KarXT for Mental Disorders

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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to assess the safety, tolerability, and pharmacokinetics (PK) of 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 in adolescents with psychiatric disorders.

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.

How is the drug KarXT different from other treatments for mental disorders?

KarXT is unique because it combines two components, xanomeline and trospium, which work together to target specific brain receptors differently than traditional treatments. This combination aims to improve symptoms with potentially fewer side effects compared to existing medications for mental disorders. ^{1 2 3 4 5}

Research Team

Bristol Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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-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, 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Toward Synergies of Ketamine and Psychotherapy. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Using classification and regression tree modelling to investigate treatment response to a single low-dose ketamine infusion: Post hoc pooled analyses of randomized placebo-controlled and open-label trials. [2021]

3. United States 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. [2023]

5. United States 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. [2022]