A Randomized, Open-Label, Multi-Center Study To Evaluate The Efficacy And Safety Of Intramuscular Ziprasidone In Patients With Agitation

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00723606
• Collaborator: (none)
• Enrollment: 376
• Locations: 9
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 41.8
• Patients Per Site Per Month: 4.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Intramuscular ziprasidone mesylate; Drug: Intramuscular haloperidol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open Label, Rater Blind, Flexible Dose Multi-Center Study Comparing The Efficacy And Safety Of Intramuscular Ziprasidone With Haloperidol For Three Days In Patients With Agitation Of Schizophrenia
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intramuscular ziprasidone	Drug: Intramuscular 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.; Other Names: Zeldox, Geodon
Active Comparator: Intramuscular haloperidol	Drug: Intramuscular haloperidol; 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.; Other Names: Haldol

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Baoding	Hebei	China	071000
2	Pfizer Investigational Site	Wuhan	Hubei	China	430060
3	Pfizer Investigational Site	Kunming	Yunnan	China	650032
4	Pfizer Investigational Site	Beijing		China	100083
5	Pfizer Investigational Site	Beijing		China	100088
6	Pfizer Investigational Site	Chang Sha		China	410011
7	Pfizer Investigational Site	Guangzhou		China	510370
8	Pfizer Investigational Site	Nanjing		China	210029
9	Pfizer Investigational Site	Xi'an		China

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: NCT00723606
• Other Study ID Numbers: A1281152
• First Posted: Jul 29, 2008
• 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.: Intramuscular ziprasidone, agitation, efficacy and safety
• Additional relevant MeSH terms: Psychomotor Agitation; Schizophrenia; Haloperidol; Haloperidol decanoate; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	189	187
COMPLETED	185	180
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	Ziprasidone	Haloperidol	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	189	187	376
Age, Customized (participants) [Number]
< 18 years	0 0%	2 1.1%	2 0.5%
18 to 44 years	161 85.2%	157 84%	318 84.6%
45 to 64 years	28 14.8%	28 15%	56 14.9%
> = 65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	99 52.4%	98 52.4%	197 52.4%
Male	90 47.6%	89 47.6%	179 47.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	167	152
Least Squares Mean (Standard Error) [scores on a scale]	-17.32 (0.692)	-18.44 (0.720)

2. Secondary Outcome

Title	BPRS Agitation Subscale Response at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAS. Missing data were replaced by last observation carried forward (LOCF).

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	188	184
Response	149 78.8%	155 82.9%
No Response	39 20.6%	29 15.5%

3. Secondary Outcome

Title	Change From Baseline in BPRS Agitation Subscale Score at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAS. Missing data were replaced by LOCF.

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	188	184
Least Squares Mean (Standard Error) [scores on a scale]	-6.97 (0.225)	-7.45 (0.228)

4. Secondary Outcome

Title	Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAS. Missing data were replaced by LOCF.

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	188	184
Least Squares Mean (Standard Error) [scores on a scale]	2.52 (0.056)	2.55 (0.057)

5. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAS. Missing data were replaced by LOCF.

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	188	184
Least Squares Mean (Standard Error) [scores on a scale]	-1.18 (0.061)	-1.21 (0.062)

6. Secondary Outcome

Title	Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAS. Missing data were replaced by LOCF.

Arm/Group Title	Ziprasidone	Haloperidol
Arm/Group Description	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.	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.
Measure Participants	186	185
Least Squares Mean (Standard Error) [scores on a scale]	-0.93 (0.044)	-1.06 (0.044)

Adverse Events

Adverse Event Reporting Description	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.
Arm/Group Title	Ziprasidone		Haloperidol
Arm/Group Description	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.		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.
All Cause Mortality
	Ziprasidone		Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone		Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/189 (0%)		0/187 (0%)
Other (Not Including Serious) Adverse Events
	Ziprasidone		Haloperidol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/189 (19%)		107/187 (57.2%)
Cardiac disorders
Sinus tachycardia	5/189 (2.6%)		2/187 (1.1%)
Gastrointestinal disorders
Constipation	5/189 (2.6%)		2/187 (1.1%)
Nausea	6/189 (3.2%)		2/187 (1.1%)
Investigations
Aspartate aminotransferase increased	0/189 (0%)		5/187 (2.7%)
Nervous system disorders
Akathisia	6/189 (3.2%)		7/187 (3.7%)
Dizziness	7/189 (3.7%)		6/187 (3.2%)
Dystonia	0/189 (0%)		7/187 (3.7%)
Extrapyramidal disorder	4/189 (2.1%)		69/187 (36.9%)
Pyramidal tract syndrome	0/189 (0%)		8/187 (4.3%)
Somnolence	7/189 (3.7%)		8/187 (4.3%)
Psychiatric disorders
Insomnia	4/189 (2.1%)		5/187 (2.7%)

Limitations/Caveats

[Not Specified]

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.