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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 ≤ 24 at Screening (Visit 1).
  * Have an identified caregiver who has sufficient contact (approximately 8 hours over a week) 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).
  * CMAI-IPA Total Score ≥ 30 at Screening (Visit 1) and Baseline (Visit 2).

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. Trazodone may be used as a hypnotic or for agitation if started at least 8 weeks prior to Screening (Visit 1).

C. Mirtazapine 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 it's running

• Imaging Endpoints
  Scottsdale, Arizona, United States Recruiting
• Advanced Research Center (ARC) - Anaheim
  Anaheim, California, United States Recruiting
• The Neurology Group
  Pomona, California, United States Recruiting
• Sunwise Clinical Research
  Walnut Creek, California, United States Recruiting
• Flourish Research
  Merritt Island, Florida, United States Recruiting
• Combined Research Orlando (CRO)
  Orlando, Florida, United States Recruiting

+112 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Email: Clinical.Trials@bms.com
• Phone: 855-907-3286

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.