A Study of Cariprazine in the Prevention of Relapse of Symptoms in Participants With Schizophrenia

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01412060
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 765
• Locations: 73
• Arms: 3
• Actual Duration (Months): 35.2
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the efficacy and safety of cariprazine relative to placebo in the prevention of relapse of symptoms in participants with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Placebo; Drug: Cariprazine	Phase 3

Detailed Description

There were 3 periods (phases) in the study. The Open-label Phase lasted 20 weeks. In the first 6 weeks, participants received 3, 6, or 9 mg cariprazine orally once a day; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this Open-label Phase. At the end of Week 8, participants had to meet the following criteria to continue in the study.

• Positive and Negative Syndrome Scale (PANSS) total score ≤ 60 at the end of Week 8

• At least 20% decrease in PANSS total score from baseline to the end of Week 8

• Clinical Global Impressions - Severity (CGI-S) score ≤ 4 at the end of Week 8

• Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 8

• Stable dose during the previous 2 weeks

• No significant tolerability issues as judged by the Investigator at the end of Week 8

At the end of the Open-label Phase, participants were randomized into 2 treatment groups, cariprazine or placebo, if they met the following criteria:

• PANSS total score ≤ 60 at the end of Week 20

• At least 20% decrease in PANSS total score from baseline to the end of Week 20

• CGI-S score ≤ 4 at the end of Week 20

• Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 20

• No significant tolerability issues as judged by the Investigator During this Double-blind Treatment Phase, participants received either placebo or cariprazine at the same dosage (3, 6, or 9 mg) that they received during the last 14 weeks of the Open-label Phase.

All participants entered the 4 week Safety Follow-up Phase. They received a treatment other than the investigational product at the discretion of the Investigator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 765 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: There was no masking in the Open-Label Phase. There was masking in the Double-Blind Phase
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Cariprazine (RGH-188) in the Prevention of Relapse in Patients With Schizophrenia
• Actual Study Start Date: Sep 27, 2011
• Actual Primary Completion Date: Sep 3, 2014
• Actual Study Completion Date: Sep 3, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine - Open-label Phase Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase.	Drug: Cariprazine; Cariprazine was supplied as 1.5 mg capsules (batch numbers BN0009242 and BN00018595) and 3 mg capsules.; Other Names: RGH-188
Experimental: Placebo - Double-blind Treatment Phase Participants received placebo orally once a day for 26 to 72 weeks.	Drug: Placebo; Placebo was supplied in capsules.
Experimental: Cariprazine - Double-blind Treatment Phase Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks	Drug: Cariprazine; Cariprazine was supplied as 1.5 mg capsules (batch numbers BN0009242 and BN00018595) and 3 mg capsules.; Other Names: RGH-188

Outcome Measures

Primary Outcome Measures

1. Time From Baseline to the First Symptom Relapse During the Double-blind Phase [Up to 34 Weeks and Bi-Weekly thereafter until Week 92]

   Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored <50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of >4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion. PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant's illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants who have provided informed consent prior to any study specific procedures.

• Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for schizophrenia.

• Participants with normal physical examination, laboratory, vital signs, and/or electrocardiogram (ECG).

• Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening).

• Positive and Negative Syndrome Scale (PANSS) total score ≥ to 70 and ≤ 120 at Visit 1 (Screening) and Visit 2 (beginning of Run-in Phase).

• Negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test (applies to female participants of childbearing potential only).

• Body mass index between 18 and 40 kg/m^2, inclusive.

Exclusion Criteria:

• Participants currently meeting DSM-IV-TR criteria for schizoaffective disorder, schizophreniform disorder, bipolar I and II and known or suspected borderline or antisocial personality disorder. or other DSM-IV-TR axis II disorders.

• Participants in their first episode of psychosis.

• Treatment-resistant schizophrenia over the last 2 years.

• Positive result from the blood alcohol test or from the urine drug screen for any prohibited medication.

• At imminent risk of injuring self or others or causing significant damage to property.

• Suicide risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 011	Little Rock	Arkansas	United States	72211
2	Forest Investigative Site 018	Cerritos	California	United States	90703
3	Forest Investigative Site 007	Costa Mesa	California	United States	92626
4	Forest Investigative Site 026	Culver City	California	United States	90230
5	Forest Investigative Site 008	Long Beach	California	United States	90813
6	Forest Investigative Site 002	Oceanside	California	United States	92056
7	Forest Investigative Site 019	Orange	California	United States	92868
8	Forest Investigative Site 001	Paramount	California	United States	90723
9	Forest Investigative Site 020	San Diego	California	United States	92123
10	Forest Investigative Site 005	Washington	District of Columbia	United States	20016
11	Forest Investigative Site 024	Leesburg	Florida	United States	34748
12	Forest Investigative Site 017	Atlanta	Georgia	United States	30331
13	Forest Investigative Site 021	Chicago	Illinois	United States	60640
14	Forest Investigative Site 023	Baltimore	Maryland	United States	21202
15	Forest Investigative Site 010	Rockville	Maryland	United States	20850
16	Forest Investigative Site 003	Flowood	Mississippi	United States	39232
17	Forest Investigative Site 006	Creve Coeur	Missouri	United States	63141
18	Forest Investigative Site 014	Saint Louis	Missouri	United States	63141
19	Forest Investigative Site 012	Cedarhurst	New York	United States	11516
20	Forest Investigative Site 022	Dayton	Ohio	United States	45417
21	Forest Investigative Site 015	Austin	Texas	United States	78731
22	Forest Investigative Site 027	Austin	Texas	United States	78754
23	Forest Investigative Site 025	Dallas	Texas	United States	75231
24	Forest Investigative Site 013	Houston	Texas	United States	77008
25	Forest Investigative Site 009	Houston	Texas	United States	77021
26	Forest Investigative Site 305	Vijayawada	Andhra Pradesh	India	520002
27	Forest Investigative Site 303	Ahmedabad	Gujarat	India	380006
28	Forest Investigative Site 308	Ahmedabad	Gujarat	India	380006
29	Forest Investigative Site 310	Ahmedabad	Gujarat	India	380015
30	Forest Investigative Site 313	Mangalore	Karnataka	India	575018
31	Forest Investigative Site 314	Manipal	Karnataka	India	576104
32	Forest Investigative Site 301	Aurangabad	Maharashtra	India	431005
33	Forest Investigative Site 306	Kalyan	Maharashtra	India	421301
34	Forest Investigative Site 311	Nashik	Maharashtra	India	422101
35	Forest Investigative Site 317	Jaipur	Rajasthan	India	302021
36	Forest Investigative Site 302	Jaipur	Rajasthan	India	303706
37	Forest Investigative Site 312	Madurai	Tamilnadu	India	625020
38	Forest Investigative Site 309	Kanpur	Uttar Pradesh	India	208005
39	Forest Investigative Site 304	Lucknow	Uttar Pradesh	India	226003
40	Forest Investigative Site 307	Varanasi	Uttar Pradesh	India	221005
41	Forest Investigative Site 403	Bucuresti		Romania	041914
42	Forest Investigative Site 405	Bucuresti		Romania	041914
43	Forest Investigative Site 406	Bucuresti		Romania	041914
44	Forest Investigative Site 408	Bucuresti		Romania	041914
45	Forest Investigative Site 410	Bucuresti		Romania	041914
46	Forest Investigative Site 407	Campulung		Romania	115100
47	Forest Investigative Site 412	Campulung		Romania	115100
48	Forest Investigative Site 402	Constanta		Romania	900002
49	Forest Investigative Site 411	Focsani		Romania	620165
50	Forest Investigative Site 401	Iasi		Romania	700282
51	Forest Investigative Site 409	Iasi		Romania	700282
52	Forest Investigative Site 404	Targoviste		Romania	130086
53	Forest Investigative Site 508	Bratislava		Slovakia	81369
54	Forest Investigative Site 507	Bratislava		Slovakia	82606
55	Forest Investigative Site 504	Liptovsky Mikulas		Slovakia	03125
56	Forest Investigative Site 505	Rimavska Sobota		Slovakia	97912
57	Forest Investigative Site 503	Roznava		Slovakia	04801
58	Forest Investigative Site 506	Trnava		Slovakia	91701
59	Forest Investigative Site 609	Kerch	AR Crimea	Ukraine	98310
60	Forest Investigative Site 610	Dnipropetrovsk		Ukraine	49115
61	Forest Investigative Site 613	Donetsk		Ukraine	83008
62	Forest Investigative Site 616	Ivano-Frankivsk		Ukraine	76014
63	Forest Investigative Site 605	Kharkiv		Ukraine	61068
64	Forest Investigative Site 606	Kharkiv		Ukraine	61068
65	Forest Investigative Site 604	Kharkiv		Ukraine	61103
66	Forest Investigative Site 607	Kherson		Ukraine	73488
67	Forest Investigative Site 602	Kyiv		Ukraine	02660
68	Forest Investigative Site 601	Kyiv		Ukraine	04080
69	Forest Investigative Site 612	Kyiv		Ukraine	04080
70	Forest Investigative Site 603	Lviv		Ukraine	79021
71	Forest Investigative Site 615	Odesa		Ukraine	65014
72	Forest Investigative Site 611	Simferopol		Ukraine	95006
73	Forest Investigative Site 608	Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Willie Earley, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01412060
• Other Study ID Numbers: RGH-MD-06; 2011-002048-29
• First Posted: Aug 8, 2011
• Last Update Posted: Jul 6, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Forest Laboratories: Schizophrenia; Schizophrenic disorder
• Additional relevant MeSH terms: Schizophrenia; Cariprazine

Study Results

Participant Flow

Pre-assignment Detail	A total of 765 participants were enrolled and received cariprazine in Run-in Phase; 751 of these, had at least 1 postbaseline Positive and Negative Syndrome Scale (PANSS) evaluation and 364 entered Stabilization Phase. Only 200 participants who completed Open-label phase, received either placebo (n=99) or cariprazine (n=101) in Double-Blind Phase.

Arm/Group Title	Cariprazine - Open-label Phase	Placebo - Double-blind Treatment Phase	Cariprazine - Double-blind Treatment Phase
Arm/Group Description	Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase.	Participants received placebo orally once a day for 26 to 72 weeks.	Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks.
Period Title: Open-label Run-in Period (RIP)
STARTED	765	0	0
COMPLETED	418	0	0
NOT COMPLETED	347	0	0
Period Title: Open-label Run-in Period (RIP)
STARTED	418	0	0
COMPLETED	364	0	0
NOT COMPLETED	54	0	0
Period Title: Open-label Run-in Period (RIP)
STARTED	364	0	0
COMPLETED	264	0	0
NOT COMPLETED	100	0	0
Period Title: Open-label Run-in Period (RIP)
STARTED	264	0	0
COMPLETED	200	0	0
NOT COMPLETED	64	0	0
Period Title: Open-label Run-in Period (RIP)
STARTED	0	99	101
COMPLETED	0	16	18
NOT COMPLETED	0	83	83

Baseline Characteristics

Arm/Group Title	Cariprazine - Open-label Phase
Arm/Group Description	Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase.
Overall Participants	765
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.4 (10.4)
Sex: Female, Male (Count of Participants)
Female	221 28.9%
Male	544 71.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	37 4.8%
Not Hispanic or Latino	728 95.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	149 19.5%
Native Hawaiian or Other Pacific Islander	1 0.1%
Black or African American	313 40.9%
White	299 39.1%
More than one race	3 0.4%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.07 (20.10)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.98 (9.95)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.50 (5.63)
Waist circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	90.39 (15.34)

Outcome Measures

1. Primary Outcome

Title	Time From Baseline to the First Symptom Relapse During the Double-blind Phase
Description	Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored <50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of >4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion. PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant's illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported.
Time Frame	Up to 34 Weeks and Bi-Weekly thereafter until Week 92

Outcome Measure Data

Analysis Population Description

Double-blind intent-to-treat population: All participants who received at least 1 dose of double-blind investigational product and who had at least 1 post-randomization assessment of PANSS or CGI-S during the Double-blind Treatment Phase.

Arm/Group Title	Placebo	Cariprazine
Arm/Group Description	Participants received placebo orally once a day for 26 to 72 weeks. Placebo: Placebo was supplied in capsules.	Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks. Cariprazine: Cariprazine was supplied in capsules.
Measure Participants	99	101
Number (95% Confidence Interval) [Days]	92	224

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio (cariprazine 3-9 mg vs placebo) is based on Cox proportional hazards regression model, with treatment group as an explanatory variable.

Adverse Events

Time Frame	First dose until 30 days after last dose of investigational product [Open-Label (Up to 184 days) and Double-Blind (Up to 536 days)]
Adverse Event Reporting Description	Run-in Phase Safety Population: All randomized participants who received at least 1 dose of investigational product and who had at least 1 post-randomization assessment of PANSS or CGI-S during the open-label phase (OLP) of the study. Double-blind Safety Population: All participants in the Randomized Population who took at least 1 dose of double-blind investigational product. Adverse events data was reported in periods as per the treatment received.
Arm/Group Title	Cariprazine - Open-label Phase		Placebo - Double-blind Treatment Phase		Cariprazine - Double-blind Treatment Phase		Open-label - Safety Follow-up Phase		Placebo - Safety Follow-up Phase		Cariprazine - Safety Follow-up Phase
Arm/Group Description	Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase.		Participants received placebo orally once a day for 26 to 72 weeks.		Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks.		Participants received no treatment during the 4 weeks Safety Follow-up Phase.		Participants received no treatment during the 4 weeks Safety Follow-up Phase.		Participants received no treatment during the 4 weeks Safety Follow-up Phase.
All Cause Mortality
	Cariprazine - Open-label Phase		Placebo - Double-blind Treatment Phase		Cariprazine - Double-blind Treatment Phase		Open-label - Safety Follow-up Phase		Placebo - Safety Follow-up Phase		Cariprazine - Safety Follow-up Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/765 (0%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Serious Adverse Events
	Cariprazine - Open-label Phase		Placebo - Double-blind Treatment Phase		Cariprazine - Double-blind Treatment Phase		Open-label - Safety Follow-up Phase		Placebo - Safety Follow-up Phase		Cariprazine - Safety Follow-up Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/765 (6.5%)		14/99 (14.1%)		14/101 (13.9%)		6/765 (0.8%)		2/99 (2%)		0/101 (0%)
Cardiac disorders
Atrial fibrillation	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Sinus tachycardia	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Tachycardia paroxysmal	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Ear and labyrinth disorders
Middle ear effusion	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Gastrointestinal disorders
Haematemesis	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
General disorders
Pyrexia	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Drug ineffective	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Immune system disorders
Hypersensitivity	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Infections and infestations
Pneumonia	1/765 (0.1%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Otitis media acute	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Injury, poisoning and procedural complications
Foreign body	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Overdose	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Ankle fracture	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Fall	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Multiple injuries	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Road traffic accident	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Investigations
Psychiatric evaluation	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Rhabdomyolysis	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Pain in extremity	0/765 (0%)		0/99 (0%)		1/101 (1%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Nervous system disorders
Convulsion	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		1/765 (0.1%)		0/99 (0%)		0/101 (0%)
Extrapyramidal disorder	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Generalised tonic-clonic seizure	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Ischaemic stroke	0/765 (0%)		1/99 (1%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Psychiatric disorders
Schizophrenia	19/765 (2.5%)		7/99 (7.1%)		5/101 (5%)		3/765 (0.4%)		0/99 (0%)		0/101 (0%)
Psychotic disorder	10/765 (1.3%)		2/99 (2%)		2/101 (2%)		3/765 (0.4%)		1/99 (1%)		0/101 (0%)
Suicidal ideation	5/765 (0.7%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Schizophrenia, paranoid type	3/765 (0.4%)		0/99 (0%)		2/101 (2%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Drug abuse	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Insomnia	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Psychotic behaviour	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Restlessness	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Suicide attempt	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/765 (0%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		1/99 (1%)		0/101 (0%)
Social circumstances
Social stay hospitalisation	2/765 (0.3%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Victim of crime	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Surgical and medical procedures
Intentional product misuse	1/765 (0.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Other (Not Including Serious) Adverse Events
	Cariprazine - Open-label Phase		Placebo - Double-blind Treatment Phase		Cariprazine - Double-blind Treatment Phase		Open-label - Safety Follow-up Phase		Placebo - Safety Follow-up Phase		Cariprazine - Safety Follow-up Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	425/765 (55.6%)		28/99 (28.3%)		35/101 (34.7%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Gastrointestinal disorders
Constipation	39/765 (5.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Dyspepsia	46/765 (6%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Nausea	48/765 (6.3%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Diarrhoea	0/765 (0%)		5/99 (5.1%)		4/101 (4%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Infections and infestations
Nasopharyngitis	0/765 (0%)		5/99 (5.1%)		8/101 (7.9%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Investigations
Weight increased	49/765 (6.4%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Nervous system disorders
Akathisia	148/765 (19.3%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Extrapyramidal disorder	55/765 (7.2%)		3/99 (3%)		6/101 (5.9%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Headache	92/765 (12%)		7/99 (7.1%)		8/101 (7.9%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Tremor	0/765 (0%)		0/99 (0%)		8/101 (7.9%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Psychiatric disorders
Anxiety	39/765 (5.1%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Insomnia	110/765 (14.4%)		8/99 (8.1%)		8/101 (7.9%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Restlessness	70/765 (9.2%)		0/99 (0%)		0/101 (0%)		0/765 (0%)		0/99 (0%)		0/101 (0%)
Schizophrenia	0/765 (0%)		6/99 (6.1%)		4/101 (4%)		0/765 (0%)		0/99 (0%)		0/101 (0%)

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.