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RecruitingPhase 3

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)

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
55 Years to 90 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how well KarXT + KarX-EC works and how safe it is. It is for adults with Alzheimer's disease who have agitation, such as restless or aggressive behavior.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have Alzheimer's disease confirmed by an approved brain scan, blood test, or spinal fluid test.
  • Score 24 or lower on the MMSE, a test of memory and thinking, at screening.
  • Have a caregiver with about 8 hours of contact each week who agrees to attend all visits, report on your health, help with study medicines and tasks, and take part in study checks.
  • Have agitation that meets the study's definition and began at least 2 weeks before screening.
  • Score at least 4 on the NPI/NPI-NH agitation and aggression rating at screening and the starting visit.
  • Score at least 30 on the CMAI-IPA agitation rating at screening and the starting visit.

Who can't join

  • Agitation mainly caused by something other than Alzheimer's disease.
  • A history of bipolar disorder, schizophrenia, or schizoaffective disorder.
  • A history of, or high risk for, trouble emptying the bladder or stomach, or narrow-angle glaucoma, an eye condition that can raise eye pressure.
  • Risk of suicidal behavior during the study, based on the study doctor's review.
  • Recent use of certain medicines for seizures, mood, depression, or other mental health symptoms. Anxiety medicine taken only as needed may be allowed.
  • Some antidepressants called SSRIs or SNRIs may be allowed if the dose has stayed the same for at least 8 weeks before screening.
  • Trazodone for sleep or agitation, or mirtazapine for sleep, may be allowed if started at least 8 weeks before screening.
  • Other study rules for who can and cannot join also apply.

Simplified for readability. The official criteria below are what the study team uses.

Official 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.

Study sites (41)

AZ

CA

CO

FL

LA

MA

MD

MI

MO

NJ

NV

NY

OK

SC

TX

UT

VT

WA