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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

31 Oct 2025 → ongoing

Decision date (initial)

2025-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2025-520613-31-00

WHO UTN

U1111-1316-5745

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the efficacy of KarXT + KarX-EC compared with placebo in the treatment of participants with agitation associated with AD as measured by the Cohen-Mansfield Agitation Inventory – International Psychogeriatric Association (CMAI-IPA) scale.

Secondary objectives 1

1. To demonstrate the efficacy of KarXT + KarX-EC compared with placebo in the treatment of participants with agitation associated with AD as measured by the Clinical Global Impressions – Severity (CGI-S) score.

Conditions and MedDRA coding

Agitation Associated with Alzheimer’s Disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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: - 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. - 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
2. Mini-Mental State Examination (MMSE) score of 5 to 22, inclusive, at Screening (Visit 1)
3. 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
4. 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).
5. AD participants are required to have NPI/NPI-NH Agitation/Aggression score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2).
6. CGI-S ≥ 4, as related to agitation, at Screening (Visit 1) and Baseline (Visit 2)
7. 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 3

1. 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
2. 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)
3. Other protocol-defined Inclusion/Exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to the end of treatment on the CMAI-IPA total score compared with placebo.

Secondary endpoints 1

1. Change from baseline to the end of treatment on the CGI-S as it relates specifically to agitation compared with placebo.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 7

Locations

6 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications