Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01838876
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 442
• Locations: 90
• Arm: 1
• Actual Duration (Months): 26.9
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the long-term safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Cariprazine; Drug: Antidepressant Therapy (ADT)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 442 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Long-term, Open-label Study of Safety and Tolerability of Cariprazine as Adjunctive Therapy in Major Depressive Disorder
• Actual Study Start Date: Apr 29, 2013
• Actual Primary Completion Date: Jul 27, 2015
• Actual Study Completion Date: Jul 27, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Cariprazine + ADT Cariprazine, flexible dose (titrated to a dose of 3.0 milligrams (mg) adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.

Drug: Cariprazine; Cariprazine capsules 0.5 mg, 1.0 mg, and 1.5 mg; Cariprazine doses 1.5, 3.0, or 4.5 mg/day (d); patients will be titrated to a starting dose of 3.0 mg/d. Patients can stay on 3.0 mg/d or the dose can be adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability. Oral administration.; Drug: Antidepressant Therapy (ADT); ADT such as citalopram, escitalopram, fluoxetine, sertraline, paroxetine, vilazodone, venlafaxine, desvenlafaxine, duloxetine or bupropion prescribed in accordance with its respective FDA approved package insert for each drug

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period [First dose of study drug to last dose of study drug in the 26-week Treatment Period and within 30 days of last dose of study drug for participants who did not participate in the 2-week Safety Follow-up Period (Up to 30 weeks)]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.

2. Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period [2 weeks following the 26-week Treatment Period]

   An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A NEAE is a new AE that occurred during the 2-week Safety Follow-up Period.

3. Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [Baseline (Week 0) to up to 26 weeks in the Treatment Period]

   Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.

4. Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters [Baseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks)]

   Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.

5. Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) [Baseline (Week 0) to up to 26 weeks]

   A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.

6. Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs [First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)]

   Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia.

7. Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period [Baseline (Lead-in study Baseline for roll-over participants and prior to first dose in this study for new participants) to Week 26 in this study]

   The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). The C-SSRS also captures information about the intensity of ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior to 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes.

8. Number of Participants With Treatment-Emergent Ocular Events [First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)]

   A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye.

9. Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score [Baseline (Lead-in study Baseline for roll-over participants and prior to first dose of this study for new participants) to End of Treatment (Up to Week 26) in this study]

   The ASEX is a participant-completed scale to evaluate overall sexual experiences over the previous 7 days consisting of 5 questions answered on a scale of 1 (best) to 6 (worst) for a total possible score of 3 to 30 (2 questions were only answered if the participant was sexually active in the past week), higher score indicates greater sexual dysfunction. There are different forms for males and females. A negative change from Baseline 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 consent prior to any study specific procedures

• Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for MDD

• New patients must have ongoing inadequate response to protocol allowed ADTs as reported in Antidepressant Treatment Response Questionnaire (ATRQ)

• For rollover patients from RGH-MD-72 [NCT01715805], completion of Study RGH-MD-72 (either double-blind or single-blind treatment periods) with continued ADT treatment.

Exclusion Criteria:

• Patients who do not meet the DSM-IV-TR criteria for MDD.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 032	Tucson	Arizona	United States	85710
2	Forest Investigative Site 109	Tucson	Arizona	United States	85724
3	Forest Investigative Site 105	Fayetteville	Arkansas	United States	72703
4	Forest Investigative Site 018	Little Rock	Arkansas	United States	72211
5	Forest Investigative Site 029	Little Rock	Arkansas	United States	72211
6	Forest Investigative Site 082	Garden Grove	California	United States	92845
7	Forest Investigative Site 107	Long Beach	California	United States	90822
8	Forest Investigative Site 104	National City	California	United States	91950
9	Forest Investigative Site 022	Newport Beach	California	United States	92660
10	Forest Investigative Site 004	Oceanside	California	United States	92056
11	Forest Investigative Site 078	Rancho Mirage	California	United States	92270
12	Forest Investigative Site 080	Redlands	California	United States	92374
13	Forest Investigative Site 113	San Diego	California	United States	92102
14	Forest Investigative Site 054	San Diego	California	United States	92108
15	Forest Investigative Site 007	San Diego	California	United States	92123
16	Forest Investigative Site 031	Temecula	California	United States	92591
17	Forest Investigative Site 048	Denver	Colorado	United States	80239
18	Forest Investigative Site 114	Norwich	Connecticut	United States	06360
19	Forest Investigative Site 037	Coral Springs	Florida	United States	33067
20	Forest Investigative Site 053	Fort Myers	Florida	United States	33912
21	Forest Investigative Site 023	Hallandale Beach	Florida	United States	33009
22	Forest Investigative Site 071	Hialeah	Florida	United States	33012
23	Forest Investigative Site 006	Leesburg	Florida	United States	34748
24	Forest Investigative Site 112	Maitland	Florida	United States	32751
25	Forest Investigative Site 026	Miami	Florida	United States	33145
26	Forest Investigative Site 075	Miami	Florida	United States	33165
27	Forest Investigative Site 027	North Miami	Florida	United States	33161
28	Forest Investigative Site 074	North Miami	Florida	United States	33161
29	Forest Investigative Site 036	Oakland Park	Florida	United States	33334
30	Forest Investigative Site 051	Orlando	Florida	United States	32803
31	Forest Investigative Site 044	South Miami	Florida	United States	33143
32	Forest Investigative Site 008	Tampa	Florida	United States	33613
33	Forest Investigative Site 019	Winter Park	Florida	United States	32789
34	Forest Investigative Site 060	Atlanta	Georgia	United States	30329
35	Forest Investigative Site 024	Atlanta	Georgia	United States	30331
36	Forest Investigative Site 017	Marietta	Georgia	United States	30060
37	Forest Investigative Site 047	Smyrna	Georgia	United States	30080
38	Forest Investigative Site 070	Chicago	Illinois	United States	60612
39	Forest Investigative Site 013	Hoffman Estates	Illinois	United States	60169
40	Forest Investigative Site 063	Libertyville	Illinois	United States	60048
41	Forest Investigative Site 062	Maywood	Illinois	United States	60153
42	Forest Investigative Site 072	Naperville	Illinois	United States	60563
43	Forest Investigative Site 010	Oak Brook	Illinois	United States	60523
44	Forest Investigative Site 068	Skokie	Illinois	United States	60076
45	Forest Investigative Site 061	Indianapolis	Indiana	United States	46260
46	Forest Investigative Site 042	Lafayette	Indiana	United States	47905
47	Forest Investigative Site 065	Overland Park	Kansas	United States	66211
48	Forest Investigative Site 073	New Orleans	Louisiana	United States	70115
49	Forest Investigative Site 049	Gaithersburg	Maryland	United States	20877
50	Forest Investigative Site 077	Rockville	Maryland	United States	20850
51	Forest Investigative Site 110	Rockville	Maryland	United States	20852
52	Forest Investigative Site 046	Boston	Massachusetts	United States	02131
53	Forest Investigative Site 045	Natick	Massachusetts	United States	01760
54	Forest Investigative Site 103	Saint Charles	Missouri	United States	63304
55	Forest Investigative Site 106	Berlin	New Jersey	United States	08009
56	Forest Investigative Site 014	Toms River	New Jersey	United States	08755
57	Forest Investigative Site 058	Albuquerque	New Mexico	United States	87109
58	Forest Investigative Site 076	Bronx	New York	United States	10467
59	Forest Investigative Site 028	Brooklyn	New York	United States	11214
60	Forest Investigative Site 016	New York	New York	United States	10023
61	Forest Investigative Site 025	Staten Island	New York	United States	10305
62	Forest Investigative Site 050	Durham	North Carolina	United States	27710
63	Forest Investigative Site 067	Bismarck	North Dakota	United States	58501
64	Forest Investigative Site 011	Cincinnati	Ohio	United States	45219
65	Forest Investigative Site 015	Cincinnati	Ohio	United States	45227
66	Forest Investigative Site 055	Columbus	Ohio	United States	43210
67	Forest Investigative Site 066	Mason	Ohio	United States	45040
68	Forest Investigative Site 064	Middleburg Heights	Ohio	United States	44130
69	Forest Investigative Site 038	Oklahoma City	Oklahoma	United States	72112
70	Forest Investigative Site 035	Oklahoma City	Oklahoma	United States	73103
71	Forest Investigative Site 039	Oklahoma City	Oklahoma	United States	73112
72	Forest Investigative Site 003	Portland	Oregon	United States	97210
73	Forest Investigative Site 052	Allentown	Pennsylvania	United States	18104
74	Forest Investigative Site 102	Norristown	Pennsylvania	United States	19403
75	Forest Investigative Site 059	Lincoln	Rhode Island	United States	02865
76	Forest Investigative Site 001	Charleston	South Carolina	United States	29425
77	Forest Investigative Site 079	Austin	Texas	United States	78732
78	Forest Investigative Site 005	Houston	Texas	United States	77008
79	Forest Investigative Site 108	The Woodlands	Texas	United States	77381
80	Forest Investigative Site 069	Wichita Falls	Texas	United States	76309
81	Forest Investigative Site 111	Murray	Utah	United States	84123
82	Forest Investigative Site 041	Charlottesville	Virginia	United States	22903
83	Forest Investigative Site 081	Bellevue	Washington	United States	98007
84	Forest Investigative Site 100	Bothell	Washington	United States	98011
85	Forest Investigative Site 043	Seattle	Washington	United States	98104
86	Forest Investigative Site 101	Middleton	Wisconsin	United States	53562
87	Forest Investigative Site 056	Milwaukee	Wisconsin	United States	53227
88	Forest Investigative Site 057	Waukesha	Wisconsin	United States	53188
89	Forest Investigative Site 033	San Juan		Puerto Rico	00918
90	Forest Investigative Site 034	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

• Study Director: Willie Earley, MD, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01838876
• Other Study ID Numbers: RGH-MD-76
• First Posted: Apr 24, 2013
• Last Update Posted: Aug 21, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Forest Laboratories: Major Depressive Disorder; MDD; Depression
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Cariprazine; Antidepressive Agents

Study Results

Participant Flow

Pre-assignment Detail	Rollover participants from Study RGH-MD-72 [NCT01715805] were eligible for this study if they had completed either the double-blind treatment or the continued-treatment periods. New patients were eligible if they had an ongoing inadequate response to a protocol-allowed antidepressant therapy (ADT).

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0milligrams (mg) adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Period Title: Overall Study
STARTED	442
Safety Population; Received Study Drug	345
Entered Safety Follow-up Period	287
COMPLETED	209
NOT COMPLETED	233

Baseline Characteristics

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Overall Participants	345
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (10.5)
Sex: Female, Male (Count of Participants)
Female	249 72.2%
Male	96 27.8%
Race/Ethnicity, Customized (Count of Participants)
White	280 81.2%
Black or African American	54 15.7%
Asian	6 1.7%
American Indian or Alaska Native	1 0.3%
Native Hawaiian or Other Pacific Islander	1 0.3%
Other	3 0.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	75 21.7%
Non-Hispanic or Latino	270 78.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.
Time Frame	First dose of study drug to last dose of study drug in the 26-week Treatment Period and within 30 days of last dose of study drug for participants who did not participate in the 2-week Safety Follow-up Period (Up to 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	274 79.4%

2. Primary Outcome

Title	Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period
Description	An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A NEAE is a new AE that occurred during the 2-week Safety Follow-up Period.
Time Frame	2 weeks following the 26-week Treatment Period

Outcome Measure Data

Analysis Population Description

Participants in the Safety Population, all participants in the enrolled population who took at least 1 dose of cariprazine in this study, who entered the Safety Follow-up period.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	287
Count of Participants [Participants]	20 5.8%

3. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
Description	Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.
Time Frame	Baseline (Week 0) to up to 26 weeks in the Treatment Period

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	0 0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
Description	Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.
Time Frame	Baseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	0 0%

5. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
Description	A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.
Time Frame	Baseline (Week 0) to up to 26 weeks

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	1 0.3%

6. Primary Outcome

Title	Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs
Description	Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia.
Time Frame	First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	98 28.4%

7. Primary Outcome

Title	Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period
Description	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). The C-SSRS also captures information about the intensity of ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior to 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes.
Time Frame	Baseline (Lead-in study Baseline for roll-over participants and prior to first dose in this study for new participants) to Week 26 in this study

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
No Suicidal Ideation	308 89.3%
Suicidal Ideation	37 10.7%
Suicidal Ideation with Specific Plan and Intent	1 0.3%
Ideation,Some Intent to Act,without Specific Plan	0 0%
Ideation,any Methods,without Intent to Act	6 1.7%
Non-specific Active Suicidal Thoughts	3 0.9%
Wish to be Dead	27 7.8%
No Suicidal Behavior	344 99.7%
Suicidal Behavior	1 0.3%
Completed Suicide	0 0%
Actual Suicide Attempt	1 0.3%

8. Primary Outcome

Title	Number of Participants With Treatment-Emergent Ocular Events
Description	A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye.
Time Frame	First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.

Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
Measure Participants	345
Count of Participants [Participants]	1 0.3%

9. Primary Outcome

Title	Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score
Description	The ASEX is a participant-completed scale to evaluate overall sexual experiences over the previous 7 days consisting of 5 questions answered on a scale of 1 (best) to 6 (worst) for a total possible score of 3 to 30 (2 questions were only answered if the participant was sexually active in the past week), higher score indicates greater sexual dysfunction. There are different forms for males and females. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Lead-in study Baseline for roll-over participants and prior to first dose of this study for new participants) to End of Treatment (Up to Week 26) in this study

Outcome Measure Data

Analysis Population Description

Participants from the Safety Population, all participants in the enrolled population who took at least 1 dose of cariprazine in this study, with data available for analysis at the given time-point.

Arm/Group Title	Cariprazine + ADT (Female)	Cariprazine + ADT (Male)
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigators judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks for female participants.	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigators judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks for male participants.
Measure Participants	229	88
Baseline	20.1 (5.9)	17.2 (5.5)
Change from Baseline to the End of Treatment	-0.9 (4.4)	-0.1 (4.6)

Adverse Events

Time Frame	First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)
Arm/Group Title	Cariprazine + ADT
Arm/Group Description	Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.
All Cause Mortality
	Cariprazine + ADT
	Affected / at Risk (%)	# Events
Total	2/345 (0.6%)
Serious Adverse Events
	Cariprazine + ADT
	Affected / at Risk (%)	# Events
Total	7/345 (2%)
Infections and infestations
Pneumonia	1/345 (0.3%)
Injury, poisoning and procedural complications
Fall	1/345 (0.3%)
Road traffic accident	1/345 (0.3%)
Spinal cord injury	1/345 (0.3%)
Investigations
Blood creatine phosphokinase increased	1/345 (0.3%)
Psychiatric disorders
Completed suicide	1/345 (0.3%)
Substance-induced psychotic disorder	1/345 (0.3%)
Suicide attempt	1/345 (0.3%)
Other (Not Including Serious) Adverse Events
	Cariprazine + ADT
	Affected / at Risk (%)	# Events
Total	274/345 (79.4%)
Gastrointestinal disorders
Nausea	21/345 (6.1%)
General disorders
Fatigue	30/345 (8.7%)
Infections and infestations
Nasopharyngitis	30/345 (8.7%)
Investigations
Weight increased	34/345 (9.9%)
Nervous system disorders
Akathisia	55/345 (15.9%)
Headache	40/345 (11.6%)
Dizziness	20/345 (5.8%)
Sedation	19/345 (5.5%)
Psychiatric disorders
Anxiety	34/345 (9.9%)
Insomnia	34/345 (9.9%)
Restlessness	34/345 (9.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.