A Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of Xanomeline With Trospium Chloride Versus KarXT in Healthy Adult and Elderly Participants of Japanese Ethnicity and to Assess the Effect of Omeprazole on the PK of Xanomeline With Trospium Chloride in Healthy Adult Participants

A 2-Part, Phase 1, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of Dual-burst Release of Xanomeline With Immediate-Release Trospium Chloride Versus KarXT in Healthy Adult and Elderly Participants of Japanese Ethnicity (Part 1) and an Open-label Study to Assess the Effect of Omeprazole on the Pharmacokinetics of Dual-burst Release of Xanomeline With Immediate-Release Trospium Chloride in Healthy Adult Participants (Part 2)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Omeprazole; Drug: KarXT; Drug: KarX-EC

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • CenExel ACT (Anaheim Clinical Trials)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Inclusion Criteria for Healthy Adult Japanese Participants (Group A):.

• Healthy adult participants must be 19 to 55 years of age, inclusive.

  i) Both participant's biological parents are of ethnic Japanese ancestry. Participants must be first generation Japanese.

ii) Must have a body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min/1.73m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the screening visit. One repeat measurement is allowed.

• Inclusion Criteria for Healthy Elderly Japanese Participants (Groups B and C):.

• Healthy elderly participants must be 56 to 90 years of age, inclusive.

  i) Both participant's biological parents are of ethnic Japanese ancestry. Participants must be first generation Japanese.

ii) Must have a BMI ≥ 18.0 and ≤ 35.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an eGFR of > 60 mL/min/1.73m2 by the CKD-EPI equation at the screening visit. One repeat measurement is allowed.

• Inclusion Criteria for Healthy Adult Participants (Groups D):.

• Healthy adult participants must be 19 to 55 years of age, inclusive.

  i) Participants with any ethnicity can be included.

ii) Must have a BMI of 18.0 to 32.0 kg/m2 (inclusive), at the time of signing the ICF.

iii) Must have an eGFR of ≥ 90 mL/min/1.73m2 by the CKD-EPI equation at the screening visit. One repeat measurement is allowed.

Exclusion Criteria

- Exclusion Criteria for All Participants (Groups A, B, C, and D):.

i) 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.

ii) History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.

iii) Participant has a history of syncope and/or symptomatic orthostatic hypotension in the year prior to Day 1.

iv) 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).

• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: Placebo; Specified dose on specified days; Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride
Experimental: Group B	Drug: Placebo; Specified dose on specified days; Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride
Experimental: Group C	Drug: Placebo; Specified dose on specified days; Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride; Drug: KarX-EC; Specified dose on specified days; Other Names: BMS-986519; Xanomeline Enteric-coated
Experimental: Group D	Drug: Omeprazole; Specified dose on specified days; Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride; Drug: KarX-EC; Specified dose on specified days; Other Names: BMS-986519; Xanomeline Enteric-coated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs)	Part 1	Up to 28 days post last dose
Number of participants with Serioues AEs (SAEs)	Part 1	Up to 28 days post last dose
Number of participants with vital sign abnormalities	Part 1	Up to 28 days post last dose
Body weight	Part 1	Up to 28 days post last dose
Number of participants with 12-lead electrocardiogram abnormalities	Part 1	Up to 28 days post last dose
Number of participants with physical examination abnormalities	Part 1	Up to 28 days post last dose
Number of participants with clinical laboratory assessment abnormalities	Part 1	Up to 28 days post last dose
Columbia-Suicide Severity Rating Scale (C-SSRS)	Part 1	On Day 30
Maximum observed plasma concentration (Cmax)	Part 2	Up to Day 29
Time of maximum observed plasma concentration (Tmax)	Part 2	Up to Day 29
Area under the concentration-time curve in 1 dosing interval (AUC(TAU))	Part 2	Up to Day 29
Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24))	Part 2	Up to Day 29
Apparent total body clearance (CLT/F)	Part 2	Up to Day 29
Apparent volume of distribution (Vz/F)	Part 2	Up to Day 29
Terminal elimination half-life (T-HALF)	Part 2	Up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Part 1	Up to Day 29
Tmax	Part 1	Up to Day 29
AUC(TAU)	Part 1	Up to Day 29
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))	Part 1	Up to Day 29
CLT/F	Part 1	Up to Day 29
Vz/F	Part 1	Up to Day 29
T-HALF	Part 1	Up to Day 29
Number of participants with AEs	Part 2	Up to 28 days post last dose
Number of participants with SAEs	Part 2	Up to 28 days post last dose
Number of participants with vital sign abnormalities	Part 2	Up to 28 days post last dose
Body weight	Part 2	Up to 28 days post last dose
Number of participants with 12-lead electrocardiogram abnormalities	Part 2	Up to 28 days post last dose
Number of participants with physical examination abnormalities	Part 2	Up to 28 days post last dose
Number of participants with clinical laboratory assessment abnormalities	Part 2	Up to 28 days post last dose
C-SSRS	Part 2	On Day 30
AUC(0-24)	Part 1	Up to Day 29

Collaborators and Investigators

• Sponsor: Karuna Therapeutics
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): May 31, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Elderly; Healthy; Pharmacokinetics; Japanese; Adult; Omeprazole; Drug interaction; BMS-986510; KarXT; BMS-986519
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Enzyme Inhibitors; Neurotransmitter Agents; Psychotropic Drugs; Urological Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Cholinergic Agonists; Anti-Ulcer Agents; Proton Pump Inhibitors; Parasympatholytics; Parasympathomimetics; Muscarinic Agonists; Xanomeline; Omeprazole; Trospium chloride
• Other Study ID Numbers: CN012-0030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria.

Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at:

https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.html

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No