Clinical trial • Phase III • Psychiatry

trospium chloride, xanomeline tartrate for Agitation associated with Alzheimer's disease

Phase III trial of trospium chloride, xanomeline tartrate for Agitation associated with Alzheimer's disease.

Overview

Trial Therapeutic Area
Psychiatry
Trial Disease
Agitation associated with Alzheimer's disease
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
30-06-2025
First CTIS Authorization Date
22-10-2025

Trial design

Randomised, placebo (karxt matching placebo and karx-ec matching placebo); dose/schedule not specified in the available record.-controlled Phase III trial across 34 sites in Italy, France, Hungary and others.

Randomised
Yes
Comparator
Placebo (KarXT matching placebo and KarX-EC matching Placebo); dose/schedule not specified in the available record.
Target Sample Size
262

Eligibility

Recruits 262 Participants are a vulnerable population (people with Alzheimer’s disease and cognitive impairment). A caregiver/study partner is required (principal inclusion criterion): the caregiver must have sufficient contact (approximately 10 hours/week) and be willing to attend visits, oversee compliance, participate in assessments and "provide IC to participate in the study". Country-specific subject information/ICF and assent documents and study-partner ICFs are included (examples: Adult Assent, Study Partner ICF, country versions for IT/FR/CZ/HU/PL), indicating use of assent/consent processes adapted for cognitively impaired adults and involvement of study partners/caregivers in consent..

Vulnerable Population
Participants are a vulnerable population (people with Alzheimer’s disease and cognitive impairment). A caregiver/study partner is required (principal inclusion criterion): the caregiver must have sufficient contact (approximately 10 hours/week) and be willing to attend visits, oversee compliance, participate in assessments and "provide IC to participate in the study". Country-specific subject information/ICF and assent documents and study-partner ICFs are included (examples: Adult Assent, Study Partner ICF, country versions for IT/FR/CZ/HU/PL), indicating use of assent/consent processes adapted for cognitively impaired adults and involvement of study partners/caregivers in consent.

Inclusion criteria

  • {"criterion_text":"- A diagnosis of Alzheimer’s disease (AD) in accordance with the 2024 Alzheimer’s Association criteria with one of the the following confirmations of AD pathology: \t- 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. \t- 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: o Amyloid PET o Aβ42/40 ratio or pTau181/Aβ42 ratio in CSF using an HA-authorized diagnostic assay\n- Mini-Mental State Examination (MMSE) score of 5 to 22, inclusive, at Screening (Visit 1)\n- Have one identified caregiver who should have sufficient contact (approximately 10 hours a week or more) and is willing to: - Attend all visits and report on participant’s status - Oversee participant compliance with medication and study procedures - Participate in the study assessments and provide IC to participate in the study\n- 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).\n- AD participants are required to have NPI/NPI-NH Agitation/Aggression score ≥ 3 at Screening (Visit 1) and Baseline (Visit 4).\n- CGI-S ≥ 4, as related to agitation, at Screening (Visit 1) and Baseline (Visit 4)\n- At least 1 of the following 3 criteria must be established from the CMAI-IPA at Screening (Visit 1) and Baseline (Visit 4; CMAI-IPA Physical/Verbal Aggression Positivity): - 1 or more aggressive behaviors occurring several times per week - 2 or more aggressive behaviors occurring once or twice per week - 3 or more aggressive behaviors occurring less than once per week"}

Exclusion criteria

  • {"criterion_text":"- Medical Conditions  Agitation symptoms that are primarily attributable to a condition other than the AD causing the dementia  History of bipolar disorder, schizophrenia, or schizoaffective disorder  History of (or at high risk for) urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator  Risk of suicidal behavior during the study as determined by the Investigator’s clinical assessment and/or C-SSR\n- Prior/Concomitant Therapy - 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)  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  Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1)\n- Other protocol-defined Inclusion/Exclusion criteria apply."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline to the end of treatment on the CMAI-IPA total score compared with placebo.","definition_or_measurement_approach":"Change from baseline to end of treatment measured using the Cohen-Mansfield Agitation Inventory – International Psychogeriatric Association (CMAI-IPA) total score."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline to the end of treatment on the CGI-S as it relates specifically to agitation compared with placebo.","definition_or_measurement_approach":"Change from baseline to end of treatment measured using the Clinical Global Impressions – Severity (CGI-S) score specifically related to agitation."}

Recruitment

Planned Sample Size
262
Recruitment Window Months
36
Consent Approach
Informed consent and assent processes account for cognitively impaired participants: study requires a caregiver/study partner who will attend visits, oversee compliance and "provide IC to participate in the study". Subject information and ICF documents (and assent forms) are provided in country-specific versions (documents available for IT, FR, CZ, HU, PL) and there are study partner ICFs and adult assent templates indicated, i.e. consent obtained using participant ICF when possible and using caregiver/study partner ICF/consent and assent processes adapted for participants with cognitive impairment.

Geography

Total Number Of Sites
34
Total Number Of Participants
92

Italy

Earliest CTIS Part Ii Submission Date
04-08-2025
Latest Decision Or Authorization Date
09-03-2026
Processing Time Days
217
Number Of Sites
7
Number Of Participants
20

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Medicina Interna Geriatrica
Principal Investigator Name
Francesco Landi
Principal Investigator Email
francesco.landi@policlinicogemelli.it
Contact Person Name
Francesco Landi
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Neuroscience
Principal Investigator Name
Vincenzo Brescia Morra
Principal Investigator Email
Vincenzo.bresciamorra2@unina.it
Contact Person Name
Vincenzo Brescia Morra
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
UO Psichiatria
Principal Investigator Name
Giulio Perugi
Principal Investigator Email
giulio.perugi@gmail.com
Contact Person Name
Giulio Perugi
Contact Person Email
giulio.perugi@gmail.com
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Human Neuroscience
Principal Investigator Name
Giuseppe Bruno
Principal Investigator Email
g.bruno@policlinicoumberto1.it
Contact Person Name
Giuseppe Bruno
Contact Person Email
g.bruno@policlinicoumberto1.it
Site Name
Istituto Auxologico Italiano
Department Name
Neurology
Principal Investigator Name
Nicola Ticozzi
Principal Investigator Email
trials@auxologico.it
Contact Person Name
Nicola Ticozzi
Contact Person Email
trials@auxologico.it
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
NESMOS
Principal Investigator Name
Franco Giubilei
Principal Investigator Email
franco.giubilei@uniroma1.it
Contact Person Name
Franco Giubilei
Contact Person Email
franco.giubilei@uniroma1.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
S.C. Neurologia
Principal Investigator Name
Salvatore Caratozzolo
Principal Investigator Email
salvatore.caratozzolo@hotmail.com
Contact Person Name
Salvatore Caratozzolo

France

Earliest CTIS Part Ii Submission Date
14-09-2025
Latest Decision Or Authorization Date
10-03-2026
Processing Time Days
177
Number Of Sites
7
Number Of Participants
17

Sites

Site Name
Hopitaux Universitaires de Strasbourg - Hopital de la Robertsau
Department Name
Centre Mémoire de Ressources et de Recherche (CMRR)
Principal Investigator Name
Alix Ravier
Principal Investigator Email
alix.ravier@chru-strasbourg.fr
Contact Person Name
Alix Ravier
Contact Person Email
alix.ravier@chru-strasbourg.fr
Site Name
Hospices Civils de Lyon (HCL) - Hôpital des Charpennes
Department Name
Centre de Recherche Clinique Vieillissement Cerveau Fragilité (CRC VCF)
Principal Investigator Name
Antoine Garnier-Crussard
Principal Investigator Email
antoine.garnier-crussard@chu-lyon.fr
Contact Person Name
Antoine Garnier-Crussard
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Gérontopole - Centre de Recherche Clinique (CRC)
Principal Investigator Name
Maria Eugenia Soto-Martin
Principal Investigator Email
soto-martin.me@chu-toulouse.fr
Contact Person Name
Maria Eugenia Soto-Martin
Contact Person Email
soto-martin.me@chu-toulouse.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Hôpital Dupuytren - Service de médecine gériatrique
Principal Investigator Name
Achille Tchalla
Principal Investigator Email
achille.tchalla@chu-limoges.fr
Contact Person Name
Achille Tchalla
Contact Person Email
achille.tchalla@chu-limoges.fr
Site Name
Hopital Fernand Widal
Department Name
Centre de neurologie cognitive
Principal Investigator Name
Emmanuel Cognat
Principal Investigator Email
emmanuel.cognat@aphp.fr
Contact Person Name
Emmanuel Cognat
Contact Person Email
emmanuel.cognat@aphp.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Hopital Gui de Chauliac - Centre Mémoire de Ressources et de Recerches (CMRR)
Principal Investigator Name
Karim Bennys
Principal Investigator Email
k-bennys@chu-montpellier.fr
Contact Person Name
Karim Bennys
Contact Person Email
k-bennys@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Hopital Roger Salengro - Centre Mémoire de Ressources et de Recerches (CMRR)
Principal Investigator Name
Lionel Trogneux
Principal Investigator Email
lionel.trogneux@chu-lille.fr
Contact Person Name
Lionel Trogneux
Contact Person Email
lionel.trogneux@chu-lille.fr

Hungary

Earliest CTIS Part Ii Submission Date
29-09-2025
Latest Decision Or Authorization Date
10-03-2026
Processing Time Days
162
Number Of Sites
7
Number Of Participants
14

Sites

Site Name
Gyoengyosi Bugat Pal Koerhaz
Department Name
Pszichiatria
Principal Investigator Name
Tibor Kelemen
Principal Investigator Email
junto@t-online.hu
Contact Person Name
Tibor Kelemen
Contact Person Email
junto@t-online.hu
Site Name
Dr. Mathe Es Tarsa Bt.
Principal Investigator Name
Eva Mathe
Principal Investigator Email
matheevazs@gmail.com
Contact Person Name
Eva Mathe
Contact Person Email
matheevazs@gmail.com
Site Name
Semmelweis University
Department Name
Neurológiai Klinika
Principal Investigator Name
Tibor Kovacs
Principal Investigator Email
kovacs.tibor@semmelweis.hu
Contact Person Name
Tibor Kovacs
Contact Person Email
kovacs.tibor@semmelweis.hu
Site Name
University Of Debrecen
Department Name
Neurologiai Klinika
Principal Investigator Name
Palma Piros
Principal Investigator Email
pirospalma@gmail.com
Contact Person Name
Palma Piros
Contact Person Email
pirospalma@gmail.com
Site Name
Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
Department Name
Pszichiatriai, Mentalhigienes és Addiktologiai Osztaly
Principal Investigator Name
Gabor Feller
Principal Investigator Email
fellerg@petz.gyor.hu
Contact Person Name
Gabor Feller
Contact Person Email
fellerg@petz.gyor.hu
Site Name
Clinexpert Kft.
Principal Investigator Name
Istvan Kapas
Principal Investigator Email
istvan.kapas00@gmail.com
Contact Person Name
Istvan Kapas
Contact Person Email
istvan.kapas00@gmail.com
Site Name
Obudai Egeszseguegyi Centrum Kft.
Principal Investigator Name
Lehel Finta
Principal Investigator Email
lehel.finta@oec.hu
Contact Person Name
Lehel Finta
Contact Person Email
lehel.finta@oec.hu

Czechia

Earliest CTIS Part Ii Submission Date
23-09-2025
Latest Decision Or Authorization Date
09-03-2026
Processing Time Days
167
Number Of Sites
7
Number Of Participants
21

Sites

Site Name
INEP medical s.r.o.
Principal Investigator Name
Alexander Nawka
Principal Investigator Email
nawka@inep.cz
Contact Person Name
Alexander Nawka
Contact Person Email
nawka@inep.cz
Site Name
Neuropsychiatrie s.r.o.
Principal Investigator Name
Jakub Hort
Principal Investigator Email
jakub.hort@gmail.com
Contact Person Name
Jakub Hort
Contact Person Email
jakub.hort@gmail.com
Site Name
A-Shine s.r.o.
Principal Investigator Name
Lubos Janu
Principal Investigator Email
lubos.janu@seznam.cz
Contact Person Name
Lubos Janu
Contact Person Email
lubos.janu@seznam.cz
Site Name
Neuro Health Centrum s.r.o.
Principal Investigator Name
Katerina Sheardova
Principal Investigator Email
nhctrials@gmail.com
Contact Person Name
Katerina Sheardova
Contact Person Email
nhctrials@gmail.com
Site Name
Neurohk s.r.o.
Principal Investigator Name
Martin Valis
Principal Investigator Email
valismar@seznam.cz
Contact Person Name
Martin Valis
Contact Person Email
valismar@seznam.cz
Site Name
Vestra Clinics s.r.o.
Principal Investigator Name
Ladislav Pazdera
Principal Investigator Email
pazdera@vestraclinics.org
Contact Person Name
Ladislav Pazdera
Contact Person Email
pazdera@vestraclinics.org
Site Name
AGE Centrum s.r.o.
Principal Investigator Name
Dagmar Malotova
Principal Investigator Email
malotova@ctcenter.cz
Contact Person Name
Dagmar Malotova
Contact Person Email
malotova@ctcenter.cz

Poland

Earliest CTIS Part Ii Submission Date
19-09-2025
Latest Decision Or Authorization Date
10-03-2026
Processing Time Days
172
Number Of Sites
6
Number Of Participants
20

Sites

Site Name
Centrum Medyczne Hcp Sp. z o.o.
Department Name
Oddział Udarowy i Neurologii, Ośrodek Badań Klinicznych
Principal Investigator Name
Przemyslaw Osip
Principal Investigator Email
przemyslaw.osip@cmhcp.pl
Contact Person Name
Przemyslaw Osip
Contact Person Email
przemyslaw.osip@cmhcp.pl
Site Name
Niepubliczny Zaklad Opieki Zdrowotnej Neuromed M. I M. Nastaj. sp.p.
Principal Investigator Name
Marcin Nastaj
Principal Investigator Email
marcinnastaj@gmail.com
Contact Person Name
Marcin Nastaj
Contact Person Email
marcinnastaj@gmail.com
Site Name
M2M Med. Sp. z o.o. Sp. j.
Principal Investigator Name
Anna Starostka-Tatar
Principal Investigator Email
a.starostka-tatar@m2m-badania.pl
Contact Person Name
Anna Starostka-Tatar
Site Name
Centrum Medyczne Neuromed Sp. z o.o.
Principal Investigator Name
Paweł Lisewski
Principal Investigator Email
lisewski.p@gmail.com
Contact Person Name
Paweł Lisewski
Contact Person Email
lisewski.p@gmail.com
Site Name
Centrum In Psyche Spersonalizowanej Psychiatrii i Terapii
Principal Investigator Name
Agnieszka Prymus
Principal Investigator Email
rejestracjapsyche@gmail.com
Contact Person Name
Agnieszka Prymus
Contact Person Email
rejestracjapsyche@gmail.com
Site Name
Rcmed Oddzial Sochaczew
Principal Investigator Name
Małgorzata Fengler-Czeczko
Principal Investigator Email
malgorzata.fenglerczeczko@rcmed.com.pl
Contact Person Name
Małgorzata Fengler-Czeczko

Sponsor

Primary sponsor

Full Name
Bristol-Myers Squibb Services Unlimited Company
Organisation Type
Pharmaceutical company
Country Of Registered Address
Ireland

Contract research organisations

Name
Iqvia Holdings Inc.
Responsibilities
Site Payments
Name
Syneos Health Inc.
Responsibilities
Subject Eligibility Review

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Data Management Platform","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"PRO/COA management, rater training, and supply of electronic devices for the collection of eCOA assessments","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Holdings Inc.","duties_or_roles":"Site Payments","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Safety Laboratory testing and pTau217/AB42, pTau181/AB42, AB42/40 Biomarker testing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Subject Eligibility Review","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Provides electronic payments, travel arrangements,electronic study-related comunications to patients","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"India","full_name":"Accenture Solutions Private Limited","duties_or_roles":"Pharmacovigilance duties: Medical review and Cases Data Entry","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
KarXT
Active Substance
trospium chloride, xanomeline tartrate
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Investigational Product Name
KarX-EC
Active Substance
xanomeline tartrate
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Investigational Product Name
KarXT matching placebo
Modality
Other
Investigational Product Name
KarX-EC matching Placebo
Modality
Other
Combination Treatment
Yes

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