A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1)

Phase 3

Recruiting

• Conditions: Psychosis Associated With Alzheimer's Disease
• Interventions: Drug: Placebo; Drug: KarXT

• Registration Number: NCT05511363
• Lead Sponsor: Karuna Therapeutics

Brief Summary

This is a Phase 3, 38-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with psychosis associated with Alzheimer's Disease.

The primary objective of the study is to evaluate relapse prevention in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo. The secondary objectives of the study are to evaluate the time from randomization to discontinuation for any reason and safety and tolerability in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-19
• Study First Submitted QC: 2022-08-19
• Study Start: 2022-08-23
• Study First Posted: 2022-08-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-11
• Primary Completion: 2026-10-05
• Study Completion: 2026-10-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

1. Is aged 55 to 90 years, inclusive, at Screening

2. Can understand the nature of the study and protocol requirements and provide a signed informed consent form before any study assessments are performed. If the subject is deemed not competent to provide consent, the following requirements for consent must be met.

   1. The subject's legally acceptable representative or caregiver/study partner, if local regulations allow, must provide informed consent
   2. The subject must provide informed assent

3. Meets clinical criteria for possible or probable Alzheimer's Disease

4. Has 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. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.

5. Living at the same home or residential assisted-living facility for a minimum of six weeks before Screening

6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver (spends approximately 10 hours/week with the subject) that is willing to:

   1. Attend all visits and report on subject's status
   2. Oversee subject compliance with medication and study procedures
   3. Participate in the study assessments and provide informed consent to participate in the study

7. History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria) for at least 2 months prior to Screening.

8. Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) at Screening and Baseline. CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions.

9. Subjects are required to meet at least one of the following criteria at Screening and Baseline:

   1. Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR
   2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items.

10. Mini-Mental State Examination (MMSE) score of 8 to 22, inclusive, at Screening

11. If the subject is taking a cholinesterase inhibitor and/or memantine, they must have been on a stable dose for 6 weeks prior to Screening and be willing to maintain a stable dose for the duration of the study.

12. Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements

13. BMI must be within 18 to 40 kg/m2 inclusive

14. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matching placebo. Sperm donation is not allowed for 30 days after the final dose of the IMP or matching placebo.

Exclusion Criteria

1. Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia

2. History of major depressive episode with psychotic features during the 12 months prior to Screening

3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder

4. Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular or oncologic disease, or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results

5. Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of <60 mL/min/1.73 m2

6. History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke

7. History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope

8. Any of the following:

   1. New York Heart Association Class 2 congestive heart failure
   2. Grade 2 or greater angina pectoris
   3. Sustained ventricular tachycardia
   4. Ventricular fibrillation
   5. Torsade de pointes
   6. Implantable cardiac defibrillator

9. Myocardial infarction within the 6 months prior to Screening

10. Personal or family history of symptoms of long QT syndrome as evaluated by the investigator

11. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results

12. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator

13. For males only, any one of the following:

    1. History of bladder stones
    2. History of recurrent urinary tract infections
    3. Serum prostate specific antigen (PSA) > 10 ng/mL at Screening
    4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6
    5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9

14. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months

15. Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS

16. Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening

17. Urine toxicology screen is positive substances other than cannabis or benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor

18. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate)

    1. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted
    2. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening. If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor.

19. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements

20. Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening; antigen or PCR local testing can be done at the discretion of the Investigator

21. Unable to taper and discontinue a concomitant medication that would preclude participation in the study

22. Prior exposure to KarXT

23. Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium

24. Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening or has participated in more than 2 clinical studies in the past year

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Capsules
KarXT	KarXT	Xanomeline and Trospium Chloride Capsules

Primary Outcome Measures

Name	Time	Method
Time from randomization to relapse during the 38-week study	Week 38

Secondary Outcome Measures

Name	Time	Method
Time from randomization to discontinuation for any reason during the 38-week study	Week 38

Trial Locations

Locations (113)

Asclepes Research; 🇺🇸 Encino, California, United States

Local Institution - 1031; 🇺🇸 Irvine, California, United States

Sunwise Clinical Research, LLC - IVY - PPDS; 🇺🇸 Lafayette, California, United States

Tilda Alabama - PPDS; 🇺🇸 Homewood, Alabama, United States

IMA Clinical Research - Phoenix - PPDS; 🇺🇸 Phoenix, Arizona, United States

ATP Clinical Research; 🇺🇸 Costa Mesa, California, United States

SC3 Research - Pasadena - 960 E. Green St; 🇺🇸 Pasadena, California, United States

The Neuron Clinic; 🇺🇸 San Marcos, California, United States

Colorado Springs Neurological Associates; 🇺🇸 Colorado Springs, Colorado, United States

Ki Health Partners LLC DBA New England Institute for Clinical Research; 🇺🇸 Stamford, Connecticut, United States

South Florida Neurology Associates; 🇺🇸 Boca Raton, Florida, United States

Envision Trials LLC; 🇺🇸 Bonita Springs, Florida, United States

Local Institution - 1015; 🇺🇸 Bradenton, Florida, United States

K2 Medical Research - Winter Garden; 🇺🇸 Clermont, Florida, United States

Arrow Clinical Trials; 🇺🇸 Daytona Beach, Florida, United States

Betancourt Research Services; 🇺🇸 Doral, Florida, United States

United Research Institute; 🇺🇸 Hialeah, Florida, United States

Local Institution - 1024; 🇺🇸 Hialeah, Florida, United States

Coral Clinic Research; 🇺🇸 Homestead, Florida, United States

K2 Medical Research - Maitland; 🇺🇸 Maitland, Florida, United States

San Marcus Research Clinic Inc; 🇺🇸 Miami Lakes, Florida, United States

Local Institution - 1115; 🇺🇸 Miami Lakes, Florida, United States

Ocean Blue Medical Research Center Inc; 🇺🇸 Miami Springs, Florida, United States

South Florida Research Phase I - IV; 🇺🇸 Miami Springs, Florida, United States

Premier Clinical Research Institute - Miami - ClinEdge - PPDS; 🇺🇸 Miami, Florida, United States

Global Medical Institutes, LLC - Miami - ClinEdge - PPDS; 🇺🇸 Miami, Florida, United States

Local Institution - 1111; 🇺🇸 Miami, Florida, United States

Miami Jewish Health Systems; 🇺🇸 Miami, Florida, United States

MedOne Clinical Research LLC; 🇺🇸 Miami, Florida, United States

Allied Biomedical Research Institute; 🇺🇸 Miami, Florida, United States

Future Care Solution LLC; 🇺🇸 Miami, Florida, United States

Local Institution - 1006; 🇺🇸 Miami, Florida, United States

Coral Research Clinic & Coral Diagnostic Center; 🇺🇸 Miami, Florida, United States

ONHEALTH Research Center; 🇺🇸 Miami, Florida, United States

Las Mercedes Clinical Research West Kendall; 🇺🇸 Miami, Florida, United States

Local Institution - 1027; 🇺🇸 Ocala, Florida, United States

Emerald Coast Center for Neurological Disorders; 🇺🇸 Pensacola, Florida, United States

Suncoast Neuroscience Associates Inc; 🇺🇸 Saint Petersburg, Florida, United States

Local Institution - 1050; 🇺🇸 Tampa, Florida, United States

K2 Medical Research - Tampa; 🇺🇸 Tampa, Florida, United States

Local Institution - 1040; 🇺🇸 The Villages, Florida, United States

Research Network America - Chicago - 3845 W 26th St; 🇺🇸 Chicago, Illinois, United States

The Feinstein Institutes for Medical Research - BRANY - PPDS; 🇺🇸 Manhasset, New York, United States

Local Institution - 1030; 🇺🇸 New York, New York, United States

Columbia University Medical Center (CUMC); 🇺🇸 New York, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Richmond Behavioral Associates; 🇺🇸 Staten Island, New York, United States

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Five Towns Neurology, PC; 🇺🇸 Woodmere, New York, United States

Local Institution - 1003; 🇺🇸 Canton, Ohio, United States

Local Institution - 1028; 🇺🇸 Oklahoma City, Oklahoma, United States

Local Institution - 1016; 🇺🇸 Oklahoma City, Oklahoma, United States

Lehigh Center for Clinical Research - 401 N 17th St; 🇺🇸 Allentown, Pennsylvania, United States

Medical University of South Carolina (MUSC) - PPDS; 🇺🇸 Charleston, South Carolina, United States

KCA Neurology, PLLC; 🇺🇸 Franklin, Tennessee, United States

North Pointe Psychiatry - Flower Mound; 🇺🇸 Flower Mound, Texas, United States

Beautiful Minds; 🇺🇸 Frisco, Texas, United States

Clinical Trial Network - 7080 Southwest Fwy; 🇺🇸 Houston, Texas, United States

Medical Center Sveti Naum EOOD; 🇧🇬 Sofia, Sofia-Grad, Bulgaria

Clinoxus s.r.o.; 🇨🇿 Praha 4, Czechia

Vestra Clinics s.r.o.; 🇨🇿 Rychnov nad Kneznou, Czechia

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD; 🇧🇬 Sofia, Sofia-Grad, Bulgaria

Medical Center Hera EOOD; 🇧🇬 Sofia, Sofia-Grad, Bulgaria

Medical Center Medconsult Pleven OOD; 🇧🇬 Pleven, Bulgaria

Center for Mental Health - Vratsa; 🇧🇬 Vratsa, Bulgaria

Klinicki bolnicki centar Zagreb; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Poliklinika Bonifarm-Hondlova 2/10; 🇭🇷 Zagreb, Grad Zagreb, Croatia

A-SHINE s.r.o.; 🇨🇿 Plzeň, Czechia

Polyclinic Neuron; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Psychiatric Clinic Sveti Ivan; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Klinika za psihijatriju Vrapce; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Local Institution - 4003; 🇨🇿 Brno, Jihomoravský Kraj, Czechia

CLINTRIAL s.r.o.; 🇨🇿 Praha, Praha, Hlavní Mesto, Czechia

Neuroterapie KH, s.r.o Psychiatricka ambulance; 🇨🇿 Kutná Hora, Czechia

CHU de Reims Hôpital Robert Debré; 🇫🇷 Reims, Marne, France

CHRU Dijon Hopital General; 🇫🇷 Dijon, France

CHU de Rouen - Hôpital Charles-Nicolle; 🇫🇷 Rouen, France

Medicum Gesundheitszentrum Flugfeld; 🇩🇪 Böblingen, Baden-Württemberg, Germany

Local Institution - 2403; 🇩🇪 Bayreuth, Bayern, Germany

Local Institution - 2402; 🇩🇪 Homburg, Saarland, Germany

Fondazione Santa Lucia IRCCS; 🇮🇹 Roma, Lazio, Italy

Azienda Ospedaliero-Universitaria di Modena - Policlinico di Modena; 🇮🇹 Baggiovara, Modena, Italy

ASL Biella - Ospedale degli Infermi; 🇮🇹 Ponderano (Biella), Piemonte, Italy

Azienda Ospedaliera Universitaria Careggi; 🇮🇹 Firenze, Toscana, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy

Fondazione IRCCS San Gerardo dei Tintori; 🇮🇹 Monza, Italy

Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara; 🇮🇹 Pisa, Italy

Fondazione Policlinico Universitario A Gemelli - Rome - PPDS; 🇮🇹 Roma, Italy

Azienda Ospedaliero-Universitaria Sant'Andrea; 🇮🇹 Roma, Italy

University Clinical Center of Serbia - Pasterova 2 - PPDS; 🇷🇸 Beograd, Belgrade, Serbia

Clinical Hospital Center Dragisa Misovic Dedinje; 🇷🇸 Belgrade, Serbia

Institute of Mental Health-Milana Kasanina 3; 🇷🇸 Belgrade, Serbia

Military Medical Academy; 🇷🇸 Belgrade, Serbia

Special Hospital for Psychiatric Diseases Kovin; 🇷🇸 Kovin, Serbia

University Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Clinical Centre of Vojvodina; 🇷🇸 Novi Sad, Serbia

Special Hospital ''Dr Slavoljub Bakalovic''; 🇷🇸 Vršac, Serbia

Univerzitna nemocnica L Pasteura Kosice-Rastislavova 43; 🇸🇰 Kosice, Košický Kraj, Slovakia

MUDr. Beata Dupejova, Neurologicka ambulancia, s.r.o.; 🇸🇰 Banská Bystrica, Slovakia

KONZILIUM s.r.o; 🇸🇰 Dubnica nad Váhom, Slovakia

EPAMED s.r.o; 🇸🇰 Košice, Slovakia

Crystal Comfort, s.r.o.; 🇸🇰 Vranov nad Topľou, Slovakia

Local Institution - 4404; 🇸🇰 Žilina, Slovakia

Ace Alzheimer Center Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario de la Princesa; 🇪🇸 Madrid, Spain

Complejo Asistencial Universitario de Salamanca - H. Clinico; 🇪🇸 Salamanca, Spain

Hospital Victoria Eugenia; 🇪🇸 Sevilla, Spain

Hospital Universitario Rio Hortega; 🇪🇸 Valladolid, Spain

Hospital Provincial de Zamora; 🇪🇸 Zamora, Spain

Hospital Viamed Montecanal; 🇪🇸 Zaragoza, Spain

Local Institution - 2103; 🇬🇧 Swindon, Wiltshire, United Kingdom

Local Institution - 2105; 🇬🇧 Aberdeen, United Kingdom

Local Institution - 2104; 🇬🇧 Motherwell, United Kingdom