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KarXT plus KarX-EC for thinking and memory problems in mild-to-moderate 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)

Phase 3 Interventional Bristol-Myers Squibb · NCT06976216

This trial will test whether the combination of KarXT and KarX-EC can help thinking and memory 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
Locations106 sites (Long Beach, California and 105 other locations)
Trial IDNCT06976216 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial compares the safety and efficacy of KarXT plus KarX-EC against placebo in people with mild-to-moderate Alzheimer's disease. Participants must have AD confirmed using the 2024 revised NIA‑AA criteria, an MMSE score of 12–22, and a caregiver who can attend visits and report on function. Enrolled participants will receive either the active combination or placebo and will be monitored at study sites for cognitive outcomes and adverse events. The protocol allows participants who are taking standard symptomatic treatments such as acetylcholinesterase inhibitors or memantine.

Who should consider this trial

Good fit: Ideal participants are adults with mild-to-moderate Alzheimer's disease confirmed by the 2024 NIA‑AA criteria, an MMSE score between 12 and 22, and a caregiver willing to attend study visits.

Not a fit: People with more severe dementia, non‑Alzheimer's causes of cognitive impairment, an MMSE outside the 12–22 range, or who cannot provide a reliable caregiver may not benefit from or be eligible for this study.

Why it matters

Potential benefit: If successful, the combination could improve cognition and daily functioning for people with mild-to-moderate Alzheimer's disease.

How similar studies have performed: KarXT combinations have shown activity in other neuropsychiatric conditions, but using KarXT plus KarX‑EC specifically for Alzheimer's cognitive impairment is a newer approach undergoing late‑stage testing.

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 reflect significant pathology other than AD or could affect safety or interfere with study procedures.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Long Beach, California and 105 other locations

+56 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.