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KarXT plus KarX-EC for cognitive impairment in Alzheimer's disease (MINDSET 2)

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 2)

Phase 3 Interventional Bristol-Myers Squibb · NCT06976203

This trial will try to see if combining KarXT and KarX-EC can improve thinking, memory, and daily functioning in people with mild to moderate Alzheimer's disease.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment586 (estimated)
Ages60 Years to 85 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations123 sites (Fullerton, California and 122 other locations)
Trial IDNCT06976203 on ClinicalTrials.gov

What this trial studies

MINDSET 2 is a Phase 3, randomized interventional study comparing the combination of KarXT plus KarX-EC to placebo for cognitive impairment in Alzheimer's disease. Participants must have mild to moderate AD confirmed by the 2024 NIA‑AA criteria and an MMSE score between 12 and 22, and each participant needs a caregiver who can attend visits and report on the participant. The study will monitor cognitive outcomes and safety while participants receive the study drugs or placebo. Sites for enrollment are located in Southern California and the sponsor is Bristol-Myers Squibb.

Who should consider this trial

Good fit: Ideal candidates are people with a confirmed diagnosis of mild to moderate Alzheimer's disease (NIA‑AA criteria) with MMSE scores of 12–22 who have a caregiver willing to attend visits and support medication adherence.

Not a fit: People with severe Alzheimer's disease, MMSE scores outside the 12–22 range, no available caregiver, or dementia primarily due to other causes are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this combination could meaningfully improve cognitive symptoms and everyday functioning for people with mild to moderate Alzheimer's disease.

How similar studies have performed: Related KarXT research has shown promise for neuropsychiatric symptoms in prior studies, but using KarXT combined with KarX-EC specifically to improve cognition in Alzheimer's is a newer approach with limited published phase 3 results.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 could affect safety or interfere with study procedures.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Fullerton, California and 122 other locations

+73 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Alzheimer's DiseaseDementiaCognitive ImpairmentKar-XTKarX-ECMild Alzheimer's DiseaseModerate Alzheimer's Disease
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.