Cariprazine for Bipolar Disorder in Youth

(3112 Ped BPD Trial)

Recruiting at 73 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Allergan

Must not be taking: Psychotropics, CYP3A4 inhibitors

Disqualifiers: Schizophrenia, Substance disorder, Seizures, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of cariprazine, an antipsychotic medication, for treating depressive episodes in young people with bipolar I disorder. Participants will receive either cariprazine or a placebo (a substance with no active medicine) to compare outcomes. The trial seeks children aged 10-17 diagnosed with bipolar I disorder who are currently experiencing a depressive episode lasting more than two weeks but less than a year. Participants will attend regular clinic visits and undergo medical assessments, including blood tests and questionnaires. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including any psychotropic drugs (medications affecting mood, perception, or behavior) or drugs with psychotropic activity. Participants also cannot take moderate or strong CYP3A4 inhibitors or inducers, which are substances that affect how certain drugs are processed in the body.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cariprazine is safe and effective for treating bipolar disorder, helping with both manic and depressive episodes. Most side effects are mild, with restlessness and sleepiness affecting about 5% of patients.

For children and teens aged 10–17, cariprazine is also considered safe and generally does not cause serious side effects. Its approval for adults with bipolar depression further supports its safety. Always consult a healthcare provider for more detailed information and to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Cariprazine is unique because it targets dopamine D3 receptors more selectively than many current treatments for bipolar disorder in youth, such as lithium and valproate, which work more broadly on neurotransmitter systems. This selectivity may lead to fewer side effects, an important consideration for young patients who are particularly sensitive to medication effects. Additionally, Cariprazine has shown potential for improving both manic and depressive symptoms, offering a more comprehensive treatment approach compared to some existing options that primarily focus on one type of symptom. Researchers are excited about these features as they could lead to more effective and tolerable treatment options for young individuals struggling with bipolar disorder.

What evidence suggests that Cariprazine might be an effective treatment for bipolar disorder in youth?

Research shows that cariprazine works well for treating bipolar disorder, including depressive episodes in adults. Studies have found it to be safe and helpful for both bipolar and psychotic disorders in young people. In adults, cariprazine effectively reduces symptoms of bipolar depression. Early research in children and teens suggests it may also benefit them. This trial will compare cariprazine with a placebo to evaluate its effectiveness in youth. Although more data is needed for children, cariprazine’s success in adults and initial positive results in younger patients offer promising hope. ^{4 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for kids aged 10-17 with Bipolar I Disorder who've had at least one manic episode and are currently in a depressive phase lasting more than 4 weeks but less than a year. They should have moderate illness severity according to specific medical scales. Kids with certain psychiatric conditions, history of seizures (except febrile seizures), or significant brain trauma can't join.

Inclusion Criteria

My mood scores are low, showing I'm not in a manic state.

I am between 10 and 17 years old.

Clinical Global Impression-Severity (CGI-S) scale score of >= 4 (moderately ill) at Visit 1 and Visit 2.

Exclusion Criteria

You have experienced serotonin syndrome or neuroleptic malignant syndrome in the past.

You have experienced four or more episodes of mood changes in the past year.

I have been diagnosed with a specific mental health condition like schizophrenia or PTSD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cariprazine or placebo over a 6-week period, with dose adjustments based on response

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cariprazine
• Placebo

Trial Overview

The study tests Cariprazine against a placebo to see if it helps with depression in young people with Bipolar I Disorder. Participants will be randomly assigned to either the drug or placebo group and doses may change based on their response after three weeks. The treatment's effects are monitored through regular visits, blood tests, side effect checks, and questionnaires.

How Is the Trial Designed?

Group I: Cariprazine Experimental Treatment 1 Intervention

Participants will receive flexible dose Cariprazine over a 6 week treatment period.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive Placebo over a 6 week treatment period.

Cariprazine is already approved in United States for the following indications:

Approved in United States as Vraylar for:

• Schizophrenia
• Acute manic or mixed episodes associated with bipolar I disorder
• Depressive episodes associated with bipolar I disorder (bipolar depression)
• Adjunctive treatment with an antidepressant therapy (ADT) for major depressive disorder (MDD)

Who Is Running the Clinical Trial?

Allergan

Lead Sponsor

Trials

782

Recruited

277,000+

Brent Saunders

Allergan

Chief Executive Officer since 2015

JD and MBA from Temple University

Dr. David Nicholson

Allergan

Chief Medical Officer since 2015

MD from Harvard Medical School

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a review of 16 patients aged 6-20 treated with cariprazine for bipolar and psychotic disorders, the medication showed a 44% response rate, indicating potential effectiveness in this age group.

While no serious adverse events were reported, weight gain was a common side effect, particularly at doses higher than 3 mg/day, suggesting that lower doses may be more tolerable for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine in Youth with Bipolar and Psychotic Disorders: A Retrospective Chart Review. Poweleit, EA., Colestock, M., Kantemneni, EC., et al.[2021]

In a 30-week study involving 296 youths aged 10-17 with bipolar I disorder, aripiprazole at doses of 10 mg/day and 30 mg/day showed significant improvements in mania symptoms compared to placebo, as measured by the Young Mania Rating Scale (YMRS).

Both doses of aripiprazole were generally well tolerated, with longer time to discontinuation compared to placebo, although common side effects included headache and somnolence, and the overall study completion rate was low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study. Findling, RL., Correll, CU., Nyilas, M., et al.[2022]

The study involving 64 pediatric patients with bipolar disorder demonstrated that an evidence-based pharmacotherapy algorithm led to significant improvements in symptoms over an 18-month period, indicating its effectiveness in treatment.

Patients treated with the algorithm showed higher treatment adherence and family satisfaction compared to those receiving standard treatment, suggesting that this structured approach may enhance overall care for pediatric bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacotherapy algorithm for stabilization and maintenance of pediatric bipolar disorder. Pavuluri, MN., Henry, DB., Devineni, B., et al.[2015]

In a phase 3 study involving 493 adults with bipolar I disorder, cariprazine at a dose of 1.5 mg/day significantly reduced depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

The 3.0 mg/day dose did not show significant benefits over placebo, and the safety profile was consistent with previous studies, with common side effects including akathisia and nausea, but minimal weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Earley, WR., Burgess, MV., Khan, B., et al.[2021]

In a study involving 157 pediatric subjects aged 10-17 with bipolar I disorder, extended-release carbamazepine (ERC) significantly reduced mania symptoms, as measured by the Young Mania Rating Scale (YMRS), from an average score of 28.6 to 13.8 after treatment (P<0.0001).

While ERC was generally well-tolerated, with no reported deaths, 26 participants discontinued due to adverse events, including rash and decreased white blood cell count, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode. Findling, RL., Ginsberg, LD.[2021]

In a retrospective study of 6 pediatric patients (ages 7-15) with bipolar disorder and uncontrolled aggression, the addition of risperidone to their mood stabilizer regimen led to significant improvements in aggressive behavior and mania symptoms over a treatment period of 3-16 months.

Risperidone was generally well tolerated, with only mild side effects like sedation and akathisia reported in one patient, suggesting it may be a safe option for managing aggression in children and adolescents with bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of aggression with risperidone in children and adolescents with bipolar disorder: a case series. Saxena, K., Chang, K., Steiner, H.[2019]

In a 12-week study involving 39 children with bipolar disorder, lamotrigine monotherapy significantly improved symptoms of mania, as indicated by a reduction in Young Mania Rating Scale scores by an average of 14.9 points (P < 0.001).

Lamotrigine was generally well tolerated, with only a slight increase in body weight and no cases of Steven Johnson syndrome, although some participants experienced skin rashes that resolved after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder. Biederman, J., Joshi, G., Mick, E., et al.[2021]

Cariprazine, a novel antipsychotic, has shown efficacy in treating both acute manic and mixed episodes of bipolar disorder, with effective doses ranging from 3-12 mg/day, and for bipolar depression, lower doses of 1.5-3 mg/day are beneficial as monotherapy.

Overall, cariprazine is well-tolerated, with common side effects including akathisia and nausea, but it does not present metabolic concerns, making it a promising treatment option for patients with bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials. Do, A., Keramatian, K., Schaffer, A., et al.[2022]

Cariprazine is effective for treating schizophrenia and bipolar I disorder, showing a favorable side effect profile due to its selective affinity for D3 receptors, which helps address a range of symptoms including negative and cognitive symptoms.

It has a longer half-life and a delayed relapse time compared to other second-generation antipsychotics, making it a potentially better option for patients with high rates of non-adherence and frequent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine. Batinic, B., Ristic, I., Zugic, M., et al.[2021]

Cariprazine, an atypical antipsychotic, significantly improved symptoms of mania in patients with bipolar I disorder, as evidenced by statistically significant changes across all 11 items of the Young Mania Rating Scale (YMRS) compared to placebo.

In a pooled analysis of 1,037 inpatients (608 on cariprazine and 429 on placebo), a greater proportion of patients treated with cariprazine achieved mild or no symptoms at the end of treatment, indicating its efficacy in managing manic episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cariprazine across the symptoms of mania in bipolar I disorder: Analyses of pooled data from phase II/III trials. Vieta, E., Durgam, S., Lu, K., et al.[2015]

Cariprazine (Vraylar) is an atypical antipsychotic that acts as a partial agonist at dopamine D3 and D2 receptors, with a preference for D3, and also affects serotonin 5-HT1A receptors, which contributes to its therapeutic effects.

Approved in the USA in September 2015, cariprazine is used to treat schizophrenia and acute manic or mixed episodes in bipolar I disorder, and is being explored for additional uses in treating negative symptoms of schizophrenia and bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: First Global Approval. McCormack, PL.[2018]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31825249/

Cariprazine in Youth with Bipolar and Psychotic Disorders

Conclusions: Cariprazine may be well tolerated and effective for pediatric bipolar and psychotic disorders; however, compared with higher doses, total daily ...

2.

liebertpub.com

liebertpub.com/doi/full/10.1089/cap.2019.0106

Cariprazine in Youth with Bipolar and Psychotic Disorders

Overall, the findings presented herein suggest that cariprazine may be a well-tolerated, effective, and adjunctive medication for treating bipolar and psychotic ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04777357

NCT04777357 | A Study to Assess Change in Disease ...

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 ...

4.

vraylarhcp.com

vraylarhcp.com/efficacy/bipolar-depression-efficacy

VRAYLAR® (cariprazine) Efficacy for Bipolar Depression

Overall, 65% of patients treated with cariprazine 1.5 mg/day or 3 mg/day had higher anxiety symptoms at baseline, defined as a HAM-D anxiety/somatization ...

5.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.769897/full

Cariprazine in the Treatment of Bipolar Disorder

Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8712443/

Cariprazine in the Treatment of Bipolar Disorder

A recent meta-analysis found that cariprazine was efficacious and safe for the treatment of acute manic, mixed and depressive episodes ...

7.

vraylarhcp.com

vraylarhcp.com/safety

VRAYLAR® (cariprazine) Tolerability and Safety

Well-established safety profile across 3 bipolar I acute manic or mixed studies · Most common adverse reactions (≥5% and at least twice that of placebo) · >92% of ...

8.

liebertpub.com

liebertpub.com/doi/10.1089/cap.2021.0139

Pharmacokinetics, Safety, and Tolerability of Cariprazine in ...

Cariprazine appeared to be safe and well-tolerated in a pediatric population aged 10–17 years. The psychiatric symptom improvement provides support for future ...

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/cariprazine-oral-route/description/drg-20152634

Cariprazine (oral route) - Side effects & dosage

Cariprazine is used to treat schizophrenia or mania and depression related with bipolar disorder. It is also used to treat major depressive disorder (MDD).