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

172 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Xanomeline/Trospium for treating schizophrenia?

Initial studies show that the combination of xanomeline and trospium significantly improved symptoms in patients with schizophrenia, with a notable reduction in the Positive and Negative Syndrome Scale (PANSS) score compared to placebo. This suggests that the drug may be effective in treating schizophrenia by targeting the cholinergic system, which is different from traditional treatments that focus on dopamine. ^{1 2 3 4 5}

Is the Xanomeline/Trospium combination safe for humans?

The combination of Xanomeline and Trospium has been studied for schizophrenia and shows improved tolerability compared to Xanomeline alone, with common side effects being constipation, dry mouth, and nausea. Trospium helps reduce the severe side effects previously seen with Xanomeline, making the combination generally safer for human use. ^{1 2 3 4 5}

How is the drug Xanomeline/Trospium unique for treating schizophrenia?

Xanomeline/Trospium is unique because it combines xanomeline, which targets specific brain receptors (M1/M4 muscarinic receptors) to reduce psychotic symptoms, with trospium, which helps minimize side effects by blocking peripheral cholinergic effects. This combination offers a novel approach compared to traditional antipsychotics that often target dopamine receptors. ^{1 2 3 4 6}

What is the purpose of this trial?

This is an open label study of the treatment satisfaction, efficacy and tolerability of xanomeline/ trospium in a population of 172 participants diagnosed with schizophrenia in the early phase of illness. Participants will be followed for 24 weeks with scheduled assessments conducted by centralized raters, local mental health professionals and self-assessments completed by patients. Recruitment will be based on insufficient efficacy of previous antipsychotic or due to dissatisfaction with treatment as a result of unacceptable side effects on previous antipsychotic/patient choice, with approximately 50% for each enrollment criteria. Participants who present with both insufficient efficacy and unacceptable side effects will be considered as belonging to the insufficient efficacy subgroup. Treatment and assessments will be identical for the 2 groups. Primary outcome for participants enrolled will be improvement in overall treatment satisfaction as measured by the MSQ.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

References

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

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

2. 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]

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

Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. [2023]

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

Comparative analysis of pharmacological properties of xanomeline and N-desmethylclozapine in rat brain membranes. [2018]