Study to Assess Safety and Tolerability of KarXT With Administration of Antiemetics in Healthy Volunteers

A Phase 4, Randomized, Open Label Study to Evaluate the Safety and Tolerability of Twice Daily Xanomeline/Trospium Chloride (KarXT) With Prophylactic and PRN Antiemetic Use in Healthy Volunteers

This study looks at how to reduce nausea and vomiting in people taking KarXT which is used to treat mental health conditions like schizophrenia. KarXT can cause stomach-related side effects, especially in the first couple of weeks. In this study, healthy volunteers will take KarXT along with anti-nausea medication, either regularly (to prevent symptoms) or as needed.

The goal is to see how well these strategies help reduce nausea and vomiting and how safe the combination is. The results will help doctors better manage side effects and make treatment more comfortable for patients starting KarXT.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: KarXT; Drug: Trimethobenzamide; Drug: Ondansetron; Drug: Meclizine

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must be healthy male and female participants as determined by no clinically significant deviation from normal in medical history, physical examination, 12-lead ECG, VS, and clinical laboratory determinations.
• Participants must be willing and able to be confined to an inpatient setting for a 3-week duration, follow instructions, and comply with the protocol requirements.
• Participants must have BMI ≥ 18 and ≤ 40 kg/m2.
• Individuals of childbearing potential (IOCBP) must be willing and able to adhere to the contraception guidelines.

Exclusion Criteria:

• Participants must not have history or presence of clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal ([GI] eg, obstructive disorders [including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis], active biliary disease [including symptomatic gallstones]), 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.
• Participants must not have history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months or a positive urine drug screen (UDS) for a substance other than cannabis at screening or baseline.
• Participants must not have history or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• Participants must not have active biliary disease (eg, symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the medical monitor.
• 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: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride; Drug: Trimethobenzamide; Specified dose on specified days
Experimental: Arm 2	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride; Drug: Ondansetron; Specified dose on specified days
Experimental: Arm 3	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride; Drug: Meclizine; Specified dose on specified days
Experimental: Arm 4	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline/Trospium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment Emergent Adverse Events (TEAEs)	Nausea and vomiting	Up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with TEAEs	Nausea and vomiting	Up to Day 14
Time to first onset of nausea and vomiting		Up to Day 21
Time to resolution of first episode of nausea or vomiting		Up to Day 21
Number of participants with TEAEs		Up to Day 28
Number of participants with serious TEAEs		Up to Day 28
Number of participants with Adverse Events of Special Interests (AESIs)		Up to Day 28
Number of participants with TEAEs leading to discontinuation		Up to Day 28
Number of participants with clinically abnormal Vital signs		Up to Day 28
Number of participants with electrocardiogram (ECG) abnormalities		Up to Day 21

Collaborators and Investigators

• Sponsor: Karuna Therapeutics, Inc., a Bristol Myers Squibb company
• 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 (Estimated): August 3, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; Antiemetics; Gastrointestinal side effects; BMS-986510; KarXT; Xanomeline/Trospium
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Nausea; Vomiting; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Imidazoles; Indoles; Benzene Derivatives; Heterocyclic Compounds, 3-Ring; Piperazines; Carbazoles; Benzhydryl Compounds; Ondansetron; xanomeline; trospium chloride; Meclizine; trimethobenzamide
• Other Study ID Numbers: CN012-0182

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.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