Trial Outcomes & Findings for A Randomized, Open-Label, Multi-Center Study To Evaluate The Efficacy And Safety Of Intramuscular Ziprasidone In Patients With Agitation (NCT NCT00723606)
NCT ID: NCT00723606
Last Updated: 2021-03-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
376 participants
Primary outcome timeframe
Baseline, 72 hours
Results posted on
2021-03-03
Participant Flow
Participant milestones
| Measure |
Ziprasidone
An initial intramuscular (IM) injection of ziprasidone 10 or 20 milligram (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 possible treatment.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
189
|
187
|
|
Overall Study
COMPLETED
|
185
|
180
|
|
Overall Study
NOT COMPLETED
|
4
|
7
|
Reasons for withdrawal
| Measure |
Ziprasidone
An initial intramuscular (IM) injection of ziprasidone 10 or 20 milligram (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 possible treatment.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
5
|
|
Overall Study
Other
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
A Randomized, Open-Label, Multi-Center Study To Evaluate The Efficacy And Safety Of Intramuscular Ziprasidone In Patients With Agitation
Baseline characteristics by cohort
| Measure |
Ziprasidone
n=189 Participants
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.
|
Haloperidol
n=187 Participants
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.
|
Total
n=376 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 18 years
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Age, Customized
18 to 44 years
|
161 participants
n=5 Participants
|
157 participants
n=7 Participants
|
318 participants
n=5 Participants
|
|
Age, Customized
45 to 64 years
|
28 participants
n=5 Participants
|
28 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Age, Customized
> = 65 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
197 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
90 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
179 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 72 hoursPopulation: 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.
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.
Outcome measures
| Measure |
Ziprasidone
n=167 Participants
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.
|
Haloperidol
n=152 Participants
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.
|
|---|---|---|
|
Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours
|
-17.32 scores on a scale
Standard Error 0.692
|
-18.44 scores on a scale
Standard Error 0.720
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: FAS. Missing data were replaced by last observation carried forward (LOCF).
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.
Outcome measures
| Measure |
Ziprasidone
n=188 Participants
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.
|
Haloperidol
n=184 Participants
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.
|
|---|---|---|
|
BPRS Agitation Subscale Response at 72 Hours
No Response
|
39 participants
|
29 participants
|
|
BPRS Agitation Subscale Response at 72 Hours
Response
|
149 participants
|
155 participants
|
SECONDARY outcome
Timeframe: Baseline, 72 hoursPopulation: FAS. Missing data were replaced by LOCF.
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.
Outcome measures
| Measure |
Ziprasidone
n=188 Participants
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.
|
Haloperidol
n=184 Participants
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.
|
|---|---|---|
|
Change From Baseline in BPRS Agitation Subscale Score at 72 Hours
|
-6.97 scores on a scale
Standard Error 0.225
|
-7.45 scores on a scale
Standard Error 0.228
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: FAS. Missing data were replaced by LOCF.
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.
Outcome measures
| Measure |
Ziprasidone
n=188 Participants
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.
|
Haloperidol
n=184 Participants
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.
|
|---|---|---|
|
Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours
|
2.52 scores on a scale
Standard Error 0.056
|
2.55 scores on a scale
Standard Error 0.057
|
SECONDARY outcome
Timeframe: Baseline, 72 hoursPopulation: FAS. Missing data were replaced by LOCF.
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.
Outcome measures
| Measure |
Ziprasidone
n=188 Participants
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.
|
Haloperidol
n=184 Participants
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.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours
|
-1.18 scores on a scale
Standard Error 0.061
|
-1.21 scores on a scale
Standard Error 0.062
|
SECONDARY outcome
Timeframe: Baseline, 72 hoursPopulation: FAS. Missing data were replaced by LOCF.
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.
Outcome measures
| Measure |
Ziprasidone
n=186 Participants
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.
|
Haloperidol
n=185 Participants
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.
|
|---|---|---|
|
Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours
|
-0.93 scores on a scale
Standard Error 0.044
|
-1.06 scores on a scale
Standard Error 0.044
|
Adverse Events
Ziprasidone
Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths
Haloperidol
Serious events: 0 serious events
Other events: 107 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ziprasidone
n=189 participants at risk
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.
|
Haloperidol
n=187 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Sinus tachycardia
|
2.6%
5/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
1.1%
2/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Constipation
|
2.6%
5/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
1.1%
2/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Nausea
|
3.2%
6/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
1.1%
2/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.7%
5/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Akathisia
|
3.2%
6/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
3.7%
7/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dizziness
|
3.7%
7/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
3.2%
6/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dystonia
|
0.00%
0/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
3.7%
7/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Extrapyramidal disorder
|
2.1%
4/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
36.9%
69/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Pyramidal tract syndrome
|
0.00%
0/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
4.3%
8/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Somnolence
|
3.7%
7/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
4.3%
8/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Insomnia
|
2.1%
4/189
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.7%
5/187
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER