Cariprazine for Bipolar Disorder in Youth

(3112 Ped BPD Trial)

Recruiting in Palo Alto (17 mi)

+76 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Allergan

Must not be taking: Psychotropics, CYP3A4 inhibitors

Disqualifiers: Schizophrenia, Substance disorder, Seizures, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and effectiveness of Cariprazine for treating depressive episodes in children and teenagers with bipolar I disorder. The goal is to find out if Cariprazine can help young people with this condition. Cariprazine is an atypical antipsychotic recently approved for the treatment of depressive episodes in adults with bipolar I disorder.

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.

What data supports the effectiveness of the drug Cariprazine for treating bipolar disorder in youth?

Research on similar drugs like aripiprazole shows they can be effective for treating bipolar disorder in young people, suggesting that Cariprazine might also be helpful. ^{1 2 3 4 5}

Is cariprazine safe for treating bipolar disorder in youth?

Cariprazine is generally well-tolerated in youth with bipolar and psychotic disorders, with no serious adverse events reported, though weight gain was a common side effect. In adults, it is considered safe for treating bipolar disorder, with common side effects including restlessness and nausea, but no significant metabolic concerns. ^{6 7 8 9 10}

What makes the drug Cariprazine unique for treating bipolar disorder in youth?

Cariprazine is unique because it is an atypical antipsychotic that works by partially activating dopamine D3 and D2 receptors, with a preference for D3, which may help manage both manic and depressive symptoms in bipolar disorder. It is also well-tolerated in youth, with fewer metabolic concerns compared to other treatments. ^{6 7 8 9 11}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Cariprazine (Atypical Antipsychotic)
• Placebo (Pharmacotherapy)

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.

Participant Groups

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.

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

Findings from Research

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]

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 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]

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]

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]

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 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]

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]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study. [2022]

2. Denmark pubmed.ncbi.nlm.nih.gov

Treatment of aggression with risperidone in children and adolescents with bipolar disorder: a case series. [2019]

3. New Zealand 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

A pharmacotherapy algorithm for stabilization and maintenance of pediatric bipolar disorder. [2015]

5. England pubmed.ncbi.nlm.nih.gov

A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cariprazine: First Global Approval. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cariprazine in Youth with Bipolar and Psychotic Disorders: A Retrospective Chart Review. [2021]

9. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. [2021]

10. Switzerland 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. [2021]

11. Netherlands 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. [2015]