Recruiting NCT07011732

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-1)

Phase III Interventional Alzheimer Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Xanomeline/Trospium Chloride Capsule, Xanomeline Enteric Capsule, Placebo.
Who it may be relevant to: Registry conditions: Alzheimer Disease. Basic parameters: 55 years — 90 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Brazil, Bulgaria, Canada +10
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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 Agitation Associated With Alzheimer's Disease

Overview

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

Drug Xanomeline/Trospium Chloride Capsule
Specified dose on specified days
Drug Xanomeline Enteric Capsule
Specified dose on specified days
Drug Placebo
Specified dose on specified days

Primary outcome measures

Change from baseline on the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) Total Score at Week 14 [Time frame: At Week 14]

Secondary outcome measures (12)

Change from baseline on the Clinical Global Impressions-Severity (CGI-S) at Week 14 [Time frame: At Week 14]
Change from baseline on the CMAI-IPA Domains at Week 14 [Time frame: At Week 14]
Change from baseline on the CMAI Total Score at Week 14 [Time frame: At Week 14]
Number of participants with Occurrence of Response at Week 14 [Time frame: At Week 14]
Change from baseline on the Neuropsychiatric Inventory/Neuropsychiatric Inventory -Nursing Home (NPI/NPI-NH) Total Score at Week 14 [Time frame: At Week 14]
Number of participants with Adverse Events (AEs) [Time frame: Up to Week 18]
Number of participants with Treatment Emergent AEs (TEAEs) [Time frame: Up to Week 18]
Number of participants with Serious AEs (SAEs) [Time frame: Up to Week 18]
Number of participants with AEs leading to study drug withdrawal [Time frame: Up to Week 14]
Number of deaths [Time frame: Up to Week 18]
Number of participants with AEs of Special Interest (AESIs) [Time frame: Up to Week 18]
Barnes Akathisia Rating Scale (BARS) [Time frame: Up to Week 14]

Eligibility criteria

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 ≤ 24 at Screening (Visit 1).
Have an identified caregiver who has sufficient contact (approximately 8 hours over a week) 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).
CMAI-IPA Total Score ≥ 30 at Screening (Visit 1) and Baseline (Visit 2).

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. Trazodone may be used as a hypnotic or for agitation if started at least 8 weeks prior to Screening (Visit 1).

C. Mirtazapine may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1).

\- Other protocol-defined Inclusion/Exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment

Study locations

United States · 39 centers

Imaging Endpoints — Scottsdale
Advanced Research Center (ARC) - Anaheim — Anaheim
Local Institution - 1637 — La Jolla
The Neurology Group — Pomona
Local Institution - 1639 — Torrance
Sunwise Clinical Research — Walnut Creek
Local Institution - 1630 — Colorado Springs
Local Institution - 1622 — Maitland
… and 31 more centers

China · 17 centers

Xuanwu Hospital Capital Medical University — Beijing
Local Institution - 1810 — Beijing
Peking University Sixth Hospital — Haidian District
The First Affiliated Hospital of Chongqing Medical University — Chongqing
The Affiliated Brain Hospital of Guangzhou Medical University — Guangzhou
Shenzhen Kangning Hospital — Shenzhen
The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou
Xiangya Hospital Central South University — Changsha
… and 9 more centers

Romania · 14 centers