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NCT06976216PHASE3Recruiting

A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease

Bristol-Myers Squibb

Start Date

7/14/2025

Completion Date

2/23/2029

Summary

The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC for cognitive impairment in Alzheimer's Disease

Eligibility Criteria

Age Range: 60 years to 85 years

Inclusion Criteria * Participants must have a confirmed diagnosis of Alzheimer's disease (AD), specifically at the mild (stage 4) or moderate (stage 5) dementia stages, as defined by the National Institute on Aging and Alzheimer's Association (NIA-AA) core clinical criteria. The diagnosis of AD pathology must be confirmed through the 2024 revised NIA-AA Workgroup criteria using a stepwise diagnostic approach. * Participants must have an Mini-Mental State Examination (MMSE) score ranging from 12 through 22, inclusive, at the time of screening. * Participants must have a designated caregiver who maintains adequate contact (around 10 hours per week or more) and is willing to attend all study visits. The caregiver must also be responsible for reporting on the participant's condition, overseeing medication compliance, and consenting to their involvement in both their own and the participant's study-related activities. * Participants on acetyl choline esterase inhibitors (AChEIs) and/or memantine, must have been on a stable dosage for at least 12 weeks prior to screening, and agree to maintain this stable dose for the study duration. Exclusion Criteria * Participants must not present with any significant or severe medical conditions that could compromise their safety, the ability to comply with or complete the study, or the integrity of the study results. This includes any grade of hepatic impairment, urinary retention, active biliary disease, moderate-severe renal impairment (eGFR of \<50 mL/min), and unstable hypertension or tachycardia. * Participants must not have any primary psychiatric diagnoses such as major depression, schizoaffective disorder, or bipolar disorder, and those with severe psychiatric symptoms that could complicate the interpretation of treatment effects, impair cognitive assessment, or impact study completion. * Participants must not have a history of schizophrenia or other chronic psychosis, as well as those who have previously been exposed to KarXT or are currently undergoing treatment with disease-modifying anti-amyloid therapies for AD within the past 6 months prior to screening. * Participants must not have significant pathological findings on brain magnetic resonance imaging (MRI) at screening that reflect significant pathology other than AD or could affect safety or interfere with study procedures. * Other protocol-defined Inclusion/Exclusion criteria apply.

Interventions

DRUG

KarXT

DRUG

KarX-EC

OTHER

Placebo

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Conditions

Alzheimer's Disease

Locations

Healthy Brain Clinic

Long Beach, California 90804

United States

Anderson Clinical Research

Redlands, California 92374

United States

Mountain Neurological Research Center

Basalt, Colorado 81621

United States

Georgetown University Medical Center

Washington D.C., District of Columbia 20007

United States

JEM Research Institute

Atlantis, Florida 33462

United States

VIN-Julie Schwartzbard

Aventura, Florida 33180

United States

Merritt Island Medical Research, LLC

Merritt Island, Florida 32952

United States

Renstar Medical Research

Ocala, Florida 34470

United States

Alzheimer's Research and Treatment Center

Stuart, Florida 34996

United States

Charter Research - Lady Lake

The Villages, Florida 32162

United States

Local Institution - 0016

Columbus, Georgia 31909

United States

Center for Advanced Research & Education

Gainesville, Georgia 30501

United States

Re:Cognition Health - Chicago

Chicago, Illinois 60611

United States

Ascension Alexian Brothers

Elk Grove Village, Illinois 60007

United States

Boston Center for Memory

Newton, Massachusetts 02459

United States

HealthPartners Neuroscience Center

Saint Paul, Minnesota 55130

United States

Advanced Memory Research Institute of New Jersey

Toms River, New Jersey 08755

United States

NYU Langone Health

New York, New York 10016

United States

Local Institution - 0259

New York, New York 10029

United States

SUNY Upstate Medical University

Syracuse, New York 13210

United States

AMC Research, LLC

Matthews, North Carolina 28105

United States

Ohio State University

Columbus, Ohio 43221

United States

NDx Clinical Research Inc.

Dayton, Ohio 45459

United States

Summit Headlands

Portland, Oregon 97210

United States

Local Institution - 0004

Abington, Pennsylvania 19001

United States

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island 02914

United States

Neurology Clinic, P.C.

Cordova, Tennessee 38018

United States

Gadolin Research

Beaumont, Texas 77702

United States

Fundación para el Estudio y Tratamiento de Enfermedades Mentales (FETEM)

Buenos Aires, Buenos Aires F.D. 1133

Argentina

Local Institution - 0271

Buenos Aires, 1280

Argentina

Fundación Lennox - Instituto Modelo de Neurología

Córdoba, 5000

Argentina

Sanatorio Morra S.A.

Córdoba, 5000

Argentina

Instituto Kremer

Córdoba, X5004AOA

Argentina

Southern Neurology

Kogarah, New South Wales 2217

Australia

KARA Institute for Neurological Diseases

Macquarie Park, New South Wales 2113

Australia

NeuroCentrix

Carlton, Victoria 3053

Australia

Neurodegenerative Disorders Research

Perth, Western Australia 6005

Australia

St Vincent's Hospital Sydney Limited

Darlinghurst, 2010

Australia

Local Institution - 0168

Brasília, Federal District 70200730

Brazil

Instituto de Neurologia de Curitiba

Curitiba, Paraná 81210310

Brazil

Local Institution - 0266

Aracaju, Sergipe 49075-000

Brazil

Hospital das Clinicas FMUSP

São Paulo, 05403-000

Brazil

OCT Research ULC

Kelowna, British Columbia V1Y 1Z9

Canada

Richmond Clinical Trials

Richmond, British Columbia V6V 2L1

Canada

Centricity Research Halifax Multispecialty

Halifax, Nova Scotia B3S 1N2

Canada

Ottawa Memory Clinic

Ottawa, Ontario K1Z 1G3

Canada

Toronto Memory Program

Toronto, Ontario M3B 2S7

Canada

MoCA Research and Innovation Inc.

Greenfield Park, Quebec J4V 2J2

Canada

Diex Recherche Victoriaville

Victoriaville, Quebec G6P 3Z8

Canada

ALPHA Recherche Clinique

Québec, G3K 2P8

Canada

Local Institution - 0094

Santiago, Santiago Metropolitan 7500710

Chile

Local Institution - 0089

Santiago, Santiago Metropolitan 7560356

Chile

Local Institution - 0241

Santiago, Santiago Metropolitan 8380420

Chile

Local Institution - 0230

Antofagasta, 1270244

Chile

Local Institution - 0215

Zagreb, City of Zagreb 10000

Croatia

Poliklinika Neuron

Zagreb, City of Zagreb 10000

Croatia

Klinika za psihijatriju "Vrapče"

Zagreb, 10090

Croatia

Neuro Health Centrum

Brno, Brno-město 628 00

Czechia

AGE Centrum

Olomouc, Olomouc Region 779 00

Czechia

A-Shine

Pilsen, Plzeň-město 301 00

Czechia

Local Institution - 0224

Prague, Praha 6 160 00

Czechia

Neuropsychiatrie

Prague, Praha 6 160 00

Czechia

Local Institution - 0222

Prague, Praha 8 18600

Czechia

Vestra Clinics

Rychnov nad Kněžnou, 516 01

Czechia

Local Institution - 0295

Nice, Alpes-Maritimes 06100

France

Local Institution - 0289

Toulouse, Haute-Garonne 31000

France

Local Institution - 0290

Rouen, Haute-Normandie 76031

France

Local Institution - 0291

Montpellier, Languedoc-Roussillon 34295

France

Local Institution - 0299

Reims, Marne 51092

France

Local Institution - 0293

Villeurbanne, Rhône 69100

France

Local Institution - 0294

Dijon, 21079

France

Universitätsklinikum Münster - Albert Schweitzer Campus

Münster, North Rhine-Westphalia 48149

Germany

Universitätsmedizin Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate 55131

Germany

Charite-Universitaetsmedizin Berlin - Campus Benjamin Franklin (CBF)

Berlin, State of Berlin 12203

Germany

Local Institution - 0277

Bremen, 28325

Germany

Local Institution - 0275

Hamburg, 20246

Germany

TUM Klinikum

Munich, 81675

Germany

University General Hospital of Alexandroupoli

Alexandroupoli, Anatolikí Makedonía Kai Thráki 681 00

Greece

Local Institution - 0256

Athens, Attikí 115 25

Greece

Aiginiteio University Hospital

Athens, Attikí 115 28

Greece

University General Hospital of Larissa

Larissa, Thessalía 41110

Greece

Local Institution - 0288

Bengaluru, Karnataka 560029

India

Local Institution - 0282

Hyderabad, Telangana 500034

India

Local Institution - 0285

Hyderabad, Telangana 500082

India

Local Institution - 0287

Varanasi, Uttar Pradesh 221005

India

Local Institution - 0286

Kolkata, West Bengal 700054

India

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy 20122

Italy

Ospedale San Raffaele

Milan, Lombardy 20132

Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy 20900

Italy

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123

Italy

Local Institution - 0296

's-Hertogenbosch, North Brabant 5223 LA

Netherlands

Local Institution - 0297

Amsterdam, North Holland 1081 GN

Netherlands

Local Institution - 0298

Zwolle, Overijssel 8025 AZ

Netherlands

Centrum Medyczne HCP

Poznan, Greater Poland Voivodeship 61-485

Poland

Osrodek Badan Klinicznych CLINSANTE S.C.

Torun, Kuyavian-Pomeranian Voivodeship 87-100

Poland

MlynowaMed Psychiatric

Bialystok, Podlaskie Voivodeship 15-404

Poland

Centrum Badan Klinicznych PI-House sp. z o.o.

Gdansk, Pomeranian Voivodeship 80-546

Poland

Instituto De Neurologia Dra. Ivonne Fraga

San Juan, 00918

Puerto Rico

Prof. Dr. Alexandru Obregia Psychiatry Hospital

Bucharest, Bucharest 041914

Romania

Prof. Dr. Alexandru Obregia Psychiatry Hospital

Bucharest, Bucharest 041914

Romania

Institutul Național de Gerontologie și Geriatrie "Ana Aslan"

Bucharest, 011241

Romania

Centrul de Sanatate Mintala

Bucharest, 040874

Romania

Institutul de Psihiatrie Socola

Iași, 700282

Romania

Chonnam National University Hospital

Gwangju, Kwangju-Kwangyǒkshi 61469

South Korea

Seoul National University Bundang Hospital

Seongnam, Kyǒnggi-do 13620

South Korea

Seoul National University Hospital

Seoul, Seoul-teukbyeolsi [Seoul] 03080

South Korea

Hanyang University Seoul Hospital

Seoul, Seoul-teukbyeolsi [Seoul] 04763

South Korea

Konkuk University Medical Center

Seoul, Seoul-teukbyeolsi [Seoul] 05030

South Korea

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul] 06351

South Korea

Ewha Womans University Seoul Hospital

Seoul, Seoul-teukbyeolsi [Seoul] 07804

South Korea

Hospital Victoria Eugenia

Seville, Andalusia 41009

Spain

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, Barcelona [Barcelona] 08915

Spain

Hospital Clínic de Barcelona

Barcelona, Catalunya [Cataluña] 08036

Spain

Hospital Universitari de Santa Maria

Lleida, Lleida [Lérida] 25198

Spain

Clinica Universidad de Navarra

Pamplona, Navarre 31008

Spain

Hospital Clinico San Carlos

Madrid, 28040

Spain