Home › Trials › NCT07011732

KarXT plus 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 · NCT07011732

This trial will test whether taking KarXT together with KarX-EC can reduce 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
Locations157 sites (Scottsdale, Arizona and 156 other locations)
Trial IDNCT07011732 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized, placebo-controlled trial gives adults with Alzheimer's-related agitation either KarXT plus KarX-EC or placebo to compare safety and symptom reduction. Participants must have Alzheimer's confirmed by biomarker testing or PET/CSF and an MMSE score between 5 and 22, and must have an identified caregiver to assist with visits and reporting. Treatment uses oral xanomeline/trospium formulations versus matching placebo with regular assessments of agitation severity, cognition, and adverse events. Primary outcomes focus on changes in agitation symptoms and safety over the treatment period, with biomarker or imaging confirmation used as required by the protocol.

Who should consider this trial

Good fit: Ideal candidates are adults with biomarker-confirmed Alzheimer's disease, an MMSE score of 5–22, clinically significant agitation, and an available caregiver to support study participation.

Not a fit: Patients with non-Alzheimer's causes of agitation, those outside the MMSE range, unable to take oral medications, or with contraindicated medical conditions may not benefit from or be eligible for this treatment.

Why it matters

Potential benefit: If successful, this treatment could meaningfully reduce agitation episodes and improve daily function and caregiver burden for people with Alzheimer's.

How similar studies have performed: Xanomeline combined with trospium (KarXT) has shown promising results for neuropsychiatric symptoms in other disorders such as schizophrenia, but its specific use for Alzheimer's-related agitation is relatively new and is being tested in larger Phase 3 trials.

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

Scottsdale, Arizona and 156 other locations

+107 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.