KarXT for Schizophrenia

Recruiting at 269 trial locations

Overseen By Michael Banov, Site 169

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Must be taking: Antipsychotics

Disqualifiers: Suicidal behavior, Pregnant, Urinary retention, others

Stay on Your Current Meds You can continue your current medications while participating

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: 52 weeks

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of a new treatment called KarXT for individuals with schizophrenia who haven't experienced sufficient improvement with their current medication. KarXT combines two drugs, xanomeline and trospium chloride, taken twice daily, to determine if it can better manage symptoms. This trial targets those who participated in a previous study with KarXT and still do not see the desired results from their regular antipsychotic medication. Participants must have a stable living situation and someone to assist with study activities. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for schizophrenia.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current antipsychotic medication. Participants are required to stay on the same antipsychotic drug and dose they were using in the previous study.

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

Research has shown that KarXT, a combination of xanomeline and trospium chloride, is generally well-tolerated by people with schizophrenia. In earlier studies, patients found KarXT effective and manageable. The most common side effects were mild to moderate, such as nausea and headache, while serious side effects were rare.

Safety data from another study indicated that most people could use KarXT without major problems. While some side effects might occur, they are not severe for most patients. For those considering joining a trial, this information suggests that KarXT is relatively safe based on current knowledge. ^{1 2 3 4 5}

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

KarXT is unique because it combines xanomeline and trospium chloride to treat schizophrenia in a novel way. Unlike most current antipsychotics that primarily target dopamine receptors, KarXT targets muscarinic receptors, which may reduce the risk of common side effects like weight gain and sedation. Researchers are excited about this treatment because it offers a new mechanism of action that could potentially improve symptoms with fewer side effects, making it a promising alternative for patients who struggle with existing therapies.

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

Research has shown that KarXT, a combination of xanomeline and trospium chloride, helps treat schizophrenia. Studies have found that this treatment reduces symptoms of psychosis and is generally well tolerated by patients. Earlier findings suggest that KarXT has a unique tolerance profile, which might address needs unmet by current schizophrenia treatments. Overall, the evidence supports KarXT as an effective option for managing schizophrenia symptoms. ^{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 adults aged 18-60 with schizophrenia who haven't responded well to current antipsychotic treatments. Participants must have completed the ARISE Study, be in a stable living situation, and have a reliable informant. Women of childbearing age must use contraception.

Inclusion Criteria

Subject resides in a stable living situation, in the opinion of the Investigator

I can sign a consent form before any tests are done.

Subject has identified a reliable informant/caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant can complete the study visits assessments via phone (as per local regulations). In Bulgaria, the informant must be physically present at all study visits

Exclusion Criteria

Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or Columbia-Suicide Severity Rating Scale (C-SSRS) as confirmed by the following: Subject answers 'Yes' to 'suicidal ideation' Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS. Non-suicidal self-injurious behavior is not exclusionary

I am currently pregnant.

History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjunctive KarXT for long-term safety and tolerability assessment

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving adjunctive KarXT to assess long-term safety and tolerability

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Xanomeline and Trospium Chloride Capsules

Trial Overview The study tests long-term safety and tolerability of KarXT (xanomeline and trospium chloride capsules) as an add-on treatment for schizophrenia over 52 weeks. It's open-label, meaning everyone knows they're getting the drug, not a placebo.

How Is the Trial Designed?

Group I: Drug: KarXT Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Karuna Therapeutics

Lead Sponsor

Trials

17

Recruited

4,100+

Published Research Related to This Trial

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 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 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]

Xanomeline, a cholinergic agonist, shows potential for improving symptoms of schizophrenia, particularly when combined with trospium, a peripheral cholinergic antagonist that may help mitigate xanomeline's adverse effects.

Initial studies of the xanomeline and trospium combination indicate promise in treating schizophrenia, with common side effects including constipation, dry mouth, and nausea, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xanomeline and Trospium: A Potential Fixed Drug Combination (FDC) for Schizophrenia-A Brief Review of Current Data. Singh, A.[2023]

A combination of xanomeline and trospium showed improved tolerability and significant antipsychotic effects in a randomized study of 182 patients with acute psychosis, with a notable reduction in symptoms as measured by the PANSS score.

The study suggests that targeting the cholinergic system may offer a new treatment avenue for schizophrenia, as the combination therapy demonstrated superior efficacy in reducing both positive and negative symptoms compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. Kidambi, N., Elsayed, OH., El-Mallakh, RS.[2023]

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 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]

Xanomeline, a muscarinic receptor agonist, has shown promise in reducing psychotic behaviors in Alzheimer's patients and may be effective for treating psychotic symptoms in schizophrenia, as it shares a similar pharmacologic profile with atypical antipsychotics like clozapine and olanzapine.

Unlike traditional dopamine antagonist antipsychotics such as haloperidol, xanomeline does not induce catalepsy in rats, suggesting it may have a better safety profile while still effectively managing psychotic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. Shannon, HE., Rasmussen, K., Bymaster, FP., et al.[2019]

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

Efficacy and Safety of Xanomeline-Trospium Chloride in ... Xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia.

3. 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 ...

4. 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.

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

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

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40047530/

Safety and Tolerability of Xanomeline and Trospium ... ... schizophrenia experiencing acute psychosis. Methods: Pooled analyses were performed on safety data from the 5-week, randomized, double-blind ...

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

A Study to Assess Efficacy and Safety of KarXT in Acutely ... Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled ...

8. cobenfyhcp.com cobenfyhcp.com/safety

Cobenfy™ (xanomeline and trospium chloride) Safety Data Learn about the safety profile & adverse reactions associated with Cobenfy™ for adult patients with schizophrenia. See Safety Info and Full Prescribing ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395624006757

Efficacy and safety of xanomeline-trospium chloride in ... Schizophrenia and psychosis in children and adolescents: An inspiring journey of scientific progress and the rich influences of history and religion. 2025, ...