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RecruitingPhase 3

A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Relapse Prevention Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease

Asset

Xanomeline / trospium

Listed sites

129

Recruiting sites

34

Enrollment

410

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 6-24•Study partner/caregiver required•AD symptomatic therapy: stable ≥6 weeks

Primary endpoint

•Time from randomization to relapse during the 38-week study

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Secondary ID2024-511740-11EU CTR
Org study IDCN012-0026
Secondary IDCN012-0026Bristol-Myers Squibb Protocol ID
Secondary IDKAR-031Karuna Pharmaceuticals Protocol ID
NCT IDNCT05511363

Timeline

Milestones

Study first posted2022-08-23actual
Study start2022-08-23actual
Last update posted2026-07-14actual
Primary completion2026-10-05estimated
Study completion2026-10-05estimated

Assets

Drug assets

Xanomeline / trospium

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years
Maximum age90 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

•Is aged 55 to 90 years, inclusive, at Screening
•Can understand the nature of the study and protocol requirements and provide a signed informed consent form before any study assessments are performed. If the subject is deemed not competent to provide consent, the following requirements for consent must be met.

i) The subject's legally acceptable representative must provide informed consent; ii) The subject must provide informed consent.

•Meets clinical criteria for possible or probable Alzheimer's Disease
•Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.
•Living at the same location for a minimum of 4 weeks before Screening, with the intention of living at the same location throughout the study.
•Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified caregiver or study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant (ie, ≥10 hours per week) on a regular basis to reliably provide accurate information regarding the participant's cognitive, behavioral, and functional status, 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 psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria) for at least 2 months prior to Screening.
•Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) at Screening and Baseline. CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions.
•Subjects are required to meet at least one of the following criteria at Screening and Baseline:

i) Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR; ii) Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items.

•Mini-Mental State Examination (MMSE) score of 6 to 24, inclusive, at Screening
•If the subject is taking a cholinesterase inhibitor and/or memantine, they must have been on a stable dose for 6 weeks prior to Screening and be willing to maintain a stable dose for the duration of the study.
•Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements
•BMI must be within 16 to 40 kg/m2 inclusive
•Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matching placebo

Exclusion criteria

•Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia
•History of major depressive episode with psychotic features during the 12 months prior to Screening
•History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder
•Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular or oncologic disease, or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results
•Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of <50 mL/min
•History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke
•History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope
•Any of the following:

i) New York Heart Association Class 2 congestive heart failure; ii) Grade 2 or greater angina pectoris; iii) Sustained ventricular tachycardia; iv) Ventricular fibrillation; v) Torsade de pointes; vi) Implantable cardiac defibrillator.

•Myocardial infarction within the 6 months prior to Screening
•Personal or family history of symptoms of long QT syndrome as evaluated by the investigator
•Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, active biliary disease, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results
•History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator
•Participants with any of the following:

i) History of bladder stones; ii) History of recurrent urinary tract infections; iii) For male participants:

1. Serum prostate specific antigen (PSA) > 10 ng/mL at Screening

2. An IPSS of 5 (almost always) on items 1, 3, 5, or 6

3. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9

•History of obstructive gastrointestinal disorder, gastric retention, irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
•Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS
•Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening
•Urine toxicology screen is positive substances other than cannabis or benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor
•Currently receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), mood stabilizers (eg, lithium) tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam) and unable to complete the washout:

i) Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted; ii) Mirtazapine or trazodone may be used if started at least 8 weeks prior to Screening. If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor.

•If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
•Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening; antigen or PCR local testing can be done at the discretion of the Investigator
•Unable to taper and discontinue a concomitant medication that would preclude participation in the study
•Prior exposure to KarXT
•Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium
•Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening or has participated in more than 2 clinical studies in the past year
•Other protocol-defined Inclusion/Exclusion criteria apply

Endpoints (19)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)
10
Safety / tolerability / PK
6
Global cognition
1
Behavior / neuropsychiatric
1
Other clinical outcomes
1

Global cognition

1 endpoint
Secondary/protocol endpoint

Assessment of cognition as measured by Mini-Mental State Examination (MMSE)

Time frame:Up to approximately Week 38

Mini-Mental State Examination (MMSE)

descriptive

Behavior / neuropsychiatric

1 endpoint
Secondary/protocol endpoint

Change in Neuropsychiatric Inventory-Clinician rating scale (NPI-C) Core Caregiver Distress score

Time frame:Up to approximately Week 38

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Safety / tolerability / PK

6 endpoints
Secondary/protocol endpoint

Number of participants with Adverse Events (AEs)

Time frame:Up to approximately Week 42

event count, event

Secondary/protocol endpoint

Number of participants with Treatment Emergent Adverse Events (TEAEs)

Time frame:Up to approximately Week 42

event count, event

Secondary/protocol endpoint

Number of participants with Serious Adverse Events (SAEs)

Time frame:Up to approximately Week 42

event count, event

Secondary/protocol endpoint

Number of participants with Adverse Events of Special Interest (AESIs)

Time frame:Up to approximately Week 42

event count, event

Secondary/protocol endpoint

Number of participants with clinically significant orthostatic vital signs

Time frame:Up to approximately Week 38

event count, event

Secondary/protocol endpoint

Number of participants with clinically significant 12-lead electrocardiogram (12-lead ECG)

Time frame:Up to approximately Week 38

event count, event

Other clinical outcomes

1 endpoint
Secondary/protocol endpoint

Number of participants with AEs including procholinergic and anticholinergic symptoms

Time frame:Up to approximately Week 42

event count, event

Other (unclassified)

10 endpoints
Primary/protocol endpoint/low confidence

Time from randomization to relapse during the 38-week study

Time frame:Week 38

descriptive

Secondary/protocol endpoint/low confidence

Time from randomization to first occurrence of treatment discontinuation for any reason or relapse during the 38-week study

Time frame:Week 38

descriptive

Secondary/protocol endpoint/low confidence

Number of participants with TEAEs leading to study withdrawal

Time frame:Up to approximately Week 42

event count, event

Secondary/protocol endpoint/low confidence

Barnes Akathisia Rating Scale (BARS)

Time frame:Up to approximately Week 38

descriptive

Secondary/protocol endpoint/low confidence

Abnormal Involuntary Movement Scale (AIMS)

Time frame:Up to approximately Week 38

descriptive

Secondary/protocol endpoint/low confidence

Body weight

Time frame:Up to approximately Week 38

descriptive

Secondary/protocol endpoint/low confidence

BMI

Time frame:Up to approximately Week 38

descriptive

Secondary/protocol endpoint/low confidence

Number of participants with clinically significant laboratory evaluations

Time frame:Up to approximately Week 38

event count, event

Secondary/protocol endpoint/low confidence

Number of participants with suicidal ideation as assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS)

Time frame:Up to approximately Week 38

event count, event

Secondary/protocol endpoint/low confidence

International Prostate Symptom Score (IPSS) (males only)

Time frame:Up to approximately Week 38

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.