Clinical trial NCT06947941: A Study to Evaluate Safety and Efficacy of KarXT + KarX-EC as a Treatment for Psychosis Associated With Alzheimer's Disease (ADEPT-5)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Psychosis Associated With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Psychosis
Keywords: Alzheimer disease
Alzheimer
Dementia
Psychosis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-04-27
Enrollment: 1046
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate KarXT + KarX-EC as a treatment for psychosis associated with Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

* Participants must be 55 to 90 years of age, inclusive, at the time of Screening (Visit 1).
* Participants must be diagnosed with Alzheimer's disease in accordance with the 2024 NIA-AA criteria.
* Participants must have a magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome, eg, major stroke, neoplasm, subdural hematoma.
* Participants must have a history of psychotic symptoms (meeting International Psychogeriatric Association criteria) for at least 2 months prior to Screening (Visit 1) (participants may or may not have symptoms of agitation).

Exclusion Criteria:

* Participants must not have psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia, eg, schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features.
* Participants must not have history of major depressive episode with psychotic features during the 12 months prior to Screening, or history of bipolar disorder, schizophrenia, or schizoaffective disorder.
* Participants must not have certain safety concerns, including certain laboratory test irregularities.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Change From Baseline in Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions (NPI-C: H+D) Score
timeFrame: Up to Week 12
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score
timeFrame: Up to Week 12
measure: Change From Baseline in Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C) Core Score
timeFrame: Up to Week 12
measure: Change From Baseline in NPI-C: Agitation Score
timeFrame: Up to Week 12
measure: Change From Baseline in NPI-C Core Score: Caregiver Distress Scale
timeFrame: Up to Week 12
measure: Responder Rate
timeFrame: Up to Week 12
measure: Change From Baseline in Cohen-Mansfield Agitation Inventory International Psychogeriatric Association (CMAI-IPA) Score
timeFrame: Up to Week 12
measure: Change From Baseline in CMAI Total Score
timeFrame: Up to Week 12
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately Week 18
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to approximately Week 18
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately Week 18
measure: Number of Participants With TEAEs Leading to Discontinuation
timeFrame: Up to approximately Week 18
measure: Number of Participants With Spontaneously Reported Procholinergic Symptoms
timeFrame: Up to approximately Week 18
measure: Number of Participants With Spontaneously Reported Anticholinergic Symptoms
timeFrame: Up to approximately Week 18
measure: Number of Participants With AEs of Special Interest (AESIs) That Require Drug-induced Liver Injury (DILI) Monitoring
timeFrame: Up to approximately Week 18
measure: Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
timeFrame: Up to approximately Week 14
measure: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
timeFrame: Up to approximately Week 14
measure: Change From Baseline in International Prostate Symptom Score (IPSS)
timeFrame: Up to approximately Week 14
measure: Change From Baseline in Body Weight
timeFrame: Up to approximately Week 14
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Orthostatic Vital Sign: Heart Rate (HR)
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Orthostatic Vital Sign: Blood Pressure (BP)
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Hematology
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Clinical Chemistry
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Coagulation Parameters
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Prolactin Levels
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Urinalysis
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in Laboratory Evaluations: Drug Screening
timeFrame: Up to approximately Week 14
measure: Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG)
timeFrame: Up to approximately Week 14
measure: Number of Participants With Suicidal Ideations and Behavior as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to approximately Week 18
measure: Number of Participants With Cognitive Impairment as Assessed by Mini-mental State Examination (MMSE)
timeFrame: Up to approximately Week 14
measure: Number of Participants With Cognitive Impairment as Assessed by 13-item Variation of ADAS-Cog Scale (ADAS-Cog-13)
timeFrame: Up to approximately Week 14
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: