KarXT for Schizophrenia

No longer recruiting at 11 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Must not be taking: Antipsychotics

Disqualifiers: Cardiovascular, Pulmonary, Renal, others

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

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: Unknown

Duration: 11 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KarXT (also known as Cobenfy or Xanomeline/Trospium chloride) for people with schizophrenia. Researchers aim to determine the safety and effectiveness of KarXT when taken on an empty stomach and with food. It targets adults diagnosed with schizophrenia who are willing to stop other antipsychotic medications and do not have severe mental health symptoms. Participants should not have other major health issues or a history of not responding to schizophrenia medications. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking all antipsychotic medications before the baseline visit.

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

Research shows that KarXT, a combination of xanomeline and trospium chloride, is generally well tolerated by people with schizophrenia. Previous studies found it effective and safe for those experiencing severe mental health episodes. Side effects such as worsening psychosis, suicidal thoughts, reduced appetite, drowsiness, and insomnia were similar to those of other treatments. However, there is a risk of urinary difficulties and concerns for patients with liver issues. Overall, the treatment appears promising with manageable side effects. ^{1 2 3 4 5}

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

Unlike the standard antipsychotic medications for schizophrenia, which typically target dopamine receptors, KarXT is unique because it works on muscarinic receptors in the brain. This novel mechanism of action is exciting for researchers as it holds the potential to reduce symptoms of schizophrenia with possibly fewer side effects related to dopamine pathways, such as weight gain and movement disorders. Additionally, KarXT combines two components, xanomeline and trospium, which together help in enhancing efficacy while minimizing peripheral side effects.

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

Studies have shown that KarXT, a combination of xanomeline and trospium chloride, effectively treats schizophrenia, particularly during severe symptom episodes. Research indicates that this treatment not only reduces symptoms but also causes fewer side effects. Specifically, previous patients with schizophrenia experienced significant improvements when taking xanomeline-trospium. This combination targets specific brain areas believed to reduce symptoms of psychosis. Overall, evidence supports KarXT as a promising option for managing schizophrenia symptoms. Participants in this trial will receive KarXT either on an empty stomach or with food to evaluate its effectiveness and safety under these conditions. ^{2 3 6 7 8}

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 adults with schizophrenia. Specific eligibility criteria are not provided, but typically participants must meet diagnostic criteria for schizophrenia and be stable enough to participate in a clinical study.

Inclusion Criteria

I am willing to stop taking all antipsychotic medications before my first visit.

Positive and Negative Syndrome Scale (PANSS) total score of ≤ 80 at screening and Baseline

I have been diagnosed with schizophrenia by a psychiatrist.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

History of allergy/hypersensitivity to KarXT

I have not been diagnosed with a mental health condition other than schizophrenia in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KarXT with a slow titration and food effect assessment

11 weeks

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, focusing on how safe and effective it is when the dose is increased slowly. It also looks at whether taking the drug with food affects its performance.

How Is the Trial Designed?

Group I: KarXT on empty stomach and with food Experimental Treatment 1 Intervention

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

Approved in United States as Cobenfy for:

• Schizophrenia

Who Is Running the Clinical Trial?

Karuna Therapeutics

Lead Sponsor

Trials

17

Recruited

4,100+

Published Research Related to This Trial

In a 5-week trial involving 125 patients with schizophrenia, KarXT (xanomeline-trospium) showed a significant improvement in cognitive performance among those with clinically meaningful cognitive impairment, with a robust effect size of 0.50.

When outliers were removed, KarXT demonstrated a statistically significant cognitive benefit compared to placebo (p=0.04), suggesting that it may effectively enhance cognition independently of overall symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study. Sauder, C., Allen, LA., Baker, E., et al.[2023]

In a 5-week randomized, double-blind study involving 148 hospitalized adults with schizophrenia, KarXT (a combination of xanomeline and trospium chloride) showed significantly greater improvement in symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS).

The study utilized blinded, site-independent ratings from audio recordings of PANSS interviews, which confirmed the efficacy of KarXT and demonstrated a high correlation with site-based ratings, suggesting this method could enhance the reliability of clinical assessments in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial. Targum, SD., Murphy, C., Breier, A., et al.[2022]

Brexpiprazole at doses of 2 mg and 4 mg significantly reduced symptoms of acute schizophrenia compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions Scale (CGI) after 6 weeks.

The treatment was generally well-tolerated, with akathisia being the most common side effect, and only moderate weight gain observed, indicating that brexpiprazole is a viable option for managing acute schizophrenia exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Correll, CU., Skuban, A., Ouyang, J., et al.[2022]

In a 5-week study involving 170 patients with schizophrenia, the combination treatment KarXT (xanomeline-trospium) showed significantly higher response rates compared to placebo, with 59% of patients achieving at least a 20% reduction in symptoms by week 2.

KarXT demonstrated early and sustained improvements across all symptom domains of schizophrenia, including positive and negative symptoms, with significant effects observed as early as 2 weeks into treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipsychotic Efficacy of KarXT (Xanomeline-Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study. Weiden, PJ., Breier, A., Kavanagh, S., et al.[2022]

In a phase 1 clinical trial with 68 healthy volunteers, the combination of xanomeline and trospium (KarXT) significantly reduced cholinergic adverse events by 46% compared to xanomeline alone, improving tolerability.

KarXT also showed a better safety profile, with no cases of syncope and lower rates of postural dizziness compared to xanomeline alone, while maintaining xanomeline's pharmacokinetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence of trospium's ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. Breier, A., Brannan, SK., Paul, SM., et al.[2023]

Brexpiprazole, a newly approved medication for schizophrenia, was found to be well-tolerated with statistically insignificant adverse reactions, making it a promising option for patients.

Unlike some other antipsychotics, brexpiprazole has a favorable metabolic profile, which is important given the metabolic side effects associated with many atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: A New Treatment Option for Schizophrenia. Scarff, JR.[2020]

KarXT, which contains xanomeline, targets muscarinic M1 and M4 receptors instead of the traditional dopamine D2 receptor, showing promise in treating schizophrenia based on successful phase 3 trials.

The effectiveness of muscarinic receptor activation may vary among individuals with schizophrenia, suggesting the need for personalized treatment approaches to identify those who would benefit most from this type of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscarinic M1 and M4 receptor agonists for schizophrenia: promising candidates for the therapeutic arsenal. Dean, B.[2023]

In a 5-week phase 2 study involving 179 patients with schizophrenia, KarXT demonstrated significant efficacy and was generally well tolerated, with a low overall burden of adverse events (AEs).

Most AEs related to muscarinic receptor activity were mild and transient, with no patients discontinuing treatment due to these side effects, indicating a favorable safety profile for KarXT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of KarXT (xanomeline-trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia. Correll, CU., Angelov, AS., Miller, AC., et al.[2022]

Brexpiprazole has been shown to significantly improve symptoms of schizophrenia in short-term studies, with a clinically meaningful reduction in the Positive and Negative Syndrome Scale (PANSS) total score, indicating its efficacy as a treatment option.

The medication also demonstrated a favorable safety profile, with minimal side effects and no significant safety concerns, making it a viable long-term maintenance therapy for adults with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies. Marder, SR., Hakala, MJ., Josiassen, MK., et al.[2018]

Cariprazine is an effective treatment for adults with schizophrenia and manic or mixed episodes of bipolar disorder, showing a favorable tolerability profile with common side effects like akathisia and nausea.

It is taken once daily and requires dose adjustments for patients on certain medications, making it a convenient option, but it should be avoided in those with severe liver or kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine for Schizophrenia and Bipolar Disorder. Scarff, JR.[2020]

Citations

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

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

2. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X24007879

Efficacy, tolerability, and safety of xanomeline-trospium ... Xanomeline-trospium is an effective treatment for schizophrenia with a unique tolerability profile, potentially addressing unmet needs.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39659157/

The Impact of Xanomeline and Trospium Chloride on ... ... xanomeline/trospium monotherapy in patients with acute schizophrenia. ... efficacy for psychosis. Evaluation of xanomeline/trospium's ...

4. nature.com nature.com/articles/s41537-024-00525-6

Efficacy of xanomeline and trospium chloride in ... The efficacy of xanomeline/trospium (formerly known as KarXT) for the treatment of adults with schizophrenia experiencing acute psychosis was ...

5. cobenfyhcp.com cobenfyhcp.com/efficacy/long-term-data

Long-term efficacy data of COBENFY for schizophrenia Long-term efficacy data of COBENFY for schizophrenia. Two 52-week, open-label studies evaluated long-term safety and efficacy.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38691387/

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

7. cobenfyhcp.com cobenfyhcp.com/safety

Cobenfy™ (xanomeline and trospium chloride) Safety Data See 52-week safety data for COBENFY in adults with schizophrenia · Risk of Urinary Retention: · Risk of Use in Patients with Hepatic Impairment: · Risk of Use in ...

8. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-ARISE-Trial-Evaluating-Cobenfy-xanomeline-and-trospium-chloride-as-an-Adjunctive-Treatment-to-Atypical-Antipsychotics-in-Adults-with-Schizophrenia/default.aspx

Cobenfy as an adjunctive treatment to atypical ... Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels and behaves. There are three symptom ...