A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-2)

Phase 3

Not yet recruiting

• Conditions: Alzheimer Disease
• Interventions: Drug: Xanomeline/Trospium Chloride Capsule; Drug: Placebo; Drug: Xanomeline Enteric Capsule

• Registration Number: NCT07011745
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-02
• Study First Submitted QC: 2025-06-02
• Study First Posted: 2025-06-10
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-27
• Study Start: 2025-07-18
• Primary Completion: 2028-10-25
• Study Completion: 2028-11-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 352

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 several times per week.

ii) 2 or more aggressive behaviors occurring 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/Exclusion criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KarXT + KarX-EC	Xanomeline/Trospium Chloride Capsule	-
KarXT + KarX-EC	Xanomeline Enteric Capsule	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Mean change from baseline on the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) total score at Week 14	At Week 14

Secondary Outcome Measures

Name	Time	Method
Number of participants with Occurrence of Response at Week 14	At Week 14	As determined by CMAI-IPA changes of 30%, 40%, and 50% from baseline
Mean 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 suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	Up to Week 18
Mean change from baseline on the Clinical Global Impressions-Severity (CGI-S) at Week 14	At Week 14
Mean change from baseline on the CMAI-IPA Domains at Week 14	At Week 14
Mean change from baseline on the CMAI Total Score at Week 14	At Week 14
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
Severity of benign prostatic hyperplasia in male participants as assessed by International Prostate Symptom Score (IPSS)	Up to Week 18

Trial Locations

Locations (191)

Local Institution - 0080; 🇺🇸 Chandler, Arizona, United States

Local Institution - 2609; 🇺🇸 Chandler, Arizona, United States

Local Institution - 2631; 🇺🇸 Chandler, Arizona, United States

Local Institution - 0117; 🇺🇸 Canoga Park, California, United States

Local Institution - 0122; 🇺🇸 Long Beach, California, United States

Local Institution - 2625; 🇺🇸 Long Beach, California, United States

Local Institution - 0074; 🇺🇸 Long Beach, California, United States

Local Institution - 2607; 🇺🇸 Long Beach, California, United States

Local Institution - 2627; 🇺🇸 Napa, California, United States

Local Institution - 0105; 🇺🇸 Pasadena, California, United States

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