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
- 20-10-2025
Trial design
Randomised, placebo (karxt matching placebo and karx-ec matching placebo); dose and schedule not specified in available documents.-controlled Phase III trial across 51 sites in Romania, Bulgaria, Portugal and others.
- Randomised
- Yes
- Comparator
- Placebo (KarXT matching Placebo and KarX-EC matching Placebo); dose and schedule not specified in available documents.
- Target Sample Size
- 251
Eligibility
Recruits 251 Participants are individuals with Alzheimer’s disease (cognitive impairment) identified as a vulnerable population. A caregiver/study partner must be identified; the caregiver is required to attend visits, oversee compliance and provide informed consent (IC) for participation. The trial includes subject information sheets, informed consent forms, study-partner ICFs and assent documents (e.g., Adult Assent) and these materials are available in multiple country/language versions (examples in the document list include EN, BG, PT, GR, HR, RO, ES)..
- Vulnerable Population
- Participants are individuals with Alzheimer’s disease (cognitive impairment) identified as a vulnerable population. A caregiver/study partner must be identified; the caregiver is required to attend visits, oversee compliance and provide informed consent (IC) for participation. The trial includes subject information sheets, informed consent forms, study-partner ICFs and assent documents (e.g., Adult Assent) and these materials are available in multiple country/language versions (examples in the document list include EN, BG, PT, GR, HR, RO, ES).
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 ≥ 4 at Screening (Visit 1) and Baseline (Visit 2).\n- CGI-S ≥ 4, as related to agitation, at Screening (Visit 1) and Baseline (Visit 2)\n- At least 1 of the following 3 criteria must be established from the CMAI-IPA at Screening (Visit 1) and Baseline (Visit 2; 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 by the Cohen-Mansfield Agitation Inventory – International Psychogeriatric Association (CMAI-IPA) total score; comparison versus placebo."}
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 by the Clinical Global Impressions – Severity (CGI-S) score specifically related to agitation; comparison versus placebo."}
Recruitment
- Planned Sample Size
- 251
- Recruitment Window Months
- 37
- Consent Approach
- Informed consent is obtained via subject information sheets and informed consent forms. For this vulnerable population (participants with AD), a caregiver/study partner is required and is expected to provide informed consent; study-partner ICFs and adult assent forms are included. Consent/assent documentation exists in multiple language/country-specific versions (examples in the document list: EN, BG, PT, GR, HR, RO, ES).
Methods
- Site-based recruitment using study-site recruitment materials: PI-to-patient/participant letters, recruitment posters, study intro trifolds and caregiver fact sheets. Country-specific recruitment materials/documents are provided (document list includes K1/K2 recruitment materials for BG, PT, GR, ES, HR, RO).
Geography
- Total Number Of Sites
- 51
- Total Number Of Participants
- 103
Romania
- Earliest CTIS Part Ii Submission Date
- 11-07-2025
- Latest Decision Or Authorization Date
- 21-04-2026
- Processing Time Days
- 284
- Number Of Sites
- 13
- Number Of Participants
- 25
Sites
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Laura Cristina Dolis
- Contact Person Email
- drcristinadolis@gmail.com
- Site Name
- Institutul De Psihiatrie Socola Iasi
- Department Name
- Psychiatry
- Contact Person Name
- Cristinel Stefanescu
- Contact Person Email
- cristinel.stefanescu@gmail.com
- Site Name
- Centrul de Evaluare și Tratament a Toxicodependenței pentru Tineri Sf.Stelian
- Department Name
- Psychiatry
- Contact Person Name
- Tr Barbu
- Contact Person Email
- trabar98@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Si Neurologie Brasov
- Department Name
- Psychiatry
- Contact Person Name
- Petru Ifteni
- Contact Person Email
- relatiicupublicul@spnbrasov.ro
- Site Name
- Spitalul Clinic De Psihiatrie Dr. Gheorghe Preda Sibiu
- Department Name
- Psychiatry
- Contact Person Name
- Ciprian Bacila
- Contact Person Email
- bacila_c@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Corina Mihaela Nicolae
- Contact Person Email
- corina_panzaru@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Mihnea Manea
- Contact Person Email
- maneamihnea@gmail.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Valentin Matei
- Contact Person Email
- valipmatei@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Simona Trifu
- Contact Person Email
- simonatrifu@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Adela Ciobanu
- Contact Person Email
- adela.ciobanu@yahoo.com
- Site Name
- Spitalul Universitar De Urgenta Militar Central Dr. Carol Davila
- Department Name
- Psychiatry
- Contact Person Name
- Octavian Vasiliu
- Contact Person Email
- octavvasiliu@yahoo.com
- Site Name
- Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
- Department Name
- Psychiatry
- Contact Person Name
- Mihaela Cleopatra Rosca
- Contact Person Email
- mihaelarosca@gmail.com
- Site Name
- Cai Ferate Clinical Hospital Constanta
- Department Name
- Neurology
- Contact Person Name
- Ana Maria Ionescu
- Contact Person Email
- iuliusana@gmail.com
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 10-10-2025
- Latest Decision Or Authorization Date
- 20-04-2026
- Processing Time Days
- 192
- Number Of Sites
- 5
- Number Of Participants
- 10
Sites
- Site Name
- Medical Center Saint Naum EOOD
- Department Name
- Psychiatry
- Contact Person Name
- Asen Karadaliev
- Contact Person Email
- xxxx@xxxx.com
- Site Name
- Outpatient Clinic for Indiv. Practice for Spec.Med. Care in Psychiatry-Dr.Madlena Dimitrova Borisova
- Department Name
- Psychiatry
- Contact Person Name
- Madlena Borisova
- Contact Person Email
- dr.madlena.d.borisova@gmail.com
- Site Name
- Medical Center Medconsult Pleven OOD
- Department Name
- Psychiatry
- Contact Person Name
- Maria Aleksandrova
- Contact Person Email
- xxxx@xxxx.com
- Site Name
- Mental Health Center Sofia EOOD
- Department Name
- Department for active treatment of individuals with severe psychiatric disorders – Psychiatry, Level
- Contact Person Name
- Emil Grashnov
- Contact Person Email
- xxxx@xxxx.com
- Site Name
- Diagnostics-Consultancy Center Mladost M Varna OOD
- Department Name
- Psychiatry
- Contact Person Name
- Hristo Kozhuharov
- Contact Person Email
- mcoffice@mkmladost.com
Portugal
- Earliest CTIS Part Ii Submission Date
- 06-10-2025
- Latest Decision Or Authorization Date
- 17-04-2026
- Processing Time Days
- 193
- Number Of Sites
- 6
- Number Of Participants
- 8
Sites
- Site Name
- CNS Saude Lda.
- Department Name
- Neurology
- Contact Person Name
- Camila Nobrega
- Contact Person Email
- xxxxx@xxxx.com
- Site Name
- Unidade Local De Saude De Matosinhos E.P.E.
- Department Name
- Neurology
- Contact Person Name
- Vítor Cruz
- Contact Person Email
- investigacao@ulsm.min-saude.pt
- Site Name
- Unidade Local De Saude De Santa Maria E.P.E.
- Department Name
- Neurology
- Contact Person Name
- Ana Verdelho
- Contact Person Email
- xxxxx@xxxx.com
- Site Name
- Unidade Local De Saude Do Alto Ave E.P.E.
- Department Name
- Neurology
- Contact Person Name
- Joana Meireles
- Contact Person Email
- centroacademico@hospitaldeguimaraes.min-saude.pt
- Site Name
- Unidade Local De Saude De Coimbra E.P.E.
- Department Name
- Neurology
- Contact Person Name
- Maria Isabel Santana
- Contact Person Email
- xxxxx@xxxx.com
- Site Name
- Unidade Local De Saude De Coimbra E.P.E.
- Department Name
- Neurology
- Contact Person Name
- Maria Isabel Santana
- Contact Person Email
- xxxxx@xxxx.com
Croatia
- Earliest CTIS Part Ii Submission Date
- 22-09-2025
- Latest Decision Or Authorization Date
- 21-04-2026
- Processing Time Days
- 211
- Number Of Sites
- 4
- Number Of Participants
- 13
Sites
- Site Name
- KBC Split
- Department Name
- Psychiatry
- Contact Person Name
- Trpimir Glavina
- Contact Person Email
- psihijatrija@kbsplit.hr
- Site Name
- Clinical Hospital Centre Rijeka
- Department Name
- Psychiatry
- Contact Person Name
- Vladimir Sabljić
- Contact Person Email
- vladimir.sabljic@ri.t-com.hr
- Site Name
- KBC Zagreb
- Department Name
- Neurology
- Contact Person Name
- Nataša Klepac
- Contact Person Email
- natasaklepac@gmail.com
- Site Name
- Opca Bolnica Varazdin
- Department Name
- Neurology
- Contact Person Name
- Spomenka Kiđemet Piskač
- Contact Person Email
- spiskac@gmail.com
Greece
- Earliest CTIS Part Ii Submission Date
- 11-07-2025
- Latest Decision Or Authorization Date
- 17-04-2026
- Processing Time Days
- 280
- Number Of Sites
- 10
- Number Of Participants
- 18
Sites
- Site Name
- Eginitio Hospital
- Department Name
- A’ Department of Neurology
- Contact Person Name
- Nikolaos Scarmeas
- Contact Person Email
- ns257@columbia.edu
- Site Name
- General University Hospital Of Patras
- Department Name
- Department of Neurology
- Contact Person Name
- John Ellul
- Contact Person Email
- ellul@upatras.gr
- Site Name
- Eginitio Hospital
- Department Name
- First Department of Psychiatry
- Contact Person Name
- Nikolaos Stefanis
- Contact Person Email
- nistefan@med.uoa.gr
- Site Name
- University General Hospital Of Ioannina
- Department Name
- Department of Neurology
- Contact Person Name
- Spyridon Konitsiotis
- Contact Person Email
- skonitso@uoi.gr
- Site Name
- University General Hospital Attikon
- Department Name
- 2nd Department of Neurology
- Contact Person Name
- Georgios Tsivgoulis
- Contact Person Email
- tsivgoulisgiorg@yahoo.gr
- Site Name
- Euromedica General Clinic Of Thessaloniki
- Department Name
- Neurological Department
- Contact Person Name
- Magdalini Tsolaki
- Contact Person Email
- tsolakim@gmail.com
- Site Name
- Henry Dunant Hospital Center
- Department Name
- 2nd Neurological Clinic
- Contact Person Name
- Konstantina Yiannopoulou
- Contact Person Email
- k.giannopoulou.14@hotmail.com
- Site Name
- Athens Medical Center S.A.
- Department Name
- Memory Clinic
- Contact Person Name
- Ioannis Papatriantafyllou
- Contact Person Email
- ipapatriantafyllou@gmail.com
- Site Name
- Eginitio Hospital
- Department Name
- A’ Department of Neurology
- Contact Person Name
- Nikolaos Scarmeas
- Contact Person Email
- ns257@columbia.edu
- Site Name
- General University Hospital Of Patras
- Department Name
- Department of Neurology
- Contact Person Name
- John Ellul
- Contact Person Email
- ellul@upatras.gr
Spain
- Earliest CTIS Part Ii Submission Date
- 14-08-2025
- Latest Decision Or Authorization Date
- 21-04-2026
- Processing Time Days
- 281
- Number Of Sites
- 13
- Number Of Participants
- 29
Sites
- Site Name
- Hospital Universitario Rio Hortega
- Department Name
- Neurología
- Contact Person Name
- Juan Muñoz Sanchez
- Contact Person Email
- jlmusa@icloud.com
- Site Name
- Hospital Universitario Virgen De La Victoria
- Department Name
- Neurología
- Contact Person Name
- Carlos De La Cruz Cosme
- Contact Person Email
- XXXX@XXXX.XX
- Site Name
- Oroitu S.L.
- Department Name
- Neurología
- Contact Person Name
- MANUEL FERNANDEZ
- Contact Person Email
- mfernandezm@oroitu.com
- Site Name
- Consorci Sanitari De Terrassa
- Department Name
- Neurología
- Contact Person Name
- Jerzy Krupinski
- Contact Person Email
- jkrupinski@mutuaterrassa.es
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Neurología
- Contact Person Name
- Jordi Matias Guiu
- Contact Person Email
- miguel.sanchez@salud.madrid.org
- Site Name
- Hospital General Universitario De Elche
- Department Name
- gonzalez_glocab@gva.es
- Contact Person Name
- Maria Gloria González Caballero
- Contact Person Email
- gonzalez_glocab@gva.es
- Site Name
- Hospital Ruber Juan Bravo
- Department Name
- Neurología
- Contact Person Name
- Juan Lopez Lozano
- Contact Person Email
- XXXX@XXXX.XX
- Site Name
- Hospital Victoria Eugenia De La Cruz Roja Espanola
- Department Name
- Neurología
- Contact Person Name
- Felix Viñuela Fernandez
- Contact Person Email
- XXXX@XXXX.XX
- Site Name
- Hospital Universitario De Salamanca
- Department Name
- Neurología
- Contact Person Name
- Angel Luis Montejo
- Contact Person Email
- amontejo@usal.es
- Site Name
- Clinica Universidad De Navarra
- Department Name
- Neurología
- Contact Person Name
- Mario Riverol Fernandez
- Contact Person Email
- mriverol@unav.es
- Site Name
- Clinica Montecanal S.L.
- Department Name
- Neurología
- Contact Person Name
- Antonio Oliveros-Cid
- Contact Person Email
- XXXX@XXXX.XX
- Site Name
- Hospital General Universitario De Elche
- Department Name
- Neurología
- Contact Person Name
- Maria Gloria González Caballero
- Contact Person Email
- gonzalez_glocab@gva.es
- Site Name
- Hospital Universitario Rio Hortega
- Department Name
- Neurología
- Contact Person Name
- Juan Muñoz Sanchez
- Contact Person Email
- jlmusa@icloud.com
Sponsor
Primary sponsor
- Full Name
- Bristol-Myers Squibb Services Unlimited Company
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Ireland
Contract research organisations
- Name
- Syneos Health Inc.
- Responsibilities
- Subject Eligibility Review
- Name
- Iqvia Holdings Inc.
- Responsibilities
- Site Payments
Third parties
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Subject Eligibility Review","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":"Iqvia Holdings Inc.","duties_or_roles":"Site Payments","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"}
- {"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"}
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
- Authorisation Status
- Not applicable
- Investigational Product Name
- KarX-EC matching Placebo
- Modality
- Other
- Authorisation Status
- Not applicable
- Combination Treatment
- Yes
Related trials
Other published trials that may interest you.