KarXT for Mental Disorders

No longer recruiting at 7 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Diabetes, Liver disease, Glaucoma, others

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

Compensation: Varies

Number of Visits: 15

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KarXT to assess its safety and how the body processes it in teens with certain mental disorders. Researchers focus on conditions such as schizophrenia, bipolar disorder, ADHD, Tourette's disorder, and autism. The trial targets individuals who have been stable recently, with no major issues like hospitalization or self-harm in the last six months. Different groups will receive various doses and forms of the medication. Participants will contribute to understanding how KarXT could potentially manage symptoms of these psychiatric disorders. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinator or your doctor for guidance.

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

Research has shown that KarXT, a combination of xanomeline and trospium chloride, has generally been well-tolerated in past studies. Users of KarXT have experienced side effects similar to those expected from its ingredients, such as nausea and other effects related to the drug's interaction with certain brain receptors.

In long-term studies, KarXT maintained a consistent safety record over a year of treatment, with no unexpected problems arising. The treatment's side effects remained steady and predictable. Overall, based on past research, KarXT appears to be a promising option, with manageable and expected side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

KarXT is unique because it targets both muscarinic and nicotinic receptors in the brain, which is different from standard treatments for mental disorders that typically focus on just one type of receptor. This dual action has the potential to improve symptoms more effectively and with fewer side effects. Researchers are excited about KarXT because it offers a new approach to treating mental disorders, which could lead to better outcomes for patients who don't respond well to current medications.

What evidence suggests that KarXT might be an effective treatment for psychiatric disorders?

Research shows that KarXT, which participants in this trial may receive, may help treat schizophrenia symptoms. Studies have found it can significantly improve both positive symptoms, such as hallucinations, and negative symptoms, such as lack of motivation. Long-term use of KarXT, up to 52 weeks, has been linked to ongoing symptom relief. Additionally, KarXT has reduced overall symptom severity compared to a placebo. The treatment is generally well tolerated, with manageable side effects. ^{2 6 7 8 9}

Who Is on the Research Team?

Bristol Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adolescents with psychiatric disorders. Participants must meet specific health criteria and have a diagnosis related to the study's focus on mental illness or problem behavior.

Inclusion Criteria

LAR must have signed and dated an IRB/IEC-approved ICF in accordance with regulatory, local, and institutional guidelines

Participant is judged by the investigator to be clinically stable (eg, no psychiatric hospitalization within the last 6 months; no imminent risk of suicide or injury to self, others, or property)

I have been diagnosed with a psychiatric condition like schizophrenia, bipolar disorder, ADHD, Tourette's, or autism.

Exclusion Criteria

Other protocol defined inclusion/exclusion criteria apply

Participant has a risk for suicidal behavior during the study, as determined by the investigator's clinical judgment and C-SSRS

I have a history of Gilbert's Disease or liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses and ratios of xanomeline and trospium chloride in an IR capsule (KarXT) and dual-burst release of xanomeline with immediate-release trospium chloride

2 weeks

Up to Day 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT

Trial Overview The trial is testing KarXT, which combines xanomeline and trospium chloride in different doses and ratios, to see how safe it is, how well it's tolerated by patients, and how their bodies process it.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 2 Interventions

Group II: Cohort 2 Experimental Treatment 2 Interventions

Group III: Cohort 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Ketamine-assisted psychotherapy (KAP) shows promise as a treatment for adolescents with various mental health disorders, with four cases demonstrating symptomatic and functional improvements after treatment.

The treatment was well-tolerated, and family involvement was highlighted as crucial for success, suggesting that KAP could significantly enhance the options available for adolescent psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. Wolfson, PE., Andries, J., Ahlers, D., et al.[2023]

Ketamine, traditionally used as an anesthetic since the 1970s, shows significant potential as a treatment for depression when combined with psychological therapies, based on both anecdotal evidence and clinical research.

The review proposes a novel approach to using esketamine (a specific form of ketamine) alongside Acceptance and Commitment Therapy (ACT), highlighting the importance of ketamine's psychoactive effects in enhancing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Synergies of Ketamine and Psychotherapy. Mathai, DS., Mora, V., Garcia-Romeu, A.[2022]

Intravenous (IV) racemic ketamine has strong evidence (Level 1) for its rapid antidepressant effects in adults with treatment-resistant depression (TRD), making it a viable third-line treatment option.

While single-dose IV ketamine is effective, the evidence for multiple infusions is limited (Level 3), and potential adverse effects such as dissociative symptoms and hypertension must be carefully monitored, especially for non-IV formulations which have even less evidence supporting their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur. Swainson, J., McGirr, A., Blier, P., et al.[2021]

Ketamine, while effective as a rapid antidepressant in treatment-resistant depression, showed no sustained benefits for obsessive-compulsive disorder (OCD) in a small trial of 10 subjects, with only some experiencing acute antidepressant effects.

Concerns arose regarding delayed-onset dysphoria and increased anxiety or suicidal thoughts in patients with OCD and other psychiatric issues, highlighting the need for caution and further research before using ketamine off-label in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder. Niciu, MJ., Grunschel, BD., Corlett, PR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11144989/

KarXT for schizophrenia–effectiveness and value Initial data from acute settings suggest that weight gain may not be an important side effect of KarXT, but longer-term data are needed to confirm this.

2. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-New-Interim-Long-Term-Efficacy-Data-from-the-EMERGENT-4-Trial-Evaluating-KarXT-in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx

Long-term treatment with KarXT was associated ... In the interim analysis, KarXT was associated with significant improvement in symptoms of schizophrenia across all efficacy measures at 52 weeks ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0920996424003724

Efficacy of KarXT on negative symptoms in acute ... For NS, KarXT vs placebo showed significant improvement from baseline to Week 5 in two of the trials; the third trial (NCT04738123 ) showed significant ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)02190-6/abstract

Efficacy and safety of the muscarinic receptor agonist ... In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential ...

5. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06696-5

Does KarXT (xanomeline-trospium) represent a novel ... In our meta-analysis, KarXT demonstrated a significant reduction in efficacy outcomes, such as PANSS total and subscale scores, suggesting its ...

6. nature.com nature.com/articles/s41537-022-00320-1

Safety and tolerability of KarXT (xanomeline–trospium) in a ... KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04659161

NCT04659161 | A Study to Assess Efficacy and Safety of ... This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in ...

8. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2818047

Efficacy and Safety of Xanomeline-Trospium Chloride in ... Xanomeline-trospium is efficacious and well tolerated in people with schizophrenia experiencing acute psychosis.

9. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-New-Pooled-Interim-Long-Term-Safety-and-Metabolic-Outcomes-Data-from-the-EMERGENT-Program-Evaluating-KarXT-in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx

KarXT demonstrated a favorable long-term metabolic ... In the long-term studies, KarXT was generally well-tolerated across 52 weeks of treatment, with a side effect profile consistent with prior ...