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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.

Phase 3
Recruiting
Conditions
Depression
Bipolar I Disorder
Interventions
Drug: Placebo
Registration Number
NCT04777357
Lead Sponsor
AbbVie
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
380
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 (except caffeine- and tobacco-related) 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.
  • History of or any current ocular disease including, but not limited to, retinal detachment, intraocular surgery, laser treatment, glaucoma, cataracts, or clinically significant ocular trauma (with the exception of refractive errors).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive Placebo over a 6 week treatment period.
CariprazineCariprazineParticipants will receive flexible dose Cariprazine over a 6 week treatment period.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Barnes Akathisia Rating Scale (BARS)Baseline (Week 0) to Week 6

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 Columbia-Suicide Severity Rating Scale (C-SSRS)Baseline (Week 0) to Week 10

The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.

Change in Electrocardiogram (ECG)Baseline (Week 0) to Week 6

12 -lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.

Change From Baseline in Simpson-Angus Scale (SAS)Baseline (Week 0) to Week 6

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 Incidence of Abnormal Clinical Laboratory Test ResultsBaseline (Week 0) to Week 6

Number of participants with incidence of abnormal clinical laboratory test results like hematology will be assessed.

Change in Children's Depression Rating Scale - Revised (CDRS-R) Total ScoreBaseline (Week 0) to Week 6

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.

Number of Participants with Adverse EventsBaseline (Week 0) to Week 10

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.

Change From Baseline in Abnormal Involuntary Movement Scale (AIMS)Baseline (Week 0) to Week 6

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.

Abnormal Change from Baseline in Vital SignsBaseline (Week 0) to Week 10

Change in vital signs like systolic and diastolic blood pressure will be assessed.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (70)

Pillar Clinical Research /ID# 226504

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Bentonville, Arkansas, United States

Advanced Research Center /ID# 227073

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Anaheim, California, United States

Care Access Research /ID# 226316

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Beverly Hills, California, United States

ProScience Research Group /ID# 226223

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Culver City, California, United States

National Institute of Clinical Research - Garden Grove /ID# 262835

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Garden Grove, California, United States

Duplicate_Alliance for Research - Long Beach /ID# 226522

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Long Beach, California, United States

CHOC Children's Hospital /ID# 260298

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Orange, California, United States

ATP Clinical Research- Orange /ID# 253719

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Orange, California, United States

Prospective Research Innovations Inc /ID# 240774

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Rancho Cucamonga, California, United States

University of California, San Diego Department of Psychiatry /ID# 226463

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San Diego, California, United States

Lumos Clinical Research Center /ID# 262805

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San Jose, California, United States

Pacific Clinical Research Management Group /ID# 227075

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Upland, California, United States

D&H Doral Research Center-Doral /ID# 255458

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Doral, Florida, United States

Advanced Research Institute of Miami /ID# 228222

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Homestead, Florida, United States

South Florida Research Ph I-IV /ID# 240778

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Miami Springs, Florida, United States

Columbus Clinical Services, Llc /Id# 229792

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Miami, Florida, United States

G+C Research Group, LLC /ID# 261399

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Miami, Florida, United States

Florida Research Center, Inc. /ID# 240775

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Miami, Florida, United States

Medical Research Group of Central Florida /ID# 256757

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Orange City, Florida, United States

APG Research, LLC /ID# 226519

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Orlando, Florida, United States

Panhandle Research and Medical Clinic, LLC /ID# 268522

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Pensacola, Florida, United States

D&H Tamarac Research Center /ID# 250434

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Tamarac, Florida, United States

The Kennedy Krieger Institute /ID# 226509

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Baltimore, Maryland, United States

University of South Florida- Neuroscience Institute /ID# 246508

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Tampa, Florida, United States

Atlanta Center for Medical Research /ID# 226480

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Atlanta, Georgia, United States

CenExcel iResearch LLC /ID# 228695

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Decatur, Georgia, United States

Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 226371

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Stockbridge, Georgia, United States

Atlanta Behavioral Research, LLC /ID# 226486

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Dunwoody, Georgia, United States

Baber Research Group /ID# 232279

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Naperville, Illinois, United States

Indiana University /ID# 260705

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Indianapolis, Indiana, United States

Ascension St. Elizabeth /ID# 240772

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Chicago, Illinois, United States

Benchmark Research /ID# 260714

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Shreveport, Louisiana, United States

Med Clinical Research Partners LLC /ID# 240773

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Irvington, New Jersey, United States

NeuroCognitive and Behavioral Institute, Inc /ID# 227077

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Mount Arlington, New Jersey, United States

UB Department of Psychiatry /ID# 226373

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Buffalo, New York, United States

New Dawn Psychiatric Services PLLC /ID# 229782

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Kinston, North Carolina, United States

Quest Therapeutics of Avon Lake /ID# 226349

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Avon Lake, Ohio, United States

University of Cincinnati /ID# 226465

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Cincinnati, Ohio, United States

CincyScience /ID# 226318

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West Chester, Ohio, United States

IPS Research Company /ID# 227072

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Oklahoma City, Oklahoma, United States

SP Research, PLLC /ID# 259428

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Oklahoma City, Oklahoma, United States

Cutting Edge Research Group /ID# 240777

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Oklahoma City, Oklahoma, United States

Relaro Medical Trials /ID# 227156

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Dallas, Texas, United States

Paradigm Research Professionals /ID# 260719

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Oklahoma City, Oklahoma, United States

Sooner Clinical Research /ID# 226384

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Oklahoma City, Oklahoma, United States

BioBehavioral Research of Austin /ID# 227076

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Austin, Texas, United States

Beaumont Psychiatric Clinic /ID# 267484

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Beaumont, Texas, United States

Independent Research Center /ID# 270050

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Coppell, Texas, United States

Earle Research /ID# 253782

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Friendswood, Texas, United States

McGovern Medical School /ID# 240779

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Houston, Texas, United States

Southwest Biomed Research Center LLC /ID# 226340

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Houston, Texas, United States

Red Oak Psychiatry Associates /ID# 240776

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Houston, Texas, United States

Livingspring Family Medical Center /ID# 262706

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Mansfield, Texas, United States

AIM Trials /ID# 226367

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Plano, Texas, United States

Perceptive Pharma Research /ID# 262219

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Richmond, Texas, United States

Family Psychiatry of The Woodlands /ID# 226290

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The Woodlands, Texas, United States

Pantheon Clinical Research /ID# 270879

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Bountiful, Utah, United States

Core Clinical Research /ID# 226374

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Everett, Washington, United States

Dr. Samuel Sanchez PSC /ID# 245952

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Caguas, Puerto Rico

GCM Medical Group PSC /ID# 245951

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San Juan, Puerto Rico

Clinica of Glazunova /ID# 229416

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Krasnodar, Krasnodarskiy Kray, Russian Federation

Orenburg Regional Clinical Psychiatric Hospital #1 /ID# 226462

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Orenburg, Orenburgskaya Oblast, Russian Federation

Psychotherapeutics Center Podderzhka /ID# 226348

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Stavropol, Stavropol Skiy Kray, Russian Federation

Scientific Centre of Personalized Medicine /ID# 226380

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Moscow, Russian Federation

Central Clinical Psychiatric Hospital /ID# 226381

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Moscow, Russian Federation

Clinical Psychiatry Hospital #1 of Nizhniy Novgorod /ID# 226226

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Nizhny Novgorod, Russian Federation

Medgard Clinic /ID# 228598

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Saratov, Russian Federation

Saratov City Clinical Hospital #2 n.a. V. I. Razumovsky /ID# 226222

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Saratov, Russian Federation

Psychiatric hospital #1 /ID# 226516

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St. Petersburg, Russian Federation

National Medical Research Center of Psychiatry and Neurology n.a. V.M. Bekhterev /ID# 226515

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St. Petersburg, Russian Federation

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