Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02670551
• Collaborator: (none)
• Enrollment: 488
• Locations: 74
• Arms: 3
• Actual Duration (Months): 16.1
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study investigates the efficacy of a fixed-dose regimen of cariprazine 1.5 milligram (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: 488 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 17, 2016
• Actual Primary Completion Date: Jul 19, 2017
• Actual Study Completion Date: Jul 19, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

   The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-rated scale that evaluates the participant's 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.

Secondary Outcome Measures

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

   The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants 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 participants." A negative change from Baseline indicates improvement.

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 --Participant 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

• Clinical Global Impressions-Severity (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: ○ Participants with a positive cannabinoid on entry may be retested before randomization. If the participant remains positive, the participant is no longer eligible ○ Participants 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	Arkansas Psychiatric Clinic Clinical Research Trials PA	Little Rock	Arkansas	United States	72211
2	ATP Clinical Research, Inc.	Costa Mesa	California	United States	92626
3	Synergy San Diego	Escondido	California	United States	92025
4	Integrated Medical and Behavioral Associates	Glendale	California	United States	91204
5	Apostle Clinical Trials, Inc.	Long Beach	California	United States	90813
6	Pacific Research Partners, LLC	Oakland	California	United States	94612
7	Artemis Institute for Clinical Research	San Diego	California	United States	92103
8	Schuster Medical Research Institute	Sherman Oaks	California	United States	91403
9	Viking Clinical Research	Temecula	California	United States	92591
10	Pacific Clinical Research Medical Group	Upland	California	United States	91786
11	Comprehensive Psychiatric Care	Norwich	Connecticut	United States	06360
12	CNS Healthcare	Jacksonville	Florida	United States	32256
13	Clinical Neuroscience Solutions, Inc	Orlando	Florida	United States	32801
14	Olympian Clinical Research	Tampa	Florida	United States	33609
15	Radiant Research	Atlanta	Georgia	United States	30328
16	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
17	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
18	Carman Research	Smyrna	Georgia	United States	30080
19	Psychiatric Medicine Associates, L.L.C	Skokie	Illinois	United States	60076
20	Neuroscience Research Institute Inc.	Winfield	Illinois	United States	60190
21	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri	United States	63304
22	Altea Research Institute	Las Vegas	Nevada	United States	89102
23	Hassman Research Institute	Berlin	New Jersey	United States	08009
24	Neurobehavioral Research, Inc.	Cedarhurst	New York	United States	11516
25	Medical & Behavioral Health Research, PC	New York	New York	United States	10023
26	Neuro-Behavioral Clinical Research	Canton	Ohio	United States	44718
27	Patient Priority Clinical Sites	Cincinnati	Ohio	United States	45215
28	Ohio State University Department of Psychiatry	Columbus	Ohio	United States	43210
29	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
30	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
31	Sooner Clinical Research	Oklahoma City	Oklahoma	United States	73112
32	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon	United States	97214
33	Oregon Center for Clinical Investigations	Salem	Oregon	United States	97301
34	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
35	Lincoln Research, LLC	Lincoln	Rhode Island	United States	02865
36	Clinical Neuroscience Solutions	Memphis	Tennessee	United States	38119
37	Red Oak Psychiatry Associates, PA	Houston	Texas	United States	77090
38	Houston Clinical Trials, LLC	Houston	Texas	United States	77098
39	Research Across America	Plano	Texas	United States	75093
40	Family Psychiatry of The Woodlands	The Woodlands	Texas	United States	77381
41	Alliance Research Group	Richmond	Virginia	United States	23230
42	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
43	Core Clinical Research	Kirkland	Washington	United States	98033
44	Summit Research Network Seattle	Seattle	Washington	United States	98104
45	Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD	Burgas		Bulgaria	8000
46	SPH - Kardzhali, EOOD	Kardzhali		Bulgaria	6600
47	MHAT "Dr. Hristo Stambolski", EOOD	Kazanlak		Bulgaria	6100
48	State Psychiatric Hospital - Lovech	Lovech		Bulgaria	5500
49	UMHAT 'Dr. Georgi Stranski', EAD	Pleven		Bulgaria	5800
50	UMHAT "Sv. Georgi", EAD	Plovdiv		Bulgaria	4000
51	MHC - Ruse, EOOD	Ruse		Bulgaria	7003
52	MHATNP "Sv.Naum", EAD	Sofia		Bulgaria	1113
53	UMHAT "Alexandrovska" EAD	Sofia		Bulgaria	1431
54	Military Medical Academy - MHAT - Sofia	Sofia		Bulgaria	1606
55	Medical Centre "Doverie" AD	Sofia		Bulgaria	1632
56	MHAT-Targovishte, AD	Targovishte		Bulgaria	7700
57	DCC "Mladost M" - Varna, OOD	Varna		Bulgaria	9020
58	Marienthal Center of Psychiatry and Psychology	Tallinn		Estonia	10617
59	West Tallinn Central Hospital	Tallinn		Estonia	13517
60	Tartu University Hospital	Tartu		Estonia	50417
61	Romuvos klinika, UAB	Kaunas		Lithuania	44279
62	Neuromeda, JSC	Kaunas		Lithuania	50185
63	Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution	Kaunas		Lithuania	53136
64	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas		Lithuania	LT-50009
65	232Antakalnis Psychiatric Consultation Center, Public Institution	Vilnius		Lithuania	10204
66	Podlaskie Centrum Psychogeriatrii	Białystok		Poland	15-756
67	Przychodnia Srodmiescie Sp. z o. o.	Bydgoszcz		Poland	85-080
68	Uniwersyteckie Centrum Kliniczne	Gdańsk		Poland	80-214
69	Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS	Leszno		Poland	64-100
70	Clinical Best Solutions	Lublin		Poland	20-045
71	Specjalistyczna Praktyka Lekarska Marek Domański	Lublin		Poland	20-442
72	NZOZ Syntonia	Pruszcz Gdański		Poland	83-000
73	Torunskie Centrum Psychiatrii Neuromed	Toruń		Poland	87-100
74	INSPIRA Clinical Research	San Juan		Puerto Rico	00918

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Clincial Director, Forest Research Institute, Inc., an affiliate of Allergan, plc

Study Documents (Full-Text)

• Study Protocol - Feb 17, 2016
• Statistical Analysis Plan - Nov 29, 2017

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02670551
• Other Study ID Numbers: RGH-MD-54; 2016-000757-13
• First Posted: Feb 1, 2016
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

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

Study Results

Participant Flow

Pre-assignment Detail	Total 782 participants were screened for eligibility; 488 participants randomized to receive double-blind treatment; 480 participants received at least 1 dose of double-blind treatment (Safety Population) and 474 participants had at least 1 postbaseline Montgomery-Åsberg Depression Rating Scale total score assessment (Intent-to-Treat Population).

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Period Title: Overall Study
STARTED	163	160	165
Received Treatment (Safety Population)	158	157	165
COMPLETED	135	134	134
NOT COMPLETED	28	26	31

Baseline Characteristics

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg	Total
Arm/Group Description	Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.	Total of all reporting groups
Overall Participants	163	160	165	488
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	43.9	42.6	41.9	42.8
Sex: Female, Male (Count of Participants)
Female	94 57.7%	101 63.1%	94 57%	289 59.2%
Male	69 42.3%	59 36.9%	71 43%	199 40.8%
Race/Ethnicity, Customized (Count of Participants)
White	118 72.4%	126 78.8%	126 76.4%	370 75.8%
Black or African American	39 23.9%	29 18.1%	37 22.4%	105 21.5%
Asian	3 1.8%	2 1.3%	0 0%	5 1%
American Indian or Alaska Native	1 0.6%	1 0.6%	1 0.6%	3 0.6%
Native Hawaiian or Other Pacific Islander	2 1.2%	0 0%	0 0%	2 0.4%
Multiple	0 0%	2 1.3%	1 0.6%	3 0.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	13 8%	15 9.4%	14 8.5%	42 8.6%
Not Hispanic or Latino	150 92%	145 90.6%	151 91.5%	446 91.4%
Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	30.3 (4.5)	30.6 (4.2)	31.1 (4.8)	30.7 (4.5)
Clinical Global Impressions-Severity (CGI-S) Score at Baseline (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	4.5 (0.5)	4.5 (0.5)	4.5 (0.5)	4.5 (0.5)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Week 6
Description	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-rated scale that evaluates the participant's 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.
Time Frame	Baseline (Week 0) to Week 6

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Measure Participants	137	135	136
Least Squares Mean (Standard Error) [score on a scale]	-12.6 (0.76)	-15.1 (0.77)	-15.6 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments	To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0331
	Comments	MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares 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	To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0103
	Comments	MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -5.1 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6
Description	The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants 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 participants." A negative change from Baseline indicates improvement.
Time Frame	Baseline (Week 0) to Week 6

Outcome Measure Data

Analysis Population Description

ITT Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Placebo	Cariprazine 1.5 mg	Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Measure Participants	137	135	136
Least Squares Mean (Standard Error) [score on a scale]	-1.3 (0.09)	-1.6 (0.10)	-1.6 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 1.5 mg
	Comments	To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0714
	Comments	MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine 3.0 mg
	Comments	To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0662
	Comments	MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	First dose to 30 days past last dose (Up to 80 Days)
Adverse Event Reporting Description	Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Arm/Group Title	Placebo		Cariprazine 1.5 mg		Cariprazine 3.0 mg
Arm/Group Description	Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.		Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.		Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by 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	0/158 (0%)		0/157 (0%)		0/165 (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	2/158 (1.3%)		2/157 (1.3%)		2/165 (1.2%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/158 (0%)		1/157 (0.6%)		0/165 (0%)
Gastrointestinal disorders
Abdominal pain	1/158 (0.6%)		0/157 (0%)		0/165 (0%)
Infections and infestations
Chronic tonsillitis	1/158 (0.6%)		0/157 (0%)		0/165 (0%)
Psychiatric disorders
Bipolar disorder	0/158 (0%)		0/157 (0%)		1/165 (0.6%)
Suicidal ideation	0/158 (0%)		0/157 (0%)		1/165 (0.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/158 (0%)		1/157 (0.6%)		0/165 (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	43/158 (27.2%)		48/157 (30.6%)		62/165 (37.6%)
Gastrointestinal disorders
Nausea	1/158 (0.6%)		6/157 (3.8%)		15/165 (9.1%)
Dry mouth	9/158 (5.7%)		6/157 (3.8%)		3/165 (1.8%)
Nervous system disorders
Headache	13/158 (8.2%)		7/157 (4.5%)		12/165 (7.3%)
Akathisia	5/158 (3.2%)		10/157 (6.4%)		9/165 (5.5%)
Dizziness	3/158 (1.9%)		8/157 (5.1%)		6/165 (3.6%)
Somnolence	3/158 (1.9%)		8/157 (5.1%)		6/165 (3.6%)
Sedation	2/158 (1.3%)		8/157 (5.1%)		5/165 (3%)
Psychiatric disorders
Insomnia	11/158 (7%)		7/157 (4.5%)		12/165 (7.3%)
Restlessness	6/158 (3.8%)		2/157 (1.3%)		12/165 (7.3%)

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.