Long-term Safety and Tolerability of Cariprazine for Bipolar I Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01059539
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 403
• Locations: 35
• Arm: 1
• Actual Duration (Months): 24
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.5

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 bipolar I disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar I Disorder	Drug: Cariprazine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 403 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-term Open-label Study of the Safety and Tolerability of Cariprazine in Patients With Bipolar I Disorder
• Actual Study Start Date: Feb 28, 2010
• Actual Primary Completion Date: Feb 29, 2012
• Actual Study Completion Date: Feb 29, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine 3-12 mg/day for 16 weeks Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.	Drug: Cariprazine; Cariprazine was supplied in capsules.; Other Names: RGH-188

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the YMRS Total Score at Week 16 [Baseline to Week 16]

   The Young Mania Rating Scale (YMRS) is an 11-item scale that assesses manic symptoms based on the patient's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11 items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of each item is rated on a 5-point (0-4) or a 9-point (0-8) scale. The total score of all 11 items can range from 0 to 60. A higher score indicates worse manic symptoms. A negative change score indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in the MADRS Total Score at Week 16 [Baseline to Week 16]

   The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated scale that evaluates the patient's depressive symptomatology during the previous week. Patients are rated on 10 items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point (0-6) scale. The total score can range from 0 to 42. A higher score indicates greater depressive symptomatology. A negative change score 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:

• Patients who have provided informed consent 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 bipolar I disorder as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID).

• Patients who experienced a manic or mixed episode that required treatment within the past 12 months.

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

Exclusion Criteria:

• Patients with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 015	Springdale	Arkansas	United States	72764
2	Forest Investigative Site 010	Carson	California	United States	90746
3	Forest Investigative Site 020	Cerritos	California	United States	90703
4	Forest Investigative Site 009	Escondido	California	United States	92025
5	Forest Investigative Site 004	Garden Grove	California	United States	92845
6	Forest Investigative Site 016	San Diego	California	United States	92102
7	Forest Investigative Site 007	Santa Ana	California	United States	92701
8	Forest Investigative Site 023	Washington	District of Columbia	United States	20016
9	Forest Investigative Site 001	Bradenton	Florida	United States	34208
10	Forest Investigative Site 006	Fort Lauderdale	Florida	United States	33308
11	Forest Investigative Site 013	Kissimmee	Florida	United States	34741
12	Forest Investigative Site 021	Rockville	Maryland	United States	20850
13	Forest Investigative Site 024	Flowood	Mississippi	United States	39232
14	Forest Investigative Site 022	Creve Coeur	Missouri	United States	63141
15	Forest Investigative Site 003	Saint Charles	Missouri	United States	63301
16	Forest Investigative Site 025	Saint Louis	Missouri	United States	63118
17	Forest Investigative Site 012	Las Vegas	Nevada	United States	89102
18	Forest Investigative Site 002	Willingboro	New Jersey	United States	08046
19	Forest Investigative Site 005	Cincinnati	Ohio	United States	45219
20	Forest Investigative Site 011	Oklahoma City	Oklahoma	United States	73112
21	Forest Investigative Site 017	Austin	Texas	United States	78731
22	Forest Investigative Site 014	Austin	Texas	United States	78754
23	Forest Investigative Site 018	DeSoto	Texas	United States	75115
24	Forest Investigative Site 019	Houston	Texas	United States	77008
25	Forest Investigative Site 309	Gyula	Bekes	Hungary	5700
26	Forest Investigative Site 301	Budapest		Hungary	1083
27	Forest Investigative Site 302	Budapest		Hungary	1135
28	Forest Investigative Site 306	Nyiregyhaza		Hungary	4400
29	Forest Investigative Site 308	Szombathely		Hungary	9700
30	Forest Investigative Site 402	Tuszyn	Kodz	Poland	95-080
31	Forest Investigative Site 404	Katowice	Silesian	Poland	40-340
32	Forest Investigative Site 407	Gdansk		Poland	80-952
33	Forest Investigative Site 401	Gorlice		Poland	38-300
34	Forest Investigative Site 408	Swiecie		Poland	86-100
35	Forest Investigative Site 505	Barcelona		Spain	08036

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Elizabeth Diaz, MD, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01059539
• Other Study ID Numbers: RGH-MD-36
• First Posted: Feb 1, 2010
• Last Update Posted: Jun 13, 2019
• Last Verified: May 1, 2019

• Keywords provided by Forest Laboratories: Mania; Acute mania; Bipolar I disorder
• Additional relevant MeSH terms: Disease; Cariprazine

Study Results

Participant Flow

Arm/Group Title	Cariprazine 3-12 mg/Day for 16 Weeks
Arm/Group Description	Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Period Title: Overall Study
STARTED	403
COMPLETED	132
NOT COMPLETED	271

Baseline Characteristics

Arm/Group Title	Cariprazine 3-12 mg/Day for 16 Weeks
Arm/Group Description	Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Overall Participants	402
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (10.5)
Sex: Female, Male (Count of Participants)
Female	172 42.8%
Male	230 57.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	32 8%
Not Hispanic or Latino	370 92%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 1.5%
Asian	4 1%
Native Hawaiian or Other Pacific Islander	1 0.2%
Black or African American	182 45.3%
White	206 51.2%
More than one race	3 0.7%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	86.52 (17.83)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.21 (5.34)
Waist circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	97.86 (14.05)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the YMRS Total Score at Week 16
Description	The Young Mania Rating Scale (YMRS) is an 11-item scale that assesses manic symptoms based on the patient's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11 items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of each item is rated on a 5-point (0-4) or a 9-point (0-8) scale. The total score of all 11 items can range from 0 to 60. A higher score indicates worse manic symptoms. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All enrolled participants who took at least 1 dose of investigational product and who had a Baseline and at least 1 post-baseline assessment of the Young Mania Rating Scale.

Arm/Group Title	Cariprazine 3-12 mg/Day for 16 Weeks
Arm/Group Description	Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Measure Participants	399
Mean (Standard Deviation) [Units on a scale]	-15.2 (9.2)

2. Secondary Outcome

Title	Change From Baseline in the MADRS Total Score at Week 16
Description	The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated scale that evaluates the patient's depressive symptomatology during the previous week. Patients are rated on 10 items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point (0-6) scale. The total score can range from 0 to 42. A higher score indicates greater depressive symptomatology. A negative change score indicates improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All enrolled participants who took at least 1 dose of investigational product and who had a Baseline and at least 1 post-baseline assessment of the Young Mania Rating Scale.

Arm/Group Title	Cariprazine 3-12 mg/Day for 16 Weeks
Arm/Group Description	Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Measure Participants	399
Mean (Standard Deviation) [Units on a scale]	-1.6 (7.5)

Adverse Events

Adverse Event Reporting Description	Safety population: All enrolled participants who took at least 1 dose of investigational product.
Arm/Group Title	Cariprazine 3-12 mg/Day for 16 Weeks
Arm/Group Description	Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
All Cause Mortality
	Cariprazine 3-12 mg/Day for 16 Weeks
	Affected / at Risk (%)	# Events
Total	0/402 (0%)
Serious Adverse Events
	Cariprazine 3-12 mg/Day for 16 Weeks
	Affected / at Risk (%)	# Events
Total	34/402 (8.5%)
Cardiac disorders
Angina pectoris	1/402 (0.2%)
Bradycardia	1/402 (0.2%)
Gastrointestinal disorders
Large intestinal obstruction/Large bowel obstruction	1/402 (0.2%)
Immune system disorders
Hypersensitivity	1/402 (0.2%)
Infections and infestations
Pneumonia	1/402 (0.2%)
Injury, poisoning and procedural complications
Intentional overdose	1/402 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Dermal cyst	1/402 (0.2%)
Nervous system disorders
Tremor	1/402 (0.2%)
Psychiatric disorders
Mania	9/402 (2.2%)
Depression	5/402 (1.2%)
Akathisia	3/402 (0.7%)
Suicidal ideation	2/402 (0.5%)
Suicide attempt	2/402 (0.5%)
Anxiety	1/402 (0.2%)
Bipolar I disorder	1/402 (0.2%)
Insomnia	1/402 (0.2%)
Panic attack	1/402 (0.2%)
Paranoia	1/402 (0.2%)
Psychotic disorder/Increased psychosis	1/402 (0.2%)
Psychotic disorder/Psychosis	1/402 (0.2%)
Mania/Increased mania	1/402 (0.2%)
Mania/Worsening of mania	1/402 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/402 (0.2%)
Chronic obstructive pulmonary disease	1/402 (0.2%)
Non-cardiac chest pain	1/402 (0.2%)
Social circumstances
Social stay hospitalization	1/402 (0.2%)
Other (Not Including Serious) Adverse Events
	Cariprazine 3-12 mg/Day for 16 Weeks
	Affected / at Risk (%)	# Events
Total	293/402 (72.9%)
Gastrointestinal disorders
Constipation	44/402 (10.9%)
Diarrhoea	22/402 (5.5%)
Dyspepsia	38/402 (9.5%)
Nausea	42/402 (10.4%)
Toothache	35/402 (8.7%)
Vomiting	25/402 (6.2%)
Investigations
Weight increased	25/402 (6.2%)
Musculoskeletal and connective tissue disorders
Back pain	32/402 (8%)
Nervous system disorders
Akathisia	129/402 (32.1%)
Extrapyramidal disorder	28/402 (7%)
Headache	69/402 (17.2%)
Sedation	24/402 (6%)
Tremor	31/402 (7.7%)
Psychiatric disorders
Insomnia	27/402 (6.7%)
Restlessness	26/402 (6.5%)

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.