BXCL501 for Schizophrenia Agitation

(DEX Trial)

Overseen By Mohini Ranganathan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

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

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

Compensation: Varies

Number of Visits: 13

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, Dexmedetomidine Hydrochloride, to manage agitation in people with schizophrenia. Agitation can include restlessness, irritability, or aggressive behavior, often leading to emergency room visits. The study aims to determine the safest and most effective dose. Suitable participants are those diagnosed with schizophrenia or schizoaffective disorder who experience agitation. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research has shown that sublingual dexmedetomidine has been tested for safety in treating agitation. Studies found that two doses—120 micrograms and 180 micrograms—were generally safe, with most patients not experiencing serious side effects. Some participants did have mild reactions, but these were typically not serious.

Dexmedetomidine is already used in medical settings to manage agitation in conditions like schizophrenia and bipolar disorder, providing some safety information. However, as this trial is in its early stages, researchers are still carefully studying the treatment's safety in humans. This phase marks the first step in testing the treatment on people, so its complete safety profile is still being developed. ^{1 2 3 4 5}

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

Unlike the standard treatments for schizophrenia agitation, which often include antipsychotics and benzodiazepines, BXCL501 uses dexmedetomidine, a unique active ingredient. This treatment is exciting because it takes a different approach by targeting specific receptors in the brain to calm agitation without heavy sedation. Moreover, it is administered sublingually, meaning it dissolves under the tongue, allowing for potentially faster and more controlled relief. Researchers are hopeful that this method could offer a quicker, more precise way to manage symptoms with fewer side effects.

What evidence suggests that Dexmedetomidine Hydrochloride might be an effective treatment for schizophrenia agitation?

Research has shown that sublingual dexmedetomidine, or BXCL501, can help treat agitation in people with schizophrenia. In this trial, participants will receive either BXCL501 or a placebo. Earlier studies found that doses of 180 micrograms and 120 micrograms significantly reduced agitation symptoms compared to a placebo. This treatment manages symptoms like excessive movement, irritability, and threatening behavior by calming certain brain activities. These findings suggest that BXCL501 could be a promising option for managing agitation in schizophrenia. ^{1 5 6 7 8}

Who Is on the Research Team?

Mohini Ranganathan, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10157019/

Sublingual Dexmedetomidine for the Treatment of Agitation ... In two phase 3 trials, two dose strengths of sublingual dexmedetomidine 180 mg and 120 mg were safe and effective in managing acute agitation in patients with ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/30/NCT05276830/Prot_SAP_000.pdf

a multicenter, randomized, double-blind The results of this study demonstrated that a single sublingual dose of BXCL501 at 180 μg or. 120 μg effectively reduced the severity of ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/215390Orig1s000MultidisciplineR.pdf

215390Orig1s000 - accessdata.fda.gov parallel group trial assessing the efficacy and safety of BXCL501 in patients with agitation associated with schizophrenia. The Applicant ...

4. psychiatrist.com psychiatrist.com/jcp/sublingual-dexmedetomidine-for-agitation-schizophrenia/

Sublingual Dexmedetomidine for the Treatment of Acute ... Treatment with sublingual dexmedetomidine 180 μg or 120 μg was more efficacious than placebo in reducing acute agitation associated with schizophrenia.

5. trial.medpath.com trial.medpath.com/clinical-trial/bc90756ade66fcb0/nct04268303-efficacy-safety-bxcl501-agitation-schizophrenia

Dexmedetomidine in the Treatment of Agitation Associated ... This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the acute treatment of agitation in schizophrenia.

6. fda.gov fda.gov/files/advisory%20committees/published/PRECEDEX-Safety-and-Drug-Utilization-Review.pdf

Precedex (dexmedetomidine) Safety and Drug Utilization ... These studies did not meet their primary efficacy endpoints and the safety data ... Sales data for dexmedetomidine HCl by the number of vials sold ...

7. dig.pharmacy.uic.edu dig.pharmacy.uic.edu/faqs/april-2023-faqs/what-data-are-available-for-sublingual-dexmedetomidine-in-the-treatment-of-acute-agitation-related-to-schizophrenia-or-bipolar-disorder/

What data are available for sublingual dexmedetomidine in ... Sublingual dexmedetomidine at a dose of 120 mcg or 180 mcg reduced the severity of agitation in participants with mild to moderate agitation associated with ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK513303/

Dexmedetomidine - StatPearls - NCBI Bookshelf [1] Dexmedetomidine is used to treat episodes of agitation associated with schizophrenia or bipolar disorder. ... data showing alteration of normal sleep ...