Xanomeline + Trospium Chloride for Healthy Subjects

No longer recruiting at 2 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Karuna Therapeutics

Disqualifiers: Cancer, Syncope, Orthostatic hypotension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effects of a new combination of medicines, KarXT and KarX-EC, both containing xanomeline and trospium chloride. The researchers aim to understand the safety profile and metabolism of these medicines, particularly in individuals of Japanese ethnicity, and how omeprazole might alter their effects. The trial seeks healthy adults and elderly individuals, including specific groups of Japanese descent, with a healthy body mass index (BMI) and normal kidney function. Participants should not have major health issues or a recent history of cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination of medicines.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KarXT, a combination of xanomeline and trospium chloride, is generally well tolerated. Studies have found that the most common side effects are mild and often involve the stomach, such as nausea and constipation. Some participants also experienced headaches and dry mouth, while serious side effects remain rare.

The treatment's safety relates to its impact on specific brain receptors. Although nervous system effects like dizziness or confusion can occur, they are uncommon. Overall, KarXT has undergone testing in other studies and is considered safe enough for further trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about KarX-EC and KarXT because they offer a fresh approach to treating conditions like cognitive disorders. Unlike traditional medications, KarXT combines xanomeline, a muscarinic receptor agonist, with trospium chloride, which helps minimize side effects by targeting peripheral receptors. This unique combination aims to enhance cognitive function while reducing common side effects associated with existing treatments. By focusing on different pathways, this treatment has the potential to improve patient outcomes in ways that standard therapies haven't achieved yet.

What evidence suggests that this trial's treatments could be effective?

Research shows that KarXT, a combination of xanomeline and trospium chloride, helps reduce symptoms of schizophrenia. Studies have found that this treatment improves symptoms of psychosis and is generally well-tolerated. Compared directly with a placebo, patients taking KarXT showed significant improvements. The treatment is easier to handle than some other options. Although this trial involves different groups of healthy participants to assess safety and drug effects, existing evidence supports KarXT's effectiveness in treating schizophrenia. ^{4 5 6 7 8}

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 healthy adults and elderly people of Japanese ethnicity. Participants will be tested with different drug combinations to see how their bodies handle them. Those with certain health conditions or on conflicting medications may not qualify.

Inclusion Criteria

I am a healthy Japanese adult aged 19-55, with Japanese parents, a BMI of 18-32, and normal kidney function.

I am between 56 and 90 years old, of Japanese descent, with a healthy weight and kidney function.

I am 19-55 years old, with a BMI of 18-32 and healthy kidney function.

Exclusion Criteria

All Participants (Groups A, B, C, and D): Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee. Participant has a history of syncope and/or symptomatic orthostatic hypotension in the year prior to Day 1. History of cancer that has not been in full remission for >5 years (except basal cell skin cancer or squamous cell skin cancer with history of curative treatment and no recurrence for > 1 year prior to the screening visit).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of KarXT + KarX-EC capsules versus KarXT capsules to assess safety, tolerability, and pharmacokinetics

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and pharmacokinetic parameters

4 weeks

Open-label extension

Participants may continue to receive the study drug to assess the effect of omeprazole on the pharmacokinetics of xanomeline and trospium

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarX-EC
• KarXT

Trial Overview The study is testing the safety and body's handling (pharmacokinetics) of a drug combo called KarXT + KarX-EC versus just KarXT, and also looking at how an acid-reducing medicine, omeprazole, affects this process in healthy participants.

How Is the Trial Designed?

Group I: Group D Experimental Treatment 3 Interventions

Group II: Group C Experimental Treatment 3 Interventions

Group III: Group B Experimental Treatment 2 Interventions

Group IV: Group A Experimental Treatment 2 Interventions

KarX-EC 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+

Published Research Related to This Trial

Sensitization to benzalkonium chloride (BAK) and benzethonium chloride (BEC) is rare but does occur, with 75% of patients showing co-reactions, indicating a potential cross-sensitivity between the two.

Testing with BAK at 0.15% in both aqueous and petrolatum forms significantly improves the detection of allergic contact dermatitis (ACD), identifying 91% of cases compared to only using the standard 0.1% aqueous concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitization prevalence for benzalkonium chloride and benzethonium chloride. Dao, H., Fricker, C., Nedorost, ST.[2022]

The study assessed the tolerability of a commercial preparation containing 1-7 Asu-eel and salmon calcitonin, along with their excipients, using an ex-vivo frog palate model that mimics human nasal mucociliary clearance, and found that these preparations did not significantly affect mucociliary transport velocity, indicating good tolerability.

However, higher concentrations of ammonium glycyrrhyzinate (10% and 20%) and benzalkonium chloride (0.05% and 0.1%) significantly slowed mucociliary transport, suggesting that while the tested formulations are safe, caution should be exercised with higher concentrations of these excipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of calcitonin nasal preparations and their excipients on mucociliary clearance in an ex-vivo frog palate test. Braga, PC., Piatti, G., Dal Sasso, M., et al.[2019]

Topical dorzolamide therapy was associated with irreversible corneal decompensation in nine patients with pre-existing corneal endothelial issues, occurring after an average of 7.8 weeks of treatment.

The study highlights the need for further research into the long-term effects of dorzolamide on corneal health, especially in patients with a history of eye surgeries or endothelial compromise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible corneal decompensation in patients treated with topical dorzolamide. Konowal, A., Morrison, JC., Brown, SV., et al.[2019]

Trospium chloride (TCL) has been evaluated in over 20 clinical trials and post-marketing studies involving more than 10,000 patients, providing a robust data set for its clinical efficacy and safety.

The pharmacological and clinical pharmacokinetic data discussed in the study help to better interpret the results of these trials, suggesting that TCL is a well-studied medication with established clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trospium chloride--an effective drug in the treatment of overactive bladder and detrusor hyperreflexia. Höfner, K., Oelke, M., Machtens, S., et al.[2019]

In a study involving 388 patients with open-angle glaucoma or ocular hypertension, the BAK-free formulation of travoprost/timolol showed equivalent efficacy in lowering intraocular pressure (IOP) compared to the BAK-preserved formulation, with mean IOP reductions of 8.0 mmHg and 8.4 mmHg respectively.

Both formulations had similar safety profiles, with the most common side effect being eye hyperemia, occurring in 11.8% of the BAK-free group and 13.0% of the BAK group, indicating that the BAK-free option is a safe alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy. Kitazawa, Y., Smith, P., Sasaki, N., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04659161

NCT04659161 | A Study to Assess Efficacy and Safety of ... The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) ...

2. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2818047

Efficacy and Safety of Xanomeline-Trospium Chloride in ... This randomized clinical trial evaluates the efficacy and safety of xanomeline-trospium chloride vs placebo in adults with schizophrenia.

3. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-ARISE-Trial-Evaluating-Cobenfy-xanomeline-and-trospium-chloride-as-an-Adjunctive-Treatment-to-Atypical-Antipsychotics-in-Adults-with-Schizophrenia/default.aspx

Cobenfy as an adjunctive treatment to atypical ... Cobenfy as an adjunctive treatment to an atypical antipsychotic was associated with improvements in symptoms of schizophrenia compared to placebo plus an ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11063924/

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.

5. 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.

6. cobenfyhcp.com cobenfyhcp.com/safety

Cobenfy™ (xanomeline and trospium chloride) Safety Data Most Common Adverse Reactions (≥5% and at least twice placebo): nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/216158s000lbl.pdf

Reference ID: 5453521 - accessdata.fda.gov Therefore, anticholinergic adverse reactions (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) are expected to be ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9719488/

Safety and tolerability of KarXT (xanomeline–trospium) in a ... KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.