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KarXT + KarX-EC for treating agitation in Alzheimer's disease

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease

Phase 3 Interventional Bristol-Myers Squibb · NCT07011745

This will test whether combining KarXT and KarX-EC reduces agitation in adults with Alzheimer's disease.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment352 (estimated)
Ages55 Years to 90 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations140 sites (Chandler, Arizona and 139 other locations)
Trial IDNCT07011745 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial compares the combination of KarXT (xanomeline/trospium) plus an enteric xanomeline capsule against placebo in adults with agitation related to Alzheimer's disease. Participants must have biomarker-confirmed AD (amyloid PET, CSF ratios, or validated plasma biomarkers when allowed), an MMSE score of 5 to 22, and a designated caregiver to support study procedures. The study uses oral capsule formulations and collects standardized measures of agitation and safety data over the treatment period. Bristol-Myers Squibb sponsors the trial, which is conducted at U.S. clinical sites.

Who should consider this trial

Good fit: Ideal candidates are adults with biomarker-confirmed Alzheimer's disease who have clinically significant agitation, an MMSE score of 5–22, and a caregiver able to attend study visits.

Not a fit: Patients without biomarker evidence of AD, with MMSE scores outside the 5–22 range, or whose agitation is primarily due to other medical or psychiatric causes may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this drug combination could provide a targeted medication to reduce agitation in people with Alzheimer's disease, improving daily functioning and caregiver burden.

How similar studies have performed: Earlier studies of xanomeline-containing regimens have shown promising signals for neuropsychiatric symptoms, but large definitive Phase 3 evidence specifically for Alzheimer’s-related agitation is still limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

\- A diagnosis of Alzheimer's disease (AD) in accordance with the 2024 Alzheimer's Association criteria with one of the following confirmations of AD pathology:

i) Historical evidence of AD diagnosis with amyloid positron emission tomography (PET), Aβ42/40 ratio in CSF, pTau181/Aβ42 ratio in CSF or pTau217/Aβ42 ratio in plasma using an Health Authority (HA)-authorized diagnostic assay.

ii) If no historical evidence available:

A. A plasma biomarker will be assessed for eligibility if allowed per regulatory requirements. The test cutoff(s) will be based on diagnostic use approval.

B. If a plasma biomarker assay cannot be used or if the assay result is inconclusive, conduct one the following:

* Amyloid PET.
* Aβ42/40 ratio or pTau181/Aβ42 ratio in CSF using an HA-authorized diagnostic assay.

  * Mini-Mental State Examination (MMSE) score of 5 to 22, inclusive, at Screening (Visit 1).
  * Have one identified caregiver who should have sufficient contact (approximately 10 hours a week or more) and is willing to:

    i) Attend all visits and report on participant's status.

ii) Oversee participant compliance with medication and study procedures.

iii) Participate in the study assessments and provide informed consent to participate in the study.

* History of agitation that meets the International Psychogeriatric Association (IPA) consensus definition for agitation in cognitive disorders with onset at least two weeks prior to Screening (Visit 1).
* AD participants are required to have NPI/NPI-NH Agitation/Aggression score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2).
* CGI-S ≥ 4, as related to agitation, at Screening (Visit 1) and Baseline (Visit 2).
* At least 1 of the following 3 criteria must be established from the CMAI-IPA at Screening (Visit 1) and Baseline (Visit 2; CMAI-IPA Physical/Verbal Aggression Positivity):

  i) 1 or more aggressive behaviors occurring at least several times per week.

ii) 2 or more aggressive behaviors occurring at least once or twice per week.

iii) 3 or more aggressive behaviors occurring less than once per week.

Exclusion Criteria

\- Medical Conditions.

i) Agitation symptoms that are primarily attributable to a condition other than the AD causing the dementia.

ii) History of bipolar disorder, schizophrenia, or schizoaffective disorder.

iii) History of (or at high risk for) urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator.

iv) Risk of suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSR.

\- Prior/Concomitant Therapy.

i) Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (eg, lamotrigine, divalproex), mood stabilizers (eg, lithium), tricyclic antidepressants (eg, imipramine, desipramine), or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam).

A. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening (Visit 1) may be permitted.

B. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1).

\- Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Chandler, Arizona and 139 other locations

+90 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 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.