A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-2)

NCT07011745 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CN012-00242025-520613-31U1111-1316-5745
• Study Type: interventional
• Target: 352
• Locations: 14 countries
• Sites: 140

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 Disease

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 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).

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. Mirtazapine or trazodone 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 (140)

Chandler Clinical Trials, LLC

Chandler, Arizona, 85224, United States

RECRUITING

Local Institution - 2631

Chandler, Arizona, 85226-3732, 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 - 2613

Pasadena, California, 91105, United States

NOT YET RECRUITING

Local Institution - 2614

San Diego, California, 92108, United States

NOT YET RECRUITING

Alliance Clinical -West Hills

West Hills, California, 91307, United States

RECRUITING

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

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

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48105, United States

RECRUITING

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

ACTIVE NOT RECRUITING

Las Vegas Clinical Trials

Las Vegas, Nevada, 89030, United States

RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

RECRUITING

Local Institution - 2644

Valley Stream, New York, 11580, United States

NOT YET 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, 77065, 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

Local Institution - 2638

Kirkland, Washington, 98034, United States

NOT YET RECRUITING

Local Institution - 2610

Milwaukee, Wisconsin, 53226, United States

NOT YET RECRUITING

Local Institution - 2005

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

NOT YET 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

Local Institution - 2000

Córdoba, 5000, Argentina

NOT YET RECRUITING

Local Institution - 2002

Córdoba, 5000, Argentina

NOT YET RECRUITING

Local Institution - 2003

Córdoba, X5003DCE, Argentina

NOT YET RECRUITING

Local Institution - 2001

Mendoza, 5502, Argentina

NOT YET RECRUITING

Local Institution - 2051

Santiago, Santiago Metropolitan, 7500710, Chile

NOT YET RECRUITING

Local Institution - 2050

Santiago, Santiago Metropolitan, 7560356, Chile

NOT YET RECRUITING

Local Institution - 2052

Santiago, Santiago Metropolitan, 8330024, Chile

NOT YET RECRUITING

Local Institution - 2054

Vitacura, Santiago Metropolitan, 2511433, Chile

NOT YET RECRUITING

Local Institution - 2055

Viña del Mar, Valparaiso, 2511433, Chile

NOT YET RECRUITING

Local Institution - 2053

Antofagasta, 1270244, Chile

NOT YET 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

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

Local Institution - 2253

Budapest, 1088, Hungary

NOT YET RECRUITING

Local Institution - 2252

Debrecen, 4032, Hungary

NOT YET RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, Central District, 5262000, Israel

RECRUITING

Local Institution - 2302

Petch Tikva, IL, 49100, Israel

NOT YET RECRUITING

Local Institution - 2301

Jerusalem, 91120, 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 - 2451

Lublin, 20-064, Poland

WITHDRAWN

Local Institution - 2452

Lublin, 20-064, Poland

WITHDRAWN

RCMed Oddzial Sochaczew

Sochaczew, 96-500, Poland

RECRUITING

Local Institution - 2641

San Juan, 00917, Puerto Rico

NOT YET RECRUITING

Local Institution - 2640

San Juan, 00918-4502, Puerto Rico

NOT YET RECRUITING

Local Institution - 2639

San Juan, 00918, Puerto Rico

NOT YET RECRUITING

Local Institution - 2645

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

CNCE "Cherkasy regional psychiatric hospital of Cherkasy regional council"

Smila, Cherkasy Oblast, 20708, Ukraine

RECRUITING

MNCC 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

CNCE of the Kyiv Regional Council "Regional Psychiatric-Narcological Medical Association"

Hlevakha, Kyiv Oblast, 08631, Ukraine

RECRUITING

CNCE of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital"

Lviv, Lviv Oblast, 79021, Ukraine

RECRUITING

CNCE "Odesa Regional Mental Health Medical Center" of the ORC"

Oleksandrivka, Odesa Oblast, 67513, Ukraine

RECRUITING

Local Institution - 2562

Ternopil, Ternopil Oblast, 460027, Ukraine

NOT YET RECRUITING

CNPE "Vinnytsia Regional Clinical Psycho-Neurological Hospital n.a. Acad. O.I. Yushchenko of Vinnytsia Regional Counsil"

Vinnytsia, Vinnytsia Oblast, 21037, Ukraine

RECRUITING

Local Institution - 2560

Lutsk, Volyn Oblast, 43005, Ukraine

NOT YET RECRUITING

Local Institution - 2556

Hlevakha, 08631, Ukraine

NOT YET RECRUITING

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

Kropyvnytskyi, 25491, Ukraine

RECRUITING

Local Institution - 2565

Kyiv, 01030, Ukraine

NOT YET RECRUITING

Local Institution - 2553

Kyiv, 04080, Ukraine

NOT YET RECRUITING

"Medical Centre "Neuroclinic" LLC

Lviv, 79035, Ukraine

RECRUITING

Local Institution - 2569

Lviv, 79035, Ukraine

NOT YET RECRUITING

Local Institution - 2568

Odesa, 65006, Ukraine

NOT YET RECRUITING

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

Poltava, 36013, Ukraine

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

Local Institution - 2503

Wolverhampton, WV4 5HN, United Kingdom

NOT YET RECRUITING

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Alzheimer Disease

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

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: April 30, 2026

Record last verified: 2026-04

Data Sharing

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

Locations

US (38); AR (7); HU (8); PR (4); KR (10); CL (6); IL (6); UA (17); GB (10); CZ (9); DE (3); FR (7); IT (8); PL (7)