Long-term Study of Cariprazine in Patients With Schizophrenia

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01104792
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 752
• Locations: 86
• Arm: 1
• Actual Duration (Months): 32.1
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the long-term safety, tolerability, and pharmacokinetics of cariprazine in patients with schizophrenia.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 752 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Long-term Safety, Tolerability, and Pharmacokinetics of Cariprazine in Patients With Schizophrenia
• Actual Study Start Date: May 31, 2010
• Actual Primary Completion Date: Jan 31, 2013
• Actual Study Completion Date: Jan 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.	Drug: Cariprazine; Cariprazine was supplied in capsules.; Other Names: RGH-188

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 48 in the PANSS Total Score [Baseline to Week 48]

   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 48 in the CGI-S Score [Baseline to Week 48]

   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:

• Patients and corresponding caregivers who have provided informed consents prior to any study specific procedures.

• Patients currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia (paranoid type, disorganized type, catatonic type, or undifferentiated type), as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID).

• Patients with normal physical examination, laboratory, vital signs, and electrocardiogram (ECG).

Exclusion Criteria:

• Patients with a DSM-IV-TR diagnosis of schizoaffective disorder, schizophreniform disorder, bipolar I or bipolar II disorder, or psychotic disorders other than schizophrenia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 072	Little Rock	Arkansas	United States	72201
2	Forest Investigative Site 021	Little Rock	Arkansas	United States	72211
3	Forest Investigative Site 086	Little Rock	Arkansas	United States	72211
4	Forest Investigative Site 014	Springdale	Arkansas	United States	72764
5	Forest Investigative Site 080	Carson	California	United States	90746
6	Forest Investigative Site 079	Cerritos	California	United States	90703
7	Forest Investigative Site 048	Costa Mesa	California	United States	92626
8	Forest Investigative Site 070	Costa Mesa	California	United States	92626
9	Forest Investigative Site 022	Garden Grove	California	United States	92845
10	Forest Investigative Site 083	Garden Grove	California	United States	92845
11	Forest Investigative Site 050	Long Beach	California	United States	90813
12	Forest Investigative Site 006	Oceanside	California	United States	92056
13	Forest Investigative Site 003	Riverside	California	United States	92506
14	Forest Investigative Site 016	San Diego	California	United States	92123
15	Forest Investigative Site 073	Santa Ana	California	United States	92701
16	Forest Investigative Site 071	New Britain	Connecticut	United States	06050
17	Forest Investigative Site 002	Bradenton	Florida	United States	34208
18	Forest Investigative Site 041	Kissimmee	Florida	United States	34741
19	Forest Investigative Site 082	North Miami	Florida	United States	33161
20	Forest Investigative Site 055	Atlanta	Georgia	United States	30308
21	Forest Investigative Site 087	Atlanta	Georgia	United States	30308
22	Forest Investigative Site 012	Honolulu	Hawaii	United States	96813
23	Forest Investigative Site 018	Chicago	Illinois	United States	60640
24	Forest Investigative Site 008	Hoffman Estates	Illinois	United States	60169
25	Forest Investigative Site 044	Rockville	Maryland	United States	20850
26	Forest Investigative Site 007	Flowood	Mississippi	United States	39232
27	Forest Investigative Site 017	Creve Coeur	Missouri	United States	63141
28	Forest Investigative Site 076	Saint Charles	Missouri	United States	63301
29	Forest Investigative Site 045	Saint Louis	Missouri	United States	63118
30	Forest Investigative Site 052	Las Vegas	Nevada	United States	89102
31	Forest Investigative Site 004	Willingboro	New Jersey	United States	08046
32	Forest Investigative Site 040	Cedarhurst	New York	United States	11516
33	Forest Investigative Site 019	Willoughby	Ohio	United States	44094
34	Forest Investigative Site 077	Philadelphia	Pennsylvania	United States	19131
35	Forest Investigative Site 047	Philadelphia	Pennsylvania	United States	19139
36	Forest Investigative Site 074	Austin	Texas	United States	78756
37	Forest Investigative Site 084	DeSoto	Texas	United States	75115
38	Forest Investigative Site 043	Irving	Texas	United States	75062
39	Forest Investigative Site 078	Bellevue	Washington	United States	98007
40	Forest Investigative Site 601	Bello	Antioquia	Colombia	051053
41	Forest Investigative Site 604	Pereira	Risaralda	Colombia	660003
42	Forest Investigative Site 602	Bogota		Colombia	110121
43	Forest Investigative Site 605	Bogota		Colombia	111166
44	Forest Investigative Site 503	Ahmedabad		India	380006
45	Forest Investigative Site 519	Ahmedabad		India	380006
46	Forest Investigative Site 501	Ahmedabad		India	380013
47	Forest Investigative Site 500	Aurangabad		India	431005
48	Forest Investigative Site 507	Kanpur		India	208005
49	Forest Investigative Site 518	Lucknow		India	226006
50	Forest Investigative Site 517	Mangalore		India	575001
51	Forest Investigative Site 515	Mangalore		India	575018
52	Forest Investigative Site 510	Mumbai		India	400026
53	Forest Investigative Site 513	Nashik		India	422101
54	Forest Investigative Site 509	Rajkot		India	360002
55	Forest Investigative Site 506	Varanasi		India	201010
56	Forest Investigative Site 505	Vijaywada		India	520002
57	Forest Investigative Site 306	Bucuresti		Romania	41914
58	Forest Investigative Site 301	Cluj-Napoca		Romania	400012
59	Forest Investigative Site 300	Craiova		Romania	200620
60	Forest Investigative Site 311	Craiova		Romania	200745
61	Forest Investigative Site 303	Targoviste		Romania	130086
62	Forest Investigative Site 304	Targu Mures		Romania	540142
63	Forest Investigative Site 102	Arkhangelsk		Russian Federation	163530
64	Forest Investigative Site 103	Chelyabinsk		Russian Federation	454087
65	Forest Investigative Site 104	Chita		Russian Federation	672090
66	Forest Investigative Site 110	Saratov		Russian Federation	410028
67	Forest Investigative Site 108	Saratov		Russian Federation	410060
68	Forest Investigative Site 112	St. Petersburg		Russian Federation	190121
69	Forest Investigative Site 105	St. Petersburg		Russian Federation	192019
70	Forest Investigative Site 106	St. Petersburg		Russian Federation	192019
71	Forest Investigative Site 113	St. Petersburg		Russian Federation	192019
72	Forest Investigative Site 107	St. Petersburg		Russian Federation	193167
73	Forest Investigative Site 109	St. Petersburg		Russian Federation	197341
74	Forest Investigative Site 100	Tomsk		Russian Federation	634014
75	Forest Investigative Site 211	Glevakha	Kyiv Region	Ukraine	08631
76	Forest Investigative Site 206	Kherson	Stepanivka	Ukraine	73488
77	Forest Investigative Site 208	Dnipropetrovsk		Ukraine	49005
78	Forest Investigative Site 205	Dnipropetrovsk		Ukraine	49027
79	Forest Investigative Site 200	Donetsk		Ukraine	83008
80	Forest Investigative Site 204	Kharkiv		Ukraine	61068
81	Forest Investigative Site 203	Kharkov		Ukraine	61068
82	Forest Investigative Site 201	Kyiv		Ukraine	04080
83	Forest Investigative Site 202	Lviv		Ukraine	79021
84	Forest Investigative Site 209	Poltava		Ukraine	36006
85	Forest Investigative Site 210	Simferopol		Ukraine	95006
86	Forest Investigative Site 207	Vinnytsya		Ukraine	21005

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Raffaele Migliore, MA, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01104792
• Other Study ID Numbers: RGH-MD-11
• First Posted: Apr 15, 2010
• Last Update Posted: Jul 26, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Forest Laboratories: Schizophrenia; Acute schizophrenia; Psychotropic drugs; Antipsychotic agents; Mental disorders; Dopamine agents; Central nervous system agents
• Additional relevant MeSH terms: Schizophrenia; Cariprazine

Study Results

Participant Flow

Pre-assignment Detail	The flexible-dose design for this study was selected to examine the relative safety and tolerability of a range of dosages of cariprazine. The starting dose of 1.5 mg/day was titrated as needed within the range of 3.0 - 9.0 mg/day based on the Investigator's judgment of response and tolerability.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.
Period Title: Overall Study
STARTED	752
COMPLETED	226
NOT COMPLETED	526

Baseline Characteristics

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.
Overall Participants	586
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.1 (10.8)
Sex: Female, Male (Count of Participants)
Female	178 30.4%
Male	408 69.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	48 8.2%
Not Hispanic or Latino	523 89.2%
Unknown or Not Reported	15 2.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%
Asian	68 11.6%
Native Hawaiian or Other Pacific Islander	3 0.5%
Black or African American	229 39.1%
White	250 42.7%
More than one race	0 0%
Unknown or Not Reported	35 6%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	79.94 (20.26)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.10 (5.80)
Waist circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	91.76 (15.85)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 48 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 48

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All participants who took at least 1 dose of cariprazine and who had at least 1 post-baseline efficacy assessment. Only participants with data at both Baseline and Week 48 were included in the analysis.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.
Measure Participants	572
Baseline	66.5 (12.1)
Change From Baseline	-5.0 (14.0)

2. Secondary Outcome

Title	Change From Baseline to Week 48 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 48

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All participants who took at least 1 dose of cariprazine and who had at least 1 post-baseline efficacy assessment.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.
Measure Participants	578
Baseline	3.0 (0.4)
Change From Baseline	-0.1 (0.8)

Adverse Events

Time Frame	52 weeks
Adverse Event Reporting Description	The flexible-dose design for this study was selected to examine the relative safety and tolerability of a range of dosages of cariprazine. The starting dose of 1.5 mg/day was titrated as needed within the range of 3.0 - 9.0 mg/day based on the Investigator's judgment of response and tolerability. Safety population: All enrolled participants who took at least 1 dose of cariprazine.
Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 3.0, 4.5, 6.0, or 9.0 mg orally once a day for 48 weeks.
All Cause Mortality
	Cariprazine
	Affected / at Risk (%)	# Events
Total	0/586 (0%)
Serious Adverse Events
	Cariprazine
	Affected / at Risk (%)	# Events
Total	59/586 (10.1%)
Blood and lymphatic system disorders
Autoimmune thrombocytopenia	1/586 (0.2%)
Cardiac disorders
Acute myocardial infarction	1/586 (0.2%)
Sick sinus syndrome	1/586 (0.2%)
General disorders
Medical device pain	1/586 (0.2%)
Non-cardiac chest pain	1/586 (0.2%)
Infections and infestations
Cellulitis	2/586 (0.3%)
Appendicitis	1/586 (0.2%)
Tracheobronchitis	1/586 (0.2%)
Injury, poisoning and procedural complications
Comminuted fracture	1/586 (0.2%)
Fall	1/586 (0.2%)
Foot fracture	1/586 (0.2%)
Gun shot wound	1/586 (0.2%)
Muscle injury	1/586 (0.2%)
Road traffic accident	1/586 (0.2%)
Investigations
Blood creatine phosphokinase increased	1/586 (0.2%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/586 (0.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/586 (0.2%)
Nervous system disorders
Brain injury	1/586 (0.2%)
Hypoglycaemic unconsciousness	1/586 (0.2%)
Psychomotor hyperactivity	1/586 (0.2%)
Psychiatric disorders
Schizophrenia	25/586 (4.3%)
Psychotic disorder	12/586 (2%)
Suicidal ideation	4/586 (0.7%)
Depression	2/586 (0.3%)
Hallucination, auditory	2/586 (0.3%)
Schizophrenia, paranoid type	2/586 (0.3%)
Aggression	1/586 (0.2%)
Agitation	1/586 (0.2%)
Homicidal ideation	1/586 (0.2%)
Paranoia	1/586 (0.2%)
Psychotic behaviour	1/586 (0.2%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/178 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/586 (0.2%)
Social circumstances
Social stay hospitalisation	6/586 (1%)
Surgical and medical procedures
Hospitalisation	1/586 (0.2%)
Other (Not Including Serious) Adverse Events
	Cariprazine
	Affected / at Risk (%)	# Events
Total	419/586 (71.5%)
Gastrointestinal disorders
Nausea	51/586 (8.7%)
Dyspepsia	42/586 (7.2%)
Constipation	33/586 (5.6%)
Toothache	31/586 (5.3%)
Diarrhoea	30/586 (5.1%)
Infections and infestations
Nasopharyngitis	30/586 (5.1%)
Investigations
Weight increased	79/586 (13.5%)
Blood creatine phosphokinase increased	35/586 (6%)
Nervous system disorders
Akathisia	118/586 (20.1%)
Headache	104/586 (17.7%)
Extrapyramidal disorder	47/586 (8%)
Tremor	46/586 (7.8%)
Dizziness	32/586 (5.5%)
Psychiatric disorders
Insomnia	104/586 (17.7%)
Anxiety	68/586 (11.6%)
Restlessness	49/586 (8.4%)

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.