Trial Outcomes & Findings for Safety and Efficacy of Cariprazine As Adjunctive Therapy In Major Depressive Disorder (NCT NCT00854100)

Last Updated: 2019-03-05

Results Overview

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. The primary efficacy parameter was the change in MADRS score totals from the scores taken at Baseline (Week 8) and during at least one more time point up to and including Week 16.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

231 participants

Primary outcome timeframe

Baseline (Week 8) to Week 16

Results posted on

2019-03-05

Participant Flow

The randomized population for RGH-MD-71 totaled 231 participants

Participant milestones

Participant milestones
Measure	Placebo Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Cariprazine 0.1 - 0.3 mg Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose	Cariprazine 1.0 - 2.0 mg Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose
Overall Study STARTED	81	76	74
Overall Study COMPLETED	72	70	63
Overall Study NOT COMPLETED	9	6	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Cariprazine 0.1 - 0.3 mg Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose	Cariprazine 1.0 - 2.0 mg Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose
Overall Study Inability to complete the study visits	0	0	1
Overall Study Lost to Follow-up	2	0	3
Overall Study Withdrawal by Subject	3	1	2
Overall Study Protocol Violation	2	4	3
Overall Study Adverse Event	2	1	2

Baseline Characteristics

Safety and Efficacy of Cariprazine As Adjunctive Therapy In Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=81 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Cariprazine 0.1 - 0.3 mg n=76 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR)+ cariprazine low dose	Cariprazine 1.0 - 2.0 mg n=73 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose	Total n=230 Participants Total of all reporting groups
Age, Continuous	45.2 Years STANDARD_DEVIATION 10.2 • n=5 Participants	46.6 Years STANDARD_DEVIATION 11.7 • n=7 Participants	44.2 Years STANDARD_DEVIATION 12.1 • n=5 Participants	45.3 Years STANDARD_DEVIATION 11.3 • n=4 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	52 Participants n=7 Participants	51 Participants n=5 Participants	164 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	66 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants n=5 Participants	67 Participants n=7 Participants	64 Participants n=5 Participants	205 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	36 Participants n=4 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	57 Participants n=7 Participants	60 Participants n=5 Participants	186 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Week 8) to Week 16

Population: 231 patients were randomized, and of them, 230 received at least 1 dose of treatment (Double-blind Safety Population), and had at least a baseline and 1 post-baseline MADRS assessment (Double-blind Intent To Treat Population). All patients in the Double-blind Intent To Treat Population were included in the efficacy analyses.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Cariprazine 0.1 - 0.3 mg n=76 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose	Cariprazine 1.0 - 2.0 mg n=73 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose
Montgomery-Asberg Depression Rating Scale (MADRS)	-8.0 Units on a Scale Standard Error 1.0	-7.5 Units on a Scale Standard Error 1.1	-9.8 Units on a Scale Standard Error 1.1

SECONDARY outcome

Timeframe: Week 16

The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale that, in this study, will be used to rate total improvement or worsening of mental illness starting at Visit 2 (Week 2) and taken at every visit through Visit 11 (Week 16). The patient will be rated on a scale from 1 to 7, 1 indicating that the patient is very much improved and 7 indicating that the patient is very much worse. The secondary efficacy parameter was the CGI-I total score at Week 16.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Cariprazine 0.1 - 0.3 mg n=76 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose	Cariprazine 1.0 - 2.0 mg n=73 Participants Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose
Clinical Global Impression - Improvement (CGI-I)	2.5 Units on a Scale Standard Error 0.1	2.5 Units on a Scale Standard Error 0.1	2.3 Units on a Scale Standard Error 0.1

Adverse Events

Prospective Antidepressant-Therapy Lead In Period

Serious events: 9 serious events

Other events: 262 other events

Deaths: 1 deaths

Placebo

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Cariprazine 0.1 - 0.3 mg

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Cariprazine 1.0 - 2.0 mg

Serious events: 1 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Allergan, Inc

Phone: 877-277-8566

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Prospective Antidepressant-Therapy Lead In Period n=502 participants at risk Interventions included: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) for 8 weeks prior to randomization	Placebo n=81 participants at risk Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	Cariprazine 0.1 - 0.3 mg n=76 participants at risk Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	Cariprazine 1.0 - 2.0 mg n=73 participants at risk Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.
Psychiatric disorders Anxiety	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Injury, poisoning and procedural complications Hip Fracture	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Injury, poisoning and procedural complications Road Traffic Accident	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Injury, poisoning and procedural complications Upper Limb Fracture	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Suicidal Ideation	0.40% 2/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Depression	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Nervous system disorders Convulsion	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Nervous system disorders Serotonin Syndrome	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Completed Suicide	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Injury, poisoning and procedural complications Intentional Overdose	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Alcohol Abuse	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Homicidal Ideation	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Suicide Attempt	0.20% 1/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Cardiac disorders Angina Unstable	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmanary Disease	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.4% 1/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.

Other adverse events
Measure	Prospective Antidepressant-Therapy Lead In Period n=502 participants at risk Interventions included: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) for 8 weeks prior to randomization	Placebo n=81 participants at risk Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	Cariprazine 0.1 - 0.3 mg n=76 participants at risk Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	Cariprazine 1.0 - 2.0 mg n=73 participants at risk Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.
Nervous system disorders Headache	14.5% 73/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	3.7% 3/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	10.5% 8/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	8.2% 6/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Nervous system disorders Dizziness	6.2% 31/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	8.6% 7/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.3% 4/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	8.2% 6/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
General disorders Fatigue	7.2% 36/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	3.7% 3/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	2.6% 2/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.8% 5/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Insomnia	12.0% 60/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	3.7% 3/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	2.6% 2/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	9.6% 7/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Infections and infestations Nasopharyngitis	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.2% 5/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.3% 1/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	8.2% 6/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Gastrointestinal disorders Nausea	13.9% 70/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.2% 5/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.6% 5/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.8% 5/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Gastrointestinal disorders Dry Mouth	10.6% 53/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	2.6% 2/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.5% 4/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Gastrointestinal disorders Constipation	7.0% 35/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.3% 1/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.5% 4/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Gastrointestinal disorders Diarrhoea	7.2% 36/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.2% 5/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.3% 4/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	4.1% 3/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Infections and infestations Upper Respiratory Tract Infection	5.8% 29/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 25/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Nervous system disorders Akathisia	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	3.7% 3/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	2.6% 2/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.5% 4/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Nervous system disorders Tremor	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	4.9% 4/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	0.00% 0/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.5% 4/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Anxiety	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	3.7% 3/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.3% 1/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.5% 4/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Psychiatric disorders Restlessness	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.3% 1/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	9.6% 7/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Metabolism and nutrition disorders Increased appetite	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.3% 1/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	6.8% 5/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/502 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.2% 1/81 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	5.3% 4/76 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.	1.4% 1/73 • Up to 20 weeks Any AE includes the prospective ADT lead-in, double-blind treatment and 30 -day safety follow up will be considered a treatment-emergent adverse event (TEAE). A TEAE that occurs more than 30 days after the last dose of the investigational product will not be summarized for the safety follow-up period.1 patient left the study after they were randomized to the Cariprazine 1.0-2.0 mg arm, but never took the drug. Therefore, that patient is only captured in the lead in period data.