Study to Assess Safety and Effectiveness of Slowly Increasing Dose and Food Effect of KarXT in Participants With Schizophrenia

A Phase 3b, Open-label, Multicenter, Two-Period, Slow-titration and Food Effect Study to Assess the Safety and Efficacy of KarXT in Participants With DSM-5 Schizophrenia

The purpose of this study is to assess the safety and efficacy of slowly increasing dose and food effect of KarXT in adult participants with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: KarXT

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720-3118
      • Local Institution - 0002
    • Riverside, California, United States, 92506-3257
      • Local Institution - 0004
  • Florida
    • Hollywood, Florida, United States, 33024
      • Local Institution - 0006
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Local Institution - 0005
    • Decatur, Georgia, United States, 30030
      • Local Institution - 0003
  • New Jersey
    • Marlton, New Jersey, United States, 08053-3449
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview (MINI) for Schizophrenia and Psychotic Disorder Studies version 7.0.2.
• Positive and Negative Syndrome Scale (PANSS) total score of ≤ 80 at screening and Baseline.
• Clinical Global Impression-Severity (CGI-S) score of ≤ 4 at screening and Baseline.
• Willing and able to discontinue all antipsychotic medications prior to baseline visit.

Exclusion Criteria:

• History or presence of clinically significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (GI), 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.
• Any primary DSM-5 disorder other than schizophrenia within 12 months before screening.
• History of treatment resistance to schizophrenia medications.
• History of allergy/hypersensitivity to KarXT.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KarXT on empty stomach and with food	Drug: KarXT; Specified dose on specified days; Other Names: BMS-986510

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With TEAEs From First Dose to End of Study Follow up.	Number of participants with Treatment Emergent Adverse Events (TEAEs) from first dose to end of study follow up. An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention.	From first dose to end of study follow up (63 days)
Number of Participants With TEAEs at the End of Period 1 and Period 2.	Number of participants with TEAEs at the end of period 1 and period 2. An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention.	Period 1 (From first dose to day 28) Period 2 (day 29 to day 56)
Number of Participants With Serious TEAEs at the End of Period 1 and Period 2.	Number of participants with TEAEs at the end of period 1 and period 2. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.	Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days)
Number of Participants With TEAEs Leading to Treatment Discontinuation.	Number of participants with TEAEs leading to treatment discontinuation.	Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days)
Number of Participants With Pro-cholinergic and Anticholinergic TEAEs.	The number of participants experiencing adverse events related to procholinergic symptoms (believed to be associated with xanomeline) and anticholinergic symptoms (believed to be associated with trospium) symptoms. Examples of procholinergic symptoms include vomiting, nausea, diarrhea, sweating and hyper-salivation. Examples of anticholinergic include dizziness, confusion, hallucinations, and somnolence.	Period 1 (From first dose to day 28); Period 2 (day 29 to day 56); Overall (63 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in PANSS Total Score, Positive Score and Negative Score	The Positive and Negative Syndrome Scale (PANSS) assesses schizophrenia symptom severity using 30 items: 7 positive, 7 negative, and 16 general psychopathology scales. Each item is rated from 1 (absent) to 7 (extreme). Positive symptoms represent excesses or distortions of normal function (e.g., hallucinations, delusions), while negative symptoms reflect diminished function. The PANSS positive and negative scores each sum their respective 7 items, ranging from 7 to 49, with higher scores indicating greater severity. The PANSS Total Score sums all 30 items, ranging from 30 to 210, with higher scores reflecting worse overall symptom severity.	From first dose to end of treatment (56 days)
Change From Baseline in Marder Factor Score.	PANSS Marder factor score is the sum of 5 negative scales and 2 general scales (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance). Participants are rated from 1 to 7 on each symptom scale, with a total score ranging from 7 to 49. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Baseline is defined as the PANSS score at screening.	From first dose to end of treatment (56 days)
Change From Baseline in CGI Severity Score	Completed independently by a clinician, the CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients, by asking the clinical 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness.	From first dose to end of treatment (56 days)
Number of Participants With Spontaneously Reported AESIs	The AEs of special interest (AESIs) will be monitored and include symptomatic orthostasis, syncope(a transient loss of consciousness or fainting),and liver function test elevations as defined below. For SAE reporting requirements for events of liver injury.	From first dose to end of study follow up (63 days)
Number of Participants With Clinically Significant Changes in Vital Signs	Number of participants with clinically significant changes in vital signs	From first dose to end of study follow up (63 days)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments	Number of participants with clinically significant changes in clinical laboratory assessments	From first dose to end of study follow up (63 days)
Number of Participants With Clinically Significant Changes in 12-lead ECGs	Number of participants with clinically significant changes in 12-lead ECGs	From first dose to end of study follow up (63 days)
Number of Participants Who Exhibited Suicidal Behavior as Assessed by C-SSRS	Number of participants who exhibited suicidal behavior as assessed by C-SSRS	From first dose to end of study follow up (63 days)

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 (Actual): October 28, 2024
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Mental Disorders; BMS-986510; KarXT; DSM-5 Schizophrenia; Diagnostic and Statistical Manual of Mental Disorders
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Schizophrenia; Disease; Mental Disorders
• Other Study ID Numbers: CN012-0048

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