Study of the Efficacy of a Fixed-dose Regimen of Cariprazine Compared to Placebo for Treatment of the Depressive Episode in Participants With Bipolar I Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02670538
• Collaborator: (none)
• Enrollment: 493
• Locations: 89
• Arms: 3
• Actual Duration (Months): 21.6
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is designed to prospectively confirm the efficacy of a fixed-dose regimen of cariprazine 1.5 milligrams (mg)/day or 3 mg/day compared to placebo for treatment of the depressive episode in participants with bipolar I disorder. The safety and tolerability of the fixed-dose regimens will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Depression	Drug: Cariprazine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 493 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Fixed-Dose Clinical Trial Evaluating The Efficacy, Safety And Tolerability Of Cariprazine In Patients With Bipolar I Depression
• Actual Study Start Date: Mar 31, 2016
• Actual Primary Completion Date: Jan 18, 2018
• Actual Study Completion Date: Jan 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine 3.0 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligrams (mg) capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.	Drug: Cariprazine; Cariprazine capsule one per day orally.; Other Names: Vraylar
Experimental: Cariprazine 1.5 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Drug: Cariprazine; Cariprazine capsule one per day orally.; Other Names: Vraylar
Placebo Comparator: Placebo Following a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Drug: Placebo; Matching placebo capsule one per day orally.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) [Baseline (Week 0) to Week 6]

   MADRS is a 10-item, clinician-rated scale that evaluates the participants depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score [Baseline (Week 0) to Week 6]

   CGI-S is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other patients the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill patients". A negative change from Baseline indicates improvement. MMRM with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder without psychotic features confirmed by the administration of the Mini International Neuropsychiatric Interview (MINI), with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration

• Currently treated as an outpatient at the time of enrollment

• A verified previous manic or mixed episode. Verification must include one of the following sources:

• Treatment of mania with an anti-manic agent (eg, lithium or divalproate) or antipsychotic medication with an approved indication for mania

• Hospital records/Medical records

• Patient report corroborated by caretaker or previous or current treating clinician

• 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≥ 20

• HAMD-17 item 1 score ≥ 2

• CGI-S score ≥ 4

• Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test (women of childbearing potential only)

• Normal physical examination, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal findings that are judged not clinically significant by the Principal Investigator (PI)

Exclusion Criteria:

• Young Mania Rating Scale (YMRS) total score > 12

• Four or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months before Visit 1

• Any current axis 1 psychiatric diagnosis other than bipolar disorder with the exception of specific phobias

• History of meeting DSM-5 criteria for:

• Dementia, amnesic, or other cognitive disorder

• Schizophrenia, schizoaffective, or other psychotic disorder

• Mental retardation

• DSM-5-based diagnosis of borderline or antisocial personality disorder or other axis II disorder of sufficient severity to interfere with participation in this study

• History of meeting DSM-5 criteria for alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 6 months before Visit 1

• Positive result on blood alcohol test or urine drug screen for any prohibited medication. Exception:

• Patients with a positive cannabinoid on entry may be retested before randomization. If the patient remains positive, the patient is no longer eligible

• Patients positive for opiates on entry, discussion with Study Physician is required.

• Electroconvulsive therapy in the 3 months before Visit 1

• Previous lack of response to electroconvulsive therapy

• Treatment with a depot antipsychotic drug within 1 treatment cycle before Visit 1

• Treatment with clozapine in a dose of > 50 mg/day in the past 2 years

• Prior participation in any investigational study of RGH-188 or cariprazine within the past 12 months

• Previous treatment with vagus nerve stimulation or transcranial magnetic stimulation within 6 months before Visit 1

• Prior participation with any clinical trials, involving experimental or investigational drugs, within 6 months before Visit 1 or during the study

• Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study.

• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

• Gastric bypass or any condition that would be expected to affect drug absorption (lap band procedures are acceptable if there is no problem with absorption)

• Known history of cataracts or retinal detachment

• Known human immunodeficiency virus infection

• Employee, or immediate relative of an employee, of the Sponsor, any of its affiliates or partners, or the study center

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Harmonex Neuroscience Research, Inc.	Dothan	Alabama	United States	36303
3	NoesisPharma, LLC	Phoenix	Arizona	United States	85032
4	Woodland International Research Group, LLC	Little Rock	Arkansas	United States	72211
5	Advanced Research Center, Inc	Anaheim	California	United States	92805
6	Radiant Research	Cerritos	California	United States	90703
7	Collaborative Neuroscience Network, LLC	Garden Grove	California	United States	92845
8	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
9	Excell Research, Inc.	Oceanside	California	United States	92056
10	Collaborative Neuroscience Network, LLC	Torrance	California	United States	90502
11	Comprehensive Clinical Research	Washington	District of Columbia	United States	20016
12	CNS Clinical Research Group	Coral Springs	Florida	United States	33067
13	MD Clinical	Hallandale Beach	Florida	United States	33009
14	Innovative Clinical Research, Inc.	Lauderhill	Florida	United States	33319
15	Innova Clinical Trials, Inc.	Miami	Florida	United States	33133
16	Research Centers of America, LLC	Oakland Park	Florida	United States	33334
17	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
18	Alexian Brothers Center for Psychiatric Research	Hoffman Estates	Illinois	United States	60169
19	Capstone Clinical Research	Libertyville	Illinois	United States	60048
20	Baber Research Group	Naperville	Illinois	United States	60563
21	J. Gary Booker, MD, APMC	Shreveport	Louisiana	United States	71104
22	Coastal Research Associates, Inc.	Weymouth	Massachusetts	United States	02190
23	Millennium Psychiatric Associates	Creve Coeur	Missouri	United States	63141
24	St. Louis Clinical Trials, LLC	Saint Louis	Missouri	United States	63141
25	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
26	Pharmaceutical Research Associates, Inc.	Marlton	New Jersey	United States	08053
27	Brooklyn Medical Institute	Brooklyn	New York	United States	11214
28	SPRI Clinical Trials, LLC	Brooklyn	New York	United States	11235
29	University at Buffalo Erie County Medical Center	Buffalo	New York	United States	14215
30	Manhattan Behavioral Medicine	New York	New York	United States	10036
31	Eastside Comprehensive Medical Center	New York	New York	United States	10128
32	Finger Lakes Clinical Research	Rochester	New York	United States	14618
33	Clinical Trials of America, Inc	Hickory	North Carolina	United States	28601
34	University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience	Cincinnati	Ohio	United States	45219
35	Professional Psychiatric Services	Mason	Ohio	United States	45040
36	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
37	Tulsa Clinical Research, LLC	Tulsa	Oklahoma	United States	74104
38	Suburban Research Associates	Media	Pennsylvania	United States	19063
39	Carolina Clinical Trials, Inc.	Charleston	South Carolina	United States	29407
40	Houston Endoscopy and Research Center	Houston	Texas	United States	77079
41	Grayline Research Center	Wichita Falls	Texas	United States	76309
42	Pacific Institute of Medical Sciences	Bothell	Washington	United States	98011
43	Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD	Burgas		Bulgaria	8001
44	MHAT "Dr. Hristo Stambolski", EOOD	Kazanlak		Bulgaria	6100
45	UMHAT 'Dr. Georgi Stranski', Dept. of Psychiatry	Pleven		Bulgaria	5800
46	UMHAT "Sv. Georgi", EAD	Plovdiv		Bulgaria	4000
47	DCC "Mladost M" - Varna, OOD Site 188	Varna		Bulgaria	9020
48	DCC "Mladost M" - Varna, OOD Site 194	Varna		Bulgaria	9020
49	Neuropsychiatric Hospital Ivan Barbot	Popovača		Croatia	44317
50	Clinical Hospital Center Rijeka	Rijeka		Croatia	51000
51	Polyclinic Neuron	Zagreb		Croatia	10000
52	University Hospital Center Zagreb	Zagreb		Croatia	10000
53	Clinic for Psychiatry Vrapce	Zagreb		Croatia	10090
54	Psychiatric Hospital "Sveti Ivan"	Zagreb		Croatia	10090
55	Barbara Diaz-Hernandez MD Research, Inc.	San Juan		Puerto Rico	00926
56	Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"	Bucuresti		Romania	010825
57	Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"	Bucuresti		Romania	030442
58	Spitalul de Psihiatrie "Elisabeta Doamna" Galati	Galati		Romania	800179
59	Institutul de Psihiatrie Socola Iasi Site 111	Iasi		Romania	700282
60	Institutul de Psihiatrie Socola Iasi Site 113	Iasi		Romania	700282
61	Clinic of Psychiatric Diseases "Dr Laza Lazarevic"	Belgrade		Serbia	11000
62	Clinical Center of Serbia	Belgrade		Serbia	11000
63	Clinical Center Zvezdara	Belgrade		Serbia	11000
64	General Hospital Euromedic	Belgrade		Serbia	11000
65	Institute of Mental Health	Belgrade		Serbia	11000
66	Clinical Center "Dr. Dragisa Misovic"	Belgrade		Serbia	11040
67	Clinical Center Kragujevac Site 154	Kragujevac		Serbia	34000
68	Clinical Centre Kragujevac Site 158	Kragujevac		Serbia	34000
69	Clinical Center Nis Site 150	Nis		Serbia	18000
70	Clinical Center Nis Site 160	Nis		Serbia	18000
71	Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"	Novi Knezevac		Serbia	23330
72	Centrum zdravia R.B.K. s.r.o.	Bardejov		Slovakia	08501
73	Vavrusova Consulting s.r.o.	Bratislava		Slovakia	85101
74	Liptovska nemocnica s poliklinikou Liptovsky Mikulas	Liptovsky Mikulas		Slovakia	03123
75	PsychoLine s.r.o.	Rimavská Sobota		Slovakia	97901
76	Nemocnica s poliklinikou sv. Barbory, Roznava a.s.	Rožňava		Slovakia	04801
77	Crystal Comfort s.r.o.	Vranov nad Toplou		Slovakia	09301
78	CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association	Glevakha		Ukraine	08631
79	Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode	Ivano-Frankivsk		Ukraine	76014
80	Regional Psychoneurological Hospital #3	Ivano-Frankivsk		Ukraine	76014
81	SI Inst.of Neurology, Psychiatry and Narcology of NAMS of Ukraine	Kharkiv		Ukraine	61068
82	CI Kherson Reg. Psychiatric Hospital of Kherson RC	Kherson		Ukraine	73488
83	CI Odesa Regional Psychiatric Hospital # 2	Komintern		Ukraine	67513
84	CI of LRC Lviv Reg. Council Lviv Reg.Clinical Psychoneurological Dispensary	Lviv		Ukraine	79017
85	CI Odesa Regional Medical Center of Mental Health	Odesa		Ukraine	65006
86	CI Cherkasy Regional Psychiatric Hospital of ChRC	Smila		Ukraine	20708
87	Ternopil Reg. Communal Clinical Psychoneurological Hospital Depts of Psychiatry #2	Ternopil		Ukraine	46027
88	Transcarpathian Regional Narcological Dispensary	Uzhgorod		Ukraine	88000
89	CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital	Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Willie Earley, Allergan

Study Documents (Full-Text)

• Study Protocol - Feb 17, 2016
• Statistical Analysis Plan - Mar 8, 2018

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02670538
• Other Study ID Numbers: RGH-MD-53; 2016-000756-98
• First Posted: Feb 1, 2016
• Last Update Posted: Mar 12, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Depression; Bipolar Disorder; Cariprazine

Study Results

Participant Flow

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Period Title: Overall Study
STARTED	167	168	158
Safety Population : Received Study Drug	165	167	158
Intent-to-Treat Population	163	162	153
COMPLETED	135	136	128
NOT COMPLETED	32	32	30

Baseline Characteristics

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Total
Arm/Group Description	Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.	Total of all reporting groups
Overall Participants	167	168	158	493
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (11.6)	42.2 (12.0)	43.9 (11.8)	43.5 (11.8)
Sex: Female, Male (Count of Participants)
Female	99 59.3%	107 63.7%	103 65.2%	309 62.7%
Male	68 40.7%	61 36.3%	55 34.8%	184 37.3%
Race/Ethnicity, Customized (Count of Participants)
White	121 72.5%	121 72%	117 74.1%	359 72.8%
Black or African American	46 27.5%	41 24.4%	39 24.7%	126 25.6%
Asian	0 0%	3 1.8%	2 1.3%	5 1%
Multiple Races	0 0%	3 1.8%	0 0%	3 0.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	18 10.8%	22 13.1%	15 9.5%	55 11.2%
Not Hispanic or Latino	149 89.2%	146 86.9%	143 90.5%	438 88.8%
Montgomery-Åsberg Depression Rating Scale (MADRS) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	31.4 (4.5)	31.5 (4.3)	31.5 (4.8)	31.5 (4.5)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)
Description	MADRS is a 10-item, clinician-rated scale that evaluates the participants depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).
Time Frame	Baseline (Week 0) to Week 6

Outcome Measure Data

Analysis Population Description

ITT Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Measure Participants	163	162	153
Least Squares Mean (Standard Error) [score on a scale]	-12.4 (0.75)	-14.8 (0.76)	-14.1 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0417
	Comments	Adjusted p-value: adjustment was performed using matched parallel gatekeeping procedure to control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6.
	Method	Contrast t-test
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -4.6 to -0.4
	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
	Comments
Statistical Test of Hypothesis	p-Value	0.1051
	Comments	Adjusted p-value: adjustment was performed using matched parallel gatekeeping procedure to control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6.
	Method	Contrast t-test
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score
Description	CGI-S is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other patients the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill patients". A negative change from Baseline indicates improvement. MMRM with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).
Time Frame	Baseline (Week 0) to Week 6

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Measure Participants	163	162	153
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.09)	-1.5 (0.09)	-1.4 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0417
	Comments	Adjusted p-value: adjustment was performed using matched parallel gatekeeping procedure to control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6.
	Method	Contrast t-test
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	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
	Comments
Statistical Test of Hypothesis	p-Value	0.1370
	Comments	Adjusted p-value: adjustment was performed using matched parallel gatekeeping procedure to control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6.
	Method	Contrast t-test
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	First dose of study drug up to Day 50
Adverse Event Reporting Description	Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Arm/Group Title	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.		Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.		Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
All Cause Mortality
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/165 (0%)		0/167 (0%)		0/158 (0%)
Serious Adverse Events
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/165 (3%)		1/167 (0.6%)		1/158 (0.6%)
General disorders
Non-cardiac chest pain	1/165 (0.6%)		0/167 (0%)		0/158 (0%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/165 (0.6%)		0/167 (0%)		0/158 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion	0/97 (0%)		0/107 (0%)		1/103 (1%)
Psychiatric disorders
Bipolar disorder	1/165 (0.6%)		0/167 (0%)		0/158 (0%)
Depression	0/165 (0%)		1/167 (0.6%)		0/158 (0%)
Mania	1/165 (0.6%)		0/167 (0%)		0/158 (0%)
Substance abuse	1/165 (0.6%)		0/167 (0%)		0/158 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/165 (21.8%)		45/167 (26.9%)		45/158 (28.5%)
Gastrointestinal disorders
Nausea	5/165 (3%)		13/167 (7.8%)		8/158 (5.1%)
General disorders
Fatigue	2/165 (1.2%)		9/167 (5.4%)		5/158 (3.2%)
Nervous system disorders
Akathisia	3/165 (1.8%)		9/167 (5.4%)		15/158 (9.5%)
Headache	14/165 (8.5%)		14/167 (8.4%)		14/158 (8.9%)
Psychiatric disorders
Insomnia	7/165 (4.2%)		8/167 (4.8%)		11/158 (7%)
Restlessness	5/165 (3%)		4/167 (2.4%)		11/158 (7%)
Agitation	10/165 (6.1%)		3/167 (1.8%)		7/158 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.