Xanomeline + Trospium Chloride for Healthy Subjects

Recruiting at2 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Karuna Therapeutics

Disqualifiers: Cancer, Syncope, Orthostatic hypotension, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple doses of KarXT + KarX-EC capsules versus KarXT capsules in healthy adult and elderly participants of Japanese ethnicity and to assess the effect of multiple doses of omeprazole on the exposure of xanomeline and trospium administered as KarXT + KarX-EC capsules in healthy adult participants.

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.

What makes the drug Xanomeline + Trospium Chloride unique?

Xanomeline + Trospium Chloride is unique because it combines two components: xanomeline, which targets specific brain receptors, and trospium chloride, which is used for overactive bladder, potentially offering a novel approach to treatment by addressing multiple symptoms or conditions simultaneously. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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).

Trial Timeline

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

Treatment Details

Interventions

• KarX-EC (Other)
• KarXT (Other)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Karuna Therapeutics

Lead Sponsor

Trials

17

Recruited

4,100+

Findings from Research

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]

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]

References

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

Sensitization prevalence for benzalkonium chloride and benzethonium chloride. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Trospium chloride--an effective drug in the treatment of overactive bladder and detrusor hyperreflexia. [2019]

3. England 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The effects of calcitonin nasal preparations and their excipients on mucociliary clearance in an ex-vivo frog palate test. [2019]

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

Irreversible corneal decompensation in patients treated with topical dorzolamide. [2019]