Brexpiprazole for Bipolar Disorder

Overseen By Nada Khalil, BA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Douglas Mental Health University Institute

Must be taking: Mood stabilizers

Must not be taking: Antipsychotics, Fluoxetine, Carbamazepine

Disqualifiers: Suicide risk, Psychotic symptoms, Drug abuse, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Brexpiprazole, a medication that may help individuals with Bipolar Disorder (BD) manage depression and improve cognitive functions like memory and decision-making. BD often causes persistent depressive episodes and cognitive issues that affect daily life. The trial aims to determine if Brexpiprazole can safely enhance mood and mental abilities for those who haven't found relief with other treatments. It seeks participants with Bipolar Disorder Type I or II who are currently experiencing a difficult-to-treat depressive episode. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications. You cannot participate if you are treated with fluoxetine, carbamazepine, risperidone, olanzapine, quetiapine (over 100mg/day), ziprazidone, or any other antipsychotic. However, you must be on a mood stabilizer like lithium, valproate, lamotrigine, or quetiapine (up to 100mg/day).

Is there any evidence suggesting that Brexpiprazole is likely to be safe for humans?

Research has shown that brexpiprazole is generally well-tolerated by people with bipolar disorder. In a study involving participants with depression from bipolar I or II disorder, researchers found brexpiprazole to be safe over an 8-week period, with most side effects being mild to moderate.

Other studies have examined brexpiprazole for conditions like major depressive disorder and irritability. These studies found the treatment to be mostly well-tolerated, with few serious side effects. Some participants might experience mild issues, such as restlessness or sleepiness, but these are usually manageable.

Brexpiprazole is currently undergoing a Phase 3 trial for bipolar disorder, indicating that earlier studies found it safe enough for further testing. This phase reflects researchers' confidence in its safety so far. ^{1 2 3 4 5}

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

Brexpiprazole is unique because it offers a different approach for treating bipolar disorder, particularly for those experiencing major depressive episodes. Unlike traditional treatments that often focus solely on mood stabilization, Brexpiprazole acts as an adjunctive therapy, potentially enhancing the effects of existing treatments. It works by targeting dopamine and serotonin receptors in the brain, which may lead to improved mood regulation and reduced depressive symptoms. Researchers are excited because this mechanism could offer more comprehensive symptom relief and improve the overall quality of life for patients with bipolar disorder.

What evidence suggests that Brexpiprazole might be an effective treatment for bipolar disorder?

Research has shown that brexpiprazole can reduce symptoms of depression in people with bipolar disorder. One study found that participants with bipolar depression felt significantly less depressed after taking brexpiprazole. This trial will evaluate brexpiprazole as an adjunctive treatment for individuals with Bipolar Disorder Type I or Type II experiencing a major depressive episode. Additionally, the treatment may improve thinking skills like memory and decision-making, which are often affected in bipolar disorder. These findings suggest that brexpiprazole could be a promising option for managing both mood and cognitive issues in bipolar disorder. ^{1 2 6 7 8}

Who Is on the Research Team?

Serge Beaulieu, MD

Principal Investigator

Douglas Mental Health University Institute

Are You a Good Fit for This Trial?

Adults aged 18-75 with Bipolar I Disorder currently experiencing treatment-resistant depression, who have tried at least one other treatment without success. Participants must be on a mood stabilizer and have normal heart function. They cannot join if they are at high suicide risk, have psychotic symptoms, certain neurocognitive disorders, uncontrolled seizures, known allergies to Brexpiprazole or its components including lactose intolerance.

Inclusion Criteria

I have been diagnosed with Bipolar Disorder type I or II.

The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin

I am taking a mood stabilizer like lithium, valproate, lamotrigine, or low-dose quetiapine.

Exclusion Criteria

I am not pregnant, breastfeeding, and I use birth control.

Drug abuse or dependence as per DSM-V (MINI)

I am lactose intolerant or have a similar condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an adjunctive and variable dose of Brexpiprazole treatment for bipolar depression

8 weeks

Regular visits for assessment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are assessed for long-term effects and changes in cognitive and global functioning

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Brexpiprazole

Trial Overview The trial is testing the effectiveness of Brexpiprazole as an additional treatment for depressive episodes in Bipolar I Disorder. It aims to improve mood symptoms and cognitive functions while monitoring changes in brain structures associated with these improvements.

How Is the Trial Designed?

Group I: Patient Experimental Treatment 1 Intervention

Individuals diagnosed with Bipolar Disorder Type I or Type II and suffering a major depressive episode who will receive an adjunctive and variable dose of Brexpiprazole treatment

Who Is Running the Clinical Trial?

Douglas Mental Health University Institute

Lead Sponsor

Trials

31

Recruited

2,800+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Jewish General Hospital

Collaborator

Trials

144

Recruited

283,000+

Published Research Related to This Trial

Brexpiprazole is an effective antipsychotic for treating schizophrenia, showing a responder rate of 46% compared to 31% for placebo in Phase 3 trials, with a number needed to treat (NNT) of 7.

While brexpiprazole can cause modest weight gain in about 10% of patients, it has minimal effects on glucose, lipids, and prolactin levels, making it a relatively safe option for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for the Treatment of Schizophrenia: A Review of this Novel Serotonin-Dopamine Activity Modulator. McEvoy, J., Citrome, L.[2016]

Brexpiprazole, taken at doses of 2-4 mg/day, has been shown to effectively improve symptoms of schizophrenia in short-term phase III studies, as measured by the Positive and Negative Symptom Scale.

In maintenance treatment, brexpiprazole (1-4 mg/day) significantly prolongs the time to disease exacerbation or relapse compared to placebo, and it is generally well tolerated with most serious side effects linked to the underlying condition rather than the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Brexpiprazole, a serotonin-dopamine activity modulator, has been shown to be more effective than standard antidepressant therapy alone in improving depressive symptoms in adults with major depressive disorder who did not fully respond to previous treatments, based on two phase III trials.

The drug was generally well tolerated over treatment periods of up to 52 weeks, suggesting a lower risk of activation-like side effects compared to similar medications like aripiprazole, making it a suitable adjunctive option for patients with persistent symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Brexpiprazole: A Review in Major Depressive Disorder. McKeage, K.[2018]

Brexpiprazole, an atypical antipsychotic, has been shown to significantly improve symptoms and psychosocial functioning in adults with acute schizophrenia exacerbations, with a dosage of 2-4 mg/day compared to placebo.

As a maintenance treatment, brexpiprazole (1-4 mg/day) effectively delayed relapse in stabilized patients and was generally well tolerated, showing a low incidence of serious side effects and only moderate weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: A Review in Schizophrenia. Frampton, JE.[2020]

Brexpiprazole is an atypical antipsychotic that acts as a serotonin-dopamine activity modulator, showing efficacy as an adjunctive treatment for major depressive disorder (MDD) and schizophrenia, with its first approval in the USA in July 2015.

The drug functions by partially activating serotonin 1A and dopamine D2 receptors while blocking 5-HT2A and noradrenergic receptors, which may contribute to its therapeutic effects in various psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: First Global Approval. Greig, SL.[2018]

Brexpiprazole is an effective new treatment for schizophrenia when used alone, providing a novel option for patients managing this condition.

Additionally, brexpiprazole can be used as an adjunctive therapy for major depressive disorder, enhancing the effectiveness of other treatments for individuals with this mental health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. Eaves, S., Rey, JA.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8366183/

Two randomized, double-blind, placebo-controlled trials ... This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081)

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03427892?cond=Brexpiprazole&viewType=Table&rank=1&tab=results

Study Results | Brexpiprazole for Bipolar Depression These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33691517/

Two randomized, double-blind, placebo-controlled trials ... This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081)

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03427892

NCT03427892 | Brexpiprazole for Bipolar Depression The investigators will conduct an 8-week, non-randomized, open-label study of brexpiprazole in 20 persons with bipolar I or II disorder, depressed mood ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032718328854

A pilot study of brexpiprazole for bipolar depression This is the first study to examine the effects of brexpiprazole on bipolar depression. We found a significant reduction in depressive symptoms and an increase ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02212613

Brexpiprazole (OPC 34712) Trial in the Treatment of Adults ... Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability. ClinicalTrials.gov ID NCT02212613. Sponsor Otsuka ...

7. fda.gov fda.gov/media/178827/download

Rexulti (brexpiprazole) Written Request Study 3: To evaluate the efficacy, safety, and tolerability of brexpiprazole in pediatric patients 10 to 17 years of age with acute manic or mixed episodes ...

8. withpower.com withpower.com/trial/phase-3-bipolar-disorder-4-2021-bae02

Brexpiprazole for Bipolar Disorder This Phase 3 medical study run by Douglas Mental Health University Institute is evaluating whether Brexpiprazole will have tolerable side effects & efficacy ...