Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and tolerability of cariprazine in the treatment of pediatric participants with schizophrenia, bipolar I disorder, or autism spectrum disorder (ASD) and to establish the benefit-risk profile of long-term treatment in this population.

Official Title
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A 52-Week, Multicenter, Open-Label, Flexible-dose Study to Evaluate the Long-term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Subjects With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder

Conditions
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Schizophrenia, Bipolar I Disorder, Autism Spectrum Disorder (ASD)

Intervention / Treatment
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* Drug: Cariprazine Flexible Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-5-TR) primary diagnosis of schizophrenia or bipolar I disorder, or autism spectrum disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) at the Screening Visit 1 (for de novo subjects, or as previously confirmed in parent study for subjects who completed Study 3112-301-001 or M21-465). De novo participants must have normal physical examination findings, clinical laboratory test results, and electrocardiogram (ECG) results at Screening Visit 1. Abnormal results must not be clinically significant as determined by the investigator. Participants enrolling after completion of Study M21-465 or 3112-301-001 have had monitoring of laboratory tests, physical examinations, ocular assessments, and ECGs, of which the results enabled ongoing trial participation. As such, eligibility for participants enrolling from these parent studies need not be contingent on results of these tests but participants must be withdrawn if results of these tests meet withdrawal criteria. Participant must have a caregiver (parent or legally authorized representative) who is willing and able to be responsible for safety monitoring of the participant, provide information about the participant's condition, oversee administration of study intervention, and accompany the participant to all study visits. Exclusion Criteria: Participants with DSM-5-TR diagnosis of major depressive disorder, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder due to another medical condition. Participants with ASD that is associated with Rett disorder, fragile-X syndrome, or childhood disintegrative disorder. Prior DSM-5-TR diagnosis of intellectual disability (IQ < 70) for schizophrenia and bipolar I disorder participants. Prior DSM-5-TR diagnosis of profound intellectual disability (IQ < 25) for ASD participants. The participant has a condition or is in a situation, which, in the investigator's opinion, may put the participant at significant risk, may confound the study results, or may interfere significantly with the participant's participation in the study.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cariprazine Dose 1<br>Participants with Schizophrenia (age 13 to 17 years and < 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 2<br>Participants with Schizophrenia (age 13 to 17 years and >= 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 3<br>Participants with Bipolar I Disorder (age 10 to 12 years and <40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 4<br>Participants with Bipolar I Disorder (age 10 to 12 years and >= 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 5<br>Participants with Bipolar I Disorder (age 13 to 17 years and < 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 6<br>Participants with Bipolar I Disorder (age 13 to 17 years and >= 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 7<br>Participants with Autism Spectrum Disorder ( age 5 to 9 years) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 8<br>Participants with Autism Spectrum Disorder (age 10 to 12 years and <40 kg weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 9<br>Participants with Autism Spectrum Disorder (age 10 to 12 years and >=40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 10<br>Participants with Autism Spectrum Disorder (age 13 to 17 years and <40 kg weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|
| Experimental: Cariprazine Dose 11<br>Participants with Autism Spectrum Disorder (age 13 to 17 years and >= 40 kg body weight) will receive cariprazine. | Drug: Cariprazine Flexible Dose<br>* 1 capsule to be taken orally at approximately the same time of day (morning or evening)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period | 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. | Baseline Day 1 to Week 82 | 
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters | Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance. | Baseline Day 1 to Week 52 | 
| Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters | Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance. | Baseline Day 1 to Week 82 | 
| Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) | A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report. | Baseline Day 1 to Week 52 | 
| Number of Participants With Suicidal Ideation or Suicidal Behavior as Recorded on the Columbia-Suicide Severity Rating (C-SSRS) Scale | C-SSRS is a clinician-rated scale that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 wish to be dead, and 5 active suicidal ideation with specific plan and intent. Suicidal behavior is classified on a 5-item scale: 0 no suicidal behavior, and 4 actual attempt. | Baseline Day 1 to Week 52 | 
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) | AIMS assesses abnormal involuntary movements, such as tardive dyskinesia, associated with antipsychotic drugs; it measures facial, oral, extremities, and trunk movements, as well as the participant's awareness of abnormal movements. The first 10 items are rated on a none (0) to severe (4) scale. There are an additional 2 items on dental status that are answered yes or no. | Baseline Day 1 to Week 52 | 
| Change From Baseline in Barnes Akathisia Rating Scale (BARS) | BARS is a 4-item rating scale used to assess drug-induced akathisia. The scale comprises items for rating the observable restless movements that characterize the condition, the subjective awareness of restlessness, and any distress associated with the akathisia (each on a 4-point scale from normal [0] to severe [3]). In addition, there is a global severity for akathisia rated on a 6-point scale (absent [0] to severe akathisia [5]). | Baseline Day 1 to Week 52 | 
| Change From Baseline in Simpson-Angus Scale (SAS) | SAS is a 10-item rating scale for assessment of antipsychotic-induced parkinsonism in both clinical practice and research settings. Each item ranges from 0 (normal) to 4 (extreme symptoms). The scale consists of 1 item measuring gait (hypokinesia), 6 items measuring rigidity, and 3 items measuring glabella tap, tremor, and salivation, respectively. | Baseline Day 1 to Week 52 | 
| Number of Participants With Clinically Significant Changes From Baseline in Opthalmologic Parameters | Ocular examination parameters included Intraocular pressure (IOP) measurement, Best-corrected visual acuity (BCVA), color fundus photography, color vision testing using Hardy Rand and Rittler (HRR) plates, and assessment of Optical coherence tomography (OCT) and cataracts. The investigator assessed the results for clinical significance. | Baseline Day 1 to Week 52 | 
| Number of Participants With Menstrual Onset Shift (Female Participants Only) | Female participants who have entered menarche will be asked for the date of the first day of their most recent menstrual period. | Baseline Day 1 to Week 52 | 
| Incidence of Participants Shifting in Tanner Staging | Tanner staging is a scale for assessing physical development in children, adolescents, and adults. The scale defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. | Baseline Day 1 to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Bipolar I Disorder, Cariprazine, Autism Spectrum Disorder (ASD)