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)

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.

Interventions

• Xanomeline/Trospium Chloride Capsule · DRUG

  Specified dose on specified days

• Xanomeline Enteric Capsule · DRUG

  Specified dose on specified days

• Placebo · DRUG

  Specified dose on specified days

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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 ≤ 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).

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. 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).

\- Other protocol-defined Inclusion/Exclusion criteria apply.

Sites (159)

• Imaging Endpoints, Scottsdale, Arizona · RECRUITING
• Advanced Research Center (ARC) - Anaheim, Anaheim, California · RECRUITING
• Local Institution - 1637, La Jolla, California · COMPLETED
• The Neurology Group, Pomona, California · RECRUITING
• Local Institution - 1639, Torrance, California · ACTIVE_NOT_RECRUITING
• Sunwise Clinical Research, Walnut Creek, California · RECRUITING
• Local Institution - 1630, Colorado Springs, Colorado · WITHDRAWN
• Local Institution - 1622, Maitland, Florida · NOT_YET_RECRUITING
• Local Institution - 1631, Maitland, Florida · NOT_YET_RECRUITING
• Local Institution - 1666, Merritt Island, Florida · NOT_YET_RECRUITING
• Local Institution - 1602, Miami, Florida · NOT_YET_RECRUITING
• Local Institution - 1618, Miami, Florida · NOT_YET_RECRUITING
• Hope Research Network - Miami, Miami, Florida · RECRUITING
• Local Institution - 1604, Miami, Florida · COMPLETED
• Local Institution - 1608, Ocala, Florida · NOT_YET_RECRUITING
• Combined Research Orlando (CRO), Orlando, Florida · RECRUITING
• Progressive Medical Research, Port Orange, Florida · RECRUITING
• Local Institution - 1655, Marrero, Louisiana · NOT_YET_RECRUITING
• CBH Health, Gaithersburg, Maryland · RECRUITING
• Local Institution - 1663, Foxborough, Massachusetts · NOT_YET_RECRUITING
• Boston Center for Memory, Newton, Massachusetts · RECRUITING
• Mayflower Clinical Research, South Dartmouth, Massachusetts · RECRUITING
• Elixia MA, Springfield, Massachusetts · RECRUITING
• NeuroBehavioral Medicine Group, Bloomfield Hills, Michigan · RECRUITING
• Oakland Medical Research, Troy, Michigan · RECRUITING
• Redbird Research, Las Vegas, Nevada · RECRUITING
• Local Institution - 1647, Middletown, New Jersey · COMPLETED
• Global Medical Institutes LLC; Princeton Medical Institute, Princeton, New Jersey · RECRUITING
• Local Institution - 1610, Inwood, New York · NOT_YET_RECRUITING
• Mid Hudson Medical Research, New Windsor, New York · RECRUITING
• Five Towns Neurology PC -Woodmere - 923 Broadway, Woodmere, New York · RECRUITING
• Local Institution - 1645, Woodmere, New York · WITHDRAWN
• Central States Research, Tulsa, Oklahoma · RECRUITING
• Local Institution - 1652, Columbia, South Carolina · WITHDRAWN
• Advanced Neurology Epilepsy and Sleep Center, El Paso, Texas · RECRUITING
• Wasatch Clinical Research, LLC, Salt Lake City, Utah · RECRUITING
• The Memory Clinic, Bennington, Vermont · RECRUITING
• Local Institution - 1644, Seattle, Washington · NOT_YET_RECRUITING
• Kingfisher Cooperative, Spokane, Washington · RECRUITING
• Local Institution - 1001, La Plata, Buenos Aires, Argentina · NOT_YET_RECRUITING
• Local Institution - 1002, Mar del Plata, Buenos Aires, Argentina · NOT_YET_RECRUITING
• CEN Centro Especializado en Neurociencias, Córdoba, Córdoba Province, Argentina · RECRUITING
• Fundacion Estudios Clinicos, Rosario, Santa Fe Province, Argentina · RECRUITING
• Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina · RECRUITING
• Instituto Privado Kremer, Córdoba, Argentina · RECRUITING
• Centro Medico Luquez, Córdoba, Argentina · RECRUITING
• L2IP - Instituto de Pesquisas Clínicas, Brasília, Federal District, Brazil · RECRUITING
• CECPAR - Centro de Estudos Clínicos do Paraná, Curitiba, Paraná, Brazil · RECRUITING
• PUCTrials, Curitiba, Paraná, Brazil · RECRUITING
• Nucleo de Pesquisa Clinica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil · RECRUITING
• Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil · RECRUITING
• Instituto de Pesquisa Clínica de Campinas, Campinas, São Paulo, Brazil · RECRUITING
• Ruschel Medicina e Pesquisa Clínica, Rio de Janeiro, Brazil · RECRUITING
• CPQuali Pesquisa Clínica, São Paulo, Brazil · RECRUITING
• Clinica Viver - Centro de Desospitalizacao Humana, São Paulo, Brazil · RECRUITING
• Medical Center Medconsult Pleven OOD, Pleven, Bulgaria · RECRUITING
• Outpatient Clinic for Individual Practice for Specialized Medical Care in Psychiatry - Dr. Madlena Dimitrova Borisova, Razgrad, Bulgaria · RECRUITING
• Medical Center Sveti Naum EOOD, Sofia, Bulgaria · RECRUITING
• Local Institution - 1104, Sofia, Bulgaria · NOT_YET_RECRUITING
• Medical Center Mladost, Varna, Bulgaria · RECRUITING
• Local Institution - 1153, Hamilton, Ontario, Canada · NOT_YET_RECRUITING
• Local Institution - 1755, London, Ontario, Canada · WITHDRAWN
• London Health Sciences Centre-Victoria Campus, London, Ontario, Canada · RECRUITING
• Sunnybrook Research Institute, Toronto, Ontario, Canada · RECRUITING
• Centre for Addiction & Mental Health, Toronto, Ontario, Canada · RECRUITING
• Ontario Shores Centre For Mental Health Sciences, Whitby, Ontario, Canada · RECRUITING
• Local Institution - 1150, Montreal, Quebec, Canada · NOT_YET_RECRUITING
• Xuanwu Hospital Capital Medical University, Beijing, Beijing Municipality, China · RECRUITING
• Beijing Anding Hospital Capital Medical University, Beijing, Beijing Municipality, China · RECRUITING
• Peking University Sixth Hospital, Haidian District, Beijing Municipality, China · RECRUITING
• The First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China · RECRUITING
• The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China · RECRUITING
• Shenzhen Kangning Hospital, Shenzhen, Guangdong, China · RECRUITING
• The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangzhou Province, China · RECRUITING
• Xiangya Hospital Central South University, Changsha, Hunan, China · RECRUITING
• Nanjing Drum Tower hospital, Nanjing, Jiangsu, China · RECRUITING
• Local Institution - 1800, Shanghai, Shanghai Municipality, China · WITHDRAWN
• Mental Health Center of Xi'an City, Xian, Shanxi, China · RECRUITING
• West China Hospital, Sichuan University, Chengdu, Sichuan, China · RECRUITING
• Tianjin Anding Hospital, Tianjin, Tianjin Municipality, China · RECRUITING
• The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China · RECRUITING
• Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China · RECRUITING
• The First Affiliated Hospital of Kunming Medical University, Kunming, China · RECRUITING
• Local Institution - 1808, Tianjin, China · WITHDRAWN
• Local Institution - 1550, Zagreb, City of Zagreb, Croatia · NOT_YET_RECRUITING
• Local Institution - 1553, Zagreb, City of Zagreb, Croatia · NOT_YET_RECRUITING
• Klinicki Bolnicki Centar Rijeka, Rijeka, Croatia · RECRUITING
• Clinical Hospital Center Split, Split, Croatia · RECRUITING
• General Hospital Varazdin, Varaždin, Croatia · RECRUITING
• Local Institution - 1555, Zagreb, Croatia · NOT_YET_RECRUITING
• University Hospital of Patras, Pátrai, Achaḯa, Greece · RECRUITING
• Henry Dunant Hospital Center, Athens, Attica, Greece · RECRUITING
• Aiginiteio University Hospital, Athens, Attikí, Greece · RECRUITING
• University General Hospital "ATTIKON" - General Hospital of West Attica "H AGIA VARVARA", Chaïdári, Attikí, Greece · RECRUITING
• Eginition Hospital, Athens, Greece · RECRUITING
• Athens Medical Center, Athens, Greece · RECRUITING
• Local Institution - 1201, Ioannina, Greece · NOT_YET_RECRUITING
• Euromedica General Clinic of Thessaloniki, Thessaloniki, Greece · RECRUITING
• Local Institution - 1255, Ahmedabad, Gujarat, India · NOT_YET_RECRUITING
• Local Institution - 1252, Hyderabad, Telangana, India · NOT_YET_RECRUITING
• Local Institution - 1254, Varanasi, Uttar Pradesh, India · NOT_YET_RECRUITING
• Local Institution - 1250, Kolkata, West Bengal, India · NOT_YET_RECRUITING
• Local Institution - 1256, Delhi, India · NOT_YET_RECRUITING
• Local Institution - 1251, Hyderabad, India · NOT_YET_RECRUITING
• Local Institution - 1253, New Delhi, India · NOT_YET_RECRUITING
• Hatano Kousei Hospital, Hadano, Kanagawa, Japan · RECRUITING
• Teikyo University Mizonokuchi Hospital, Kawasaki, Kanagawa, Japan · RECRUITING
• Asakayama Hospital, Sakai, Osaka, Japan · RECRUITING
• National Hospital Organization Hizen Psychiatric Center, Kanzaki-Gun Yoshinogari-Cho, Saga-ken, Japan · RECRUITING
• Rainbow and Sea Hospital, Karatsu-shi, Saga-ken, Japan · RECRUITING
• Nippon Medical School Hospital, Bunkyo-ku, Tokyo, Japan · RECRUITING
• Kuramitsu Hospital, Fukuoka, Japan · RECRUITING
• Okayama City General Medical Center Okayama City Hospital, Okayama, Japan · RECRUITING
• Local Institution - 1308, Shimotsuke-shi, Tochigi, Japan · NOT_YET_RECRUITING
• Hospital Universitario de Saltillo, Saltillo, Coahuila, Mexico · RECRUITING
• Boca Clinical Trials Mexico S.C., Guadalajara, Jalisco, Mexico · RECRUITING
• Innovacion y Desarrollo en Ciencias de la Salud, Mexico City, Mexico City, Mexico · RECRUITING
• Local Institution - 1360, Mexico City, Mexico City, Mexico · NOT_YET_RECRUITING
• AVIX Investigacion Clinica, Monterrey, Nuevo León, Mexico · RECRUITING
• Local Institution - 1350, Monterrey, Nuevo León, Mexico · NOT_YET_RECRUITING
• Local Institution - 1361, Mexico City, Mexico · NOT_YET_RECRUITING
• Neurociencias PRISMA A.C., San Luis Potosí City, Mexico · RECRUITING
• Clinical Research Institute S.C., Tlalnepantla, Mexico · RECRUITING
• Unidade Local de Saúde de Coimbra, E.P.E., Coimbra, Portugal · RECRUITING
• Centro Hospitalar do Alto Ave, Guimarães, Portugal · RECRUITING
• Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria, Lisbon, Portugal · RECRUITING
• Unidade Local de Saúde de Matosinhos SA, Senhora da Hora, Portugal · RECRUITING
• Campus Neurologico Senior, Torres Vedras, Portugal · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Prof. Dr. Alexandru Obregia Psychiatry Hospital, Bucharest, Bucharest, Romania · RECRUITING
• Local Institution - 1451, Bucharest, Romania · WITHDRAWN
• Local Institution - 1463, Bucharest, Romania · NOT_YET_RECRUITING
• Local Institution - 1459, Bucharest, Romania · WITHDRAWN
• Prof Dr Alexandru Obregia Clinical Psychiatric Hospital- Centrul de Sanatate Mintala, Bucharest, Romania · RECRUITING
• Cai Ferate Clinical Hospital Constanta, Constanța, Romania · RECRUITING
• Institutul de Psihiatrie Socola, Iași, Romania · RECRUITING
• Spitalul de Psihiatrie și Neurologie Brașov, Sanpetru /Brasov, Romania · RECRUITING
• Local Institution - 1464, Sibiu, Romania · NOT_YET_RECRUITING
• Clinical Psychiatric Hospital "Dr. Gheorghe Preda", Sibiu, Romania · RECRUITING
• Oroitu CAE, Getxo, Bizkaia, Spain · RECRUITING
• Hospital General Universitario de Elche, Elche (alicante), Spain · RECRUITING
• Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain · RECRUITING
• Hospital Clinico San Carlos, Madrid, Spain · RECRUITING
• Hospital Clinico Universitario Virgen de La Victoria, Málaga, Spain · RECRUITING
• Clinica Universidad de Navarra, Pamplona, Spain · RECRUITING
• Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca, Salamanca, Spain · RECRUITING
• Hospital Victoria Eugenia de Sevilla, Seville, Spain · RECRUITING
• Hospital Mutua Terrassa, Terrassa, Spain · RECRUITING
• Hospital Universitario De Rio Hortega, Valladolid, Spain · RECRUITING
• Hospital Viamed Montecanal, Zaragoza, Spain · RECRUITING
• Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan · RECRUITING
• National Cheng Kung University Hospital, Tainan, Taiana, Taiwan · RECRUITING
• National Taiwan University Hospital, Taipei, Taiwan · RECRUITING
• Taipei Veterans General Hospital, Taipei, Taiwan · RECRUITING
• Chang Gung Medical Foundation-Linkou Branch, Taoyuan, Taiwan · RECRUITING