A Study to Assess Change in Disease Activity and Adverse Events (AEs) With Cariprazine in the Treatment of Depressive Episodes in Pediatric Participants Participants (10 to 17 Years of Age) With Bipolar I Disorder.

Study Overview
=================
Brief Summary
-----------------
Bipolar disorder is a severe chronic mood disorder that affects up to 4% of the adult population and 1.8% of the pediatric population in the United States. The treatment of the depressive episodes of bipolar disorder in the pediatric population has not been as widely studied as the treatment of depressive episodes in bipolar disorder in adults, therefore pharmacotherapeutic options are limited. Given the change in disease state and safety demonstrated in adults with depressive episodes associated with bipolar I disorder, the purpose of this study is to evaluate the change in disease state and safety of cariprazine in the treatment of depressive episodes associated with bipolar I disorder in the pediatric population. Cariprazine is an approved drug for the treatment of depressive episodes in adult participants with bipolar I disorder. Study doctors put participants in 1 of 2 groups, called treatment arms. There is a 1 in 2 chance that a participant will be assigned to placebo. Around 380 Participants ages 10-17 years with bipolar I disorder will be enrolled in approximately 60 sites worldwide. Participants receiving the study drug will receive Dose A or B of Cariprazine based on age and weight. At Week 3, participants with insufficient response will have their dose increased to Dose B or Dose C, while participants with sufficient response will continue receiving the Dose A or B for the remainder of the treatment period. The treatment period will be followed by a safety follow-up (SFU) period for 4 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular weekly visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
-----------------
A 6-week, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of the Efficacy and Safety of Cariprazine in Pediatric Participants (10 to 17 Years of Age) in the Treatment of Depressive Episodes Associated With Bipolar I Disorder

Conditions
-----------------
Depression, Bipolar I Disorder

Intervention / Treatment
-----------------
* Drug: Cariprazine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) primary diagnosis of bipolar I disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Current depressive episode is more than 2 weeks and less than 12 months in duration. Participant has a lifetime history of at least one manic episode. Children's Depression Rating Scale - Revised (CDRS-R) score > = 45 at Visit 1 and Visit 2. Young-Mania Rating Scale (YMRS) score < 12 with YMRS Item 1 (elevated mood) score < 2 at Visit 1 and Visit 2. Clinical Global Impression-Severity (CGI-S) scale score of > = 4 (moderately ill) at Visit 1 and Visit 2. Exclusion Criteria: Participants with DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, psychotic disorder due to another medical condition, PTSD, antisocial personality disorder, or borderline personality disorder. Participant has a history of meeting DSM-5 diagnosis for any substance-related disorder within the 3 months before Screening Visit 1. History of serotonin syndrome or neuroleptic malignant syndrome. Four or more episodes of a mood disturbance within the 12 months before Visit 1. DSM-5 diagnosis of intellectual disability (IQ < 70), autism spectrum disorders, or documented history of chromosomal disorder with developmental impairment. History of seizures, with the exception of febrile seizures. Significant head trauma, history of tumor of the CNS, or any other condition that predisposes to seizures. Participant requires concomitant treatment with moderate or strong CYP3A4 inhibitors or with any CYP3A4 inducers. Participant requires concomitant treatment with any prohibited medication, supplement, or herbal product, including any psychotropic drug or any drug with psychotropic activity or with a potentially psychotropic component. Use of a depot antipsychotic within 2 cycles of their respective dosing interval prior to Screening Visit 1. Treatment with clozapine in a dose of >= 50 mg/d in the past 2 years. Participants with cataracts, ocular trauma, ocular disease, history of amiodarone or systemic corticosteroid use for >= 3 consecutive months in the past year, and IOP of >= 21 mm Hg in either eye.

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive Placebo over a 6 week treatment period. | Drug: Placebo<br>* Oral Capsule<br>|
| Experimental: Cariprazine<br>Participants will receive flexible dose Cariprazine over a 6 week treatment period. | Drug: Cariprazine<br>* Oral Capsule<br>* Other names: Vraylar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a casual relationship with this treatment. The investigator assesses the relationship of each event to the use of the study. A serious adverse event (SAE) is an event that results in death, is life threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event, that based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/ treatment emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of the study drug. | Baseline (Week 0) to Week 10 | 
| Abnormal Change from Baseline in Vital Signs | Change in vital signs like systolic and diastolic blood pressure will be assessed. | Baseline (Week 0) to Week 10 | 
| Number of Participants with Incidence of Abnormal Clinical Laboratory Test Results | Number of participants with incidence of abnormal clinical laboratory test results like hematology will be assessed. | Baseline (Week 0) to Week 6 | 
| Change in Electrocardiogram (ECG) | 12 -lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration. | Baseline (Week 0) to Week 6 | 
| Change in Children's Depression Rating Scale - Revised (CDRS-S) Total Score | The CDRS R is a 17-item clinician-administered scale specifically developed for the assessment of depressive symptoms in children and adolescents. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. The CDRS R will be administered by a clinician with extensive professional training in mental illness. | Baseline (Week 0) to Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, RGH-188, Bipolar I Disorder, Vraylar, Cariprazine