KarXT for Schizophrenia

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

173 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of slowly increasing dose and food effect of KarXT in adult participants with schizophrenia.

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

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

What data supports the idea that KarXT for Schizophrenia is an effective drug?

The available research shows that KarXT is effective for treating schizophrenia. In a study, KarXT improved symptoms in patients with schizophrenia and was generally well tolerated. Another study found that KarXT helped improve cognitive function in patients with cognitive impairment. Compared to a placebo, KarXT showed significant positive effects, especially when outliers were removed from the analysis. Additionally, KarXT does not target the dopamine D2 receptor, which is different from many other schizophrenia treatments, making it a promising alternative. ^{1 2 3 4 5}

What safety data is available for KarXT in treating schizophrenia?

The safety, tolerability, and efficacy of KarXT, a combination of xanomeline and trospium chloride, were assessed in a 5-week, randomized, double-blind study involving hospitalized adults with schizophrenia experiencing an acute exacerbation of psychosis (EMERGENT-1; ClinicalTrials.gov identifier: NCT3697252). The study included site-independent ratings from audio-digital recordings of PANSS interviews, ensuring unbiased assessment of treatment emergent adverse events (TEAEs). ^{6 7 8 9 10}

Is the drug KarXT a promising treatment for schizophrenia?

Yes, KarXT is a promising drug for treating schizophrenia. It has shown success in clinical trials by effectively reducing symptoms without targeting the usual dopamine receptors, which is a new approach. The drug combines xanomeline, which helps with symptoms, and trospium, which reduces side effects, making it generally well tolerated. ^{1 2 4 5 6}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

I have been diagnosed with schizophrenia by a psychiatrist.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Evidence of trospium's ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. [2023]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Germany 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial. [2022]

7. United States 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. [2022]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies. [2018]

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

Cariprazine for Schizophrenia and Bipolar Disorder. [2020]