MINDSET 1

RecruitingPhase 3

A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for the Treatment of Cognitive Impairment Associated With Mild to Moderate Alzheimer's Disease (MINDSET 1)

Lead sponsor

Bristol-Myers Squibb

Assets

Xanomeline / Xanomeline / trospium

Listed sites

116

Recruiting sites

Enrollment

586

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 12-22•Study partner/caregiver required•AD symptomatic therapy: stable

Primary endpoints

•ADAS-Cog•Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2025-520746-30

Org study IDCN012-0051

NCT IDNCT06976216

Secondary IDU1111-1317-4462UTN

Timeline

Milestones

Study first posted2025-05-16actual

Study start2025-07-14actual

Last update posted2026-06-26actual

Primary completion2028-09-11estimated

Study completion2029-02-23estimated

Assets

Drug assets

Xanomeline Xanomeline / trospium

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participants must have a confirmed diagnosis of Alzheimer's disease (AD), specifically at the mild (stage 4) or moderate (stage 5) dementia stages, as defined by the National Institute on Aging and Alzheimer's Association (NIA-AA) core clinical criteria. The diagnosis of AD pathology must be confirmed through the 2024 revised NIA-AA Workgroup criteria using a stepwise diagnostic approach.

•Participants must have an Mini-Mental State Examination (MMSE) score ranging from 12 through 22, inclusive, at the time of screening.

•Participants must have a designated caregiver who maintains adequate contact (around 10 hours per week or more) and is willing to attend all study visits. The caregiver must also be responsible for reporting on the participant's condition, overseeing medication compliance, and consenting to their involvement in both their own and the participant's study-related activities.

•Participants on acetyl choline esterase inhibitors (AChEIs) and/or memantine, must have been on a stable dosage for at least 12 weeks prior to screening, and agree to maintain this stable dose for the study duration

Exclusion criteria

•Participants must not present with any significant or severe medical conditions that could compromise their safety, the ability to comply with or complete the study, or the integrity of the study results. This includes any grade of hepatic impairment, urinary retention, active biliary disease, moderate-severe renal impairment (eGFR of <50 mL/min), and unstable hypertension or tachycardia.

•Participants must not have any primary psychiatric diagnoses such as major depression, schizoaffective disorder, or bipolar disorder, and those with severe psychiatric symptoms that could complicate the interpretation of treatment effects, impair cognitive assessment, or impact study completion.

•Participants must not have a history of schizophrenia or other chronic psychosis, as well as those who have previously been exposed to KarXT or are currently undergoing treatment with disease-modifying anti-amyloid therapies for AD within the past 6 months prior to screening.

•Participants must not have significant pathological findings on brain magnetic resonance imaging (MRI) at screening that reflect significant pathology other than AD or could affect safety or interfere with study procedures.

•Other protocol-defined Inclusion/Exclusion criteria apply.

Endpoints (15)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Other (unclassified)

Function / daily living

Behavior / neuropsychiatric

Caregiver / quality of life

Other clinical outcomes

Function / daily living

1 endpoint

Secondary/protocol endpoint

Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL)

Time frame:At week 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

1 endpoint

Secondary/protocol endpoint

Change from baseline in neuro psychiatric inventory (NPI) total score

Time frame:At week 24

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Caregiver / quality of life

1 endpoint

Primary/protocol endpoint

Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+)

Time frame:At week 24

descriptive

Safety / tolerability / PK

6 endpoints

Secondary/protocol endpoint

Number of participants with adverse events (AEs)

Time frame:At week 24

event count, event

Secondary/protocol endpoint

Number of participants with serious adverse events (SAEs)

Time frame:At week 24

event count, event

Secondary/protocol endpoint

Number of participants with adverse event of special interest (AESIs)

Time frame:At week 24

event count, event

Secondary/protocol endpoint

Number of participants with clinically significant changes in vital signs

Time frame:At week 24

event count, event

Secondary/protocol endpoint

Number of participants with clinically significant changes in electrocardiogram (ECG) tests

Time frame:At week 24

event count, event

Secondary/protocol endpoint

Number of participants with clinically significant changes in safety laboratory tests

Time frame:At week 24

event count, event

Other clinical outcomes

1 endpoint

Secondary/protocol endpoint

Number of participants with AEs leading to death

Time frame:At week 24

event count, event

Other (unclassified)

5 endpoints

Primary/protocol endpoint/low confidence

Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11)

Time frame:At week 24

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Number of participants with AEs leading to study intervention discontinuation

Time frame:At week 24

event count, event

Secondary/protocol endpoint/low confidence

Number of participants with AEs leading to study discontinuation

Time frame:At week 24

event count, event

Secondary/protocol endpoint/low confidence

Number of participants with clinically significant changes in Columbia-Suicide Severity Rating Scale (C-SSRS) tests

Time frame:At week 24

event count, event

Secondary/protocol endpoint/low confidence

Number of participants with clinically significant changes in weight

Time frame:At week 24

event count, event

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.