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-1)
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease
3 other identifiers
interventional
426
15 countries
158
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 alzheimer-disease
Started Jul 2025
Typical duration for phase_3 alzheimer-disease
158 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 2, 2025
CompletedFirst Posted
Study publicly available on registry
June 10, 2025
CompletedStudy Start
First participant enrolled
July 10, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 24, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 8, 2028
July 13, 2026
July 1, 2026
3.4 years
June 2, 2025
July 10, 2026
Conditions
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 the CMAI-IPA Domains at Week 14
At Week 14
Change from baseline on the 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
- +15 more secondary outcomes
Study Arms (2)
KarXT + KarX-EC
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
Specified dose on specified days
Specified dose on specified days
Eligibility Criteria
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).
- CMAI-IPA Total Score ≥ 30 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. 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (158)
Imaging Endpoints
Scottsdale, Arizona, 85258, United States
Advanced Research Center (ARC) - Anaheim
Anaheim, California, 92805, United States
Local Institution - 1637
La Jolla, California, 92037, United States
The Neurology Group
Pomona, California, 91767, United States
Local Institution - 1639
Torrance, California, 90505, United States
Sunwise Clinical Research
Walnut Creek, California, 94596, United States
Local Institution - 1630
Colorado Springs, Colorado, 80907, United States
Local Institution - 1622
Maitland, Florida, 32751, United States
Local Institution - 1631
Maitland, Florida, 32751, United States
Local Institution - 1666
Merritt Island, Florida, 32952, United States
Local Institution - 1602
Miami, Florida, 33122, United States
Local Institution - 1618
Miami, Florida, 33135, United States
Hope Research Network - Miami
Miami, Florida, 33166, United States
Local Institution - 1604
Miami, Florida, 33186, United States
Local Institution - 1608
Ocala, Florida, 34471, United States
Combined Research Orlando (CRO)
Orlando, Florida, 32807, United States
Progressive Medical Research
Port Orange, Florida, 32127, United States
Local Institution - 1655
Marrero, Louisiana, 70072, United States
CBH Health
Gaithersburg, Maryland, 20877, United States
Local Institution - 1663
Foxborough, Massachusetts, 02035-1309, United States
Boston Center for Memory
Newton, Massachusetts, 02459, United States
Mayflower Clinical Research
South Dartmouth, Massachusetts, 02747, United States
Elixia MA
Springfield, Massachusetts, 01103, United States
NeuroBehavioral Medicine Group
Bloomfield Hills, Michigan, 48302, United States
Oakland Medical Research
Troy, Michigan, 48085, United States
Redbird Research
Las Vegas, Nevada, 89119, United States
Local Institution - 1647
Middletown, New Jersey, 07748, United States
Global Medical Institutes LLC; Princeton Medical Institute
Princeton, New Jersey, 08540, United States
Local Institution - 1610
Inwood, New York, 11096, United States
Mid Hudson Medical Research
New Windsor, New York, 12553, United States
Five Towns Neurology PC -Woodmere - 923 Broadway
Woodmere, New York, 11598-1739, United States
Local Institution - 1645
Woodmere, New York, 11598-1739, United States
Central States Research
Tulsa, Oklahoma, 74136, United States
Local Institution - 1652
Columbia, South Carolina, 29205, United States
Advanced Neurology Epilepsy and Sleep Center
El Paso, Texas, 79912, United States
Wasatch Clinical Research, LLC
Salt Lake City, Utah, 84107, United States
The Memory Clinic
Bennington, Vermont, 05201-9810, United States
Local Institution - 1644
Seattle, Washington, 98122, United States
Kingfisher Cooperative
Spokane, Washington, 99201, United States
Local Institution - 1001
La Plata, Buenos Aires, 1900, Argentina
Local Institution - 1002
Mar del Plata, Buenos Aires, B7602CBM, Argentina
CEN Centro Especializado en Neurociencias
Córdoba, Córdoba Province, 5004, Argentina
Fundacion Estudios Clinicos
Rosario, Santa Fe Province, S2000DEJ, Argentina
Local Institution - 1003
Buenos Aires, C1428AQK, Argentina
Instituto Privado Kremer
Córdoba, 5004, Argentina
Centro Medico Luquez
Córdoba, 5006, Argentina
L2IP - Instituto de Pesquisas Clínicas
Brasília, Federal District, 70200730, Brazil
CECPAR - Centro de Estudos Clínicos do Paraná
Curitiba, Paraná, 80030-310, Brazil
PUCTrials
Curitiba, Paraná, 80230-130, Brazil
Nucleo de Pesquisa Clinica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001, Brazil
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90560-032, Brazil
Instituto de Pesquisa Clínica de Campinas
Campinas, São Paulo, 13060-080, Brazil
Ruschel Medicina e Pesquisa Clínica
Rio de Janeiro, 22270-060, Brazil
CPQuali Pesquisa Clínica
São Paulo, 01228-000, Brazil
Clinica Viver - Centro de Desospitalizacao Humana
São Paulo, 04020-060, Brazil
Medical Center Medconsult Pleven OOD
Pleven, 5800, Bulgaria
Outpatient Clinic for Individual Practice for Specialized Medical Care in Psychiatry - Dr. Madlena Dimitrova Borisova
Razgrad, 7200, Bulgaria
Medical Center Sveti Naum EOOD
Sofia, 1113, Bulgaria
Local Institution - 1104
Sofia, 1202, Bulgaria
Medical Center Mladost
Varna, 9020, Bulgaria
Local Institution - 1153
Hamilton, Ontario, L8M 1W9, Canada
Local Institution - 1755
London, Ontario, N6A 5W9, Canada
London Health Sciences Centre-Victoria Campus
London, Ontario, N6A 5W9, Canada
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5, Canada
Centre for Addiction & Mental Health
Toronto, Ontario, M6J 1H4, Canada
Ontario Shores Centre For Mental Health Sciences
Whitby, Ontario, L1N 5S9, Canada
Local Institution - 1150
Montreal, Quebec, H4A 3T2, Canada
Xuanwu Hospital Capital Medical University
Beijing, Beijing Municipality, 100053, China
Local Institution - 1810
Beijing, Beijing Municipality, 100088, China
Peking University Sixth Hospital
Haidian District, Beijing Municipality, 100191, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 630014, China
The Affiliated Brain Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 0, China
Shenzhen Kangning Hospital
Shenzhen, Guangdong, 518118, China
The Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangzhou Province, 510260, China
Xiangya Hospital Central South University
Changsha, Hunan, 410008, China
Nanjing Drum Tower hospital
Nanjing, Jiangsu, 210008, China
Local Institution - 1800
Shanghai, Shanghai Municipality, 200025, China
Mental Health Center of Xi'an City
Xian, Shanxi, 710061, China
Local Institution - 1819
Chengdu, Sichuan, 610041, China
Tianjin Anding Hospital
Tianjin, Tianjin Municipality, 300074, China
The First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310003, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Hangzhou, 310016, China
The First Affiliated Hospital of Kunming Medical University
Kunming, 650032, China
Local Institution - 1808
Tianjin, 300350, China
Local Institution - 1550
Zagreb, City of Zagreb, 10000, Croatia
Local Institution - 1553
Zagreb, City of Zagreb, 10000, Croatia
Klinicki Bolnicki Centar Rijeka
Rijeka, 51000, Croatia
Clinical Hospital Center Split
Split, HR-21000, Croatia
General Hospital Varazdin
Varaždin, 42000, Croatia
Local Institution - 1555
Zagreb, 10 090, Croatia
University Hospital of Patras
Pátrai, Achaḯa, 26504, Greece
Henry Dunant Hospital Center
Athens, Attica, 115 26, Greece
Aiginiteio University Hospital
Athens, Attikí, 115 28, Greece
University General Hospital "ATTIKON" - General Hospital of West Attica "H AGIA VARVARA"
Chaïdári, Attikí, 124 62, Greece
Eginition Hospital
Athens, 11528, Greece
Athens Medical Center
Athens, 15125, Greece
Local Institution - 1201
Ioannina, 45500, Greece
Euromedica General Clinic of Thessaloniki
Thessaloniki, 54645, Greece
Local Institution - 1255
Ahmedabad, Gujarat, 380060, India
Local Institution - 1252
Hyderabad, Telangana, 500082, India
Local Institution - 1254
Varanasi, Uttar Pradesh, 221005, India
Local Institution - 1250
Kolkata, West Bengal, 700054, India
Local Institution - 1256
Delhi, 110 095, India
Local Institution - 1251
Hyderabad, 500034, India
Local Institution - 1253
New Delhi, 110029, India
Hatano Kousei Hospital
Hadano, Kanagawa, 257-0003, Japan
Teikyo University Mizonokuchi Hospital
Kawasaki, Kanagawa, 213-8507, Japan
Asakayama Hospital
Sakai, Osaka, 590-0018, Japan
National Hospital Organization Hizen Psychiatric Center
Kanzaki-Gun Yoshinogari-Cho, Saga-ken, 842-0192, Japan
Rainbow and Sea Hospital
Karatsu-shi, Saga-ken, 847-0031, Japan
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, 113-8603, Japan
Kuramitsu Hospital
Fukuoka, 819-0037, Japan
Okayama City General Medical Center Okayama City Hospital
Okayama, 700-8557, Japan
Local Institution - 1308
Shimotsuke-shi, Tochigi, 329-0498, Japan
Hospital Universitario de Saltillo
Saltillo, Coahuila, 25000, Mexico
Boca Clinical Trials Mexico S.C.
Guadalajara, Jalisco, 44600, Mexico
Innovacion y Desarrollo en Ciencias de la Salud
Mexico City, Mexico City, 14090, Mexico
Local Institution - 1360
Mexico City, Mexico City, 14269, Mexico
AVIX Investigacion Clinica
Monterrey, Nuevo León, 64623, Mexico
Local Institution - 1350
Monterrey, Nuevo León, 66460, Mexico
Local Institution - 1361
Mexico City, 10200, Mexico
Neurociencias PRISMA A.C.
San Luis Potosí City, 78216, Mexico
Clinical Research Institute S.C.
Tlalnepantla, 54055, Mexico
Unidade Local de Saúde de Coimbra, E.P.E.
Coimbra, 3049, Portugal
Centro Hospitalar do Alto Ave
Guimarães, 4835-044, Portugal
Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035, Portugal
Unidade Local de Saúde de Matosinhos SA
Senhora da Hora, 4464-513, Portugal
Campus Neurologico Senior
Torres Vedras, 2560-280, Portugal
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041919, Romania
Local Institution - 1451
Bucharest, 010825, Romania
Local Institution - 1463
Bucharest, 011241, Romania
Local Institution - 1459
Bucharest, 060222, Romania
Prof Dr Alexandru Obregia Clinical Psychiatric Hospital- Centrul de Sanatate Mintala
Bucharest, 40874, Romania
Cai Ferate Clinical Hospital Constanta
Constanța, 90123, Romania
Institutul de Psihiatrie Socola
Iași, 700282, Romania
Spitalul de Psihiatrie și Neurologie Brașov
Sanpetru /Brasov, 507190, Romania
Clinical Psychiatric Hospital "Dr. Gheorghe Preda"
Sibiu, 550082, Romania
Oroitu CAE
Getxo, Bizkaia, 48993, Spain
Hospital General Universitario de Elche
Elche (alicante), 03203, Spain
Complejo Hospitalario Ruber Juan Bravo
Madrid, 28006, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Clinico Universitario Virgen de La Victoria
Málaga, 29010, Spain
Clinica Universidad de Navarra
Pamplona, 31008, Spain
Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Victoria Eugenia de Sevilla
Seville, 41009, Spain
Hospital Mutua Terrassa
Terrassa, 8221, Spain
Hospital Universitario De Rio Hortega
Valladolid, 47012, Spain
Hospital Viamed Montecanal
Zaragoza, 50012, Spain
Chang Gung Memorial Hospital at Kaohsiung
Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan
National Cheng Kung University Hospital
Tainan, Taiana, 704, Taiwan
National Taiwan University Hospital
Taipei, 100229, Taiwan
Taipei Veterans General Hospital
Taipei, 112, Taiwan
Chang Gung Medical Foundation-Linkou Branch
Taoyuan, 333, Taiwan
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Central Study Contacts
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACT
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 10, 2025
Primary Completion (Estimated)
November 24, 2028
Study Completion (Estimated)
December 8, 2028
Last Updated
July 13, 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
BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html