Safety and Efficacy of Cariprazine (RGH-188) in the Acute Exacerbation of Schizophrenia

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00694707
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 732
• Locations: 65
• Arms: 5
• Actual Duration (Months): 14
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is a study to evaluate the safety, efficacy, and tolerability of cariprazine (RGH-188) relative to placebo in adult patients (18-60 years of age) with acute exacerbation of schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Placebo; Drug: Cariprazine; Drug: Risperidone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 732 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Safety and Efficacy of RGH-188 in the Acute Exacerbation of Schizophrenia
• Actual Study Start Date: Jun 30, 2008
• Actual Primary Completion Date: Aug 31, 2009
• Actual Study Completion Date: Aug 31, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo orally once a day for 6 weeks.	Drug: Placebo; Placebo was supplied in capsules.
Experimental: Cariprazine 1.5 mg Participants received cariprazine 1.5 mg orally once a day for 6 weeks.	Drug: Cariprazine; Cariprazine was supplied in capsules; Other Names: RGH-188
Experimental: Cariprazine 3.0 mg Participants received cariprazine 3.0 mg orally once a day for 6 weeks.	Drug: Cariprazine; Cariprazine was supplied in capsules; Other Names: RGH-188
Experimental: Cariprazine 4.5 mg Participants received cariprazine 4.5 mg orally once a day for 6 weeks.	Drug: Cariprazine; Cariprazine was supplied in capsules; Other Names: RGH-188
Active Comparator: Risperidone 4.0 mg Participants received risperidone 4.0 mg orally once a day for 6 weeks.	Drug: Risperidone; Risperidone was supplied in capsules; Other Names: Risperdal

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 6 in the PANSS Total Score [Baseline to Week 6]

   The Positive and Negative Syndrome Scale (PANSS) is a 30-item rating scale that assesses the positive and negative symptoms of individuals with schizophrenia. Responses to the 30 items are based on a structured clinical interview with the patient and on supporting clinical information obtained from family, hospital staff, or other reliable informants. Of the 30 psychiatric parameters measured by the scale, 7 assess positive symptoms (eg, delusions, grandiosity); 7 assess negative symptoms (eg, blunted affect, emotional withdrawal); and 16 assess general psychopathology (eg, poor attention, active social avoidance). Each item is scored on a 7-point scale (1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, and 7 = extreme). The PANSS total score can range from 30 to 210. A higher score indicates worse symptoms. A negative change score indicates improvement.

Secondary Outcome Measures

1. Change From Baseline to Week 6 in the CGI-S Score [Baseline to Week 6]

   The Clinical Global Impressions-Severity (CGI-S) scale is a 7-point scale that measures the overall severity of the illness compared with the severity of illness in other patients the Investigator has observed. The Investigator assesses the severity of the patient's illness as one of the following: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients. The CGI-S score can range from 1 to 7. A higher score indicates more severe illness. A negative change score indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, 18 to 60 years of age.

• Meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia (paranoid type, disorganized type, catatonic type, or undifferentiated type) based on a Structured Clinical Interview for DSM-IV (SCID).

• Total Positive and Negative Syndrome Scale (PANSS) score ≥ 80 and ≤ 120.

• Diagnosis of schizophrenia for at least 1 year.

Exclusion Criteria:

• Abnormalities on physical examination or abnormal vital signs, electrocardiogram, or clinical laboratory values.

• First episode of psychosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site	Costa Mesa	California	United States	92626
2	Forest Investigative Site	Long Beach	California	United States	90813
3	Forest Investigative Site	Oceanside	California	United States	92056
4	Forest Investigative Site	Paramount	California	United States	90723
5	Forest Investigative Site	Riverside	California	United States	92506
6	Forest Investigative Site	Washington	District of Columbia	United States	20016
7	Forest Investigative Site	Bradenton	Florida	United States	34208
8	Forest Investigative Site	Kissimmee	Florida	United States	34741
9	Forest Investigative Site	Lake Charles	Louisiana	United States	70601
10	Forest Investigative Site	Baltimore	Maryland	United States	21202
11	Forest Investigative Site	Flowood	Mississippi	United States	39232
12	Forest Investigative Site	Bridgeton	Missouri	United States	63044
13	Forest Investigative Site	Cincinnati	Ohio	United States	45219
14	Forest Investigative Site	Charleston	South Carolina	United States	29405
15	Forest Investigative Site	Memphis	Tennessee	United States	28117
16	Forest Investigative Site	Houston	Texas	United States	77008
17	Forest Investigative Site	Houston	Texas	United States	77021
18	Forest Investigative Site	Irving	Texas	United States	75062
19	Forest Investigative Site	Vijaywada	Andh Prad	India	520002
20	Forest Investigative Site	Visakhapatnam	Andh Prad	India	530017
21	Forest Investigative Site	Ahmedabad	Gujarat	India	380013
22	Forest Investigative Site	Ahmedabad	Gujarat	India	380015
23	Forest Investigative Site	Bangalore	Karna	India	560010
24	Forest Investigative Site	Bangalore	Karna	India	560027
25	Forest Investigative Site	Mangalore	Karna	India	574160
26	Forest Investigative Site	Mangalore	Karna	India	575001
27	Forest Investigative Site	Manipal	Karna	India	576104
28	Forest Investigative Site	Mysore	Karna	India	570004
29	Forest Investigative Site	Pune	Mahara	India	411004
30	Forest Investigative Site	Jaipur	Rajasthan	India	302021
31	Forest Investigative Site	Chennai	Tamilnadu	India	600003
32	Forest Investigative Site	Chennai	Tamilnadu	India	600101
33	Forest Investigative Site	Tirupati	Tamilnadu	India	517507
34	Forest Investigative Site	Kanpur	Uttar Prad	India	208005
35	Forest Investigative Site	Johor Bahru	Johor	Malaysia	80100
36	Forest Investigative Site	Kota Bharu	Kelantan	Malaysia	15586
37	Forest Investigative Site	Lembah Pantai	Kuala Lumpur	Malaysia	59100
38	Forest Investigative Site	Ipoh	Perak	Malaysia	30990
39	Forest Investigative Site	Ulu Kinta	Perak	Malaysia	31250
40	Forest Investigative Site	Arkhangelsk		Russian Federation	163060
41	Forest Investigative Site	Gatchina		Russian Federation	188357
42	Forest Investigative Site	Kazan		Russian Federation	420012
43	Forest Investigative Site 1	Moscow		Russian Federation	115522
44	Forest Investigative Site 2	Moscow		Russian Federation	115522
45	Forest Investigative Site	Moscow		Russian Federation	117152
46	Forest Investigative Site	Nizhniy Novgorod		Russian Federation	603155
47	Forest Investigative Site	Samara		Russian Federation	443016
48	Forest Investigative Site	St. Petersburg		Russian Federation	190005
49	Forest Investigative Site	St. Petersburg		Russian Federation	190121
50	Forest Investigative Site	St. Petersburg		Russian Federation	191119
51	Forest Investigative Site 2	St. Petersburg		Russian Federation	193019
52	Forest Investigative Site1	St. Petersburg		Russian Federation	193019
53	Forest Investigative Site	St. Petersburg		Russian Federation	193167
54	Forest Investigative Site	St. Petersburg		Russian Federation	197341
55	Forest Investigative Site	Dnipropetrovsk	Dnipropetrovsk Oblast	Ukraine	49616
56	Forest Investigative Site	Donetsk	Donetsk Oblast	Ukraine	83037
57	Forest Investigative Site	Kharkiv	Kharkiv Oblast	Ukraine	61068
58	Forest Investigative Site	Glevakha	Kyiv Oblast	Ukraine	08630
59	Forest Investigative Site	Kyiv	Kyiv Oblast	Ukraine	04080
60	Forest Investigative Site	Kyiv	Kyiv Oblast	Ukraine	04655
61	Forest Investigative Site	Odessa	Odessa Oblast	Ukraine	65006
62	Forest Investigative Site	Ternopil	Ternopil Oblast	Ukraine	46020
63	Forest Investigative Site	Chernigiv		Ukraine	14000
64	Forest Investigative Site	Kherson, Vil. Stepanivka		Ukraine	73488
65	Forest Investigative Site	Kiev		Ukraine	02660

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Suresh Durgam, MD, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00694707
• Other Study ID Numbers: RGH-MD-16; NCT00892528
• First Posted: Jun 10, 2008
• Last Update Posted: Jun 12, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Schizophrenia; Risperidone; Cariprazine

Study Results

Participant Flow

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Cariprazine 4.5 mg	Risperidone 4.0 mg
Arm/Group Description	Participants received placebo orally once a day for 6 weeks.	Participants received cariprazine 1.5 mg orally once a day for 6 weeks.	Participants received cariprazine 3.0 mg orally once a day for 6 weeks.	Participants received cariprazine 4.5 mg orally once a day for 6 weeks.	Participants received risperidone 4.0 mg orally once a day for 6 weeks.
Period Title: Overall Study
STARTED	151	145	147	148	141
COMPLETED	79	90	96	98	101
NOT COMPLETED	72	55	51	50	40

Baseline Characteristics

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Cariprazine 4.5 mg	Risperidone 4.0 mg	Total
Arm/Group Description	Participants received placebo orally once a day for 6 weeks.	Participants received cariprazine 1.5 mg orally once a day for 6 weeks.	Participants received cariprazine 3.0 mg orally once a day for 6 weeks.	Participants received cariprazine 4.5 mg orally once a day for 6 weeks.	Participants received risperidone 4.0 mg orally once a day for 6 weeks.	Total of all reporting groups
Overall Participants	151	145	146	147	140	729
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.0 (10.8)	36.8 (9.6)	37.1 (10.4)	35.8 (10.8)	36.5 (11.1)	36.4 (10.5)
Sex: Female, Male (Count of Participants)
Female	50 33.1%	52 35.9%	39 26.7%	44 29.9%	42 30%	227 31.1%
Male	101 66.9%	93 64.1%	107 73.3%	103 70.1%	98 70%	502 68.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 4%	7 4.8%	2 1.4%	4 2.7%	5 3.6%	24 3.3%
Not Hispanic or Latino	145 96%	138 95.2%	144 98.6%	143 97.3%	135 96.4%	705 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	2 1.4%	0 0%	0 0%	0 0%	3 0.4%
Asian	36 23.8%	34 23.4%	37 25.3%	39 26.5%	37 26.4%	183 25.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	34 22.5%	32 22.1%	38 26%	32 21.8%	35 25%	171 23.5%
White	80 53%	77 53.1%	71 48.6%	75 51%	67 47.9%	370 50.8%
More than one race	0 0%	0 0%	0 0%	1 0.7%	1 0.7%	2 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.4 (18.6)	71.7 (17.7)	74.8 (16.3)	72.4 (16.6)	75.1 (18.2)	73.7 (17.5)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.8 (11.2)	169.0 (10.5)	170.7 (10.3)	170.3 (10.4)	170.0 (10.5)	170.2 (10.6)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.2 (4.5)	24.9 (4.9)	25.6 (4.6)	24.8 (4.2)	25.8 (4.8)	25.2 (4.6)
Waist circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	86.7 (12.9)	85.2 (13.1)	87.6 (12.6)	85.8 (12.7)	88.0 (13.0)	86.7 (12.9)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 6 in the PANSS Total Score
Description	The Positive and Negative Syndrome Scale (PANSS) is a 30-item rating scale that assesses the positive and negative symptoms of individuals with schizophrenia. Responses to the 30 items are based on a structured clinical interview with the patient and on supporting clinical information obtained from family, hospital staff, or other reliable informants. Of the 30 psychiatric parameters measured by the scale, 7 assess positive symptoms (eg, delusions, grandiosity); 7 assess negative symptoms (eg, blunted affect, emotional withdrawal); and 16 assess general psychopathology (eg, poor attention, active social avoidance). Each item is scored on a 7-point scale (1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, and 7 = extreme). The PANSS total score can range from 30 to 210. A higher score indicates worse symptoms. A negative change score indicates improvement.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All participants who took at least 1 dose of double-blind investigational product and who had at least 1 post-baseline assessment of the primary efficacy parameter, the PANSS total score.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Cariprazine 4.5 mg	Risperidone 4.0 mg
Arm/Group Description	Participants received placebo orally once a day for 6 weeks.	Participants received cariprazine 1.5 mg orally once a day for 6 weeks.	Participants received cariprazine 3.0 mg orally once a day for 6 weeks.	Participants received cariprazine 4.5 mg orally once a day for 6 weeks.	Participants received risperidone 4.0 mg orally once a day for 6 weeks.
Measure Participants	148	140	140	145	138
Baseline	97.3 (0.8)	97.1 (0.8)	97.2 (0.7)	96.7 (0.8)	98.1 (0.8)
Change at Week 6	-9.5 (1.6)	-17.3 (1.7)	-18.7 (1.8)	-20.2 (1.6)	-25.3 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline PANSS total score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-7.5
	Confidence Interval	(2-Sided) 95%; -11.8 to -3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 3.0 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline PANSS total score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-8.8
	Confidence Interval	(2-Sided) 95%; -13.1 to -4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 4.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline PANSS total score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-10.4
	Confidence Interval	(2-Sided) 95%; -14.6 to -6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risperidone 4.0 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline PANSS total score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-15.0
	Confidence Interval	(2-Sided) 95%; -19.4 to -10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 6 in the CGI-S Score
Description	The Clinical Global Impressions-Severity (CGI-S) scale is a 7-point scale that measures the overall severity of the illness compared with the severity of illness in other patients the Investigator has observed. The Investigator assesses the severity of the patient's illness as one of the following: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients. The CGI-S score can range from 1 to 7. A higher score indicates more severe illness. A negative change score indicates improvement.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All participants who took at least 1 dose of double-blind investigational product and who had at least 1 post-baseline assessment of the primary efficacy parameter, the PANSS total score.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Cariprazine 4.5 mg	Risperidone 4.0 mg
Arm/Group Description	Participants received placebo orally once a day for 6 weeks.	Participants received cariprazine 1.5 mg orally once a day for 6 weeks.	Participants received cariprazine 3.0 mg orally once a day for 6 weeks.	Participants received cariprazine 4.5 mg orally once a day for 6 weeks.	Participants received risperidone 4.0 mg orally once a day for 6 weeks.
Measure Participants	148	140	140	145	138
Baseline	4.9 (0.1)	4.7 (0.1)	4.9 (0.1)	4.8 (0.1)	4.8 (0.1)
Change at Week 6	-0.6 (0.1)	-0.9 (0.1)	-1.1 (0.1)	-1.2 (0.1)	-1.4 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline CGI-S score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.6 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 3.0 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline CGI-S score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 4.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline CGI-S score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Risperidone 4.0 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The analysis of covariance (ANCOVA) included treatment group and study center as factors and the Baseline CGI-S score as the covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Safety population: All randomized participants who took at least 1 dose of double-blind investigational product.
Arm/Group Title	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg		Cariprazine 4.5 mg		Risperidone 4.0 mg
Arm/Group Description	Participants received placebo orally once a day for 6 weeks.		Participants received cariprazine 1.5 mg orally once a day for 6 weeks.		Participants received cariprazine 3.0 mg orally once a day for 6 weeks.		Participants received cariprazine 4.5 mg orally once a day for 6 weeks.		Participants received risperidone 4.0 mg orally once a day for 6 weeks.
All Cause Mortality
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg		Cariprazine 4.5 mg		Risperidone 4.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		0/145 (0%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Serious Adverse Events
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg		Cariprazine 4.5 mg		Risperidone 4.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/151 (4.6%)		5/145 (3.4%)		0/146 (0%)		4/147 (2.7%)		3/140 (2.1%)
Cardiac disorders
Atrioventricular block second degree	0/151 (0%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Chest pain	0/151 (0%)		0/145 (0%)		0/146 (0%)		0/147 (0%)		1/140 (0.7%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/151 (0%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Foot fracture	0/151 (0%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Investigations
HIV test positive	0/151 (0%)		0/145 (0%)		0/146 (0%)		1/147 (0.7%)		0/140 (0%)
Blood creatine phosphokinase increased	1/151 (0.7%)		0/145 (0%)		0/146 (0%)		0/147 (0%)		1/140 (0.7%)
Metabolism and nutrition disorders
Spinal compression fracture	0/151 (0%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Nervous system disorders
Agitation	0/151 (0%)		0/145 (0%)		0/146 (0%)		1/147 (0.7%)		0/140 (0%)
Grand mal convulsion	1/151 (0.7%)		0/145 (0%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Psychiatric disorders
Schizophrenia	1/151 (0.7%)		1/145 (0.7%)		0/146 (0%)		1/147 (0.7%)		0/140 (0%)
Aggression	0/151 (0%)		0/145 (0%)		0/146 (0%)		1/147 (0.7%)		0/140 (0%)
Fear of needles	0/151 (0%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Psychotic behaviour	3/151 (2%)		1/145 (0.7%)		0/146 (0%)		0/147 (0%)		0/140 (0%)
Psychotic disorder	1/151 (0.7%)		0/145 (0%)		0/146 (0%)		0/147 (0%)		1/140 (0.7%)
Other (Not Including Serious) Adverse Events
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg		Cariprazine 4.5 mg		Risperidone 4.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/151 (44.4%)		73/145 (50.3%)		74/146 (50.7%)		87/147 (59.2%)		80/140 (57.1%)
Gastrointestinal disorders
Nausea	5/151 (3.3%)		7/145 (4.8%)		11/146 (7.5%)		11/147 (7.5%)		9/140 (6.4%)
Constipation	6/151 (4%)		14/145 (9.7%)		9/146 (6.2%)		8/147 (5.4%)		13/140 (9.3%)
Vomiting	5/151 (3.3%)		4/145 (2.8%)		9/146 (6.2%)		8/147 (5.4%)		4/140 (2.9%)
Investigations
Weight increased	1/151 (0.7%)		3/145 (2.1%)		5/146 (3.4%)		0/147 (0%)		7/140 (5%)
Nervous system disorders
Extrapyramidal disorder	9/151 (6%)		17/145 (11.7%)		14/146 (9.6%)		19/147 (12.9%)		21/140 (15%)
Akathisia	8/151 (5.3%)		13/145 (9%)		14/146 (9.6%)		13/147 (8.8%)		12/140 (8.6%)
Headache	17/151 (11.3%)		17/145 (11.7%)		11/146 (7.5%)		12/147 (8.2%)		13/140 (9.3%)
Sedation	6/151 (4%)		8/145 (5.5%)		7/146 (4.8%)		12/147 (8.2%)		16/140 (11.4%)
Dizziness	3/151 (2%)		5/145 (3.4%)		3/146 (2.1%)		9/147 (6.1%)		8/140 (5.7%)
Tremor	6/151 (4%)		5/145 (3.4%)		7/146 (4.8%)		4/147 (2.7%)		10/140 (7.1%)
Psychiatric disorders
Insomnia	11/151 (7.3%)		15/145 (10.3%)		24/146 (16.4%)		24/147 (16.3%)		21/140 (15%)
Schizophrenia	12/151 (7.9%)		6/145 (4.1%)		7/146 (4.8%)		9/147 (6.1%)		1/140 (0.7%)
Anxiety	5/151 (3.3%)		6/145 (4.1%)		8/146 (5.5%)		8/147 (5.4%)		3/140 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.