Xanomeline + Trospium for Schizophrenia

Not yet recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Collaborative Neuroscience Research, LLC

Must be taking: Atypical antipsychotics

Must not be taking: Tricyclics, Paroxetine, Antispasmodics, Antihistamines

Disqualifiers: Substance use disorder, Cardiovascular disease, Hepatic impairment, 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: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment for people with schizophrenia. The goal is to determine how well patients can transition from their current medication to a combination of xanomeline and trospium, a potential new drug that might offer better safety or effectiveness. Participants will switch medications either slowly over four weeks or more quickly over two weeks to identify the best method. This trial suits individuals managing schizophrenia with a stable dose of certain oral medications but who have concerns about side effects or effectiveness. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved treatment benefits more patients, offering a chance to improve current management of schizophrenia.

Will I have to stop taking my current medications?

Participants must stop taking their current atypical antipsychotic (AP) medication to switch to the trial medication. However, they can continue taking other non-prohibited psychotropic medications that are not secondary AP treatments.

What is the safety track record for Xanomeline/Trospium?

Research shows that the combination of xanomeline and trospium is generally well tolerated by people with schizophrenia. Studies have found this treatment effective, and patients have adjusted to it well. Earlier research indicated that common side effects, such as drowsiness or insomnia, were similar to those of other treatments. This suggests the treatment is generally safe for use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of Xanomeline and Trospium for treating schizophrenia because it offers a novel approach compared to typical antipsychotic medications. Unlike standard treatments that primarily target dopamine receptors, Xanomeline acts on muscarinic receptors in the brain, which may improve symptoms with potentially fewer side effects. Trospium, added to counteract possible side effects like nausea, is a peripheral anticholinergic that doesn't cross into the brain, maintaining a more focused action. This unique mechanism and combination could offer a new pathway to manage schizophrenia more effectively and safely.

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

Research has shown that the combination of xanomeline and trospium can effectively reduce symptoms of schizophrenia, particularly during severe episodes. Studies indicate that this treatment works well and is generally easy for patients to manage. It has a unique safety profile, potentially addressing needs unmet by current schizophrenia treatments. Notably, this is the first FDA-approved treatment for schizophrenia not classified as an antipsychotic, offering a new option for those seeking different therapies. Strong evidence supports this combination, showing promise for people with schizophrenia. Participants in this trial will be assigned to either a slower transition arm, reducing atypical antipsychotic treatment by 25% over four weeks, or an accelerated transition arm, reducing it by 50% over two weeks. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with schizophrenia who are currently on atypical antipsychotic medications. Participants will switch to a new treatment involving Xanomeline/Trospium, and their response and tolerance to the medication will be monitored.

Inclusion Criteria

Participant has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 12 weeks of Screening and is psychiatrically stable in the opinion of the Investigator

Individuals of childbearing potential (IOCBP) must be willing and able to adhere to the contraception guidelines as defined in Appendix 1

Participant is willing and able, in the opinion of the Investigator, to discontinue all secondary AP medications prior to Baseline visit

Exclusion Criteria

Pregnant, breastfeeding, or less than 3 months postpartum

Participant has a history of moderate to severe alcohol use disorder or a substance use disorder within the past 6 months or a positive urine drug screen for a substance other than cannabis at Screening or Baseline

History or presence of clinically significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the participant or the validity of the study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Pre-switch Baseline

Baseline visit before switching from atypical AP treatment to X/T

Treatment

Participants undergo an 8-week open-label treatment phase with X/T

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Xanomeline/Trospium

Trial Overview

The study tests how patients with schizophrenia transition from their current atypical antipsychotic treatments to a maintenance dose of Xanomeline/Trospium Chloride. The process aims to reflect real-world conditions in an 8-week open-label setup.

How Is the Trial Designed?

Group I: slower transition Experimental Treatment 1 Intervention

slower transition arm will reduce the atypical AP treatment at a rate of 25% of the initial treatment over a 4-week period

Group II: accelerated transition Experimental Treatment 1 Intervention

accelerated transition arm will reduce the atypical AP treatment at a rate of 50% of the initial treatment over a 2-week period,

Who Is Running the Clinical Trial?

Collaborative Neuroscience Research, LLC

Lead Sponsor

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

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]

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]

Second-generation antipsychotic long-acting injections (SGA-LAIs) generally have safety profiles similar to their oral counterparts, but they also present new safety concerns, such as the risk of postinjection syndrome and worsening psychosis, particularly with olanzapine-LAI.

The review highlighted serious risks associated with risperidone-LAI and paliperidone palmitate, including worsening psychotic symptoms and a concerning link to increased suicide rates, emphasizing the need for further research to clarify these safety signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects associated with second-generation antipsychotic long-acting injection treatment: a comprehensive systematic review. Gentile, S.[2018]

Citations

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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.

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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.

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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.

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nature.com

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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 ...

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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 ...

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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 ...

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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.