Dexmedetomidine for Agitation in Schizophrenia and Bipolar Disorder

Recruiting at 1 trial location

Overseen By Michel Duval, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BioXcel Therapeutics Inc

Must be taking: Psychotropic treatment

Must not be taking: Alpha blockers, Adrenergic agonists

Disqualifiers: Serious medical illnesses, Personality disorders, others

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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

452 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that patients in Part 2 stay on their current stable psychotropic treatment for the duration of the study. However, patients currently treated with certain medications like alpha-1 noradrenergic blockers or alpha-2 adrenergic agonists cannot participate.

What data supports the effectiveness of the drug Dexmedetomidine for treating agitation in schizophrenia and bipolar disorder?

Research shows that sublingual dexmedetomidine is effective in reducing agitation in adults with schizophrenia and bipolar disorder, as demonstrated in two phase 3 trials where it significantly improved symptoms compared to a placebo without causing serious side effects. ^{1 2 3 4 5}

Is sublingual dexmedetomidine safe for treating agitation in schizophrenia and bipolar disorder?

Sublingual dexmedetomidine has been shown to be safe for treating acute agitation in adults with schizophrenia or bipolar disorder, with the most common side effect being mild drowsiness. Clinical trials reported no serious adverse events. ^{1 2 3 4 5}

What makes the drug Dexmedetomidine unique for treating agitation in schizophrenia and bipolar disorder?

Dexmedetomidine is unique because it is administered as a sublingual film (placed under the tongue), which is non-invasive compared to the common intramuscular injections used for agitation. It works by targeting specific receptors in the brain (alpha-2 adrenergic receptors) and has been shown to be effective without causing serious side effects, making it a novel option for managing acute agitation in these conditions. ^{1 2 3 4 5}

What is the purpose of this trial?

In this study, an investigational medication named BXCL501 is being tested for the treatment of episodes of agitation associated with bipolar I and bipolar II disorder, schizophrenia, schizoaffective and schizophreniform disorder. This study compares the study drug to a placebo.

Research Team

Matt Mandel, MD

Principal Investigator

BioXcel Therapeutics

Eligibility Criteria

Adults aged 18-75 with bipolar I or II, schizophrenia, schizoaffective, or schizophreniform disorder who've had recent agitation episodes may join. They must be in good health based on medical exams and agree to use birth control. Exclusions include certain mental disorders pre-dating their diagnosis, recent investigational drug use, specific medication treatments, pregnancy/breastfeeding women, and those with serious neurological conditions.

Inclusion Criteria

Do you often get upset or feel agitated?

Exclusion Criteria

Have you been diagnosed with Parkinson's Disease?

Have you been diagnosed with Meningitis?

Have you been diagnosed with Concussion?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

One-day, in-clinic treatment of 60 mcg dose and post-treatment observation for acute agitation

1 day

1 visit (in-clinic)

Treatment Part 2

12-week study to determine the safety of a 120 mcg dose used as needed for agitation at home

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BXCL501
• Matching Placebo

Trial Overview The trial is testing BXCL501 against a placebo for reducing agitation in patients with bipolar disorder or schizophrenia-related conditions. Participants are randomly assigned to receive either the study drug or a placebo to compare effectiveness.

Participant Groups

Group I: Part 2: 120 mcg of BXCL501 Experimental Treatment 1 Intervention

Sublingual film containing 120 Micrograms Dexmedetomidine

Group II: Part 1: 60 mcg of BXCL501 Experimental Treatment 1 Intervention

Sublingual film containing 60 Micrograms Dexmedetomidine

Group III: Part 2: Matching Placebo Placebo Group 1 Intervention

Sublingual Placebo film

Group IV: Part 1: Matching Placebo Placebo Group 1 Intervention

Sublingual Placebo film

BXCL501 is already approved in United States for the following indications:

Approved in United States as IGALMI for:

• Agitation associated with schizophrenia or bipolar I or II disorder in adults

Who Is Running the Clinical Trial?

BioXcel Therapeutics Inc

Lead Sponsor

Trials

20

Recruited

2,400+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

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]

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]

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]

Dexmedetomidine sublingual film has been shown to be effective in reducing acute agitation in patients with schizophrenia and bipolar disorder, with significant improvements observed as early as 20 minutes after administration in pivotal trials involving these conditions.

The most common side effect was somnolence, while cardiovascular effects were generally mild and temporary, making dexmedetomidine a promising non-invasive alternative to traditional antipsychotics and benzodiazepines for managing agitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine Sublingual Film: A New Treatment to Reduce Agitation in Schizophrenia and Bipolar Disorders. Karlin, DM., Nelson, LA., Campbell, AR.[2023]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Dexmedetomidine Sublingual Film: A New Treatment to Reduce Agitation in Schizophrenia and Bipolar Disorders. [2023]