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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by Bristol-Myers Squibb
Sponsor
Bristol-Myers Squibb
Information Provided by (Responsible Party)
Bristol-Myers Squibb
Clinicaltrials.gov Identifier
NCT06976216
Other Study ID Numbers:
CN012-0051
First Submitted
May 8, 2025
First Posted
May 15, 2025
Last Update Posted
May 6, 2026
Last Verified
April 2026

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

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Alzheimer's Disease
Drug: KarXTOther: Placebo

Study Design

Study TypeInterventional
Actual Enrollment586 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for the Treatment of Cognitive Impairment Associated With Mild to Moderate Alzheimer's Disease (MINDSET 1)
Study Start DateJuly 13, 2025
Actual Primary Completion Date2yrs 3mos from now
Actual Study Completion Date2yrs 9mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
KarXT + KarX-EC
Drug: KarXT
Specified dose on specified days
Placebo
Other: Placebo
Specified dose on specified days

Outcome Measures

Primary Outcome Measures
  1. Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11)
  2. Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+)
Secondary Outcome Measures
  1. Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL)
  2. Change from baseline in neuro psychiatric inventory (NPI) total score
  3. Number of participants with adverse events (AEs)
  4. Number of participants with serious adverse events (SAEs)
  5. Number of participants with adverse event of special interest (AESIs)
  6. Number of participants with AEs leading to study intervention discontinuation
  7. Number of participants with AEs leading to study discontinuation
  8. Number of participants with AEs leading to death
  9. Number of participants with clinically significant changes in vital signs
  10. Number of participants with clinically significant changes in electrocardiogram (ECG) tests
  11. Number of participants with clinically significant changes in Columbia-Suicide Severity Rating Scale (C-SSRS) tests
  12. Number of participants with clinically significant changes in weight
  13. Number of participants with clinically significant changes in safety laboratory tests

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
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
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.

Contacts and Locations

Sponsors and CollaboratorsBristol-Myers Squibb
Locations
Healthy Brain Clinic | Long Beach California, United States, 90804Anderson Clinical Research | Redlands California, United States, 92374Mountain Neurological Research Center | Basalt Colorado, United States, 81621Georgetown University Medical Center | Washington D.C. District of Columbia, United States, 20007JEM Research Institute | Atlantis Florida, United States, 33462VIN-Julie Schwartzbard | Aventura Florida, United States, 33180Merritt Island Medical Research, LLC | Merritt Island Florida, United States, 32952Renstar Medical Research | Ocala Florida, United States, 34470Alzheimer's Research and Treatment Center | Stuart Florida, United States, 34997Charter Research - Lady Lake | The Villages Florida, United States, 32162Local Institution - 0016 | Columbus Georgia, United States, 31909Center for Advanced Research & Education | Gainesville Georgia, United States, 30501Re:Cognition Health - Chicago | Chicago Illinois, United States, 60611Ascension Alexian Brothers | Elk Grove Village Illinois, United States, 60007Boston Center for Memory | Newton Massachusetts, United States, 02459HealthPartners Neuroscience Center | Saint Paul Minnesota, United States, 55130Advanced Memory Research Institute of New Jersey | Toms River New Jersey, United States, 08755NYU Langone Health | New York New York, United States, 10016Local Institution - 0259 | New York New York, United States, 10029SUNY Upstate Medical University | Syracuse New York, United States, 13210AMC Research, LLC | Matthews North Carolina, United States, 28105Ohio State University | Columbus Ohio, United States, 43221NDx Clinical Research Inc. | Dayton Ohio, United States, 45459Summit Headlands | Portland Oregon, United States, 97210Local Institution - 0004 | Abington Pennsylvania, United States, 19001Rhode Island Mood & Memory Research Institute | East Providence Rhode Island, United States, 02914Neurology Clinic, P.C. | Cordova Tennessee, United States, 38018Gadolin Research | Beaumont Texas, United States, 77702Fundación para el Estudio y Tratamiento de Enfermedades Mentales (FETEM) | Buenos Aires Buenos Aires F.D., Argentina, 1133Local Institution - 0271 | Buenos Aires , Argentina, 1280Fundación Lennox - Instituto Modelo de Neurología | Córdoba , Argentina, 5000Sanatorio Morra S.A. | Córdoba , Argentina, 5000Instituto Kremer | Córdoba , Argentina, X5004AOASouthern Neurology | Kogarah New South Wales, Australia, 2217KARA Institute for Neurological Diseases | Macquarie Park New South Wales, Australia, 2113NeuroCentrix | Carlton Victoria, Australia, 3053Neurodegenerative Disorders Research | Perth Western Australia, Australia, 6005St Vincent's Hospital Sydney Limited | Darlinghurst , Australia, 2010Local Institution - 0168 | Brasília Federal District, Brazil, 70200730Instituto de Neurologia de Curitiba | Curitiba Paraná, Brazil, 81210310Local Institution - 0266 | Aracaju Sergipe, Brazil, 49075-000Hospital das Clinicas FMUSP | São Paulo , Brazil, 05403-000OCT Research ULC | Kelowna British Columbia, Canada, V1Y 1Z9Richmond Clinical Trials | Richmond British Columbia, Canada, V6V 2L1Centricity Research Halifax Multispecialty | Halifax Nova Scotia, Canada, B3S 1N2Ottawa Memory Clinic | Ottawa Ontario, Canada, K1Z 1G3Toronto Memory Program | Toronto Ontario, Canada, M3B 2S7MoCA Research and Innovation Inc. | Greenfield Park Quebec, Canada, J4V 2J2Diex Recherche Victoriaville | Victoriaville Quebec, Canada, G6P 3Z8ALPHA Recherche Clinique | Québec , Canada, G3K 2P8Local Institution - 0094 | Santiago Santiago Metropolitan, Chile, 7500710Local Institution - 0089 | Santiago Santiago Metropolitan, Chile, 7560356Local Institution - 0241 | Santiago Santiago Metropolitan, Chile, 8380420Local Institution - 0230 | Antofagasta , Chile, 1270244Local Institution - 0215 | Zagreb City of Zagreb, Croatia, 10000Poliklinika Neuron | Zagreb City of Zagreb, Croatia, 10000Klinika za psihijatriju "Vrapče" | Zagreb , Croatia, 10090Neuro Health Centrum | Brno Brno-město, Czechia, 628 00AGE Centrum | Olomouc Olomouc Region, Czechia, 779 00A-Shine | Pilsen Plzeň-město, Czechia, 301 00Neurologická Ambulance - Forbeli | Prague Praha 6, Czechia, 160 00Neuropsychiatrie | Prague Praha 6, Czechia, 160 00Institut neuropsychiatricke pece (INEP), Praha | Prague Praha 8, Czechia, 18600Vestra Clinics | Rychnov nad Kněžnou , Czechia, 516 01Universitätsklinikum Münster - Albert Schweitzer Campus | Münster North Rhine-Westphalia, Germany, 48149Local Institution - 0276 | Mainz Rhineland-Palatinate, Germany, 55131Local Institution - 0218 | Berlin , Germany, 13125Local Institution - 0277 | Bremen , Germany, 28325Local Institution - 0275 | Hamburg , Germany, 20246TUM Klinikum | Munich , Germany, 81675University General Hospital of Alexandroupoli | Alexandroupoli Anatolikí Makedonía Kai Thráki, Greece, 681 00Local Institution - 0256 | Athens Attikí, Greece, 115 25Aiginiteio University Hospital | Athens Attikí, Greece, 115 28Local Institution - 0257 | Larissa Thessalía, Greece, 41110Local Institution - 0288 | Bengaluru Karnataka, India, 560029Local Institution - 0282 | Hyderabad Telangana, India, 500034Local Institution - 0285 | Hyderabad Telangana, India, 500082Local Institution - 0287 | Varanasi Uttar Pradesh, India, 221005Local Institution - 0286 | Kolkata West Bengal, India, 700054Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milan Lombardy, Italy, 20122Ospedale San Raffaele | Milan Lombardy, Italy, 20132Fondazione IRCCS San Gerardo dei Tintori | Monza Lombardy, Italy, 20900Azienda Ospedaliera Spedali Civili di Brescia | Brescia , Italy, 25123Local Institution - 0262 | Poznan Greater Poland Voivodeship, Poland, 61-485Osrodek Badan Klinicznych CLINSANTE S.C. | Torun Kuyavian-Pomeranian Voivodeship, Poland, 87-100MlynowaMed Psychiatric | Bialystok Podlaskie Voivodeship, Poland, 15-404Centrum Badan Klinicznych PI-House sp. z o.o. | Gdansk Pomeranian Voivodeship, Poland, 80-546Local Institution - 0181 | San Juan , Puerto Rico, 00918Local Institution - 0273 | Bucharest Bucharest, Romania, 041914Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041914Prof. Dr. Alexandru Obregia Psychiatry Hospital | Bucharest Bucharest, Romania, 041914Institutul Național de Gerontologie și Geriatrie "Ana Aslan" | Bucharest , Romania, 011241Institutul de Psihiatrie Socola | Iași , Romania, 700282Chonnam National University Hospital | Gwangju Kwangju-Kwangyǒkshi, South Korea, 61469Seoul National University Bundang Hospital | Seongnam Kyǒnggi-do, South Korea, 13620Seoul National University Hospital | Seoul Seoul-teukbyeolsi [Seoul], South Korea, 03080Hanyang University Seoul Hospital | Seoul Seoul-teukbyeolsi [Seoul], South Korea, 04763Konkuk University Medical Center | Seoul Seoul-teukbyeolsi [Seoul], South Korea, 05030Samsung Medical Center | Seoul Seoul-teukbyeolsi [Seoul], South Korea, 06351Ewha Womans University Seoul Hospital | Seoul Seoul-teukbyeolsi [Seoul], South Korea, 07804Hospital Victoria Eugenia | Seville Andalusia, Spain, 41009Hospital Universitari General de Catalunya | Sant Cugat del Vallès Barcelona [Barcelona], Spain, 08915Hospital Clínic de Barcelona | Barcelona Catalunya [Cataluña], Spain, 08036Hospital Universitari de Santa Maria | Lleida Lleida [Lérida], Spain, 25198Clinica Universidad de Navarra | Pamplona Navarre, Spain, 31008Hospital Clinico San Carlos | Madrid , Spain, 28040
Investigators
Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb