Xanomeline/Trospium for Schizophrenia

Overseen By Cristina Gonzalez

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanguard Research Group

Must be taking: Antipsychotics

Must not be taking: Clozapine, Anticholinergics

Disqualifiers: Substance abuse, Cardiovascular, Glaucoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination, xanomeline and trospium, for individuals with early-stage schizophrenia. The main goal is to determine if this treatment can improve satisfaction and manage symptoms better than previous medications. It is open to those who find their current antipsychotic treatment unsatisfactory due to poor results or bothersome side effects. Participants should have been treated for schizophrenia for less than five years and feel their current medication isn't effective or causes issues. The study will follow participants for 24 weeks to measure satisfaction with the new treatment. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients, offering a chance to enhance the treatment experience.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you will need to stop taking anticholinergic drugs (like benztropine) within 1 week after starting the trial medication. You can stay on other non-prohibited medications that are not your primary antipsychotic.

What is the safety track record for xanomeline/trospium?

Research has shown that the combination of xanomeline and trospium is generally well tolerated by people with schizophrenia. Studies have found this treatment effective and safe for those experiencing severe symptoms. In these studies, side effects such as worsening symptoms, suicidal thoughts, reduced appetite, drowsiness, and sleep problems were similar to those seen with other treatments. Overall, patients handled the treatment well, making it a promising option for managing schizophrenia. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Xanomeline/Trospium is unique because it combines two active compounds that target schizophrenia symptoms differently than typical antipsychotics. Most treatments for schizophrenia, like risperidone and olanzapine, work by blocking dopamine receptors. However, Xanomeline acts on muscarinic receptors, which are part of the cholinergic system, offering a novel mechanism of action. Trospium is included to reduce potential side effects associated with Xanomeline. Researchers are excited about this treatment because it could provide relief for patients who don't respond well to current medications and may have a different side effect profile.

What evidence suggests that Xanomeline/Trospium might be an effective treatment for schizophrenia?

Research has shown that xanomeline-trospium, the treatment under study in this trial, helps reduce symptoms of psychosis in people with schizophrenia. It effectively aids those experiencing severe episodes and is generally well tolerated. This treatment stands out because it may cause fewer side effects, which is crucial for many patients. The combination of xanomeline and trospium is also the first FDA-approved treatment for schizophrenia that differs from the usual drugs used for this condition. Overall, the evidence appears promising for those who haven't found other treatments satisfactory. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with early phase schizophrenia who have either found previous antipsychotic treatments ineffective or experienced unacceptable side effects. Participants should be willing to undergo a 24-week treatment with Xanomeline/Trospium and complete various assessments.

Inclusion Criteria

I started my first antipsychotic treatment for psychosis less than 5 years ago.

I am not satisfied with my current medication.

Subject can provide informed consent. Female participants must be willing and capable to use birth control throughout the time of the trial

Exclusion Criteria

Any DSM-5 disorder other than schizophrenia within 6 months before screening

Active substance or alcohol abuse or dependence in the past 6 months

Urine toxicology screen is positive for specific substances

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive xanomeline/trospium for 24 weeks with scheduled assessments

24 weeks

Regular assessments by centralized raters, local mental health professionals, and self-assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Xanomeline/Trospium

Trial Overview The study tests the satisfaction, efficacy, and tolerability of Xanomeline/Trospium in treating schizophrenia. It involves regular evaluations by mental health professionals and self-assessments by patients over a six-month period.

How Is the Trial Designed?

Group I: Xanomeline/Trospium Active Control 1 Intervention

Cobenfy

Who Is Running the Clinical Trial?

Vanguard Research Group

Lead Sponsor

Trials

2

Recruited

690+

Bristol-Myers Squibb

Industry 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

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]

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]

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. 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.

2. 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.

3. 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.

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. psychiatrist.com psychiatrist.com/jcp/real-world-implementation-xanomeline-trospium-schizophrenia-consensus-report/

Real-World Implementation of Xanomeline-Trospium in ... The fixed-dose combination of xanomeline and trospium (XT) is the first FDA-approved treatment for schizophrenia that is not classified as an ...

6. psychiatrist.com psychiatrist.com/news/stable-outcomes-transition-xanomeline-trospium-schizophrenia/

Stable Outcomes Seen in Transition to Xanomeline- ... Stable Outcomes Seen in Transition to Xanomeline-Trospium Therapy for Schizophrenia · Clinical Relevance · Symptom Stability During Transition to ...

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.focus.20250022

Xanomeline-Trospium for the Treatment of Schizophrenia XT demonstrated efficacy and safety. It was well tolerated in adults with schizophrenia with acute psychosis who received 4 weeks of treatment.