BXCL501 for Schizophrenia Agitation

(DEX Trial)

Overseen By Mohini Ranganathan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Disqualifiers: Significant medical condition, Substance dependence, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 1 day

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Agitation is characterized by excessive motor or verbal activity, irritability, uncooperativeness, threatening gestures, and, in some cases, aggressive or violent behavior. While agitation may have various underlying causes, patients with schizophrenia are especially vulnerable to acute episodes of agitation, especially during exacerbation of disease, and clinicians do not always diagnose these episodes early enough. Agitation associated with psychosis is a frequent reason for emergency department visits, and unless it is recognized early and managed effectively, it can rapidly escalate to potentially dangerous behaviors, including physical violence. Educating psychiatric professionals about the timely and accurate diagnosis of agitation among patients with schizophrenia or bipolar disorder and developing a well-tolerated easily administered medication will contribute to the prompt and effective management of this condition and could help reduce the risk of violent behavior and other undesirable outcomes. This study is designed to identify the ideal dose range and tolerability of sublingual Dexmedetomidine in patients with schizophrenia.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BXCL501 for treating agitation in schizophrenia?

Research shows that sublingual dexmedetomidine, the active ingredient in BXCL501, is effective in reducing agitation in people with schizophrenia. In clinical trials, it significantly improved agitation symptoms without serious side effects, making it a safe and effective option. ^{1 2 3 4 5}

Is BXCL501 (sublingual dexmedetomidine) safe for treating agitation in schizophrenia?

Sublingual dexmedetomidine has been shown to be safe in clinical trials for treating acute agitation in adults with schizophrenia or bipolar disorder, with the most common side effect being mild drowsiness. ^{1 3 4 5 6}

How is the drug BXCL501 different from other treatments for schizophrenia agitation?

BXCL501, a sublingual film of dexmedetomidine, is unique because it is a non-invasive treatment that acts as a selective alpha-2 adrenergic receptor agonist, offering a rapid and effective option for managing acute agitation in schizophrenia without the need for injections and with minimal side effects. ^{1 2 3 4 5}

Research Team

Mohini Ranganathan, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults aged 18-65 with schizophrenia or schizoaffective disorder, who can give informed consent. It's not for those with substance dependence, pregnant or breastfeeding women, or individuals with significant medical conditions.

Inclusion Criteria

I have been diagnosed with Schizophrenia or Schizoaffective disorder.

Ability to give informed consent

Exclusion Criteria

I am not pregnant or breastfeeding.

I have a serious health condition besides my cancer.

Current substance dependence

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a sublingual formulation of BXCL501 (dexmedetomidine) or placebo

1 day

Continuous monitoring for approximately 11 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Dexmedetomidine Hydrochloride

Trial Overview The study tests sublingual Dexmedetomidine Hydrochloride to manage agitation in schizophrenia patients. A placebo group is included for comparison. The goal is to find the best dose range and assess how well patients tolerate it.

Participant Groups

Group I: Order 1 Active Control 1 Intervention

Subjects will be given a sublingual formulation of BXCL501 (dexmedetomidine)

Group II: Order 2 Placebo Group 1 Intervention

Subjects will be given a sublingual film of placebo.

Dexmedetomidine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Precedex for:

• Sedation for mechanically ventilated patients
• Procedural sedation
• Acute agitation associated with schizophrenia or bipolar disorder

Approved in European Union as Dexdor for:

• Sedation for mechanically ventilated patients
• Procedural sedation

Approved in Canada as Dexmedetomidine Hydrochloride for:

• Sedation for mechanically ventilated patients
• Procedural sedation

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

Sublingual dexmedetomidine has a favorable efficacy profile for treating agitation in adults with schizophrenia or bipolar disorder, with a number needed to treat of 3 for significant response at 2 hours post-dose in both conditions.

The treatment's safety profile is also acceptable, as the number needed to harm for adverse events is generally greater than 10, except for somnolence, which has a number needed to harm of 7, indicating that the benefits outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Citrome, L., Risinger, R., Rajachandran, L., et al.[2023]

Sublingual dexmedetomidine is an effective and well-tolerated treatment for agitation in adults with schizophrenia and bipolar disorder, with effects starting as quickly as 20 minutes after administration.

While it shows promise, potential side effects include somnolence and hypotension, and further research is needed to assess its use in patients taking other psychiatric medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent. Faden, J., Musselman, M., Citrome, L.[2023]

In a phase 3 study involving 380 adults with schizophrenia or schizoaffective disorder, sublingual dexmedetomidine (180 μg and 120 μg) significantly reduced symptoms of acute agitation compared to placebo, as measured by the Positive and Negative Syndrome Scale-Excited Component (PEC) scores at 2 hours postdose.

The most common side effects of dexmedetomidine included somnolence, dizziness, and hypotension, indicating that while it is effective, monitoring for these adverse events is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. Citrome, L., Preskorn, SH., Lauriello, J., et al.[2022]

Dexmedetomidine film (BXCL501) and intranasal olanzapine (INP105) are two investigational medications showing promise for the rapid management of acute agitation in patients with schizophrenia or bipolar disorder, based on a review of clinical trials.

While olanzapine is already established in psychiatric treatment, dexmedetomidine represents a novel approach, and both medications offer unique noninvasive administration methods that could enhance patient compliance and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of acute agitation associated with schizophrenia or bipolar disorder: investigational drugs in early stages of their clinical development, and their clinical context and potential place in therapy. Ward, K., Citrome, L.[2020]

Sublingual dexmedetomidine (Igalmi) is a safe and effective treatment for acute agitation in adults with schizophrenia or bipolar disorder, as demonstrated in two phase 3 trials involving different dose strengths (180 μg and 120 μg).

Both doses significantly improved agitation scores compared to placebo within two hours, with mild somnolence being the most common side effect, indicating a favorable safety profile without serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder. Smith, CM., Santalucia, M., Bunn, H., et al.[2023]

In a study of 263 critically ill elderly patients, dexmedetomidine was found to provide better sedation for delirium control compared to olanzapine, with lower RASS scores indicating less agitation.

However, olanzapine was associated with fewer adverse effects, such as respiratory depression and hypotension, making it a safer option for managing delirium in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study. Liu, S., Zhao, R., Yang, R., et al.[2021]

References

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

Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent. [2023]

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

Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The treatment of acute agitation associated with schizophrenia or bipolar disorder: investigational drugs in early stages of their clinical development, and their clinical context and potential place in therapy. [2020]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study. [2021]