Safety and Efficacy of RGH-188 (Cariprazine) in Bipolar Depression
Sponsor
Forest Laboratories (Industry)
Overall Status
Completed
CT.gov ID
NCT00852202
Collaborator
Gedeon Richter Ltd. (Industry)
234
26
3
11.5
9
0.8
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of cariprazine in the treatment of outpatients with bipolar depression.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
234 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double-blind, Placebo-controlled Study of RGH-188 (Cariprazine) in Bipolar Depression
Actual Study Start Date
:
Jun 30, 2009
Actual Primary Completion Date
:
Jun 15, 2010
Actual Study Completion Date
:
Jun 15, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 0.25 - 0.75 mg/day cariprazine capsules, oral administration, once daily dosing. |
Drug: cariprazine
Drug: cariprazine (0.25 - 0.75 mg/day)
|
| Experimental: 2 1.5 - 3.0 mg/day cariprazine capsules, oral administration, once daily dosing. |
Drug: cariprazine
Drug: cariprazine (1.5 - 3.0 mg/day)
|
| Placebo Comparator: 3 Matching placebo capsules, oral administration, once daily dosing. |
Drug: placebo
placebo capsules, oral administration, once daily dosing
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) [Baseline to Week 8]
The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity.
Secondary Outcome Measures
- Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) [Baseline to Week 8]
The patient was rated on a scale from 1 to 7, with 1 indicating the patient was very much improved and 7 indicating that the patient was very much worse.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women, 18-65 years old
-
Currently meet the DSM-IV-TR criteria for Bipolar I or II Disorder without psychotic features, with a current depressive episode
-
A verified previous manic, hypomanic, or mixed episode
-
Score of 20 or higher on the HAMD-17
-
Score of 2 or higher on Item 1 of the HAMD
Exclusion Criteria:
-
Score greater than 12 on the Young Mania Rating Scale
-
Eight or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months prior to Visit 1
-
Principal DSM-IV-TR-based diagnosis of an axis I disorder other than bipolar disorder (a secondary diagnosis of comorbid Generalized Anxiety Disorder, Social Anxiety Disorder, or specific phobias is acceptable)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Forest Investigative Site 005 | Encino | California | United States | 91316 |
| 2 | Forest Investigative Site 017 | Garden Grove | California | United States | 92845 |
| 3 | Forest Investigative Site 027 | National City | California | United States | 91950 |
| 4 | Forest Investigative Site 013 | Newport Beach | California | United States | 92660 |
| 5 | Forest Investigative Site 010 | Oceanside | California | United States | 92056 |
| 6 | Forest Investigative Site 020 | Bradenton | Florida | United States | 34208 |
| 7 | Forest Investigative Site 007 | Jacksonville | Florida | United States | 32216 |
| 8 | Forest Investigative Site 019 | Kissimmee | Florida | United States | 34741 |
| 9 | Forest Investigative Site 026 | Orlando | Florida | United States | 32806 |
| 10 | Forest Investigative Site 012 | West Palm Beach | Florida | United States | 33407 |
| 11 | Forest Investigative Site 024 | Glen Burnie | Maryland | United States | 21061 |
| 12 | Forest Investigative Site 029 | Creve Coeur | Missouri | United States | 63141 |
| 13 | Forest Investigative Site 002 | Omaha | Nebraska | United States | 68131 |
| 14 | Forest Investigative Site 028 | Cherry Hill | New Jersey | United States | 08002 |
| 15 | Forest Investigative Site 001 | Bronx | New York | United States | 10467 |
| 16 | Forest Investigative Site 018 | Durham | North Carolina | United States | 27710 |
| 17 | Forest Investigative Site 004 | Dayton | Ohio | United States | 45417 |
| 18 | Forest Investigative Site 022 | Mason | Ohio | United States | 45040 |
| 19 | Forest Investigative Site 015 | Portland | Oregon | United States | 97210 |
| 20 | Forest Investigative Site 006 | Media | Pennsylvania | United States | 19063 |
| 21 | Forest Investigative Site 011 | Philadelphia | Pennsylvania | United States | 19107 |
| 22 | Forest Investigative Site 014 | Nashville | Tennessee | United States | 37212 |
| 23 | Forest Investigative Site 023 | Irving | Texas | United States | 75062 |
| 24 | Forest Investigative Site 003 | Woodstock | Vermont | United States | 05091 |
| 25 | Forest Investigative Site 009 | Bellevue | Washington | United States | 98004 |
| 26 | Forest Investigative Site 016 | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- Forest Laboratories
- Gedeon Richter Ltd.
Investigators
- Study Director: William Greenberg, 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:
NCT00852202
Other Study ID Numbers:
- RGH-MD-52
First Posted:
Feb 26, 2009
Last Update Posted:
Aug 23, 2018
Last Verified:
Aug 1, 2018
Keywords provided by Forest Laboratories
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 233 patients were randomized to receive double-blind treatment, 227 patients received at least 1 dose of double-blind treatment and were included in safety Population |
| Arm/Group Title | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine |
|---|---|---|---|
| Arm/Group Description | Matching placebo capsules, orally administered for 8 weeks | Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | 1.5 to 3.0 mg Cariprazine capsules, orally administrated once daily for 8 weeks |
| Period Title: Overall Study | |||
| STARTED | 77 | 75 | 75 |
| COMPLETED | 60 | 63 | 49 |
| NOT COMPLETED | 17 | 12 | 26 |
Baseline Characteristics
| Arm/Group Title | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine | Total |
|---|---|---|---|---|
| Arm/Group Description | Matching placebo capsules, orally administered for 8 weeks | Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | Cariprazine capsules 1.5 to 3.0 mg was orally administrated once daily for 8 weeks | Total of all reporting groups |
| Overall Participants | 77 | 75 | 75 | 227 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
40.6
(10.7)
|
37.4
(10.7)
|
38.8
(12.1)
|
38.9
(11.2)
|
| Age, Customized (Number) [Number] | ||||
| < 20 |
1
1.3%
|
1
1.3%
|
2
2.7%
|
4
1.8%
|
| 20, 30 |
11
14.3%
|
21
28%
|
18
24%
|
50
22%
|
| 30, 40 |
24
31.2%
|
20
26.7%
|
20
26.7%
|
64
28.2%
|
| 40, 50 |
23
29.9%
|
23
30.7%
|
20
26.7%
|
66
29.1%
|
| 50, 60 |
17
22.1%
|
10
13.3%
|
13
17.3%
|
40
17.6%
|
| ≥ 60 |
1
1.3%
|
0
0%
|
2
2.7%
|
3
1.3%
|
| Sex/Gender, Customized (participant) [Number] | ||||
| Female |
46
|
48
|
51
|
145
|
| Male |
31
|
27
|
24
|
82
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
3
3.9%
|
4
5.3%
|
6
8%
|
13
5.7%
|
| Not Hispanic or Latino |
74
96.1%
|
71
94.7%
|
69
92%
|
214
94.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| Caucasian |
54
70.1%
|
56
74.7%
|
62
82.7%
|
172
75.8%
|
| Non-Caucasian |
23
29.9%
|
19
25.3%
|
13
17.3%
|
55
24.2%
|
| Black |
19
24.7%
|
16
21.3%
|
11
14.7%
|
46
20.3%
|
| Asian |
2
2.6%
|
2
2.7%
|
1
1.3%
|
5
2.2%
|
| Other |
2
2.6%
|
1
1.3%
|
1
1.3%
|
4
1.8%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) |
|---|---|
| Description | The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity. |
| Time Frame | Baseline to Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| of the 227 included to the safety population, the mixed-effects model for repeated measures (MMRM) of the Intent to Treat study population was 60 for placebo, 64 for 0.25-0.75 mg Cariprazine and 54 for 1.5 to 3.0 mg Cariprazine |
| Arm/Group Title | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine |
|---|---|---|---|
| Arm/Group Description | Matching placebo capsules, orally administered for 8 weeks | Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | Cariprazine capsules 1.5 to 3.0 mg was orally administrated once daily for 8 weeks |
| Measure Participants | 60 | 64 | 54 |
| Mean (Standard Error) [Score on scale] |
29.9
(0.6)
|
30.2
(0.6)
|
30.9
(0.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 0.25 to 0.75 mg Cariprazine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7408 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1.5 to 3.0 mg Cariprazine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9961 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) |
|---|---|
| Description | The patient was rated on a scale from 1 to 7, with 1 indicating the patient was very much improved and 7 indicating that the patient was very much worse. |
| Time Frame | Baseline to Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| of the 227 included to the safety population, the mixed-effects model for repeated measures (MMRM) of the Intent to Treat study population was 60 for placebo, 64 for 0.25-0.75 mg Cariprazine and 53 for 1.5 to 3.0 mg Cariprazine |
| Arm/Group Title | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0mg Cariprazine |
|---|---|---|---|
| Arm/Group Description | Matching placebo capsules, orally administered for 8 weeks | Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | Cariprazine capsules 1.5 to 3.0 mg was orally administrated once daily for 8 weeks |
| Measure Participants | 60 | 64 | 74 |
| Mean (Standard Error) [Score on Scale] |
2.1
(0.1)
|
2.1
(0.1)
|
2.1
(0.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 0.25 to 0.75 mg Cariprazine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3441 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1.5 to 3.0 mg Cariprazine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2683 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine | |||
| Arm/Group Description | Matching placebo capsules, orally administered for 8 weeks | Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | 1.5 to 3.0 mg Cariprazine capsules, orally administrated once daily for 8 weeks | |||
All Cause Mortality |
||||||
| Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/77 (2.6%) | 2/75 (2.7%) | 2/75 (2.7%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion spontaneous | 0/77 (0%) | 1/75 (1.3%) | 0/75 (0%) | |||
| Psychiatric disorders | ||||||
| Bipolar I disorder | 0/77 (0%) | 0/75 (0%) | 1/75 (1.3%) | |||
| Suicidal ideation | 1/77 (1.3%) | 0/75 (0%) | 1/75 (1.3%) | |||
| Suicidal attempt | 0/77 (0%) | 1/75 (1.3%) | 0/75 (0%) | |||
| Bipolar disorder | 1/77 (1.3%) | 0/75 (0%) | 0/75 (0%) | |||
| Depression | 0/77 (0%) | 0/75 (0%) | 1/75 (1.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 51/77 (66.2%) | 48/75 (64%) | 52/75 (69.3%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 4/77 (5.2%) | 9/75 (12%) | 9/75 (12%) | |||
| Diarrhoea | 5/77 (6.5%) | 10/75 (13.3%) | 5/75 (6.7%) | |||
| Vomiting | 1/77 (1.3%) | 1/75 (1.3%) | 5/75 (6.7%) | |||
| Dry mouth | 4/77 (5.2%) | 7/75 (9.3%) | 10/75 (13.3%) | |||
| Constipation | 5/77 (6.5%) | 5/75 (6.7%) | 3/75 (4%) | |||
| Flatulence | 4/77 (5.2%) | 1/75 (1.3%) | 0/75 (0%) | |||
| General disorders | ||||||
| Fatigue | 5/77 (6.5%) | 7/75 (9.3%) | 6/75 (8%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 5/77 (6.5%) | 7/75 (9.3%) | 7/75 (9.3%) | |||
| Upper respiratory tract infection | 8/77 (10.4%) | 11/75 (14.7%) | 8/75 (10.7%) | |||
| Investigations | ||||||
| Weight Increase | 1/77 (1.3%) | 1/75 (1.3%) | 6/75 (8%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Musculoskeletal stiffness | 0/77 (0%) | 0/75 (0%) | 4/75 (5.3%) | |||
| Nervous system disorders | ||||||
| Akathisia | 5/77 (6.5%) | 2/75 (2.7%) | 13/75 (17.3%) | |||
| Headache | 12/77 (15.6%) | 11/75 (14.7%) | 12/75 (16%) | |||
| Migraine | 1/77 (1.3%) | 5/75 (6.7%) | 0/75 (0%) | |||
| Dizziness | 5/77 (6.5%) | 2/75 (2.7%) | 3/75 (4%) | |||
| Dysgeusia | 4/77 (5.2%) | 1/75 (1.3%) | 2/75 (2.7%) | |||
| Sedation | 5/77 (6.5%) | 2/75 (2.7%) | 1/75 (1.3%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 7/77 (9.1%) | 13/75 (17.3%) | 15/75 (20%) | |||
| Anxiety | 5/77 (6.5%) | 2/75 (2.7%) | 5/75 (6.7%) | |||
| Restlessness | 3/77 (3.9%) | 2/75 (2.7%) | 5/75 (6.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/77 (1.3%) | 4/75 (5.3%) | 0/75 (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.
Results Point of Contact
| Name/Title | Therapeutic Area Head, |
|---|---|
| Organization | Allergan Sales LLC |
| Phone | 877-277-8566 |
| IR-CTRegistration@allergan.com |
Responsible Party:
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00852202
Other Study ID Numbers:
- RGH-MD-52
First Posted:
Feb 26, 2009
Last Update Posted:
Aug 23, 2018
Last Verified:
Aug 1, 2018