A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease

NCT07011745 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CN012-00242025-520612-34U1111-1316-5827
• Study Type: interventional
• Target: 426
• Locations: 14 countries
• Sites: 145

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC in adult participants with agitation related to Alzheimer's Disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease (AD); Agitation; ADAGIO; KarXT; KarX-EC

Outcome Measures

Primary Outcomes (1)

• Change from baseline on the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) total score at Week 14

  At Week 14

Secondary Outcomes (20)

• Change from baseline on the Clinical Global Impressions-Severity (CGI-S) at Week 14

  At Week 14

• Change from baseline on CMAI-IPA Domains at Week 14

  At Week 14

• Change from baseline on CMAI Total Score at Week 14

  At Week 14

• Number of participants with Occurrence of Response at Week 14

  At Week 14

• Change from baseline on the Neuropsychiatric Inventory/Neuropsychiatric Inventory -Nursing Home (NPI/NPI-NH) Total Score at Week 14

  At Week 14

Study Arms (2)

KarXT + KarX-EC

EXPERIMENTAL

Drug: Xanomeline/Trospium Chloride Capsule; Drug: Xanomeline Enteric Capsule

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Xanomeline/Trospium Chloride Capsule DRUG

Specified dose on specified days

Also known as: KarXT, BMS-986510

KarXT + KarX-EC

Xanomeline Enteric Capsule DRUG

Specified dose on specified days

Also known as: KarX-EC, BMS-986519

KarXT + KarX-EC

Placebo DRUG

Specified dose on specified days

Placebo

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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).
• Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) Total Score ≥ 30 at Screening (Visit 1) and Visit 2.

You may not qualify if:

• \- 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).
• Note: Mirtazapine may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (145)

Chandler Clinical Trials, LLC

Chandler, Arizona, 85224, United States

RECRUITING

Local Institution - 2631

Chandler, Arizona, 85226-3732, United States

NOT YET RECRUITING

Local Institution - 2646

Chandler, Arizona, 85286, United States

NOT YET RECRUITING

National Institute of Clinical Research

Garden Grove, California, 92844, United States

RECRUITING

Local Institution - 2607

Long Beach, California, 90805, United States

NOT YET RECRUITING

Accellacare

Long Beach, California, 90807, United States

RECRUITING

Local Institution - 2627

Napa, California, 94558, United States

NOT YET RECRUITING

Local Institution - 2649

Orange, California, 92866, United States

NOT YET RECRUITING

Local Institution - 2613

Pasadena, California, 91105, United States

NOT YET RECRUITING

Local Institution - 2614

San Diego, California, 92108, United States

NOT YET RECRUITING

Local Institution - 2620

West Hills, California, 91307, United States

COMPLETED

Local Institution - 2601

Basalt, Colorado, 81621, United States

WITHDRAWN

Local Institution - 2635

Colorado Springs, Colorado, 80907, United States

NOT YET RECRUITING

Local Institution - 2632

Norwalk, Connecticut, 06851, United States

NOT YET RECRUITING

Local Institution - 2648

Aventura, Florida, 33180, United States

NOT YET RECRUITING

Envision Trials LLC

Bonita Springs, Florida, 34134-4154, United States

RECRUITING

Key Clinical Research

Bradenton, Florida, 34207, United States

RECRUITING

Local Institution - 2636

Doral, Florida, 33122, United States

NOT YET RECRUITING

Local Institution - 2606

Homestead, Florida, 33032, United States

NOT YET RECRUITING

Local Institution - 2633

Miami, Florida, 33137, United States

NOT YET RECRUITING

Local Institution - 2637

Miami, Florida, 33165, United States

NOT YET RECRUITING

Local Institution - 2634

Orlando, Florida, 32806, United States

NOT YET RECRUITING

IPTB Clinical Research

Tampa, Florida, 33629, United States

RECRUITING

Agile Clinical Research Trials, LLC

Atlanta, Georgia, 30328, United States

RECRUITING

Vitalix Clinical

Worcester, Massachusetts, 01608, United States

RECRUITING

Local Institution - 2618

Ann Arbor, Michigan, 48105, United States

COMPLETED

Local Institution - 2630

Saint Paul, Minnesota, 55130, United States

NOT YET RECRUITING

Hattiesburg Clinic

Hattiesburg, Mississippi, 39402, United States

RECRUITING

Local Institution - 2603

Ozark, Missouri, 65721, United States

COMPLETED

Las Vegas Clinical Trials

Las Vegas, Nevada, 89030, United States

RECRUITING

Local Institution - 2650

Toms River, New Jersey, 08755, United States

NOT YET RECRUITING

Local Institution - 2647

Brooklyn, New York, 11229, United States

NOT YET RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

RECRUITING

Walnut Clinical Research

Valley Stream, New York, 11580, United States

RECRUITING

West Clinical Research

Morehead City, North Carolina, 28557, United States

RECRUITING

Velocity Clinical Research - Blue Ash

Blue Ash, Ohio, 45242, United States

RECRUITING

Epic Medical Research, LLC - Carrolton

Carrollton, Texas, 75006, United States

RECRUITING

Horizon Clinical Research Center - Houston

Cypress, Texas, 77429, United States

RECRUITING

Epic Medical Research, LLC - Mesquite

Mesquite, Texas, 75150, United States

RECRUITING

UT Health - San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Local Institution - 2612

Bountiful, Utah, 84010, United States

ACTIVE NOT RECRUITING

EvergreenHealth Medical Center

Kirkland, Washington, 98034, United States

RECRUITING

Local Institution - 2610

Milwaukee, Wisconsin, 53226, United States

NOT YET RECRUITING

Centro Neurobiológico y de Estrés Traumático - CENydET S.R.L.

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1058, Argentina

RECRUITING

Fundacion para el Estudio y Tratamiento de Enfermedades mentales- FETEM

Buenos Aires, 1133, Argentina

RECRUITING

Local Institution - 2004

Buenos Aires, 1199, Argentina

NOT YET RECRUITING

Instituto Modelo de Neurología, Fundación Lennox

Córdoba, 5000, Argentina

RECRUITING

Local Institution - 2002

Córdoba, 5000, Argentina

NOT YET RECRUITING

Instituto Médico DAMIC

Córdoba, X5003DCE, Argentina

RECRUITING

Resolution Psychopharmacology Research Institute

Mendoza, 5502, Argentina

RECRUITING

Biomedica Research Group

Santiago, Santiago Metropolitan, 7500710, Chile

RECRUITING

Local Institution - 2050

Santiago, Santiago Metropolitan, 7560356, Chile

NOT YET RECRUITING

Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, 8330024, Chile

RECRUITING

Clinica Alemana

Vitacura, Santiago Metropolitan, 2511433, Chile

RECRUITING

Local Institution - 2055

Viña del Mar, Valparaiso, 2511433, Chile

NOT YET RECRUITING

Psicomed Estudios Médicos Cía Ltda

Antofagasta, 1270244, Chile

RECRUITING

AGE Centrum

Olomouc, Olomouc Region, 779 00, Czechia

RECRUITING

Neuropsychiatrie

Prague, Praha 6, 160 00, Czechia

RECRUITING

Institut neuropsychiatricke pece (INEP), Praha

Prague, Praha 8, 18600, Czechia

RECRUITING

Neuro Health Centrum s.r.o.

Brno, South Moravian, 628 00, Czechia

RECRUITING

NEUROHK

Choceň, 565 01, Czechia

RECRUITING

A-SHINE s.r.o.

Pilsen, 301 00, Czechia

RECRUITING

Local Institution - 2102

Prague, 100 000, Czechia

WITHDRAWN

Local Institution - 2105

Prague, 100 00, Czechia

WITHDRAWN

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, 516 01, Czechia

RECRUITING

Centre Hospitalier Universitaire Toulouse - Cité de la Santé

Toulouse, Haute-Garonne, 31000, France

RECRUITING

Hôpital des Charpennes - Hospices Civils de Lyon (HCL)

Villeurbanne, Rhône, 69100, France

RECRUITING

Centre Hospitalier Régional Universitaire de Lille - Hôpital Roger Salengro

Lille, 59037, France

RECRUITING

Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren

Limoges, 87042, France

RECRUITING

Hopital Gui Chauliac - Chu Montpellier

Montpellier, 34295, France

RECRUITING

Centres Memoire de Ressources et de Recherche (CMRR) - Hopital Lariboisiere-Fernand-Widal Location

Paris, 75010, France

RECRUITING

Les Hôpitaux Universitaires de Strasbourg - Hôpital de la Robertsau

Strasbourg, 67091, France

RECRUITING

Local Institution - 2201

Düsseldorf, 40221, Germany

NOT YET RECRUITING

Local Institution - 2205

Halle, 06120, Germany

NOT YET RECRUITING

Local Institution - 2206

Westerstede, 26655, Germany

NOT YET RECRUITING

Local Institution - 2257

Kalocsa, Bács-Kiskun county, 6300, Hungary

NOT YET RECRUITING

Local Institution - 2250

Győr, Győr-Moson-Sopron, 0, Hungary

NOT YET RECRUITING

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hajdú-Bihar, 4031, Hungary

RECRUITING

Local Institution - 2254

Gyöngyös, Heves County, 3200, Hungary

NOT YET RECRUITING

Local Institution - 2256

Budapest, 1033, Hungary

NOT YET RECRUITING

Local Institution - 2255

Budapest, 1036, Hungary

NOT YET RECRUITING

Local Institution - 2251

Budapest, 1083, Hungary

WITHDRAWN

Semmelweis Egyetem

Budapest, 1083, Hungary

RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, Central District, 5262000, Israel

RECRUITING

Local Institution - 2302

Petch Tikva, IL, 49100, Israel

NOT YET RECRUITING

Sanz MC, Laniado Hospital

Netanya, 4244916, Israel

RECRUITING

The Israeli Alzheimer Medical Center

Ramat Gan, 5265601, Israel

RECRUITING

Bayit Balev Ltd.

Rishon Le'Tzion, 7590653, Israel

RECRUITING

University of Naples Federico II

Naples, Campania, 80131, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Policlinico Umberto I - Viale del Policlinico 155

Rome, Lazio, 00185, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, Lazio, 00189, Italy

RECRUITING

Auxologico IRCCS - Auxologico San Luca

Milan, Lombardy, 20149, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56126, Italy

RECRUITING

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

Local Institution - 2355

Isernia, 86077, Italy

WITHDRAWN

Fondazione Policlinico Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Centrum Medyczne HCP Szpital im. Jana Pawla II

Poznan, Greater Poland Voivodeship, 61-485, Poland

RECRUITING

Centrum Medyczne NEUROMED

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163, Poland

RECRUITING

M2M Med

Chorzów, 41-500, Poland

RECRUITING

Centrum In Psyche Spersonalizowanej Psychiatrii I Terapii

Katowice, 40-146, Poland

RECRUITING

Local Institution - 2458

Krakow, 31-505, Poland

NOT YET RECRUITING

Local Institution - 2451

Lublin, 20-064, Poland

WITHDRAWN

Local Institution - 2452

Lublin, 20-064, Poland

WITHDRAWN

RCMed Oddzial Sochaczew

Sochaczew, 96-500, Poland

RECRUITING

Local Institution - 2457

Wroclaw, 53-659, Poland

NOT YET RECRUITING

Local Institution - 2641

San Juan, 00917, Puerto Rico

NOT YET RECRUITING

CMRC Headlands

San Juan, 00918, Puerto Rico

RECRUITING

Instituto De Neurologia Dra. Ivonne Fraga

San Juan, 00918, Puerto Rico

RECRUITING

Local Institution - 2639

San Juan, 00918, Puerto Rico

NOT YET RECRUITING

Inha University Hospital

Incheon, Incheon Gwang'yeogsi, 22332, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul-teukbyeolsi [Seoul], 03080, South Korea

RECRUITING

Konkuk University Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 05030, South Korea

RECRUITING

Local Institution - 2406

Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea

WITHDRAWN

Kyungpook National University Chilgok Hospital

Deagu, Taegu-Kwangyǒkshi, 41404, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, 405-760, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

RECRUITING

SMG-SNU Borame Medical Center

Seoul, 07061, South Korea

RECRUITING

The Catholic University of Korea, Yeouido St.Mary's Hospital

Seoul, 07345, South Korea

RECRUITING

Communal non-commercial enterprise "Cherkasy regional psychiatric hospital of Cherkasy regional council"

Smila, Cherkasy Oblast, 20708, Ukraine

RECRUITING

MUNICIPAL NON-COMMERCIAL COMPANY Dnipropetrovsk Multiprofile Clinical Hospital for Provision of Psychiatric Care DRC

Dnipro, Dnipropetrovsk Oblast, 49115, Ukraine

RECRUITING

Municipal Non-Commercial Enterprise "Khmelnytskyi Regional Psychiatric Care Facility" of the Khmelnytskyi Regional Council

Skarzhyntsi, Khmelnytskyi Oblast, 32120, Ukraine

RECRUITING

Communal non-commercial enterprise of the Kyiv Regional Council "Regional Psychiatric-Narcological Medical Association"

Hlevakha, Kyiv Oblast, 08631, Ukraine

RECRUITING

COMMUNAL NONCOMMERCIAL ENTERPRISE of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital"

Lviv, Lviv Oblast, 79021, Ukraine

RECRUITING

Municipal Non-Commercial Enterprise "Odesa Regional Medical Centre of Mental Health" of Odesa Regional Council

Oleksandrivka, Odesa Oblast, 67513, Ukraine

RECRUITING

Communal non-profit enterprise "Vinnytsia Regional Clinical Psycho-Neurological Hospital n.a. acad. O.I. Yushchenko of VRC"

Vinnytsia, Vinnytsia Oblast, 21037, Ukraine

RECRUITING

Local Institution - 2560

Lutsk, Volyn Oblast, 43005, Ukraine

NOT YET RECRUITING

CNCE "Clinical Facility for Mental Health Care "PSYCHIATRY" of executive body of Kyiv City Council (KCSA)"

Hlevakha, 08631, Ukraine

RECRUITING

Communal Non-Commercial Enterprise "Regional Clinical Psychiatric Hospital of the Kirovohrad Regional Council

Kropyvnytskyi, 25491, Ukraine

RECRUITING

Local Institution - 2565

Kyiv, 01030, Ukraine

NOT YET RECRUITING

CNCE "Clinical Facility for Mental Health Care "PSYCHIATRY" of executive body of Kyiv City Council (KCSA)

Kyiv, 04080, Ukraine

RECRUITING

"Medical Centre "Neuroclinic" LLC

Lviv, 79035, Ukraine

RECRUITING

Limited Liability Company "Iqmed"

Lviv, 79035, Ukraine

RECRUITING

Communal Enterprise "Regional Institution of Mental Psychiatric Care of the Poltava Regional Council"

Poltava, 36013, Ukraine

RECRUITING

Local Institution - 2562

Ternopil, 46027, Ukraine

NOT YET RECRUITING

Lancashire & South Cumbria NHS Foundation Trust

Preston, Lancashire, PR2 9HT, United Kingdom

RECRUITING

Surrey and Borders Partnership NHS Foundation Trust

Chertsey, Surrey, KT16 9AU, United Kingdom

RECRUITING

Local Institution - 2502

Cambridge, CB21 5EF, United Kingdom

NOT YET RECRUITING

South London and Maudsley NHS Foundation Trust

London, SE5 8AZ, United Kingdom

RECRUITING

Local Institution - 2500

London, W12 0NN, United Kingdom

NOT YET RECRUITING

NeuroClin Glasgow

Motherwell, ML1 4UF, United Kingdom

RECRUITING

Cornwall Partnership NHS Foundation Trust

Redruth, TR15 3QE, United Kingdom

RECRUITING

Sheffield Health and Social care NHS Foundation Trust

Sheffield, S5 7JT, United Kingdom

RECRUITING

Local Institution - 2509

Stafford, ST16 3SR, United Kingdom

WITHDRAWN

Black Country Healthcare NHS Foundation Trust

Wolverhampton, WV4 5HN, United Kingdom

RECRUITING

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Alzheimer Disease; Psychomotor Agitation

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 10, 2025
• Study Start: July 16, 2025
• Primary Completion (Estimated): November 3, 2028
• Study Completion (Estimated): November 13, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (43); AR (7); HU (8); PR (4); UA (16); DE (3); FR (7); IT (8); PL (9); GB (10); IL (5); CL (6); CZ (9); KR (10)