A Study of Cariprazine in Patients With Chronic Stable Schizophrenia

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00839852
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 97
• Locations: 65
• Arm: 1
• Actual Duration (Months): 15
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an outpatient study 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 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-term, Open-label Extension Study of the Safety and Tolerability of RGH-188 (Cariprazine) in Patients With Schizophrenia
• Actual Study Start Date: May 31, 2009
• Actual Primary Completion Date: Aug 31, 2010
• Actual Study Completion Date: Aug 31, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine 1.5mg Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability	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 61 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have completed the double-blind treatment period of the lead-in study RGH-MD-16 (NCT 00694707)

• Patients who have responded to double-blind treatment in the lead-in study as defined as ≥ 20% reduction relative to Visit 2 (Baseline) of the Positive and Negative Syndrome Scale (PANSS) total score and a Clinical Global Impressions-Severity (CGI-S) score of ≤ 3.

• Patients eligible to continue as outpatients based on the opinion of the Principal Investigator.

• Patients must have a caregiver to ensure treatment compliance.

Exclusion Criteria:

• Patients with clinically significant abnormalities on physical examination, laboratory, vital signs, and/or electrocardiogram (ECG).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site	Costa Mesa	California	United States	92626
2	Forest Investigative Site	Long Beach	California	United States	90813
3	Forest Investigative Site	Oceanside	California	United States	92056
4	Forest Investigative Site	Paramount	California	United States	90723
5	Forest Investigative Site	Riverside	California	United States	92506
6	Forest Investigative Site	Washington	District of Columbia	United States	20016
7	Forest Investigative Site	Bradenton	Florida	United States	34208
8	Forest Investigative Site	Kissimmee	Florida	United States	34741
9	Forest Investigative Site	Lake Charles	Louisiana	United States	70601
10	Forest Investigative Site	Baltimore	Maryland	United States	21202
11	Forest Investigative Site	Flowood	Mississippi	United States	39232
12	Forest Investigative Site	Creve Coeur	Missouri	United States	63141
13	Forest Investigative Site	Cincinnati	Ohio	United States	45267
14	Forest Investigative Site	Charleston	South Carolina	United States	29405
15	Forest Investigative Site	Memphis	Tennessee	United States	38119
16	Forest Investigative Site	Houston	Texas	United States	77008
17	Forest Investigative Site	Irving	Texas	United States	75062
18	Forest Investigative Site	Vijaywada	Andh Prad	India	520002
19	Forest Investigative Site	Visakhapatnam	Andh Prad	India	530017
20	Forest Investigative Site	Ahmedabad	Gujarat	India	380013
21	Forest Investigative Site	Ahmedabad	Gujarat	India	380015
22	Forest Investigative Site	Bangalore	Karna	India	560010
23	Forest Investigative Site	Bangalore	Karna	India	560027
24	Forest Investigative Site	Mangalore	Karna	India	574160
25	Forest Investigative Site	Mangalore	Karna	India	575001
26	Forest Investigative Site	Manipal	Karna	India	576104
27	Forest Investigative Site	Mysore	Karna	India	570004
28	Forest Investigative Site	Pune	Mahara	India	411004
29	Forest Investigative Site	Jaipur	Rajasthan	India	302021
30	Forest Investigative Site	Chennai	Tamilnadu	India	600003
31	Forest Investigative Site	Chennai	Tamilnadu	India	600101
32	Forest Investigative Site	Tirupati	Tamilnadu	India	517507
33	Forest Investigative Site	Kanpur	Uttar Prad	India	208005
34	Forest Investigative Site	Johor Bahru		Malaysia	80100
35	Forest Investigative Site	Kuala Lumpur		Malaysia	59100
36	Forest Investigative Site	Perak		Malaysia	30990
37	Forest Investigative Site	Arkhangelsk		Russian Federation	163060
38	Forest Investigative Site	Gatchina		Russian Federation	188357
39	Forest Investigative Site	Ivanovo		Russian Federation	153462
40	Forest Investigative Site	Kazan		Russian Federation	420012
41	Forest Investigative Site	Krasnodar		Russian Federation	350007
42	Forest Investigative Site 204	Moscow		Russian Federation	115522
43	Forest Investigative Site 206	Moscow		Russian Federation	115522
44	Forest Investigative Site	Moscow		Russian Federation	117152
45	Forest Investigative Site	Nizhniy Novgorod		Russian Federation	603155
46	Forest Investigative Site	Samara		Russian Federation	443016
47	Forest Investigative Site 214	St. Petersburg		Russian Federation	190005
48	Forest Investigative Site 217	St. Petersburg		Russian Federation	190005
49	Forest Investigative Site	St. Petersburg		Russian Federation	190121
50	Forest Investigative Site	St. Petersburg		Russian Federation	191119
51	Forest Investigative Site 202	St. Petersburg		Russian Federation	193019
52	Forest Investigative Site 203	St. Petersburg		Russian Federation	193019
53	Forest Investigative Site	St. Petersburg		Russian Federation	193167
54	Forest Investigative Site	St. Petersburg		Russian Federation	197341
55	Forest Investigative Site	Kherson	Vil. Stepanivka	Ukraine	73488
56	Forest Investigative Site	Chernigov		Ukraine	14000
57	Forest Investigative Site	Dnipropetrovsk		Ukraine	49616
58	Forest Investigative Site	Donetsk		Ukraine	83037
59	Forest Investigative Site	Glevakha		Ukraine	8630
60	Forest Investivative Site	Kharkiv		Ukraine	61068
61	Forest Investigative Site	Kiev		Ukraine	2660
62	Forest Investigative Site	Kyiv		Ukraine	4080
63	Forest Investigative Site	Kyiv		Ukraine	4655
64	Forest Investigative Site	Odessa		Ukraine	65006
65	Forest Investigative Site	Ternopil		Ukraine	46020

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Suresh Durgam, MD, Forest Research Institute, a subsidiary of Forest Laboratories, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00839852
• Other Study ID Numbers: RGH-MD-17
• First Posted: Feb 10, 2009
• Last Update Posted: Aug 22, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Schizophrenia; Cariprazine

Study Results

Participant Flow

Recruitment Details	The Enrolled Population consisted of 97 participants who completed the lead-in study, RGH-MD-16, and signed an informed consent form to continue in this extension study. The Safety Population consisted of 93 participants from the Enrolled Population who took at least 1 dose of cariprazine in this extension study.
Pre-assignment Detail	The study was designed as a one-arm study where patients were not randomized or analyzed by dose, rather they were flexibly dosed with Cariprazine 1.5, 3.0, or 4.5 mg/day via oral administration. The starting dose of 1.5 mg/day was titrated as needed within the range of 1.5-4.5 mg/d based on investigator's judgment of response and tolerability.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability
Period Title: Overall Study
STARTED	93
COMPLETED	46
NOT COMPLETED	47

Baseline Characteristics

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability
Overall Participants	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.4 (10.1)
Sex: Female, Male (Count of Participants)
Female	30 32.3%
Male	63 67.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 5.4%
Not Hispanic or Latino	88 94.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	30 32.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	11 11.8%
White	52 55.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	72.19 (17.66)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169.09 (10.73)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.99 (4.46)
Waist circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	84.90 (11.19)

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 assessment of the PANSS total score.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability
Measure Participants	92
Mean (Standard Error) [Units on a scale]	-38.5 (1.5)

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 assessment of the PANSS total score.

Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability
Measure Participants	92
Mean (Standard Error) [Units on a scale]	-2.0 (0.1)

Adverse Events

Time Frame	Baseline to Week 52
Adverse Event Reporting Description	Safety population: All enrolled participants who took at least 1 dose of cariprazine.
Arm/Group Title	Cariprazine
Arm/Group Description	Participants received cariprazine 1.5 mg capsule once, twice or three times a day depending on their response and tolerability
All Cause Mortality
	Cariprazine
	Affected / at Risk (%)	# Events
Total	0/93 (0%)
Serious Adverse Events
	Cariprazine
	Affected / at Risk (%)	# Events
Total	12/93 (12.9%)
Gastrointestinal disorders
Haemorrhoidal haemorrhage	1/93 (1.1%)
Infections and infestations
Filariasis	1/93 (1.1%)
Orchitis	1/93 (1.1%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/93 (1.1%)
Intentional overdose	1/93 (1.1%)
Psychiatric disorders
Schizophrenia	4/93 (4.3%)
Psychotic disorder	2/93 (2.2%)
Agitation	1/93 (1.1%)
Completed suicide	1/93 (1.1%)
Renal and urinary disorders
Adjustment disorder	1/93 (1.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/93 (1.1%)
Chronic obstructive pulmonary disease	1/93 (1.1%)
Social circumstances
Social stay hospitalisation	1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	Cariprazine
	Affected / at Risk (%)	# Events
Total	62/93 (66.7%)
Gastrointestinal disorders
Constipation	5/93 (5.4%)
Diarrhoea	5/93 (5.4%)
Dyspepsia	5/93 (5.4%)
General disorders
Fatigue	5/93 (5.4%)
Infections and infestations
Nasopharyngitis	8/93 (8.6%)
Investigations
Weight increased	11/93 (11.8%)
Nervous system disorders
Akathisia	13/93 (14%)
Headache	8/93 (8.6%)
Dizziness	7/93 (7.5%)
Tremor	7/93 (7.5%)
Extrapyramidal disorder	6/93 (6.5%)
Sedation	5/93 (5.4%)
Somnolence	5/93 (5.4%)
Psychiatric disorders
Insomnia	13/93 (14%)
Agitation	7/93 (7.5%)
Anxiety	7/93 (7.5%)
Psychotic disorder	5/93 (5.4%)

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.