BXCL501 for Pediatric Schizophrenia and Bipolar Agitation

Recruiting at 5 trial locations

Overseen By Carl Gommoll

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: BioXcel Therapeutics Inc

Must not be taking: Benzodiazepines, Hypnotics, Antipsychotics

Disqualifiers: Acute intoxication, Suicide risk, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1-2 weeks

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of BXCL501, a new treatment taken as a dissolvable film under the tongue, for children and teens experiencing intense restlessness or agitation due to bipolar disorder or schizophrenia. Researchers aim to compare the treatment's effectiveness to a placebo (a dummy treatment) by testing three different doses. Children and teenagers who frequently experience intense agitation and have been diagnosed with schizophrenia or bipolar disorder may be suitable candidates for this trial. 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 requires that you do not use benzodiazepines or other hypnotics, or certain antipsychotic drugs in the 4 hours before the study treatment. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BXCL501, a type of medication, is generally safe and effective in medical settings. Studies with adults have found it reduces agitation better than a placebo. In one study, more than 2,400 episodes of agitation treated with BXCL501 showed a significant decrease in severity within two hours.

Additionally, the FDA has granted BXCL501 Breakthrough Therapy status for treating agitation in dementia, indicating confidence in its safety for that condition. However, this clinical trial focuses on children and teenagers, who might experience different safety outcomes.

Overall, current data supports its safety in adults, but more trials are needed to confirm its safety for younger individuals. ^{1 2 3 4 5}

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

Researchers are excited about BXCL501 for pediatric schizophrenia and bipolar agitation because it offers a unique approach compared to standard treatments like antipsychotics and mood stabilizers. BXCL501 contains dexmedetomidine, which targets calming effects through a different pathway by acting on the adrenergic system, potentially reducing agitation without the heavy sedation or side effects typically associated with current drugs. Additionally, it comes in a sublingual film, making it easy and fast-acting, which is particularly beneficial in acute settings where quick relief is needed. This innovative delivery method and mechanism of action could provide a more targeted and tolerable option for young patients.

What evidence suggests that BXCL501 might be an effective treatment for pediatric schizophrenia and bipolar agitation?

Research has shown that BXCL501 may help reduce agitation in people with bipolar disorder and schizophrenia. In previous studies, patients who took BXCL501 experienced a noticeable decrease in agitation compared to those who took a placebo. Specifically, agitation levels significantly dropped just two hours after taking the treatment. This calming effect was observed in over 2,400 episodes, indicating that BXCL501 could effectively help patients during acute agitation. The treatment was also well-tolerated when used at home, suggesting it could be a practical option for managing agitation in these conditions. Participants in this trial will receive different dosages of BXCL501—60, 80, or 120 micrograms—or a placebo to further evaluate its effectiveness and safety. ^{1 2 4 6 7}

Who Is on the Research Team?

Robert Risinger, MD

Principal Investigator

BioXcel Therapeutics

Are You a Good Fit for This Trial?

This trial is for children and teens aged 10-17 with bipolar disorder, and those aged 13-17 with schizophrenia who are experiencing significant agitation. They must have a specific level of agitation on the PANSS Excited Component scale and agree to use effective birth control. It's not for those who've used certain sedatives recently, are at suicide risk, have serious health issues, or have taken experimental drugs within the last month.

Inclusion Criteria

Patients who are judged to be clinically agitated at Screening and Baseline with a total score of ≥14 on the 5 items comprising the PANSS Excited Component (PEC)

I am between 10-17 years old and have been diagnosed with bipolar disorder.

I am a teenager aged 13-17 with schizophrenia.

Exclusion Criteria

Patients with serious or unstable medical illnesses

Patients with agitation caused by acute intoxication, including alcohol or drugs of abuse (with the exception of THC) during urine screening

I haven't taken any sleep or antipsychotic medication in the last 4 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sublingual film containing Dexmedetomidine or placebo

1-2 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• BXCL501

Trial Overview The study tests BXCL501 at different doses (60, 80, and 120 micrograms) against a placebo to see if it helps calm down kids and teens with bipolar disorder or schizophrenia during acute agitation episodes. The effectiveness and safety of these treatments are being compared.

How Is the Trial Designed?

Group I: 80 Micrograms Experimental Treatment 1 Intervention

Sublingual film containing 80 micrograms Dexmedetomidine

Group II: 60 Micrograms Experimental Treatment 1 Intervention

Sublingual film containing 60 micrograms Dexmedetomidine Europe Only

Group III: 120 Micrograms Experimental Treatment 1 Intervention

Sublingual film containing 120 micrograms Dexmedetomidine

Group IV: 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+

Cognitive Research Corporation

Industry Sponsor

Trials

25

Recruited

2,400+

Published Research Related to This Trial

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 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]

Aripiprazole is an effective treatment for schizophrenia and bipolar I disorder, showing superior efficacy compared to placebo and haloperidol, and similar efficacy to other second-generation antipsychotics like perphenazine and risperidone, but is less effective than olanzapine.

It has a favorable tolerability profile, with a low risk of weight gain and metabolic issues, although some patients may experience akathisia and gastrointestinal symptoms at the start of treatment, which are often temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder. Citrome, L.[2021]

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 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]

Clozapine treatment in 20 adolescents with treatment-refractory schizophrenia led to a significant reduction in aggressive behaviors, as evidenced by fewer emergency medication administrations and seclusion events during weeks 12 to 24 of treatment.

The study suggests that clozapine can effectively improve aggressive behaviors in adolescents, allowing for potential discharge to less restrictive settings, although further controlled trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clozapine: its impact on aggressive behavior among children and adolescents with schizophrenia. Kranzler, H., Roofeh, D., Gerbino-Rosen, G., et al.[2013]

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]

Clinical trials indicate that agents targeting the glycine modulatory site on NMDA receptors, such as glycine and D-cycloserine, can improve cognitive function and reduce negative symptoms in schizophrenia patients already on typical antipsychotics.

Preliminary findings suggest that clozapine may enhance the effects of these glycine modulators, and an allosteric modulator of the AMPA receptor shows promise in improving cognitive functions in treated subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ionotropic glutamate receptors as therapeutic targets in schizophrenia. Coyle, JT., Tsai, G., Goff, DC.[2022]

Subanaesthetic doses of dissociative anaesthetics can mimic cognitive impairments and negative symptoms of schizophrenia in healthy individuals, suggesting a link between NMDA receptor activity and the disorder.

Clinical trials show that activating the glycine modulatory site on the NMDA receptor can reduce negative symptoms and improve cognition in chronic schizophrenia patients, indicating it as a promising therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Coyle, JT., Tsai, G.[2018]

Current antipsychotic medications are not very effective in treating the negative and cognitive symptoms of schizophrenia, which significantly impact patients' quality of life.

Recent studies suggest that indirectly targeting the glycine modulatory site (GMS) of NMDA receptors, particularly through GlyT1 and DAO inhibitors, may provide a promising and safer approach to improve cognitive and negative symptoms in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia. Pei, JC., Luo, DZ., Gau, SS., et al.[2021]

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]

Citations

1. bioxceltherapeutics.gcs-web.com bioxceltherapeutics.gcs-web.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-topline-exploratory

Press Release - BioXcel Therapeutics BXCL501 demonstrated a significant mean reduction in mCGI-S score from baseline compared to placebo at 2 hours across 2,433 treated episodes ...

2. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-serenity-home-pivotal-phase-3

BioXcel Therapeutics Announces SERENITY At-Home ... BXCL501 achieved SERENITY At-Home's primary endpoint of being well tolerated in the at-home treatment of agitation episodes in patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05025605

Study Details | NCT05025605 | Determining Efficacy and ... This is a study of the efficacy and safety of BXCL501 in children and adolescents with acute agitation and either bipolar disorder or schizophrenia. Detailed ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/385703

Determining Efficacy and Safety of BXCL501 in Agitation ... This is a study of the efficacy and safety of BXCL501 in children and adolescents with acute agitation and either bipolar disorder or schizophrenia. Fill out a ...

5. igalmihcp.com igalmihcp.com/efficacy/exploratory-endpoints

Exploratory Endpoints - IGALMI® (dexmedetomidine) SERENITY II (bipolar disorder). 75% of patients had moderate agitation. 25% of patients had severe agitation.

6. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announce-topline-results-serenity-home

Press Release BXCL501 has been granted Breakthrough Therapy designation by the FDA for the acute treatment of agitation associated with dementia and Fast ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05658510

Study Details | NCT05658510 | Dexmedetomidine in the ... Part 2 of the study is a 12-week study to determine the safety of a BXCL501 120 mcg dose when used as needed for episodes of agitation at home. Official Title.