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

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04578756

Collaborator

(none)

200

Enrollment

Locations

Arms

39.9

Anticipated Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Bipolar I Disorder Autism Spectrum Disorder (ASD)	Drug: Cariprazine Flexible Dose	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 26-Week, Multicenter, 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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Jun 4, 2023

Anticipated Study Completion Date :

May 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine Dose 1 Participants with Schizophrenia 13 to 17 years will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 2 Participants with Bipolar I Disorder, 10 to 12 years (weighing <=40 kg) will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 3 Participants with Bipolar I Disorder, 10 to 12 years (weighing >40 kg) will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 4 Participants with Bipolar I Disorder, 13 to 17 years will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 5 Participants with Autism Spectrum Disorder, 10 to 12 years (weighing <=40 kg) will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 6 Participants with Autism Spectrum Disorder, 10 to 12 years (weighing >40 kg) will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)
Experimental: Cariprazine Dose 7 Participants with Autism Spectrum Disorder, 13 to 17 years will receive cariprazine.	Drug: Cariprazine Flexible Dose 1 capsule to be taken orally at approximately the same time of day (morning or evening)

Outcome Measures

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period [Baseline Day 1 to Week 30]
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.
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [Baseline Day 1 to Week 26]
Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters [Baseline Day 1 to Week 30]
Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) [Baseline Day 1 to Week 26]
A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.
Number of Participants With Suicidal Ideation or Suicidal Behavior as Recorded on the Columbia-Suicide Severity Rating (C-SSRS) Scale [Baseline Day 1 to Week 26]
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".
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) [Baseline Day 1 to Week 26]
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.
Change From Baseline in Barnes Akathisia Rating Scale (BARS) [Baseline Day 1 to Week 26]
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]).
Change From Baseline in Simpson-Angus Scale (SAS) [Baseline Day 1 to Week 26]
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.
Number of Participants With Clinically Significant Changes From Baseline in Opthalmologic Parameters [Baseline Day 1 to Week 26]
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.
Number of Participants With Menstrual Onset Shift (Female Participants Only) [Baseline Day 1 to Week 26]
Female participants who have entered menarche will be asked for the date of the first day of their most recent menstrual period.
Incidence of Participants Shifting in Tanner Staging [Baseline Day 1 to Week 26]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).
Participant must have normal physical examination findings, clinical laboratory test results, and ECG results at Screening Visit 1, or abnormal results that are determined to be not clinically significant by the investigator.
Negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test (all female participants).
Participants (if reached his spermarche or her menarche) and is sexually active, must agree to sexual abstinence or to use an approved birth control method for the full duration of participation in the study. The investigator and each participant will determine the appropriate method of contraception for the participant during their participation in the study.
Parent(s) or participant's legal representative(s) must be capable of giving signed Informed Consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol as explained by the investigator. Written informed consent from the parent(s) or participant's legal representative(s) must be obtained prior to any study-related procedures.
Informed assent (unless local regulations require consent) must be obtained for all participants before eligibility evaluation for enrollment in the study.
For 10-11-year-old participants, a different assent form will be used than that for 12-17-year-old participants.
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.
Participant must be able to swallow the study intervention.

Exclusion Criteria:

Participants with DSM-5-TR diagnosis of schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder due to another medical condition.
DSM-5-TR diagnosis of intellectual disability (IQ < 70).
Participant has a history of meeting DSM-5-TR diagnosis for any substance-related disorder (except caffeine- and tobacco-related) within the 3 months before Screening (Visit 1).
Participant with an acute or unstable medical condition, including (but not limited to) inadequately controlled diabetes, hepatic insufficiency (specifically any degree of jaundice), uncorrected hyper- or hypothyroidism, acute systemic infection, renal, gastrointestinal, respiratory, or cardiovascular disease.
History of severe head trauma.
History of seizures, with the exception of febrile seizures.
History of tumor of the central nervous system.
Participant requires concomitant treatment with strong CYP3A4 inhibitors or CYP3A4 inducers. If applicable, these drugs must be discontinued 7 days prior to Baseline (Visit 2).
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, with the exception of permitted interventions.
Use of an antipsychotic depot within 2 cycles of their respective dosing interval prior to Screening (Visit 1).
ECT within 1 month of Screening (Visit 1).
Participant is unwilling to discontinue or, in the opinion of the investigator, unable to safely taper off any protocol-specified prohibited treatment prior to the Baseline (Visit 2) without significant destabilization or increased suicidality.
Participant is currently enrolled in another investigational drug or device study or participation in such a study within 3 months of Baseline (Visit 2).
Known history of human immunodeficiency virus infection.
Female participant who entered menarche and is sexually active, and with any of the following at Screening (Visit 1): positive pregnancy test, nursing, or planning to become pregnant at any time during participation in the study.
Known allergy or sensitivity to the study intervention or its components.
History of serious homicidal risk or behavior that resulted in hospitalization or adjudication (legal sentencing) within 6 months of Screening (Visit 1).
History of suicide attempt within 6 months of Screening (Visit 1) in the judgment of the investigator.
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.
Current suicidal or homicidal ideation in the judgment of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harmonex Neuroscience Research /ID# 234938	Dothan	Alabama	United States	36303
2	Pillar Clinical Research /ID# 236434	Bentonville	Arkansas	United States	72712
3	Advanced Research Center /ID# 241903	Anaheim	California	United States	92805
4	Alliance for Research - Long Beach /ID# 236261	Long Beach	California	United States	90807
5	Prospective Research Innovations Inc /ID# 236098	Rancho Cucamonga	California	United States	91730
6	University of California, San Diego Department of Psychiatry /ID# 236466	San Diego	California	United States	92103-8229
7	Pacific Clinical Research Management Group /ID# 234377	Upland	California	United States	91786-3676
8	Sarkis Clinical Trials /ID# 236893	Gainesville	Florida	United States	32607
9	Galiz Research - Palmetto Medical Plaza /ID# 236277	Hialeah	Florida	United States	33016
10	Advanced Research Institute of Miami /ID# 242505	Homestead	Florida	United States	33030-4613
11	South Florida Research Ph I-IV /ID# 237453	Miami Springs	Florida	United States	33166-7225
12	Columbus Clinical Services, Llc /Id# 234281	Miami	Florida	United States	33125-5114
13	Florida Research Center, Inc. /ID# 236515	Miami	Florida	United States	33174
14	Links Clinical Trials /ID# 240975	Miami	Florida	United States	33176-3227
15	Atlanta Center for Medical Research /ID# 234698	Atlanta	Georgia	United States	30331
16	iResearch Atlanta, LLC /ID# 237391	Decatur	Georgia	United States	30030
17	Atlanta Behavioral Research, LLC /ID# 236374	Dunwoody	Georgia	United States	30338
18	Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 242611	Stockbridge	Georgia	United States	30281
19	AMITA Health St. Mary and St. Elizabeth Medical Ctr /ID# 235857	Chicago	Illinois	United States	60622
20	The Kennedy Krieger Institute /ID# 236360	Baltimore	Maryland	United States	21205
21	Med Clinical Research Partners LLC /ID# 236071	Irvington	New Jersey	United States	07111
22	Erie County Medical Center /ID# 237204	Buffalo	New York	United States	14215
23	University of Cincinnati /ID# 236913	Cincinnati	Ohio	United States	45267-0585
24	CincyScience /ID# 236390	West Chester	Ohio	United States	45069
25	Cutting Edge Research Group /ID# 236664	Oklahoma City	Oklahoma	United States	73116-1423
26	BioBehavioral Research of Austin /ID# 236479	Austin	Texas	United States	78759-5290
27	Relaro Medical Trials /ID# 241960	Dallas	Texas	United States	75243
28	McGovern Medical School /ID# 238506	Houston	Texas	United States	77054
29	Red Oak Psychiatry Associates /ID# 236602	Houston	Texas	United States	77090-2641
30	AIM Trials /ID# 236368	Plano	Texas	United States	75093
31	Family Psychiatry of The Woodlands /ID# 236426	The Woodlands	Texas	United States	77381
32	Dr. Samuel Sanchez PSC /ID# 246047	Caguas		Puerto Rico	00727
33	GCM Medical Group PSC /ID# 246048	San Juan		Puerto Rico	00917-3104