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

NCT06976216 · Bristol-Myers Squibb
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Official title
A 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)
About this study
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
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.
Study design
Enrollment target: 586 participants
Allocation: randomized
Masking: double
Age groups: adult, older_adult
Timeline
Starts: 2025-07-14
Estimated completion: 2029-02-23
Last updated: 2026-04-14
Interventions
Drug: KarXTDrug: KarX-ECOther: Placebo
Primary outcomes
  • Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) (At week 24)
  • Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+) (At week 24)
Sponsor
Bristol-Myers Squibb · industry
Contacts & investigators
ContactBMS Clinical Trials Contact Center www.BMSClinicalTrials.com · contact · Clinical.Trials@bms.com · 855-907-3286
ContactFirst line of the email MUST contain NCT # and Site #. · contact
InvestigatorBristol-Myers Squibb · study_director, Bristol-Myers Squibb
All locations (106)
Healthy Brain ClinicRecruiting
Long Beach, California, United States
Anderson Clinical ResearchRecruiting
Redlands, California, United States
Mountain Neurological Research CenterRecruiting
Basalt, Colorado, United States
Georgetown University Medical CenterRecruiting
Washington D.C., District of Columbia, United States
JEM Research InstituteRecruiting
Atlantis, Florida, United States
VIN-Julie SchwartzbardRecruiting
Aventura, Florida, United States
Merritt Island Medical Research, LLCRecruiting
Merritt Island, Florida, United States
Renstar Medical ResearchRecruiting
Ocala, Florida, United States
Alzheimer's Research and Treatment CenterRecruiting
Stuart, Florida, United States
Charter Research - Lady LakeRecruiting
The Villages, Florida, United States
Local Institution - 0016Withdrawn
Columbus, Georgia, United States
Center for Advanced Research & EducationRecruiting
Gainesville, Georgia, United States
Re:Cognition Health - ChicagoRecruiting
Chicago, Illinois, United States
Ascension Alexian BrothersRecruiting
Elk Grove Village, Illinois, United States
Boston Center for MemoryRecruiting
Newton, Massachusetts, United States
HealthPartners Neuroscience CenterRecruiting
Saint Paul, Minnesota, United States
Advanced Memory Research Institute of New JerseyRecruiting
Toms River, New Jersey, United States
NYU Langone HealthRecruiting
New York, New York, United States
Local Institution - 0259Active Not Recruiting
New York, New York, United States
SUNY Upstate Medical UniversityRecruiting
Syracuse, New York, United States
AMC Research, LLCRecruiting
Matthews, North Carolina, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
NDx Clinical Research Inc.Recruiting
Dayton, Ohio, United States
Summit HeadlandsRecruiting
Portland, Oregon, United States
Local Institution - 0004Withdrawn
Abington, Pennsylvania, United States
Rhode Island Mood & Memory Research InstituteRecruiting
East Providence, Rhode Island, United States
Neurology Clinic, P.C.Recruiting
Cordova, Tennessee, United States
Gadolin ResearchRecruiting
Beaumont, Texas, United States
Local Institution - 0001Not Yet Recruiting
Buenos Aires, Buenos Aires F.D., Argentina
Local Institution - 0271Not Yet Recruiting
Buenos Aires, Argentina
Fundación Lennox - Instituto Modelo de NeurologíaRecruiting
Córdoba, Argentina
Sanatorio Morra S.A.Recruiting
Córdoba, Argentina
Instituto KremerRecruiting
Córdoba, Argentina
Southern NeurologyRecruiting
Kogarah, New South Wales, Australia
KARA Institute for Neurological DiseasesRecruiting
Macquarie Park, New South Wales, Australia
NeuroCentrixRecruiting
Carlton, Victoria, Australia
Neurodegenerative Disorders ResearchRecruiting
Perth, Western Australia, Australia
St Vincent's Hospital Sydney LimitedRecruiting
Darlinghurst, Australia
Local Institution - 0168Not Yet Recruiting
Brasília, Federal District, Brazil
Instituto de Neurologia de CuritibaRecruiting
Curitiba, Paraná, Brazil
Local Institution - 0266Not Yet Recruiting
Aracaju, Sergipe, Brazil
Hospital das Clinicas FMUSPRecruiting
São Paulo, Brazil
OCT Research ULCRecruiting
Kelowna, British Columbia, Canada
Richmond Clinical TrialsRecruiting
Richmond, British Columbia, Canada
Centricity Research Halifax MultispecialtyRecruiting
Halifax, Nova Scotia, Canada
Ottawa Memory ClinicRecruiting
Ottawa, Ontario, Canada
Toronto Memory ProgramRecruiting
Toronto, Ontario, Canada
MoCA Research and Innovation Inc.Recruiting
Greenfield Park, Quebec, Canada
Diex Recherche VictoriavilleRecruiting
Victoriaville, Quebec, Canada
ALPHA Recherche CliniqueRecruiting
Québec, Canada
Local Institution - 0230Not Yet Recruiting
Antofagasta, AN, Chile
Local Institution - 0094Not Yet Recruiting
Santiago, Santiago Metropolitan, Chile
Local Institution - 0089Not Yet Recruiting
Santiago, Santiago Metropolitan, Chile
Local Institution - 0241Not Yet Recruiting
Santiago, Santiago Metropolitan, Chile
Local Institution - 0215Not Yet Recruiting
Zagreb, City of Zagreb, Croatia
Poliklinika NeuronRecruiting
Zagreb, City of Zagreb, Croatia
Klinika za psihijatriju "Vrapče"Recruiting
Zagreb, Croatia
Neuro Health CentrumRecruiting
Brno, Brno-město, Czechia
AGE CentrumRecruiting
Olomouc, Olomouc Region, Czechia
A-ShineRecruiting
Pilsen, Plzeň-město, Czechia
Neurologická Ambulance - ForbeliRecruiting
Prague, Praha 6, Czechia
NeuropsychiatrieRecruiting
Prague, Praha 6, Czechia
Institut neuropsychiatricke pece (INEP), PrahaRecruiting
Prague, Praha 8, Czechia
Vestra ClinicsRecruiting
Rychnov nad Kněžnou, Czechia
Local Institution - 0219Not Yet Recruiting
Münster, North Rhine-Westphalia, Germany
Local Institution - 0276Not Yet Recruiting
Mainz, Rhineland-Palatinate, Germany
Local Institution - 0218Not Yet Recruiting
Berlin, Germany
Local Institution - 0277Withdrawn
Bremen, Germany
Local Institution - 0275Withdrawn
Hamburg, Germany
TUM KlinikumRecruiting
Munich, Germany
University General Hospital of AlexandroupoliRecruiting
Alexandroupoli, Anatolikí Makedonía Kai Thráki, Greece
Local Institution - 0256Withdrawn
Athens, Attikí, Greece
Aiginiteio University HospitalRecruiting
Athens, Attikí, Greece
Local Institution - 0257Not Yet Recruiting
Larissa, Thessalía, Greece
Local Institution - 0288Not Yet Recruiting
Bengaluru, Karnataka, India
Local Institution - 0282Not Yet Recruiting
Hyderabad, Telangana, India
Local Institution - 0285Not Yet Recruiting
Hyderabad, Telangana, India
Local Institution - 0287Not Yet Recruiting
Varanasi, Uttar Pradesh, India
Local Institution - 0286Not Yet Recruiting
Kolkata, West Bengal, India
Fondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoRecruiting
Milan, Lombardy, Italy
Ospedale San RaffaeleRecruiting
Milan, Lombardy, Italy
Local Institution - 0248Not Yet Recruiting
Monza, Lombardy, Italy
Azienda Ospedaliera Spedali Civili di BresciaRecruiting
Brescia, Italy
Local Institution - 0262Not Yet Recruiting
Poznan, Greater Poland Voivodeship, Poland
Osrodek Badan Klinicznych CLINSANTE S.C.Recruiting
Torun, Kuyavian-Pomeranian Voivodeship, Poland
MlynowaMed PsychiatricRecruiting
Bialystok, Podlaskie Voivodeship, Poland
Centrum Badan Klinicznych PI-House sp. z o.o.Recruiting
Gdansk, Pomeranian Voivodeship, Poland
Local Institution - 0181Not Yet Recruiting
San Juan, Puerto Rico
Local Institution - 0273Not Yet Recruiting
Bucharest, Bucharest, Romania
Prof. Dr. Alexandru Obregia Psychiatry HospitalRecruiting
Bucharest, Bucharest, Romania
Prof. Dr. Alexandru Obregia Psychiatry HospitalRecruiting
Bucharest, Bucharest, Romania
Institutul Național de Gerontologie și Geriatrie "Ana Aslan"Recruiting
Bucharest, Romania
Local Institution - 0268Not Yet Recruiting
Iași, Romania
Chonnam National University HospitalRecruiting
Gwangju, Kwangju-Kwangyǒkshi, South Korea
Seoul National University Bundang HospitalRecruiting
Seongnam, Kyǒnggi-do, South Korea
Seoul National University HospitalRecruiting
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Hanyang University Seoul HospitalRecruiting
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Konkuk University Medical CenterRecruiting
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Samsung Medical CenterRecruiting
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Ewha Womans University Seoul HospitalRecruiting
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Hospital Victoria EugeniaRecruiting
Seville, Andalusia, Spain
Hospital Universitari General de CatalunyaRecruiting
Sant Cugat del Vallès, Barcelona [Barcelona], Spain
Hospital Clínic de BarcelonaRecruiting
Barcelona, Catalunya [Cataluña], Spain
Hospital Universitari de Santa MariaRecruiting
Lleida, Lleida [Lérida], Spain
Clinica Universidad de NavarraRecruiting
Pamplona, Navarre, Spain
Hospital Clinico San CarlosRecruiting
Madrid, Spain
A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease · TrialPath