Cariprazine for Bipolar Disorder

Overseen By Martin Lan, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: New York State Psychiatric Institute

Must be taking: Antidepressants, Antipsychotics

Must not be taking: Fluoxetine, Strong CYP3A4 inducers

Disqualifiers: Schizoaffective, Psychotic depression, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the medication cariprazine (Vraylar) treats depression in individuals with bipolar disorder. Participants will take the medication and undergo brain imaging to observe its effects on the brain, particularly focusing on the D3 dopamine receptor, crucial for mood regulation. The trial involves two different doses of cariprazine to determine if one is more effective. It may suit individuals with bipolar I disorder who are currently experiencing depression and have not found relief from their current medication regimen. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with cariprazine or if you have not achieved partial remission with your current antidepressant or antipsychotic. However, you can continue taking mood stabilizers if the dose hasn't changed recently, and benzodiazepines and hypnotics are allowed. If you're on stimulant medications, you'll need to stop them during the study.

What is the safety track record for this treatment?

Research has shown that cariprazine (Vraylar) is generally safe for treating bipolar disorder. In past studies, over 92% of patients tolerated the medication well. The most common side effects included restlessness, insomnia, and nausea, affecting at least 5% of users. Additionally, the FDA has approved cariprazine for treating schizophrenia and various stages of bipolar disorder, indicating confidence in its safety for patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Cariprazine is unique because it targets dopamine D3 receptors more selectively than many current bipolar disorder treatments, which often focus on D2 receptors or other neurotransmitter systems. This specificity might lead to fewer side effects and improved mood stabilization. Researchers are excited because cariprazine could offer a new option for patients who haven't responded well to existing treatments like lithium, valproate, or atypical antipsychotics.

What is the effectiveness track record for cariprazine in treating bipolar disorder?

Research has shown that cariprazine works well for treating bipolar depression. In this trial, participants will receive either 1.5 mg or 3 mg of cariprazine daily for six weeks. One study found that taking 1.5 mg of cariprazine each day significantly reduced depression symptoms in people with bipolar I depression after six weeks. Another study found that cariprazine helps lessen both manic and depressive symptoms in bipolar I disorder. Cariprazine has also been shown to improve overall functioning in people with bipolar disorder. These findings support using cariprazine to manage symptoms of bipolar depression. ^{3 6 7 8 9}

Who Is on the Research Team?

Martin Lan, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with bipolar I disorder and current major depressive episode, scoring at least 16 on the Hamilton Depression Rating Scale. They must be willing to use birth control if applicable, tolerate medication washout, and can continue certain mood stabilizers. Excluded are those with head trauma affecting cognition, metal implants incompatible with MRI, excessive radiation exposure, claustrophobia preventing scans, weight over 350 lbs., failed or intolerable past cariprazine treatment.

Inclusion Criteria

I have bipolar I disorder and am currently experiencing a major depressive episode.

I am experiencing severe depression, as measured by a specific depression scale.

I understand the study and have given my consent.

Exclusion Criteria

Participant meets DSM5 criteria for manic episode at the time of screening, or has YMRS > 12

Metal implants, cardiac pacemaker, metal prostheses, metal orthodontic appliances or shrapnel in the body unless there is confirmation that the substance is MRI compatible

I've gotten worse in the past when stopping any of my current medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cariprazine (Vraylar) for six weeks with brain imaging using PET scans before and during treatment

6 weeks

3 visits (in-person) for PET scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cariprazine

Trial Overview The study tests cariprazine (Vraylar) in treating bipolar depression while examining its effect on D3 dopamine receptors using PET brain imaging. Participants will undergo a medication regimen followed by brain scans before and during treatment to understand how the drug interacts with specific brain receptors.

How Is the Trial Designed?

Group I: Cariprazine 3 mg Experimental Treatment 1 Intervention

Participants will receive 3 mg daily of cariprazine (Vraylar) for six weeks

Group II: Cariprazine 1.5 mg Experimental Treatment 1 Intervention

Participants will receive 1.5 mg daily of cariprazine (Vraylar) for six weeks

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?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Published Research Related to This Trial

In clinical trials, cariprazine significantly improved schizophrenia symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a longer time to relapse in a long-term study.

Cariprazine was more effective than risperidone in treating negative symptoms of schizophrenia, which are often challenging to address, and it was generally well tolerated with mostly mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine: A Review in Schizophrenia. Garnock-Jones, KP.[2018]

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]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7318333/

Efficacy and safety of cariprazine in bipolar I depression In this phase 3 study, cariprazine 1.5 mg/day significantly reduced depressive symptoms in patients with bipolar I depression at the primary endpoint (Week 6).

2. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165032724013533

Full-spectrum efficacy of cariprazine across manic and ... Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34034612/

The efficacy of cariprazine on function in patients with ... Conclusion: At week 8, statistically significant improvements in FAST outcomes were observed for cariprazine versus placebo in patients with bipolar I ...

5. ajgponline.org ajgponline.org/article/S1064-7481(24)00563-3/fulltext

Effect of Cariprazine on Outcomes in Older-aged and ... Conclusions. Cariprazine appears to be effective for both depressive and manic/mixed episodes of bipolar I disorder, regardless of age.

6. 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).

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. rxabbvie.com rxabbvie.com/pdf/vraylar_pi.pdf

Vraylar - master-uspi and mg-cariprazine - 11-26-24 In short-term controlled trials, dosages above. 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions [see.

9. vraylar.com vraylar.com/bipolar/why-vraylar-bipolar

Why VRAYLAR® (cariprazine)? - Bipolar I Disorder Learn about VRAYLAR®, a bipolar I disorder medication. See how VRAYLAR® is thought to work, VRAYLAR® dosing, more. See full Prescribing, Safety Info & Boxed