Alzheimer Disease
Conditions
Brief 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
Specified dose on specified days
Specified dose on specified days
DRUGPlacebo
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
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 5 to 22, inclusive, at Screening (Visit 1). * Have one identified caregiver who should have sufficient contact (approximately 10 hours a week or more) 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). * CGI-S ≥ 4, as related to agitation, at Screening (Visit 1) and Baseline (Visit 2). * 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): i) 1 or more aggressive behaviors occurring at least several times per week. ii) 2 or more aggressive behaviors occurring at least once or twice per week. iii) 3 or more aggressive behaviors occurring less than once per week.
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. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1). \- Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline on the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) total score at Week 14 | At Week 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline on the Clinical Global Impressions-Severity (CGI-S) at Week 14 | At Week 14 | — |
| Change from baseline on the CMAI-IPA Domains at Week 14 | At Week 14 | — |
| Change from baseline on the CMAI Total Score at Week 14 | At Week 14 | — |
| Number of participants with Occurrence of Response at Week 14 | At Week 14 | As determined by CMAI-IPA changes of at least 30%, 40%, and 50% from baseline |
| Change from baseline on the Neuropsychiatric Inventory/Neuropsychiatric Inventory -Nursing Home (NPI/NPI-NH) Total Score at Week 14 | At Week 14 | — |
| Number of participants with Adverse Events (AEs) | Up to Week 18 | — |
| Number of participants with Treatment Emergent AEs (TEAEs) | Up to Week 18 | — |
| Number of participants with Serious AEs (SAEs) | Up to Week 18 | — |
| Number of participants with AEs leading to study drug withdrawal | Up to Week 18 | — |
| Number of deaths | Up to Week 18 | — |
| Number of participants with AEs of Special Interest (AESIs) | Up to Week 18 | — |
| Barnes Akathisia Rating Scale (BARS) | Up to Week 18 | — |
| Abnormal Involuntary Movement Scale (AIMS) | Up to Week 18 | — |
| Body Weight | Up to Week 18 | — |
| Body Mass Index (BMI) | Up to Week 18 | — |
| Number of participants with vital sign abnormalities | Up to Week 18 | — |
| Number of participants with clinical laboratory abnormalities | Up to Week 18 | — |
| Number of participants with electrocardiogram (ECG) abnormalities | Up to Week 18 | — |
| Number of participants with suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to Week 18 | — |
| Severity of benign prostatic hyperplasia in male participants as assessed by International Prostate Symptom Score (IPSS) | Up to Week 18 | — |
Countries
Argentina, Brazil, Bulgaria, Canada, China, Croatia, Greece, India, Japan, Mexico, Portugal, Romania, Spain, Taiwan, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed