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)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Bristol-Myers Squibb
Sponsor
Bristol-Myers Squibb
Information Provided by (Responsible Party)
Bristol-Myers Squibb
Clinicaltrials.gov Identifier
NCT07011732
Other Study ID Numbers:
CN012-0023
First Submitted
June 1, 2025
First Posted
June 9, 2025
Last Update Posted
April 29, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Alzheimer Disease
Drug: Xanomeline/Trospium Chloride CapsuleDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment352 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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
Study Start DateJuly 9, 2025
Actual Primary Completion Date2yrs 6mos from now
Actual Study Completion Date2yrs 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
KarXT + KarX-EC
Drug: Xanomeline/Trospium Chloride Capsule
Specified dose on specified days
Placebo
Drug: Placebo
Specified dose on specified days

Outcome Measures

Primary Outcome Measures
  1. Change from baseline on the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) total score at Week 14
Secondary Outcome Measures
  1. Change from baseline on the Clinical Global Impressions-Severity (CGI-S) at Week 14
  2. Change from baseline on the CMAI-IPA Domains at Week 14
  3. Change from baseline on the CMAI Total Score at Week 14
  4. Number of participants with Occurrence of Response at Week 14
    As determined by CMAI-IPA changes of at least 30%, 40%, and 50% from baseline
  5. Change from baseline on the Neuropsychiatric Inventory/Neuropsychiatric Inventory -Nursing Home (NPI/NPI-NH) Total Score at Week 14
  6. Number of participants with Adverse Events (AEs)
  7. Number of participants with Treatment Emergent AEs (TEAEs)
  8. Number of participants with Serious AEs (SAEs)
  9. Number of participants with AEs leading to study drug withdrawal
  10. Number of deaths
  11. Number of participants with AEs of Special Interest (AESIs)
  12. Barnes Akathisia Rating Scale (BARS)
  13. Abnormal Involuntary Movement Scale (AIMS)
  14. Body Weight
  15. Body Mass Index (BMI)
  16. Number of participants with vital sign abnormalities
  17. Number of participants with clinical laboratory abnormalities
  18. Number of participants with electrocardiogram (ECG) abnormalities
  19. Number of participants with suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
  20. Severity of benign prostatic hyperplasia in male participants as assessed by International Prostate Symptom Score (IPSS)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Inclusion Criteria \- 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).
At least 1 of the following 3 criteria must be established from the CMAI-IPA at Screening (Visit 1) and Baseline (Visit 2; CMAI-IPA Physical/Verbal Aggression Positivity): i) 1 or more aggressive behaviors occurring at least several times per week. ii) 2 or more aggressive behaviors occurring at least once or twice per week. iii) 3 or more aggressive behaviors occurring less than once per week.
Exclusion Criteria
Inclusion Criteria \- 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).
At least 1 of the following 3 criteria must be established from the CMAI-IPA at Screening (Visit 1) and Baseline (Visit 2; CMAI-IPA Physical/Verbal Aggression Positivity): i) 1 or more aggressive behaviors occurring at least several times per week. ii) 2 or more aggressive behaviors occurring at least once or twice per week. iii) 3 or more aggressive behaviors occurring less than once per week. Exclusion Criteria \- 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). \- Other protocol-defined Inclusion/Exclusion criteria apply.

Contacts and Locations

Sponsors and CollaboratorsBristol-Myers Squibb
Locations
Imaging Endpoints | Scottsdale Arizona, United States, 85258Advanced Research Center (ARC) - Anaheim | Anaheim California, United States, 92805Kaizen Brain Center | La Jolla California, United States, 92037The Neurology Group | Pomona California, United States, 91767Torrance Clinical Research | Torrance California, United States, 90505Sunwise Clinical Research | Walnut Creek California, United States, 94596Local Institution - 1630 | Colorado Springs Colorado, United States, 80907Local Institution - 1622 | Maitland Florida, United States, 32751Local Institution - 1631 | Maitland Florida, United States, 32751Local Institution - 1602 | Miami Florida, United States, 33122Local Institution - 1618 | Miami Florida, United States, 33135Hope Research Network - Miami | Miami Florida, United States, 33166Local Institution - 1604 | Miami Florida, United States, 33186Local Institution - 1608 | Ocala Florida, United States, 34471Combined Research Orlando (CRO) | Orlando Florida, United States, 32807Progressive Medical Research | Port Orange Florida, United States, 32127Local Institution - 1661 | Savannah Georgia, United States, 31406Local Institution - 1655 | Marrero Louisiana, United States, 70072CBH Health | Gaithersburg Maryland, United States, 20877Local Institution - 1663 | Foxborough Massachusetts, United States, 02035-1309Boston Center for Memory | Newton Massachusetts, United States, 02459Mayflower Clinical Research | South Dartmouth Massachusetts, United States, 02747Elixia MA | Springfield Massachusetts, United States, 01103Local Institution - 1665 | Bloomfield Hills Michigan, United States, 48302Oakland Medical Research | Troy Michigan, United States, 48085Redbird Research | Las Vegas Nevada, United States, 89119Patient First MD | Middletown New Jersey, United States, 07748Local Institution - 1664 | Princeton New Jersey, United States, 08540Local Institution - 1610 | Inwood New York, United States, 11096Mid Hudson Medical Research | New Windsor New York, United States, 12553Five Towns Neurology PC -Woodmere - 923 Broadway | Woodmere New York, United States, 11598-1739Local Institution - 1645 | Woodmere New York, United States, 11598-1739Local Institution - 1659 | Centerville Ohio, United States, 45459Central States Research | Tulsa Oklahoma, United States, 74136Local Institution - 1652 | Columbia South Carolina, United States, 29205Advanced Neurology Epilepsy and Sleep Center | El Paso Texas, United States, 79912Wasatch Clinical Research, LLC | Salt Lake City Utah, United States, 84107The Memory Clinic | Bennington Vermont, United States, 05201-9810Local Institution - 1644 | Seattle Washington, United States, 98122Kingfisher Cooperative | Spokane Washington, United States, 99201Local Institution - 1001 | La Plata Buenos Aires, Argentina, 1900Local Institution - 1002 | Mar del Plata Buenos Aires, Argentina, B7602CBMFundacion Estudios Clinicos | Rosario Santa Fe Province, Argentina, S2000DEJLocal Institution - 1003 | Buenos Aires , Argentina, C1428AQKLocal Institution - 1004 | Córdoba , Argentina, 5000Instituto Privado Kremer | Córdoba , Argentina, 5004Centro Medico Luquez | Córdoba , Argentina, 5006Local Institution - 1051 | Brasília Federal District, Brazil, 70200730CECPAR - Centro de Estudos Clínicos do Paraná | Curitiba Paraná, Brazil, 80030-310PUCTrials | Curitiba Paraná, Brazil, 80230-130Local Institution - 1058 | Porto Alegre Rio Grande do Sul, Brazil, 90430-001Hospital Moinhos de Vento | Porto Alegre Rio Grande do Sul, Brazil, 90560-032Local Institution - 1057 | Campinas São Paulo, Brazil, 13060-080Ruschel Medicina e Pesquisa Clínica | Rio de Janeiro , Brazil, 22270-060CPQuali Pesquisa Clínica | São Paulo , Brazil, 01228-000Clinica Viver - Centro de Desospitalizacao Humana | São Paulo , Brazil, 04020-060Medical Center Sveti Naum EOOD | Sofia Sofia-Grad, Bulgaria, 1113Local Institution - 1104 | Sofia Sofia-Grad, Bulgaria, 1202Medical Center Medconsult Pleven OOD | Pleven , Bulgaria, 5800Outpatient Clinic for Individual Practice for Specialized Medical Care in Psychiatry - Dr. Madlena Dimitrova Borisova | Razgrad , Bulgaria, 7200Medical Center Mladost | Varna , Bulgaria, 9020Local Institution - 1153 | Hamilton Ontario, Canada, ON L8M 1W9Local Institution - 1755 | London Ontario, Canada, N6A 5W9London Health Sciences Centre-Victoria Campus | London Ontario, Canada, N6A 5W9Sunnybrook Research Institute | Toronto Ontario, Canada, M4N 3M5Centre for Addiction & Mental Health | Toronto Ontario, Canada, M6J 1H4Ontario Shores Centre For Mental Health Sciences | Whitby Ontario, Canada, L1N 5S9Local Institution - 1150 | Montreal Quebec, Canada, H4A 3T2Xuanwu Hospital Capital Medical University | Beijing Beijing Municipality, China, 100053Local Institution - 1810 | Beijing Beijing Municipality, China, 100088Local Institution - 1815 | Haidian District Beijing Municipality, China, 100191Local Institution - 1813 | Chongqing Chongqing Municipality, China, 630014Local Institution - 1809 | Guangzhou Guangdong, China, 0Shenzhen Kangning Hospital | Shenzhen Guangdong, China, 518118Local Institution - 1802 | Guangzhou Guangzhou Province, China, 510260Local Institution - 1803 | Changsha Hunan, China, 410008Local Institution - 1801 | Nanjing Jiangsu, China, 210008Local Institution - 1800 | Shanghai Shanghai Municipality, China, 200025Local Institution - 1816 | Xian Shanxi, China, 710061Local Institution - 1819 | Chengdu Sichuan, China, 610041Tianjin Anding Hospital | Tianjin Tianjin Municipality, China, 300074Local Institution - 1804 | Hangzhou Zhejiang, China, 310003Local Institution - 1817 | Hangzhou , China, 310016Local Institution - 1812 | Kunming , China, 650032Local Institution - 1808 | Tianjin , China, 300350Local Institution - 1550 | Zagreb City of Zagreb, Croatia, 10000Local Institution - 1553 | Zagreb City of Zagreb, Croatia, 10000Local Institution - 1554 | Rijeka , Croatia, 51000Clinical Hospital Center Split | Split , Croatia, HR-21000General Hospital Varazdin | Varaždin , Croatia, 42000University Hospital of Patras | Pátrai Achaḯa, Greece, 26504Henry Dunant Hospital Center | Athens Attica, Greece, 115 26Aiginiteio University Hospital | Athens Attikí, Greece, 115 28University General Hospital "ATTIKON" - General Hospital of West Attica "H AGIA VARVARA" | Chaïdári Attikí, Greece, 124 62Eginition Hospital | Athens , Greece, 11528Local Institution - 1207 | Athens , Greece, 15125Local Institution - 1201 | Ioannina , Greece, 45500Euromedica General Clinic of Thessaloniki | Thessaloniki , Greece, 54645Local Institution - 1255 | Ahmedabad Gujarat, India, 380060Local Institution - 1252 | Hyderabad Telangana, India, 500082Local Institution - 1254 | Varanasi Uttar Pradesh, India, 221005Local Institution - 1250 | Kolkata West Bengal, India, 700054Local Institution - 1256 | Delhi , India, 110 095Local Institution - 1251 | Hyderabad , India, 500034Local Institution - 1253 | New Delhi , India, 110029Local Institution - 1301 | Hadano Kanagawa, Japan, 257-0003Teikyo University Mizonokuchi Hospital | Kawasaki Kanagawa, Japan, 213-8507Local Institution - 1304 | Sakai Osaka, Japan, 590-0018National Hospital Organization Hizen Psychiatric Center | Kanzaki-Gun Yoshinogari-Cho Saga-ken, Japan, 842-0192Rainbow and Sea Hospital | Karatsu-shi Saga-ken, Japan, 847-0031Local Institution - 1305 | Bunkyo-ku Tokyo, Japan, 113-8603Kuramitsu Hospital | Fukuoka , Japan, 819-0037Okayama City General Medical Center Okayama City Hospital | Okayama , Japan, 700-8557Local Institution - 1308 | Shimotsuke-shi, Tochigi , Japan, 329-0498Hospital Universitario de Saltillo | Saltillo Coahuila, Mexico, 25000Boca Clinical Trials Mexico S.C. | Guadalajara Jalisco, Mexico, 44600Innovacion y Desarrollo en Ciencias de la Salud | Mexico City Mexico City, Mexico, 14090Local Institution - 1360 | Mexico City Mexico City, Mexico, 14269AVIX Investigacion Clinica | Monterrey Nuevo León, Mexico, 64623Local Institution - 1350 | Monterrey Nuevo León, Mexico, 66460Local Institution - 1361 | Mexico City , Mexico, 10200Neurociencias PRISMA A.C. | San Luis Potosí City , Mexico, 78216Clinical Research Institute S.C. | Tlalnepantla , Mexico, 54055Local Institution - 1401 | Coimbra , Portugal, 3049Centro Hospitalar do Alto Ave | Guimarães , Portugal, 4835-044Local Institution - 1404 | Lisbon , Portugal, 1649-035Unidade Local de Saúde de Matosinhos SA | Senhora da Hora , Portugal, 4464-513Campus Neurologico Senior | Torres Vedras , Portugal, 2560-280Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041919Local Institution - 1451 | Bucharest , Romania, 010825Local Institution - 1459 | Bucharest , Romania, 060222Prof Dr Alexandru Obregia Clinical Psychiatric Hospital- Centrul de Sanatate Mintala | Bucharest , Romania, 40874Local Institution - 1461 | Constanța , Romania, 90123Institutul de Psihiatrie Socola | Iași , Romania, 700282Local Institution - 1460 | Sanpetru /Brasov , Romania, 507190Local Institution - 1462 | Sibiu , Romania, 550082Oroitu CAE | Getxo Bizkaia, Spain, 48993Hospital General Universitario de Elche | Elche (alicante) , Spain, 03203Complejo Hospitalario Ruber Juan Bravo | Madrid , Spain, 28006Hospital Clinico San Carlos | Madrid , Spain, 28040Hospital Clinico Universitario Virgen de La Victoria | Málaga , Spain, 29010Clinica Universidad de Navarra | Pamplona , Spain, 31008Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca | Salamanca , Spain, 37007Hospital Victoria Eugenia de Sevilla | Seville , Spain, 41009Hospital Mutua Terrassa | Terrassa , Spain, 8221Hospital Universitario De Rio Hortega | Valladolid , Spain, 47012Hospital Viamed Montecanal | Zaragoza , Spain, 50012Chang Gung Memorial Hospital at Kaohsiung | Kaohsiung Niao Sung Dist Kaohsiung, Taiwan, 83301National Cheng Kung University Hospital | Tainan, Taiana , Taiwan, 704National Taiwan University Hospital | Taipei , Taiwan, 100229Taipei Veterans General Hospital | Taipei , Taiwan, 112Chang Gung Medical Foundation-Linkou Branch | Taoyuan , Taiwan, 333
Investigators
Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb