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

Primary outcomes

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period

   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)

   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

   Time frame: 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

   Time frame: 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

   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)

   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)

   Time frame: 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

   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)

   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

   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

   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

   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)

   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

   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

   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.