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)

Purpose

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.

Condition

  • Alzheimer Disease

Eligibility

Eligible Ages
Between 55 Years and 90 Years
Eligible Sex
All
Accepts 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/Exclusion criteria apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
KarXT + KarX-EC
  • Drug: Xanomeline/Trospium Chloride Capsule
    Specified dose on specified days
    Other names:
    • KarXT
    • BMS-986510
  • Drug: Xanomeline Enteric Capsule
    Specified dose on specified days
    Other names:
    • KarX-EC
    • BMS-986519
Placebo Comparator
Placebo
  • Drug: Placebo
    Specified dose on specified days

Recruiting Locations

Chandler Clinical Trials, LLC
Chandler, Arizona 85224
Contact:
Ari Magill, Site 2609
480-382-7909

National Institute of Clinical Research
Garden Grove, California 92844
Contact:
Michael Dao, Site 2625

Accellacare
Long Beach, California 90807
Contact:
Elizabeth Zarate Rowell, Site 2642

Alliance Clinical -West Hills
West Hills, California 91307
Contact:
Leon Barkodar, Site 2620
818-257-3140

Envision Trials LLC
Bonita Springs, Florida 34134-4154
Contact:
Daniel Mandri, Site 2602
305-819-2909

Key Clinical Research
Bradenton, Florida 34207
Contact:
Nicholas Weber, Site 2624
+61736460818

IPTB Clinical Research
Tampa, Florida 33629
Contact:
Jamie Fernandez, Site 2621
813-251-1800

Agile Clinical Research Trials, LLC
Atlanta, Georgia 30328
Contact:
Vasundhara Cheekati, Site 2611
404-382-8660

Vitalix Clinical
Worcester, Massachusetts 01608
Contact:
James Carroll, Site 2615
413-214-3546

Michigan Clinical Research Institute PC
Ann Arbor, Michigan 48105
Contact:
Ravi Kirbat, Site 2618
734-834-8954

Hattiesburg Clinic
Hattiesburg, Mississippi 39402
Contact:
Ronald Schwartz, Site 2629
601-606-0911

Las Vegas Clinical Trials
Las Vegas, Nevada 89030
Contact:
Alton Walters, Site 2628
702-637-3223

Richmond Behavioral Associates
Staten Island, New York 10312
Contact:
Romana Kulikova, Site 2619
718-619-4403

West Clinical Research
Morehead City, North Carolina 28557
Contact:
Patrick Morgante, Site 2608
252-515-0050

Velocity Clinical Research - Blue Ash
Blue Ash, Ohio 45242
Contact:
Babu Gupta, Site 2617
513-769-2767

Epic Medical Research, LLC - Carrolton
Carrollton, Texas 75006
Contact:
Andrea Brown, Site 2616
972-782-2405

Horizon Clinical Research Center - Houston
Cypress, Texas 77065
Contact:
Harpaul Gill, Site 2605
770-205-5292

Epic Medical Research, LLC - Mesquite
Mesquite, Texas 75150
Contact:
Laquita Shepherd, Site 2622
972-777-6956

UT Health - San Antonio
San Antonio, Texas 78229
Contact:
Antonio Teixeira, Site 2623
210-567-8229

More Details

Status
Recruiting
Sponsor
Bristol-Myers Squibb

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
855-907-3286
Clinical.Trials@bms.com