Safety, Tolerability, and Pharmacokinetics of KarXT and Dual-burst Release of Xanomeline With Immediate-release Trospium Chloride in Adolescents With Psychiatric Disorders

An Open-label, Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of KarXT and Dual-burst Release of Xanomeline With Immediate-release Trospium Chloride in Adolescents With Psychiatric Disorders

This study is designed to assess the safety, tolerability, and pharmacokinetics (PK) of multiple doses and ratios of xanomeline and trospium chloride in an IR capsule (KarXT) and dual-burst release of xanomeline with immediate-release trospium chloride in adolescents with psychiatric disorders.

Study Overview

• Status: Completed
• Conditions: Psychiatric Disorders
• Intervention / Treatment: Drug: KarXT; Drug: KarX-EC

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Local Institution - 0005
  • California
    • Orange, California, United States, 92868
      • Local Institution - 0006
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Local Institution - 0007
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Local Institution - 0008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• LAR (ie, legal guardian or caregiver) must have signed and dated an IRB/IEC-approved ICF in accordance with regulatory, local, and institutional guidelines.

• Confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) psychiatric diagnosis of 1 of the following:

  1. Schizophrenia or schizoaffective disorder
  2. Bipolar I or II disorder
  3. Attention-deficit/hyperactivity disorder (ADHD)
  4. Tourette's disorder
  5. Autism spectrum disorder (ASD)
• Participant is judged by the investigator to be clinically stable (eg, no psychiatric hospitalization within the last 6 months; no imminent risk of suicide or injury to self, others, or property).

Exclusion Criteria:

• Any clinically significant neurological, metabolic (including type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, GI (including active obstructive GI disorders), carcinoma, active biliary disorders (eg, symptomatic gallstones) and/or urological disorder, congestive heart failure (uncontrolled), or CNS infection that would pose a risk to the participants if they were to participate in the study or that might confound the results of the study.
• Participant has a risk for suicidal behavior during the study, as determined by the investigator's clinical judgment and C-SSRS.
• eGFR < 60 mL/min.
• History of Gilbert's Disease or history of liver disease (Child-Pugh class A and higher).
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• Participants with history of bladder stones or recurrent UTIs.
• 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline and Trospium Chloride Capsule
Experimental: Cohort 2	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline and Trospium Chloride Capsule; Drug: KarX-EC; Specified dose on specified days; Other Names: BMS-986519; Xanomeline Enteric-coated
Experimental: Cohort 3	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510; Xanomeline and Trospium Chloride Capsule; 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	Time Frame
Number of participants with Adverse Events (AEs)	Up to Day 43
Number of participants with Serioues AEs (SAEs)	Up to Day 43
Number of participants with AEs of Special Interest (AESIs)	Up to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)		Up to Day 15
Area under the concentration-time curve in 1 dosing interval (AUC(TAU))		Up to Day 15
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))		Up to Day 15
Time of maximum observed plasma concentration (Tmax)		Up to Day 15
Concentration at the end of a dosing interval (Ctau)		Up to Day 15
Cmax accumulation index (AI_Cmax)	Ratio of maximum observed plasma concentration at steady-state on Day 5 to maximum observed plasma concentration after first dose	Up to Day 15
AUC accumulation index (AI_AUC)	Ratio of area under the concentration-time curve in 1 dosing interval at steady-state on Day 5 to area under the concentration-time curve in 1 dosing interval after first dose	Up to Day 15
Ctau accumulation index (AI_Ctau)	Ratio of concentration at the end of the dosing interval at steady-state on Day 5 to maximum observed plasma concentration after first dose	Up to Day 15
Average concentration within a dosing interval at steady-state (Css-avg)		Up to Day 15
Apparent total body clearance (CLT/F)		Up to Day 15
Effective elimination half-life during dosing interval (T-HALF(eff))		Up to Day 15
T-HALFeff based on AUC observed (T-HALFeff_AUC)	Effective elimination half-life based on degree of area under the plasma concentration-time curve accumulation observed	Up to Day 15

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• 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): April 29, 2025
• Primary Completion (Actual): July 22, 2025
• Study Completion (Actual): July 22, 2025

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): February 28, 2025

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Problem Behavior; Mental Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Psychotropic Drugs; Urological Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Cholinergic Agonists; Parasympatholytics; Parasympathomimetics; Muscarinic Agonists; Xanomeline; Trospium chloride
• Other Study ID Numbers: CN012-0022

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 Myers 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