A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease

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).
* Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) Total Score ≥ 30 at Screening (Visit 1) and 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).

Note: 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 (145)

• Chandler Clinical Trials, LLC, Chandler, Arizona · RECRUITING
• Local Institution - 2631, Chandler, Arizona · NOT_YET_RECRUITING
• Local Institution - 2646, Chandler, Arizona · NOT_YET_RECRUITING
• National Institute of Clinical Research, Garden Grove, California · RECRUITING
• Local Institution - 2607, Long Beach, California · NOT_YET_RECRUITING
• Accellacare, Long Beach, California · RECRUITING
• Local Institution - 2627, Napa, California · NOT_YET_RECRUITING
• Local Institution - 2649, Orange, California · NOT_YET_RECRUITING
• Local Institution - 2613, Pasadena, California · NOT_YET_RECRUITING
• Local Institution - 2614, San Diego, California · NOT_YET_RECRUITING
• Local Institution - 2620, West Hills, California · COMPLETED
• Local Institution - 2601, Basalt, Colorado · WITHDRAWN
• Local Institution - 2635, Colorado Springs, Colorado · NOT_YET_RECRUITING
• Local Institution - 2632, Norwalk, Connecticut · NOT_YET_RECRUITING
• Local Institution - 2648, Aventura, Florida · NOT_YET_RECRUITING
• Envision Trials LLC, Bonita Springs, Florida · RECRUITING
• Key Clinical Research, Bradenton, Florida · RECRUITING
• Local Institution - 2636, Doral, Florida · NOT_YET_RECRUITING
• Local Institution - 2606, Homestead, Florida · NOT_YET_RECRUITING
• Local Institution - 2633, Miami, Florida · NOT_YET_RECRUITING
• Local Institution - 2637, Miami, Florida · NOT_YET_RECRUITING
• Local Institution - 2634, Orlando, Florida · NOT_YET_RECRUITING
• IPTB Clinical Research, Tampa, Florida · RECRUITING
• Agile Clinical Research Trials, LLC, Atlanta, Georgia · RECRUITING
• Vitalix Clinical, Worcester, Massachusetts · RECRUITING
• Local Institution - 2618, Ann Arbor, Michigan · COMPLETED
• Local Institution - 2630, Saint Paul, Minnesota · NOT_YET_RECRUITING
• Hattiesburg Clinic, Hattiesburg, Mississippi · RECRUITING
• Local Institution - 2603, Ozark, Missouri · COMPLETED
• Las Vegas Clinical Trials, Las Vegas, Nevada · RECRUITING
• Local Institution - 2650, Toms River, New Jersey · NOT_YET_RECRUITING
• Local Institution - 2647, Brooklyn, New York · NOT_YET_RECRUITING
• Richmond Behavioral Associates, Staten Island, New York · RECRUITING
• Walnut Clinical Research, Valley Stream, New York · RECRUITING
• West Clinical Research, Morehead City, North Carolina · RECRUITING
• Velocity Clinical Research - Blue Ash, Blue Ash, Ohio · RECRUITING
• Epic Medical Research, LLC - Carrolton, Carrollton, Texas · RECRUITING
• Horizon Clinical Research Center - Houston, Cypress, Texas · RECRUITING
• Epic Medical Research, LLC - Mesquite, Mesquite, Texas · RECRUITING
• UT Health - San Antonio, San Antonio, Texas · RECRUITING
• Local Institution - 2612, Bountiful, Utah · ACTIVE_NOT_RECRUITING
• EvergreenHealth Medical Center, Kirkland, Washington · RECRUITING
• Local Institution - 2610, Milwaukee, Wisconsin · NOT_YET_RECRUITING
• Centro Neurobiológico y de Estrés Traumático - CENydET S.R.L., Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina · RECRUITING
• Fundacion para el Estudio y Tratamiento de Enfermedades mentales- FETEM, Buenos Aires, Argentina · RECRUITING
• Local Institution - 2004, Buenos Aires, Argentina · NOT_YET_RECRUITING
• Instituto Modelo de Neurología, Fundación Lennox, Córdoba, Argentina · RECRUITING
• Local Institution - 2002, Córdoba, Argentina · NOT_YET_RECRUITING
• Instituto Médico DAMIC, Córdoba, Argentina · RECRUITING
• Resolution Psychopharmacology Research Institute, Mendoza, Argentina · RECRUITING
• Biomedica Research Group, Santiago, Santiago Metropolitan, Chile · RECRUITING
• Local Institution - 2050, Santiago, Santiago Metropolitan, Chile · NOT_YET_RECRUITING
• Pontificia Universidad Catolica de Chile, Santiago, Santiago Metropolitan, Chile · RECRUITING
• Clinica Alemana, Vitacura, Santiago Metropolitan, Chile · RECRUITING
• Local Institution - 2055, Viña del Mar, Valparaiso, Chile · NOT_YET_RECRUITING
• Psicomed Estudios Médicos Cía Ltda, Antofagasta, Chile · RECRUITING
• AGE Centrum, Olomouc, Olomouc Region, Czechia · RECRUITING
• Neuropsychiatrie, Prague, Praha 6, Czechia · RECRUITING
• Institut neuropsychiatricke pece (INEP), Praha, Prague, Praha 8, Czechia · RECRUITING
• Neuro Health Centrum s.r.o., Brno, South Moravian, Czechia · RECRUITING
• NEUROHK, Choceň, Czechia · RECRUITING
• A-SHINE s.r.o., Pilsen, Czechia · RECRUITING
• Local Institution - 2102, Prague, Czechia · WITHDRAWN
• Local Institution - 2105, Prague, Czechia · WITHDRAWN
• Vestra Clinics s.r.o., Rychnov nad Kněžnou, Czechia · RECRUITING
• Centre Hospitalier Universitaire Toulouse - Cité de la Santé, Toulouse, Haute-Garonne, France · RECRUITING
• Hôpital des Charpennes - Hospices Civils de Lyon (HCL), Villeurbanne, Rhône, France · RECRUITING
• Centre Hospitalier Régional Universitaire de Lille - Hôpital Roger Salengro, Lille, France · RECRUITING
• Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren, Limoges, France · RECRUITING
• Hopital Gui Chauliac - Chu Montpellier, Montpellier, France · RECRUITING
• Centres Memoire de Ressources et de Recherche (CMRR) - Hopital Lariboisiere-Fernand-Widal Location, Paris, France · RECRUITING
• Les Hôpitaux Universitaires de Strasbourg - Hôpital de la Robertsau, Strasbourg, France · RECRUITING
• Local Institution - 2201, Düsseldorf, Germany · NOT_YET_RECRUITING
• Local Institution - 2205, Halle, Germany · NOT_YET_RECRUITING
• Local Institution - 2206, Westerstede, Germany · NOT_YET_RECRUITING
• Local Institution - 2257, Kalocsa, Bács-Kiskun county, Hungary · NOT_YET_RECRUITING
• Local Institution - 2250, Győr, Győr-Moson-Sopron, Hungary · NOT_YET_RECRUITING
• Debreceni Egyetem Klinikai Kozpont, Debrecen, Hajdú-Bihar, Hungary · RECRUITING
• Local Institution - 2254, Gyöngyös, Heves County, Hungary · NOT_YET_RECRUITING
• Local Institution - 2256, Budapest, Hungary · NOT_YET_RECRUITING
• Local Institution - 2255, Budapest, Hungary · NOT_YET_RECRUITING
• Local Institution - 2251, Budapest, Hungary · WITHDRAWN
• Semmelweis Egyetem, Budapest, Hungary · RECRUITING
• The Chaim Sheba Medical Center, Ramat Gan, Central District, Israel · RECRUITING
• Local Institution - 2302, Petch Tikva, IL, Israel · NOT_YET_RECRUITING
• Sanz MC, Laniado Hospital, Netanya, Israel · RECRUITING
• The Israeli Alzheimer Medical Center, Ramat Gan, Israel · RECRUITING
• Bayit Balev Ltd., Rishon Le'Tzion, Israel · RECRUITING
• University of Naples Federico II, Naples, Campania, Italy · RECRUITING
• Azienda Ospedaliero-Universitaria Policlinico Umberto I - Viale del Policlinico 155, Rome, Lazio, Italy · RECRUITING
• Azienda Ospedaliero-Universitaria Sant'Andrea, Rome, Lazio, Italy · RECRUITING
• Auxologico IRCCS - Auxologico San Luca, Milan, Lombardy, Italy · RECRUITING
• Azienda Ospedaliero Universitaria Pisana, Pisa, PI, Italy · RECRUITING
• Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy · RECRUITING
• Local Institution - 2355, Isernia, Italy · WITHDRAWN
• Fondazione Policlinico Gemelli IRCCS, Roma, Italy · RECRUITING
• Centrum Medyczne HCP Szpital im. Jana Pawla II, Poznan, Greater Poland Voivodeship, Poland · RECRUITING
• Centrum Medyczne NEUROMED, Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland · RECRUITING
• M2M Med, Chorzów, Poland · RECRUITING
• Centrum In Psyche Spersonalizowanej Psychiatrii I Terapii, Katowice, Poland · RECRUITING
• Local Institution - 2458, Krakow, Poland · NOT_YET_RECRUITING
• Local Institution - 2451, Lublin, Poland · WITHDRAWN
• Local Institution - 2452, Lublin, Poland · WITHDRAWN
• RCMed Oddzial Sochaczew, Sochaczew, Poland · RECRUITING
• Local Institution - 2457, Wroclaw, Poland · NOT_YET_RECRUITING
• Local Institution - 2641, San Juan, Puerto Rico · NOT_YET_RECRUITING
• CMRC Headlands, San Juan, Puerto Rico · RECRUITING
• Instituto De Neurologia Dra. Ivonne Fraga, San Juan, Puerto Rico · RECRUITING
• Local Institution - 2639, San Juan, Puerto Rico · NOT_YET_RECRUITING
• Inha University Hospital, Incheon, Incheon Gwang'yeogsi, South Korea · RECRUITING
• Seoul National University Hospital, Seoul, Seoul-teukbyeolsi [Seoul], South Korea · RECRUITING
• Konkuk University Medical Center, Seoul, Seoul-teukbyeolsi [Seoul], South Korea · RECRUITING
• Local Institution - 2406, Seoul, Seoul-teukbyeolsi [Seoul], South Korea · WITHDRAWN
• Kyungpook National University Chilgok Hospital, Deagu, Taegu-Kwangyǒkshi, South Korea · RECRUITING
• Gachon University Gil Medical Center, Incheon, South Korea · RECRUITING
• Asan Medical Center, Seoul, South Korea · RECRUITING
• Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea · RECRUITING
• SMG-SNU Borame Medical Center, Seoul, South Korea · RECRUITING
• The Catholic University of Korea, Yeouido St.Mary's Hospital, Seoul, South Korea · RECRUITING
• Communal non-commercial enterprise "Cherkasy regional psychiatric hospital of Cherkasy regional council", Smila, Cherkasy Oblast, Ukraine · RECRUITING
• MUNICIPAL NON-COMMERCIAL COMPANY Dnipropetrovsk Multiprofile Clinical Hospital for Provision of Psychiatric Care DRC, Dnipro, Dnipropetrovsk Oblast, Ukraine · RECRUITING
• Municipal Non-Commercial Enterprise "Khmelnytskyi Regional Psychiatric Care Facility" of the Khmelnytskyi Regional Council, Skarzhyntsi, Khmelnytskyi Oblast, Ukraine · RECRUITING
• Communal non-commercial enterprise of the Kyiv Regional Council "Regional Psychiatric-Narcological Medical Association", Hlevakha, Kyiv Oblast, Ukraine · RECRUITING
• COMMUNAL NONCOMMERCIAL ENTERPRISE of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Lviv, Lviv Oblast, Ukraine · RECRUITING
• Municipal Non-Commercial Enterprise "Odesa Regional Medical Centre of Mental Health" of Odesa Regional Council, Oleksandrivka, Odesa Oblast, Ukraine · RECRUITING
• Communal non-profit enterprise "Vinnytsia Regional Clinical Psycho-Neurological Hospital n.a. acad. O.I. Yushchenko of VRC", Vinnytsia, Vinnytsia Oblast, Ukraine · RECRUITING
• Local Institution - 2560, Lutsk, Volyn Oblast, Ukraine · NOT_YET_RECRUITING
• CNCE "Clinical Facility for Mental Health Care "PSYCHIATRY" of executive body of Kyiv City Council (KCSA)", Hlevakha, Ukraine · RECRUITING
• Communal Non-Commercial Enterprise "Regional Clinical Psychiatric Hospital of the Kirovohrad Regional Council, Kropyvnytskyi, Ukraine · RECRUITING
• Local Institution - 2565, Kyiv, Ukraine · NOT_YET_RECRUITING
• CNCE "Clinical Facility for Mental Health Care "PSYCHIATRY" of executive body of Kyiv City Council (KCSA), Kyiv, Ukraine · RECRUITING
• "Medical Centre "Neuroclinic" LLC, Lviv, Ukraine · RECRUITING
• Limited Liability Company "Iqmed", Lviv, Ukraine · RECRUITING
• Communal Enterprise "Regional Institution of Mental Psychiatric Care of the Poltava Regional Council", Poltava, Ukraine · RECRUITING
• Local Institution - 2562, Ternopil, Ukraine · NOT_YET_RECRUITING
• Lancashire & South Cumbria NHS Foundation Trust, Preston, Lancashire, United Kingdom · RECRUITING
• Surrey and Borders Partnership NHS Foundation Trust, Chertsey, Surrey, United Kingdom · RECRUITING
• Local Institution - 2502, Cambridge, United Kingdom · NOT_YET_RECRUITING
• South London and Maudsley NHS Foundation Trust, London, United Kingdom · RECRUITING
• Local Institution - 2500, London, United Kingdom · NOT_YET_RECRUITING
• NeuroClin Glasgow, Motherwell, United Kingdom · RECRUITING
• Cornwall Partnership NHS Foundation Trust, Redruth, United Kingdom · RECRUITING
• Sheffield Health and Social care NHS Foundation Trust, Sheffield, United Kingdom · RECRUITING
• Local Institution - 2509, Stafford, United Kingdom · WITHDRAWN
• Black Country Healthcare NHS Foundation Trust, Wolverhampton, United Kingdom · RECRUITING