS. Missing data were replaced by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Change From Baseline in BPRS Agitation Subscale Score at 72 Hours | -6.97 scores on a scale | Standard Error 0.225 |
| Haloperidol | Change From Baseline in BPRS Agitation Subscale Score at 72 Hours | -7.45 scores on a scale | Standard Error 0.228 |
Secondary
Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours
CGI-S: 7-point clinician rated scale to assess severity of subject's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline.
Time frame: Baseline, 72 hours
Population: FAS. Missing data were replaced by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours | -1.18 scores on a scale | Standard Error 0.061 |
| Haloperidol | Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours | -1.21 scores on a scale | Standard Error 0.062 |
Secondary
Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: 72 hours
Population: FAS. Missing data were replaced by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ziprasidone | Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours | 2.52 scores on a scale | Standard Error 0.056 |
| Haloperidol | Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours | 2.55 scores on a scale | Standard Error 0.057 |